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Pessler, Frank
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Ogdie, Alexis R
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Kretzschmar, Warren W
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Elsaman, Ahmed M
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2014-03
Amyloid arthropathy associated with multiple myeloma: polyarthritis without synovial infiltration of CD20+ or CD38+ cells. 2014, 21 (1):28-34 Amyloid
1744-2818
24286442
10.3109/13506129.2013.862229
http://hdl.handle.net/10033/321804
Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis
To describe histological, immunohistochemical and ultrastructural features of synovial biopsies of amyloid arthropathy associated with multiple myeloma (MM).
en
Archived with thanks to Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis
Amyloid arthropathy associated with multiple myeloma: polyarthritis without synovial infiltration of CD20+ or CD38+ cells.
Article
2018-06-12T22:37:53Z
To describe histological, immunohistochemical and ultrastructural features of synovial biopsies of amyloid arthropathy associated with multiple myeloma (MM).
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oai:repository.helmholtz-hzi.de:10033/6209552019-08-30T11:24:31Zcom_10033_620601col_10033_620603
Möller, Jana C
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500
Cron, Randy Q
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500
Young, Daniel W
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Girschick, Hermann J
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500
Levy, Deborah M
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500
Sherry, David D
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500
Kukita, Akiko
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Saijo, Kaoru
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Pessler, Frank
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2017-06-16T08:07:40Z
2017-06-16T08:07:40Z
2011-02-01
2015-09-04T08:24:15Z
Pediatric Rheumatology. 2011 Feb 01;9(1):5
http://dx.doi.org/10.1186/1546-0096-9-5
http://hdl.handle.net/10033/620955
Abstract Spinal epidural lipomatosis is a rare complication of chronic corticosteroid treatment. We report a new pediatric case and an analysis of this and 19 pediatric cases identified in the international literature. The youngest of these combined 20 patients was 5 years old when lipomatosis was diagnosed. Lipomatosis manifested after a mean of 1.3 (+/- 1.5) years (SD) (median, 0.8 years; range, 3 weeks - 6.5 years) of corticosteroid treatment. The corticosteroid dose at the time of presentation of the lipomatosis ranged widely, between 5 and 80 mg of prednisone/day. Back pain was the most common presenting symptom. Imaging revealed that lipomatosis almost always involved the thoracic spine, extending into the lumbosacral region in a subset of patients. Predominantly lumbosacral involvement was documented in only two cases. Although a neurological deficit at presentation was documented in about half of the cases, surgical decompression was not performed in the cases reported after 1996. Instead, reducing the corticosteroid dose (sometimes combined with dietary restriction to mobilize fat) sufficed to induce remission. In summary, pediatric spinal epidural lipomatosis remains a potentially serious untoward effect of corticosteroid treatment, which, if recognized in a timely manner, can have a good outcome with conservative treatment.
Corticosteroid-induced spinal epidural lipomatosis in the pediatric age group: report of a new case and updated analysis of the literature
Journal Article
en
Möller et al; licensee BioMed Central Ltd.
2018-06-13T04:14:28Z
Abstract
Spinal epidural lipomatosis is a rare complication of chronic corticosteroid treatment. We report a new pediatric case and an analysis of this and 19 pediatric cases identified in the international literature. The youngest of these combined 20 patients was 5 years old when lipomatosis was diagnosed. Lipomatosis manifested after a mean of 1.3 (+/- 1.5) years (SD) (median, 0.8 years; range, 3 weeks - 6.5 years) of corticosteroid treatment. The corticosteroid dose at the time of presentation of the lipomatosis ranged widely, between 5 and 80 mg of prednisone/day. Back pain was the most common presenting symptom. Imaging revealed that lipomatosis almost always involved the thoracic spine, extending into the lumbosacral region in a subset of patients. Predominantly lumbosacral involvement was documented in only two cases. Although a neurological deficit at presentation was documented in about half of the cases, surgical decompression was not performed in the cases reported after 1996. Instead, reducing the corticosteroid dose (sometimes combined with dietary restriction to mobilize fat) sufficed to induce remission. In summary, pediatric spinal epidural lipomatosis remains a potentially serious untoward effect of corticosteroid treatment, which, if recognized in a timely manner, can have a good outcome with conservative treatment.
ORIGINAL
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oai:repository.helmholtz-hzi.de:10033/6207152019-08-30T11:26:42Zcom_10033_620601col_10033_620603
Klawonn, Frank
d40a2d4a33038bf1ab5a9c39b1d4852a
500
Jayaram, Balasubramaniam
6b4506eb45b670ba6771591caa5378e1
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Crull, Katja
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Kukita, Akiko
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Pessler, Frank
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2017-01-17T09:49:01Z
2017-01-17T09:49:01Z
2013-05-30
2015-09-04T08:29:46Z
Health Information Science and Systems. 2013 May 30;1(1):11
http://dx.doi.org/10.1186/2047-2501-1-11
http://hdl.handle.net/10033/620715
Abstract Contingency tables are a very common basis for the investigation of effects of different treatments or influences on a disease or the health state of patients. Many journals put a strong emphasis on p-values to support the validity of results. Therefore, even small contingency tables are analysed by techniques like t-test or ANOVA. Both these concepts are based on normality assumptions for the underlying data. For larger data sets, this assumption is not so critical, since the underlying statistics are based on sums of (independent) random variables which can be assumed to follow approximately a normal distribution, at least for a larger number of summands. But for smaller data sets, the normality assumption can often not be justified. Robust methods like the Wilcoxon-Mann-Whitney-U test or the Kruskal-Wallis test do not lead to statistically significant p-values for small samples. Median polish is a robust alternative to analyse contingency tables providing much more insight than just a p-value. Median polish is a technique that provides more information than just a p-value. It explains the contingency table in terms of an overall effect, row and columns effects and residuals. The underlying model for median polish is an additive model which is sometimes too restrictive. In this paper, we propose two related approach to generalise median polish. A power transformation can be applied to the values in the table, so that better results for median polish can be achieved. We propose a graphical method how to find a suitable power transformation. If the original data should be preserved, one can apply other transformations – based on so-called additive generators – that have an inverse transformation. In this way, median polish can be applied to the original data, but based on a non-additive model. The non-linearity of such a model can also be visualised to better understand the joint effects of rows and columns in a contingency table.
Analysis of contingency tables based on generalised median polish with power transformations and non-additive models
Journal Article
en
Klawonn et al.; licensee BioMed Central Ltd.
2018-06-13T05:22:22Z
Abstract
Contingency tables are a very common basis for the investigation of effects of different treatments or influences on a disease or the health state of patients. Many journals put a strong emphasis on p-values to support the validity of results. Therefore, even small contingency tables are analysed by techniques like t-test or ANOVA. Both these concepts are based on normality assumptions for the underlying data. For larger data sets, this assumption is not so critical, since the underlying statistics are based on sums of (independent) random variables which can be assumed to follow approximately a normal distribution, at least for a larger number of summands. But for smaller data sets, the normality assumption can often not be justified.
Robust methods like the Wilcoxon-Mann-Whitney-U test or the Kruskal-Wallis test do not lead to statistically significant p-values for small samples. Median polish is a robust alternative to analyse contingency tables providing much more insight than just a p-value.
Median polish is a technique that provides more information than just a p-value. It explains the contingency table in terms of an overall effect, row and columns effects and residuals. The underlying model for median polish is an additive model which is sometimes too restrictive. In this paper, we propose two related approach to generalise median polish. A power transformation can be applied to the values in the table, so that better results for median polish can be achieved. We propose a graphical method how to find a suitable power transformation. If the original data should be preserved, one can apply other transformations – based on so-called additive generators – that have an inverse transformation. In this way, median polish can be applied to the original data, but based on a non-additive model. The non-linearity of such a model can also be visualised to better understand the joint effects of rows and columns in a contingency table.
ORIGINAL
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2019-08-30 11:26:42.693
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6207052019-08-30T11:25:43Zcom_10033_620626com_10033_620601com_10033_311308col_10033_620721col_10033_620627col_10033_620603
Preusse, Matthias
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Tantawy, Mohamed A
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Klawonn, Frank
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http://orcid.org/0000-0001-9613-182X
Schughart, Klaus
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Pessler, Frank
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2017-01-16T15:28:50Z
2017-01-16T15:28:50Z
2013-12-17
2015-09-04T08:30:14Z
BMC Microbiology. 2013 Dec 17;13(1):293
http://dx.doi.org/10.1186/1471-2180-13-293
http://hdl.handle.net/10033/620705
Abstract Background Investigating the host response in the early stage of influenza A virus (IAV) infection is of considerable interest. However, it is conceivable that effects due to the anesthesia and/or intranasal infection procedure might introduce artifacts. We therefore aimed to evaluate the effects of anesthesia and/or intranasal infection on transcription of selected pulmonary mRNAs in two inbred mouse strains with differential susceptibility to IAV infection. Results DBA/2J and C57BL/6J mice were evaluated in a time course experiment in which lung tissue was sampled after 6, 12, 18, 24, 48 and 120 h. After anesthesia with ketamine and xylazine, a suspension of mouse-adapted IAV strain PR8_Mun in 20 μl sterile buffer, or 20 μl sterile buffer only, was instilled intranasally. The mice receiving anesthesia and PBS only were designated the “mock treatment” group. Pulmonary expression of 10 host mRNAs (Fos, Retnla, Irg1, Il6, Il1b, Cxcl10, Stat1, Ifng, Ifnl2, and Mx1) and viral hemagglutinin (HA) mRNA were determined at the designated time points. As expected, weight loss and viral replication were greater in the DBA/2J strain (which is more susceptible to IAV infection). Four mRNAs (Retnla, Irg1, Il6, and Cxcl10) were procedure-dependently regulated in DBA/2J mice between 6 and 24 h, and two (Retnla and Il6) in C57BL/6J mice, although to a lesser extent. All 10 mRNAs rose after infection, but one (Fos) only in DBA/2J mice. These infection-dependent effects could be separated from procedure-dependent effects beginning around 12 h in DBA/2J and 18 h in C57BL/6J mice. The interferon-related mRNAs Stat1, Ifng, Infl2, and Mx1 were unaffected by mock treatment in either mouse strain. Mx1 and Infl2 correlated best with HA mRNA expression (r = 0.97 and 0.93, respectively, in DBA/2J). Conclusions These results demonstrate effects of the anesthesia and/or intranasal infection procedure on pulmonary gene expression, which are detectable between approximately 6 and 24 h post procedure and vary in intensity and temporal evolution depending on the mouse strain used. Mock infection controls should be included in all studies on pulmonary gene expression in the early phase of infection with IAV and, likely, other respiratory pathogens.
Infection- and procedure-dependent effects on pulmonary gene expression in the early phase of influenza A virus infection in mice
Journal Article
en
Preusse et al.; licensee BioMed Central Ltd.
2018-06-12T17:21:08Z
Abstract
Background
Investigating the host response in the early stage of influenza A virus (IAV) infection is of considerable interest. However, it is conceivable that effects due to the anesthesia and/or intranasal infection procedure might introduce artifacts. We therefore aimed to evaluate the effects of anesthesia and/or intranasal infection on transcription of selected pulmonary mRNAs in two inbred mouse strains with differential susceptibility to IAV infection.
Results
DBA/2J and C57BL/6J mice were evaluated in a time course experiment in which lung tissue was sampled after 6, 12, 18, 24, 48 and 120 h. After anesthesia with ketamine and xylazine, a suspension of mouse-adapted IAV strain PR8_Mun in 20 μl sterile buffer, or 20 μl sterile buffer only, was instilled intranasally. The mice receiving anesthesia and PBS only were designated the “mock treatment” group. Pulmonary expression of 10 host mRNAs (Fos, Retnla, Irg1, Il6, Il1b, Cxcl10, Stat1, Ifng, Ifnl2, and Mx1) and viral hemagglutinin (HA) mRNA were determined at the designated time points. As expected, weight loss and viral replication were greater in the DBA/2J strain (which is more susceptible to IAV infection). Four mRNAs (Retnla, Irg1, Il6, and Cxcl10) were procedure-dependently regulated in DBA/2J mice between 6 and 24 h, and two (Retnla and Il6) in C57BL/6J mice, although to a lesser extent. All 10 mRNAs rose after infection, but one (Fos) only in DBA/2J mice. These infection-dependent effects could be separated from procedure-dependent effects beginning around 12 h in DBA/2J and 18 h in C57BL/6J mice. The interferon-related mRNAs Stat1, Ifng, Infl2, and Mx1 were unaffected by mock treatment in either mouse strain. Mx1 and Infl2 correlated best with HA mRNA expression (r = 0.97 and 0.93, respectively, in DBA/2J).
Conclusions
These results demonstrate effects of the anesthesia and/or intranasal infection procedure on pulmonary gene expression, which are detectable between approximately 6 and 24 h post procedure and vary in intensity and temporal evolution depending on the mouse strain used. Mock infection controls should be included in all studies on pulmonary gene expression in the early phase of infection with IAV and, likely, other respiratory pathogens.
ORIGINAL
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2019-08-30 11:25:43.344
Helmholtz Zentrum für Infektionsforschung Repository
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oai:repository.helmholtz-hzi.de:10033/5801112019-08-30T11:35:14Zcom_10033_211390com_10033_620601col_10033_211409col_10033_620603
Schweitzer, A
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Krause, Gerard
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Pessler, F
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Akmatov, M K
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2015-10-22T08:39:41Z
2015-10-22T08:39:41Z
2015
Improved coverage and timing of childhood vaccinations in two post-Soviet countries, Armenia and Kyrgyzstan. 2015, 15 (1):798 BMC Public Health
1471-2458
26285702
10.1186/s12889-015-2091-9
http://hdl.handle.net/10033/580111
BMC public health
Timing of childhood vaccinations has received close attention in many countries. Little is known about the trends in correctly timed vaccination in former Soviet countries. We examined trends in vaccination coverage and correct timing of vaccination in two post-Soviet countries, Armenia and Kyrgyzstan, and analyzed factors associated with delayed vaccinations.
en
Improved coverage and timing of childhood vaccinations in two post-Soviet countries, Armenia and Kyrgyzstan.
Article
2018-06-13T21:25:31Z
Timing of childhood vaccinations has received close attention in many countries. Little is known about the trends in correctly timed vaccination in former Soviet countries. We examined trends in vaccination coverage and correct timing of vaccination in two post-Soviet countries, Armenia and Kyrgyzstan, and analyzed factors associated with delayed vaccinations.
ORIGINAL
schweitzer et al_final.pdf
schweitzer et al_final.pdf
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Helmholtz Zentrum für Infektionsforschung Repository
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oai:repository.helmholtz-hzi.de:10033/5800702019-08-30T11:36:33Zcom_10033_620626com_10033_620601com_10033_311308col_10033_620721col_10033_620627col_10033_620603
Preusse, Matthias
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Schughart, Klaus
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Wilk, Esther
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Klawonn, Frank
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Pessler, Frank
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Helmholz Centre for Infection Research
2015-10-22T10:22:07Z
2015-10-22T10:22:07Z
2015
Hematological parameters in the early phase of influenza A virus infection in differentially susceptible inbred mouse strains. 2015, 8:225 BMC Res Notes
1756-0500
26047817
10.1186/s13104-015-1195-8
http://hdl.handle.net/10033/580070
BMC research notes
Hematological parameters have not received much attention in small animal models of infection, particularly at very early time points. We therefore studied changes in leukocyte and thrombocyte numbers in a mouse model of influenza A virus (IAV) infection, including measurements within the first 24 h after infection, and also assessing effects, if any, of the infection/anesthesia procedure on these parameters.
en
Hematological parameters in the early phase of influenza A virus infection in differentially susceptible inbred mouse strains.
Article
2018-06-12T23:05:36Z
Hematological parameters have not received much attention in small animal models of infection, particularly at very early time points. We therefore studied changes in leukocyte and thrombocyte numbers in a mouse model of influenza A virus (IAV) infection, including measurements within the first 24 h after infection, and also assessing effects, if any, of the infection/anesthesia procedure on these parameters.
ORIGINAL
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Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/5944072019-08-30T11:37:44Zcom_10033_620601col_10033_620603
Möller, Jana C
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Cron, Randy Q
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Young, Daniel W
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Girschick, Hermann J
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Levy, Deborah M
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Sherry, David D
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Kukita, Akiko
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Saijo, Kaoru
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Pessler, Frank
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Helmholtz Centre for infection research, Inhoffenstr. 7, D-38124 Braunschweig, Germany.
2016-01-20T14:24:12Z
2016-01-20T14:24:12Z
2011
Corticosteroid-induced spinal epidural lipomatosis in the pediatric age group: report of a new case and updated analysis of the literature. 2011, 9 (1):5 Pediatr Rheumatol Online J
1546-0096
21284882
10.1186/1546-0096-9-5
http://hdl.handle.net/10033/594407
Pediatric rheumatology online journal
Spinal epidural lipomatosis is a rare complication of chronic corticosteroid treatment. We report a new pediatric case and an analysis of this and 19 pediatric cases identified in the international literature. The youngest of these combined 20 patients was 5 years old when lipomatosis was diagnosed. Lipomatosis manifested after a mean of 1.3 (+/- 1.5) years (SD) (median, 0.8 years; range, 3 weeks - 6.5 years) of corticosteroid treatment. The corticosteroid dose at the time of presentation of the lipomatosis ranged widely, between 5 and 80 mg of prednisone/day. Back pain was the most common presenting symptom. Imaging revealed that lipomatosis almost always involved the thoracic spine, extending into the lumbosacral region in a subset of patients. Predominantly lumbosacral involvement was documented in only two cases. Although a neurological deficit at presentation was documented in about half of the cases, surgical decompression was not performed in the cases reported after 1996. Instead, reducing the corticosteroid dose (sometimes combined with dietary restriction to mobilize fat) sufficed to induce remission. In summary, pediatric spinal epidural lipomatosis remains a potentially serious untoward effect of corticosteroid treatment, which, if recognized in a timely manner, can have a good outcome with conservative treatment.
en
Corticosteroid-induced spinal epidural lipomatosis in the pediatric age group: report of a new case and updated analysis of the literature.
Article
2018-06-13T00:11:43Z
Spinal epidural lipomatosis is a rare complication of chronic corticosteroid treatment. We report a new pediatric case and an analysis of this and 19 pediatric cases identified in the international literature. The youngest of these combined 20 patients was 5 years old when lipomatosis was diagnosed. Lipomatosis manifested after a mean of 1.3 (+/- 1.5) years (SD) (median, 0.8 years; range, 3 weeks - 6.5 years) of corticosteroid treatment. The corticosteroid dose at the time of presentation of the lipomatosis ranged widely, between 5 and 80 mg of prednisone/day. Back pain was the most common presenting symptom. Imaging revealed that lipomatosis almost always involved the thoracic spine, extending into the lumbosacral region in a subset of patients. Predominantly lumbosacral involvement was documented in only two cases. Although a neurological deficit at presentation was documented in about half of the cases, surgical decompression was not performed in the cases reported after 1996. Instead, reducing the corticosteroid dose (sometimes combined with dietary restriction to mobilize fat) sufficed to induce remission. In summary, pediatric spinal epidural lipomatosis remains a potentially serious untoward effect of corticosteroid treatment, which, if recognized in a timely manner, can have a good outcome with conservative treatment.
ORIGINAL
Möller et al.pdf
Möller et al.pdf
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Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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Antony, Paul M
e51ba953932004d11e114739db4c6228
500
Jäger, Christian
a512c1058862fa470168eeb89214c2c9
500
Fritz, Joëlle V
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500
Vallar, Laurent
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500
Balling, Rudi
7a10c90e297f2fc48dc2944e22e8e57a
500
Del Sol, Antonio
9b0f39969d6c7f5533b617d9e08ffdb0
500
Michelucci, Alessandro
8190f7c2f9c5bf0d0255fdb83304067e
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Twincore Centre of Experimental and Clinical Infection Research; a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover 30625, Germany.
2016-05-25T13:35:19Z
2016-05-25T13:35:19Z
2016
Gene Regulatory Network Inference of Immunoresponsive Gene 1 (IRG1) Identifies Interferon Regulatory Factor 1 (IRF1) as Its Transcriptional Regulator in Mammalian Macrophages. 2016, 11 (2):e0149050 PLoS ONE
1932-6203
26872335
10.1371/journal.pone.0149050
http://hdl.handle.net/10033/610686
PloS one
Immunoresponsive gene 1 (IRG1) is one of the highest induced genes in macrophages under pro-inflammatory conditions. Its function has been recently described: it codes for immune-responsive gene 1 protein/cis-aconitic acid decarboxylase (IRG1/CAD), an enzyme catalysing the production of itaconic acid from cis-aconitic acid, a tricarboxylic acid (TCA) cycle intermediate. Itaconic acid possesses specific antimicrobial properties inhibiting isocitrate lyase, the first enzyme of the glyoxylate shunt, an anaplerotic pathway that bypasses the TCA cycle and enables bacteria to survive on limited carbon conditions. To elucidate the mechanisms underlying itaconic acid production through IRG1 induction in macrophages, we examined the transcriptional regulation of IRG1. To this end, we studied IRG1 expression in human immune cells under different inflammatory stimuli, such as TNFα and IFNγ, in addition to lipopolysaccharides. Under these conditions, as previously shown in mouse macrophages, IRG1/CAD accumulates in mitochondria. Furthermore, using literature information and transcription factor prediction models, we re-constructed raw gene regulatory networks (GRNs) for IRG1 in mouse and human macrophages. We further implemented a contextualization algorithm that relies on genome-wide gene expression data to infer putative cell type-specific gene regulatory interactions in mouse and human macrophages, which allowed us to predict potential transcriptional regulators of IRG1. Among the computationally identified regulators, siRNA-mediated gene silencing of interferon regulatory factor 1 (IRF1) in macrophages significantly decreased the expression of IRG1/CAD at the gene and protein level, which correlated with a reduced production of itaconic acid. Using a synergistic approach of both computational and experimental methods, we here shed more light on the transcriptional machinery of IRG1 expression and could pave the way to therapeutic approaches targeting itaconic acid levels.
en
Gene Regulatory Network Inference of Immunoresponsive Gene 1 (IRG1) Identifies Interferon Regulatory Factor 1 (IRF1) as Its Transcriptional Regulator in Mammalian Macrophages.
Article
2018-06-12T22:48:16Z
Immunoresponsive gene 1 (IRG1) is one of the highest induced genes in macrophages under pro-inflammatory conditions. Its function has been recently described: it codes for immune-responsive gene 1 protein/cis-aconitic acid decarboxylase (IRG1/CAD), an enzyme catalysing the production of itaconic acid from cis-aconitic acid, a tricarboxylic acid (TCA) cycle intermediate. Itaconic acid possesses specific antimicrobial properties inhibiting isocitrate lyase, the first enzyme of the glyoxylate shunt, an anaplerotic pathway that bypasses the TCA cycle and enables bacteria to survive on limited carbon conditions. To elucidate the mechanisms underlying itaconic acid production through IRG1 induction in macrophages, we examined the transcriptional regulation of IRG1. To this end, we studied IRG1 expression in human immune cells under different inflammatory stimuli, such as TNFα and IFNγ, in addition to lipopolysaccharides. Under these conditions, as previously shown in mouse macrophages, IRG1/CAD accumulates in mitochondria. Furthermore, using literature information and transcription factor prediction models, we re-constructed raw gene regulatory networks (GRNs) for IRG1 in mouse and human macrophages. We further implemented a contextualization algorithm that relies on genome-wide gene expression data to infer putative cell type-specific gene regulatory interactions in mouse and human macrophages, which allowed us to predict potential transcriptional regulators of IRG1. Among the computationally identified regulators, siRNA-mediated gene silencing of interferon regulatory factor 1 (IRF1) in macrophages significantly decreased the expression of IRG1/CAD at the gene and protein level, which correlated with a reduced production of itaconic acid. Using a synergistic approach of both computational and experimental methods, we here shed more light on the transcriptional machinery of IRG1 expression and could pave the way to therapeutic approaches targeting itaconic acid levels.
ORIGINAL
Tallam et al.PDF
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oai:repository.helmholtz-hzi.de:10033/6119822019-08-30T11:30:32Zcom_10033_620601col_10033_620603
Samir, Mohamed
3ba58b492a09c4846819000955e8b756
500
Pessler, Frank
9fc33677a3eea5c4e77542200bd20f05
500
Twincore Centre for Experimental and Clinical Infection Research, Hannover, Germany.
2016-06-07T13:09:29Z
2016-06-07T13:09:29Z
2016
Small Non-coding RNAs Associated with Viral Infectious Diseases of Veterinary Importance: Potential Clinical Applications. 2016, 3:22 Front Vet Sci
2297-1769
27092305
10.3389/fvets.2016.00022
http://hdl.handle.net/10033/611982
Frontiers in veterinary science
MicroRNAs (miRNAs) represent a class of small non-coding RNA (sncRNA) molecules that can regulate mRNAs by inducing their degradation or by blocking translation. Considering that miRNAs are ubiquitous, stable, and conserved across animal species, it seems feasible to exploit them for clinical applications. Unlike in human viral diseases, where some miRNA-based molecules have progressed to clinical application, in veterinary medicine, this concept is just starting to come into view. Clinically, miRNAs could represent powerful diagnostic tools to pinpoint animal viral diseases and/or prognostic tools to follow up disease progression or remission. Additionally, the possible consequences of miRNA dysregulation make them potential therapeutic targets and open the possibilities to use them as tools to generate viral disease-resistant livestock. This review presents an update of preclinical studies on using sncRNAs to combat viral diseases that affect pet and farm animals. Moreover, we discuss the possibilities and challenges of bringing these bench-based discoveries to the veterinary clinic.
en
Small Non-coding RNAs Associated with Viral Infectious Diseases of Veterinary Importance: Potential Clinical Applications.
Article
2018-06-13T01:06:54Z
MicroRNAs (miRNAs) represent a class of small non-coding RNA (sncRNA) molecules that can regulate mRNAs by inducing their degradation or by blocking translation. Considering that miRNAs are ubiquitous, stable, and conserved across animal species, it seems feasible to exploit them for clinical applications. Unlike in human viral diseases, where some miRNA-based molecules have progressed to clinical application, in veterinary medicine, this concept is just starting to come into view. Clinically, miRNAs could represent powerful diagnostic tools to pinpoint animal viral diseases and/or prognostic tools to follow up disease progression or remission. Additionally, the possible consequences of miRNA dysregulation make them potential therapeutic targets and open the possibilities to use them as tools to generate viral disease-resistant livestock. This review presents an update of preclinical studies on using sncRNAs to combat viral diseases that affect pet and farm animals. Moreover, we discuss the possibilities and challenges of bringing these bench-based discoveries to the veterinary clinic.
ORIGINAL
Samir and Pessler.pdf
Samir and Pessler.pdf
Open Access publication
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oai:repository.helmholtz-hzi.de:10033/6190432019-08-30T11:30:58Zcom_10033_620601col_10033_620603
Hendel, N
1285267af92f4dc8012bd3ce13878351
500
Akmatov, M K
f1418c78f200f63114201f373d9491f4
500
Hamel, J
1022111f5a3abd93b7d1b09c994b37a6
500
Vogelberg, C
13430ac83cd1df989fbb14069bbd448a
500
Pessler, F
c3a6b198a476d879a84442561dd87c99
500
TWINCORE Centre for Experimental and Clinical Infection Research Feodor-Lynen-Str. 7 30625 Hannover, Germany.
2016-08-30T11:19:08Z
2016-08-30T11:19:08Z
2016-06
Exhaled breath analysis in childhood rheumatic disorders--a longitudinal study. 2016, 10 (2):021001 J Breath Res
1752-7163
27093271
10.1088/1752-7155/10/2/021001
http://hdl.handle.net/10033/619043
Journal of breath research
We aimed to evaluate the fraction of exhaled nitric oxide (FENO50) and deaerated exhaled breath condensate pH (dEBCpH) as non-invasive markers of subclinical airway inflammation in pediatric patients with rheumatologic disorders. We determined FENO50 and dEBCpH in a prospective study spanning at least 12 months, comprising 85 pediatric patients with rheumatologic disorders, including juvenile idiopathic arthritis (JIA, n = 63), chronic recurrent multifocal osteomyelitis (CRMO, n = 6), systemic lupus erythematosus (SLE, n = 3), juvenile dermatomyositis (JDM, n = 1) and other rheumatic disorders (n = 12). dEBCpH was determined once in a group of children without evidence of rheumatologic or pulmonary disease (controls, n = 90). Findings were correlated with results of pulmonary function tests. Atopic sensitization was assessed by RAST or skin prick test in 76 patients. Atopic sensitization was detected in 34% (26/76) of patients. Neither FENO50 nor dEBCpH correlated with disease activity, but intermediately (20-35 ppb) or highly elevated (>35 ppb) levels were observed at least once in 26 patients (31%), 19 of whom had atopic sensitization. Median dEBCpH did not differ between cases and controls (8.05 versus 8.02; p = 0.48). Median dEBCpH decreased slightly over the study period (p = 0.02), whereas FENO50 values did not change significantly (p = 0.89). There were several patients with significantly abnormal dEBCpH values that could not be readily explained by diagnosis, higher disease activity, medications, or atopic sensitization. Thus, there were no consistent abnormalities in FENO50 or dEBCpH in this cohort of Caucasian patients with relatively stable rheumatologic disorders, but there were some patients with abnormal values of unknown significance.
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
Exhaled breath analysis in childhood rheumatic disorders--a longitudinal study.
Article
2017-09-10T00:00:00Z
We aimed to evaluate the fraction of exhaled nitric oxide (FENO50) and deaerated exhaled breath condensate pH (dEBCpH) as non-invasive markers of subclinical airway inflammation in pediatric patients with rheumatologic disorders. We determined FENO50 and dEBCpH in a prospective study spanning at least 12 months, comprising 85 pediatric patients with rheumatologic disorders, including juvenile idiopathic arthritis (JIA, n = 63), chronic recurrent multifocal osteomyelitis (CRMO, n = 6), systemic lupus erythematosus (SLE, n = 3), juvenile dermatomyositis (JDM, n = 1) and other rheumatic disorders (n = 12). dEBCpH was determined once in a group of children without evidence of rheumatologic or pulmonary disease (controls, n = 90). Findings were correlated with results of pulmonary function tests. Atopic sensitization was assessed by RAST or skin prick test in 76 patients. Atopic sensitization was detected in 34% (26/76) of patients. Neither FENO50 nor dEBCpH correlated with disease activity, but intermediately (20-35 ppb) or highly elevated (>35 ppb) levels were observed at least once in 26 patients (31%), 19 of whom had atopic sensitization. Median dEBCpH did not differ between cases and controls (8.05 versus 8.02; p = 0.48). Median dEBCpH decreased slightly over the study period (p = 0.02), whereas FENO50 values did not change significantly (p = 0.89). There were several patients with significantly abnormal dEBCpH values that could not be readily explained by diagnosis, higher disease activity, medications, or atopic sensitization. Thus, there were no consistent abnormalities in FENO50 or dEBCpH in this cohort of Caucasian patients with relatively stable rheumatologic disorders, but there were some patients with abnormal values of unknown significance.
ORIGINAL
Hendel et al.pdf
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oai:repository.helmholtz-hzi.de:10033/6190492019-08-30T11:30:58Zcom_10033_620601col_10033_620603
Akmatov, Manas K
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500
Stumme, Melanie
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Pessler, Frank
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TWINCORE Centre for Experimental and Clinical Infection Research Feodor-Lynen-Str. 7 30625 Hannover, Germany.
2016-08-30T15:08:52Z
2016-08-30T15:08:52Z
2016-08-30
Real-life practice of methotrexate toxicity monitoring in juvenile idiopathic arthritis in Germany, Switzerland and Austria: results of a cross-sectional assessment conducted in 2012., 34 (3):548-53 Clin. Exp. Rheumatol.
0392-856X
27156925
http://hdl.handle.net/10033/619049
Clinical and experimental rheumatology
Methotrexate (MTX) is used at low doses to treat rheumatologic disorders in the paediatric age group. Toxicity is observed despite the low doses used. Even though recommendations for monitoring of early signs of toxicity exist in many countries, real-life practice may vary. We therefore assessed current practice in Germany, Switzerland and Austria.
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
Adolescent
Antirheumatic Agents
Arthritis, Juvenile
Austria
Child
Child, Preschool
Cross-Sectional Studies
Drug Monitoring
Drug-Related Side Effects and Adverse Reactions
Female
Germany
Humans
Male
Medication Therapy Management
Methotrexate
Switzerland
Young Adult
Real-life practice of methotrexate toxicity monitoring in juvenile idiopathic arthritis in Germany, Switzerland and Austria: results of a cross-sectional assessment conducted in 2012.
Article
2017-02-01T00:00:00Z
Methotrexate (MTX) is used at low doses to treat rheumatologic disorders in the paediatric age group. Toxicity is observed despite the low doses used. Even though recommendations for monitoring of early signs of toxicity exist in many countries, real-life practice may vary. We therefore assessed current practice in Germany, Switzerland and Austria.
ORIGINAL
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oai:repository.helmholtz-hzi.de:10033/6192652019-08-30T11:30:32Zcom_10033_620601col_10033_620603
Schweitzer, A
047252a79130d83d05b3b99db37f98e2
500
Pessler, F.
9c37eed309b9fd83086d3630ea1096c0
500
Akmatov, M K
f1418c78f200f63114201f373d9491f4
500
Twincore Centre of Experimental and Clinical Infection Research; a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover 30625, Germany.
2016-09-02T09:22:12Z
2016-09-02T09:22:12Z
2016-05-03
Impact of rotavirus vaccination on coverage and timing of pentavalent vaccination - Experience from 2 Latin American countries. 2016, 12 (5):1250-6 Hum Vaccin Immunother
2164-554X
26833132
10.1080/21645515.2015.1127486
http://hdl.handle.net/10033/619265
Human vaccines & immunotherapeutics
We examined the coverage and timing of rotavirus vaccination and the impact of rotavirus vaccine introduction on coverage and timing of the pentavalent vaccine. We used data from the Demographic and Health Surveys in Honduras (2011/2012) and Peru (2012). The samples were divided into 2 subcohorts: children born before and after the introduction of rotavirus vaccine. We compared coverage and timing of the pentavalent vaccine in the aforementioned subcohorts. Coverage with the first and second doses of rotavirus vaccination was 95% (95% confidence intervals: 93-97%) and 91% (89-95%) in Honduras and 79% (77-82%) and 72% (69-75%) in Peru, respectively. Coverage increased in both countries over the years. The proportion of children vaccinated according to age-appropriate vaccination schedules varied between 67% (second dose of rotavirus vaccinations in Peru) and 89% (first dose of rotavirus vaccination in Honduras). Coverage with the first and second doses of pentavalent vaccination remained constant over the years in Honduras, while in Peru there was a significant increase in coverage over the years (p for trend, <0.0001). In both countries, timing of pentavalent vaccination was better in post-rota-cohorts than in pre-rota-cohorts. Since its introduction, coverage of rotavirus vaccination has improved over time in both countries. An introduction of rotavirus vaccination in both countries appears to have improved the coverage and timing of other similarly scheduled vaccinations.
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
Impact of rotavirus vaccination on coverage and timing of pentavalent vaccination - Experience from 2 Latin American countries.
Article
2017-05-10T00:00:00Z
We examined the coverage and timing of rotavirus vaccination and the impact of rotavirus vaccine introduction on coverage and timing of the pentavalent vaccine. We used data from the Demographic and Health Surveys in Honduras (2011/2012) and Peru (2012). The samples were divided into 2 subcohorts: children born before and after the introduction of rotavirus vaccine. We compared coverage and timing of the pentavalent vaccine in the aforementioned subcohorts. Coverage with the first and second doses of rotavirus vaccination was 95% (95% confidence intervals: 93-97%) and 91% (89-95%) in Honduras and 79% (77-82%) and 72% (69-75%) in Peru, respectively. Coverage increased in both countries over the years. The proportion of children vaccinated according to age-appropriate vaccination schedules varied between 67% (second dose of rotavirus vaccinations in Peru) and 89% (first dose of rotavirus vaccination in Honduras). Coverage with the first and second doses of pentavalent vaccination remained constant over the years in Honduras, while in Peru there was a significant increase in coverage over the years (p for trend, <0.0001). In both countries, timing of pentavalent vaccination was better in post-rota-cohorts than in pre-rota-cohorts. Since its introduction, coverage of rotavirus vaccination has improved over time in both countries. An introduction of rotavirus vaccination in both countries appears to have improved the coverage and timing of other similarly scheduled vaccinations.
ORIGINAL
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Schweitzer et al.pdf
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Helmholtz Zentrum für Infektionsforschung Repository
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oai:repository.helmholtz-hzi.de:10033/6205402019-08-30T11:27:16Zcom_10033_620601col_10033_620603
Dudek, M
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Puttur, F
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Arnold-Schrauf, C
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Kühl, A A
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Holzmann, B
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Henriques-Normark, B
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Berod, L
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Sparwasser, T
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Twincore
2016-09-29T09:03:26Z
2016-09-29T09:03:26Z
2016-09
Lung epithelium and myeloid cells cooperate to clear acute pneumococcal infection. 2016, 9 (5):1288-302 Mucosal Immunol
1935-3456
26627460
10.1038/mi.2015.128
http://hdl.handle.net/10033/620540
Mucosal immunology
The Gram-positive bacterium Streptococcus pneumoniae causes life-threatening infections, especially among immunocompromised patients. The host's immune system senses S. pneumoniae via different families of pattern recognition receptors, in particular the Toll-like receptor (TLR) family that promotes immune cell activation. Yet, while single TLRs are dispensable for initiating inflammatory responses against S. pneumoniae, the central TLR adapter protein myeloid differentiation factor 88 (MyD88) is of vital importance, as MyD88-deficient mice succumb rapidly to infection. Since MyD88 is ubiquitously expressed in hematopoietic and non-hematopoietic cells, the extent to which MyD88 signaling is required in different cell types to control S. pneumoniae is unknown. Therefore, we used novel conditional knockin mice to investigate the necessity of MyD88 signaling in distinct lung-resident myeloid and epithelial cells for the initiation of a protective immune response against S. pneumoniae. Here, we show that MyD88 signaling in lysozyme M (LysM)- and CD11c-expressing myeloid cells, as well as in pulmonary epithelial cells, is critical to restore inflammatory cytokine and antimicrobial peptide production, leading to efficient neutrophil recruitment and enhanced bacterial clearance. Overall, we show a novel synergistic requirement of compartment-specific MyD88 signaling in S. pneumoniae immunity.
en
Lung epithelium and myeloid cells cooperate to clear acute pneumococcal infection.
Article
2018-06-12T23:23:34Z
The Gram-positive bacterium Streptococcus pneumoniae causes life-threatening infections, especially among immunocompromised patients. The host's immune system senses S. pneumoniae via different families of pattern recognition receptors, in particular the Toll-like receptor (TLR) family that promotes immune cell activation. Yet, while single TLRs are dispensable for initiating inflammatory responses against S. pneumoniae, the central TLR adapter protein myeloid differentiation factor 88 (MyD88) is of vital importance, as MyD88-deficient mice succumb rapidly to infection. Since MyD88 is ubiquitously expressed in hematopoietic and non-hematopoietic cells, the extent to which MyD88 signaling is required in different cell types to control S. pneumoniae is unknown. Therefore, we used novel conditional knockin mice to investigate the necessity of MyD88 signaling in distinct lung-resident myeloid and epithelial cells for the initiation of a protective immune response against S. pneumoniae. Here, we show that MyD88 signaling in lysozyme M (LysM)- and CD11c-expressing myeloid cells, as well as in pulmonary epithelial cells, is critical to restore inflammatory cytokine and antimicrobial peptide production, leading to efficient neutrophil recruitment and enhanced bacterial clearance. Overall, we show a novel synergistic requirement of compartment-specific MyD88 signaling in S. pneumoniae immunity.
ORIGINAL
dudek et al_final.pdf
dudek et al_final.pdf
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oai:hzi.openrepository.com:10033/620540
2019-08-30 11:27:16.17
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6206792019-08-30T11:37:24Zcom_10033_620601col_10033_620603
de Araujo, Leonardo S
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Vaas, Lea A I
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Ribeiro-Alves, Marcelo
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Geffers, Robert
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Mello, Fernanda C Q
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de Almeida, Alexandre S
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Moreira, Adriana da S R
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Kritski, Afrânio L
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Lapa E Silva, José R
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Moraes, Milton O
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Pessler, Frank
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Saad, Maria H F
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Twincore Centre of Experimental and Clinical Infection Research; a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover 30625, Germany.
2017-01-05T10:48:04Z
2017-01-05T10:48:04Z
2016
Transcriptomic Biomarkers for Tuberculosis: Evaluation of DOCK9. EPHA4, and NPC2 mRNA Expression in Peripheral Blood. 2016, 7:1586 Front Microbiol
27826286
10.3389/fmicb.2016.01586
http://hdl.handle.net/10033/620679
Frontiers in microbiology
Lately, much effort has been made to find mRNA biomarkers for tuberculosis (TB) disease/infection with microarray-based approaches. In a pilot investigation, through RNA sequencing technology, we observed a prominent modulation of DOCK9, EPHA4, and NPC2 mRNA abundance in the blood of TB patients. To corroborate these findings, independent validations were performed in cohorts from different areas. Gene expression levels in blood were evaluated by quantitative real-time PCR (Brazil, n = 129) or reanalysis of public microarray data (UK: n = 96; South Africa: n = 51; Germany: n = 26; and UK/France: n = 63). In the Brazilian cohort, significant modulation of all target-genes was observed comparing TB vs. healthy recent close TB contacts (rCt). With a 92% specificity, NPC2 mRNA high expression (NPC2(high)) showed the highest sensitivity (85%, 95% CI 65%-96%; area under the ROC curve [AUROC] = 0.88), followed by EPHA4 (53%, 95% CI 33%-73%, AUROC = 0.73) and DOCK9 (19%, 95% CI 7%-40%; AUROC = 0.66). All the other reanalyzed cohorts corroborated the potential of NPC2(high) as a biomarker for TB (sensitivity: 82-100%; specificity: 94-97%). An NPC2(high) profile was also observed in 60% (29/48) of the tuberculin skin test positive rCt, and additional follow-up evaluation revealed changes in the expression levels of NPC2 during the different stages of Mycobacterium tuberculosis infection, suggesting that further studies are needed to evaluate modulation of this gene during latent TB and/or progression to active disease. Considering its high specificity, our data indicate, for the first time, that NPC2(high) might serve as an accurate single-gene biomarker for TB.
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
Transcriptomic Biomarkers for Tuberculosis: Evaluation of DOCK9. EPHA4, and NPC2 mRNA Expression in Peripheral Blood.
Article
2018-06-12T23:16:14Z
Lately, much effort has been made to find mRNA biomarkers for tuberculosis (TB) disease/infection with microarray-based approaches. In a pilot investigation, through RNA sequencing technology, we observed a prominent modulation of DOCK9, EPHA4, and NPC2 mRNA abundance in the blood of TB patients. To corroborate these findings, independent validations were performed in cohorts from different areas. Gene expression levels in blood were evaluated by quantitative real-time PCR (Brazil, n = 129) or reanalysis of public microarray data (UK: n = 96; South Africa: n = 51; Germany: n = 26; and UK/France: n = 63). In the Brazilian cohort, significant modulation of all target-genes was observed comparing TB vs. healthy recent close TB contacts (rCt). With a 92% specificity, NPC2 mRNA high expression (NPC2(high)) showed the highest sensitivity (85%, 95% CI 65%-96%; area under the ROC curve [AUROC] = 0.88), followed by EPHA4 (53%, 95% CI 33%-73%, AUROC = 0.73) and DOCK9 (19%, 95% CI 7%-40%; AUROC = 0.66). All the other reanalyzed cohorts corroborated the potential of NPC2(high) as a biomarker for TB (sensitivity: 82-100%; specificity: 94-97%). An NPC2(high) profile was also observed in 60% (29/48) of the tuberculin skin test positive rCt, and additional follow-up evaluation revealed changes in the expression levels of NPC2 during the different stages of Mycobacterium tuberculosis infection, suggesting that further studies are needed to evaluate modulation of this gene during latent TB and/or progression to active disease. Considering its high specificity, our data indicate, for the first time, that NPC2(high) might serve as an accurate single-gene biomarker for TB.
ORIGINAL
de Araujo et al.pdf
de Araujo et al.pdf
Open Access publication
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TwinCore, Zentrum für experimentelle und klinische Infektionsforschung GmbH, Feodor-Lynen Str. 7, 30625 Hannover, Germany.
2017-04-04T14:01:28Z
2017-04-04T14:01:28Z
2017-02-21
Seroprevalence of hepatitis B, hepatitis C, human immunodeficiency virus, Treponema pallidum, and co-infections among blood donors in Kyrgyzstan: a retrospective analysis (2013-2015). 2017, 6 (1):45 Infect Dis Poverty
2049-9957
28222792
10.1186/s40249-017-0255-9
http://hdl.handle.net/10033/620885
Infectious diseases of poverty
Post-Soviet Kyrgyzstan has experienced a major surge in blood-borne infections, but data from adequately powered, up-to-date studies are lacking. We thus examined a) the seroprevalences of hepatitis B virus surface antigen (HBsAg), HIV-1 p24 antigen and antibodies against hepatitis C virus (anti-HCV), human immunodeficiency viruses (anti-HIV-1/2, HIV-1 group O), and Treponema pallidum among blood donors in Kyrgyzstan and assess their distribution according to sex, age, and provinces of residence; b) trends in the respective seroprevalences; and c) co-infection rates among the pathogens studied.
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
Adolescent
Adult
Antibodies, Bacterial
Antibodies, Viral
Blood Donors
Coinfection
Enzyme-Linked Immunosorbent Assay
Female
HIV Core Protein p24
HIV Infections
HIV Seroprevalence
HIV-1
Hepacivirus
Hepatitis B
Hepatitis B Surface Antigens
Hepatitis B virus
Hepatitis C
Hepatitis C Antibodies
Humans
Kyrgyzstan
Male
Mass Screening
Middle Aged
Retrospective Studies
Seroepidemiologic Studies
Syphilis
Treponema pallidum
Young Adult
Seroprevalence of hepatitis B, hepatitis C, human immunodeficiency virus, Treponema pallidum, and co-infections among blood donors in Kyrgyzstan: a retrospective analysis (2013-2015).
Article
2018-06-12T16:47:24Z
Post-Soviet Kyrgyzstan has experienced a major surge in blood-borne infections, but data from adequately powered, up-to-date studies are lacking. We thus examined a) the seroprevalences of hepatitis B virus surface antigen (HBsAg), HIV-1 p24 antigen and antibodies against hepatitis C virus (anti-HCV), human immunodeficiency viruses (anti-HIV-1/2, HIV-1 group O), and Treponema pallidum among blood donors in Kyrgyzstan and assess their distribution according to sex, age, and provinces of residence; b) trends in the respective seroprevalences; and c) co-infection rates among the pathogens studied.
ORIGINAL
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Karabaev et al.pdf
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oai:repository.helmholtz-hzi.de:10033/6208922019-08-30T11:29:47Zcom_10033_267632com_10033_211390com_10033_620601col_10033_267633col_10033_211409col_10033_620603
Rübsamen, Nicole
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http://orcid.org/0000-0003-1271-7204
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
2017-04-07T10:09:11Z
2017-04-07T10:09:11Z
2017
Comparison of response patterns in different survey designs: a longitudinal panel with mixed-mode and online-only design. 2017, 14:4 Emerg Themes Epidemiol
28344629
10.1186/s12982-017-0058-2
http://hdl.handle.net/10033/620892
Emerging themes in epidemiology
Increasing availability of the Internet allows using only online data collection for more epidemiological studies. We compare response patterns in a population-based health survey using two survey designs: mixed-mode (choice between paper-and-pencil and online questionnaires) and online-only design (without choice).
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
Comparison of response patterns in different survey designs: a longitudinal panel with mixed-mode and online-only design.
Article
2018-06-12T17:33:24Z
Increasing availability of the Internet allows using only online data collection for more epidemiological studies. We compare response patterns in a population-based health survey using two survey designs: mixed-mode (choice between paper-and-pencil and online questionnaires) and online-only design (without choice).
ORIGINAL
Rübsamen et al.pdf
Rübsamen et al.pdf
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Twincore, Zentrum für experimentelle und klinische Infektionsforschung GmbH, Feodor-Lynen Str. 7, 30625 Hannover, Germany.
2017-04-13T13:15:22Z
2017-04-13T13:15:22Z
2017-02-02
Motivations for (non)participation in population-based health studies among the elderly - comparison of participants and nonparticipants of a prospective study on influenza vaccination. 2017, 17 (1):18 BMC Med Res Methodol
1471-2288
28148221
10.1186/s12874-017-0302-z
http://hdl.handle.net/10033/620896
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Participation in epidemiological studies has strongly declined in recent years. We examined the reasons for (non)participation in population-based health studies among participants and nonparticipants of a prospective study on influenza vaccination among the elderly.
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http://creativecommons.org/licenses/by-nc-sa/4.0/
Motivations for (non)participation in population-based health studies among the elderly - comparison of participants and nonparticipants of a prospective study on influenza vaccination.
Article
2018-06-12T17:19:16Z
Participation in epidemiological studies has strongly declined in recent years. We examined the reasons for (non)participation in population-based health studies among participants and nonparticipants of a prospective study on influenza vaccination among the elderly.
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2017-05-17T12:45:45Z
2017-05-17T12:45:45Z
2017-05-12
Determination of nasal and oropharyngeal microbiomes in a multicenter population-based study - findings from Pretest 1 of the German National Cohort. 2017, 7 (1):1855 Sci Rep
2045-2322
28500287
10.1038/s41598-017-01212-6
http://hdl.handle.net/10033/620922
Scientific reports
We examined acceptability, preference and feasibility of collecting nasal and oropharyngeal swabs, followed by microbiome analysis, in a population-based study with 524 participants. Anterior nasal and oropharyngeal swabs were collected by certified personnel. In addition, participants self-collected nasal swabs at home four weeks later. Four swab types were compared regarding (1) participants' satisfaction and acceptance and (2) detection of microbial community structures based on deep sequencing of the 16 S rRNA gene V1-V2 variable regions. All swabbing methods were highly accepted. Microbial community structure analysis revealed 846 phylotypes, 46 of which were unique to oropharynx and 164 unique to nares. The calcium alginate tipped swab was found unsuitable for microbiome determinations. Among the remaining three swab types, there were no differences in oropharyngeal microbiomes detected and only marginal differences in nasal microbiomes. Microbial community structures did not differ between staff-collected and self-collected nasal swabs. These results suggest (1) that nasal and oropharyngeal swabbing are highly feasible methods for human population-based studies that include the characterization of microbial community structures in these important ecological niches, and (2) that self-collection of nasal swabs at home can be used to reduce cost and resources needed, particularly when serial measurements are to be taken.
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
Determination of nasal and oropharyngeal microbiomes in a multicenter population-based study - findings from Pretest 1 of the German National Cohort.
Article
2018-06-13T00:03:37Z
We examined acceptability, preference and feasibility of collecting nasal and oropharyngeal swabs, followed by microbiome analysis, in a population-based study with 524 participants. Anterior nasal and oropharyngeal swabs were collected by certified personnel. In addition, participants self-collected nasal swabs at home four weeks later. Four swab types were compared regarding (1) participants' satisfaction and acceptance and (2) detection of microbial community structures based on deep sequencing of the 16 S rRNA gene V1-V2 variable regions. All swabbing methods were highly accepted. Microbial community structure analysis revealed 846 phylotypes, 46 of which were unique to oropharynx and 164 unique to nares. The calcium alginate tipped swab was found unsuitable for microbiome determinations. Among the remaining three swab types, there were no differences in oropharyngeal microbiomes detected and only marginal differences in nasal microbiomes. Microbial community structures did not differ between staff-collected and self-collected nasal swabs. These results suggest (1) that nasal and oropharyngeal swabbing are highly feasible methods for human population-based studies that include the characterization of microbial community structures in these important ecological niches, and (2) that self-collection of nasal swabs at home can be used to reduce cost and resources needed, particularly when serial measurements are to be taken.
ORIGINAL
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Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
2017-07-14T13:15:38Z
2017-07-14T13:15:38Z
2017-06-06
Anti-nuclear autoantibodies in the general German population: prevalence and lack of association with selected cardiovascular and metabolic disorders-findings of a multicenter population-based study. 2017, 19 (1):127 Arthritis Res. Ther.
1478-6362
28587625
10.1186/s13075-017-1338-5
http://hdl.handle.net/10033/621013
Arthritis research & therapy
We determined the prevalence of anti-nuclear autoantibodies (ANAs) in the German adult population and examined the association between ANAs and cardiovascular and metabolic disorders.
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
Anti-nuclear autoantibodies in the general German population: prevalence and lack of association with selected cardiovascular and metabolic disorders-findings of a multicenter population-based study.
Article
2018-06-12T23:29:58Z
We determined the prevalence of anti-nuclear autoantibodies (ANAs) in the German adult population and examined the association between ANAs and cardiovascular and metabolic disorders.
ORIGINAL
Akmatov et al.pdf
Akmatov et al.pdf
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Host Genetic Background Strongly Affects Pulmonary microRNA Expression before and during Influenza A Virus Infection. 2017, 8:246 Front Immunol
1664-3224
28377766
10.3389/fimmu.2017.00246
http://hdl.handle.net/10033/621071
Frontiers in immunology
Expression of host microRNAs (miRNAs) changes markedly during influenza A virus (IAV) infection of natural and adaptive hosts, but their role in genetically determined host susceptibility to IAV infection has not been explored. We, therefore, compared pulmonary miRNA expression during IAV infection in two inbred mouse strains with differential susceptibility to IAV infection.
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Host Genetic Background Strongly Affects Pulmonary microRNA Expression before and during Influenza A Virus Infection.
Article
2018-06-12T17:23:51Z
Expression of host microRNAs (miRNAs) changes markedly during influenza A virus (IAV) infection of natural and adaptive hosts, but their role in genetically determined host susceptibility to IAV infection has not been explored. We, therefore, compared pulmonary miRNA expression during IAV infection in two inbred mouse strains with differential susceptibility to IAV infection.
ORIGINAL
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Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr.7, 38124 Braunschweig, Germany.
2017-12-20T14:12:08Z
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2017-10-30
Development of a Bead-Based Multiplex Assay for the Analysis of the Serological Response against the Six Pathogens HAV, HBV, HCV, CMV, T. gondii, and H. pylori 2017, 6 (4):14 High-Throughput
2571-5135
29855458
10.3390/ht6040014
http://hdl.handle.net/10033/621213
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http://creativecommons.org/licenses/by-nc-sa/4.0/
Development of a Bead-Based Multiplex Assay for the Analysis of the Serological Response against the Six Pathogens HAV, HBV, HCV, CMV, T. gondii, and H. pylori
Article
2018-06-12T17:29:52Z
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Open Access publication
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THUMBNAIL
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BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56, 38106 Braunschweig, Germany.
2018-01-03T08:52:06Z
2018-01-03T08:52:06Z
2017-03-01
Hepatitis B vaccination timing: results from demographic health surveys in 47 countries. 2017, 95 (3):199-209G Bull. World Health Organ.
1564-0604
28250533
10.2471/BLT.16.178822
http://hdl.handle.net/10033/621220
Bulletin of the World Health Organization
To examine the impact of hepatitis B vaccination schedules and types of vaccines on hepatitis B vaccination timing.
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
Age Factors
Developing Countries
Global Health
Hepatitis B Vaccines
Humans
Immunization Schedule
Socioeconomic Factors
Hepatitis B vaccination timing: results from demographic health surveys in 47 countries.
Article
2018-06-13T01:31:15Z
To examine the impact of hepatitis B vaccination schedules and types of vaccines on hepatitis B vaccination timing.
ORIGINAL
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2019-08-30 11:25:11.304
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6212212019-08-30T11:35:13Zcom_10033_620601col_10033_620603
De Jaime-Soguero, Anchel
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500
Aulicino, Francesco
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500
Ertaylan, Gokhan
3b26b6594dd0dfb3e2fb938710ef7cb0
500
Griego, Anna
9ac6ac52909e3826cce84a6f47004c0b
500
Cerrato, Aniello
d4df750263ea088bd5a6e96d9e039d11
500
Tallam, Aravind
f23db3bfec9bcaf1aa09fcff084bf8b1
500
Del Sol, Antonio
9b0f39969d6c7f5533b617d9e08ffdb0
500
Cosma, Maria Pia
3115a9782c6926d32ad57edd65a4622f
500
Lluis, Frederic
62e7589c2f570653515a6e5d9b1cd094
500
TwinCore, Zentrum für experimentelle und klinische Infektionsforschung GmbH, Feodor-Lynen-Str. 7, 30625 Hannover, Germany.
2018-01-03T09:14:00Z
2018-01-03T09:14:00Z
2017-03
Wnt/Tcf1 pathway restricts embryonic stem cell cycle through activation of the Ink4/Arf locus. 2017, 13 (3):e1006682 PLoS Genet.
1553-7404
28346462
10.1371/journal.pgen.1006682
http://hdl.handle.net/10033/621221
PLoS genetics
Understanding the mechanisms regulating cell cycle, proliferation and potency of pluripotent stem cells guarantees their safe use in the clinic. Embryonic stem cells (ESCs) present a fast cell cycle with a short G1 phase. This is due to the lack of expression of cell cycle inhibitors, which ultimately determines naïve pluripotency by holding back differentiation. The canonical Wnt/β-catenin pathway controls mESC pluripotency via the Wnt-effector Tcf3. However, if the activity of the Wnt/β-catenin controls the cell cycle of mESCs remains unknown. Here we show that the Wnt-effector Tcf1 is recruited to and triggers transcription of the Ink4/Arf tumor suppressor locus. Thereby, the activation of the Wnt pathway, a known mitogenic pathway in somatic tissues, restores G1 phase and drastically reduces proliferation of mESCs without perturbing pluripotency. Tcf1, but not Tcf3, is recruited to a palindromic motif enriched in the promoter of cell cycle repressor genes, such as p15Ink4b, p16Ink4a and p19Arf, which mediate the Wnt-dependent anti-proliferative effect in mESCs. Consistently, ablation of β-catenin or Tcf1 expression impairs Wnt-dependent cell cycle regulation. All together, here we showed that Wnt signaling controls mESC pluripotency and proliferation through non-overlapping functions of distinct Tcf factors.
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
Animals
Base Sequence
Blotting, Western
Cell Cycle
Cell Proliferation
Cells, Cultured
Cyclin-Dependent Kinase Inhibitor p15
Cyclin-Dependent Kinase Inhibitor p16
Gene Expression Regulation
Gene Knockdown Techniques
HEK293 Cells
Hepatocyte Nuclear Factor 1-alpha
Humans
Mice
Mice, Transgenic
Mouse Embryonic Stem Cells
Promoter Regions, Genetic
Reverse Transcriptase Polymerase Chain Reaction
Wnt Signaling Pathway
Wnt/Tcf1 pathway restricts embryonic stem cell cycle through activation of the Ink4/Arf locus.
Article
2018-06-13T01:01:56Z
Understanding the mechanisms regulating cell cycle, proliferation and potency of pluripotent stem cells guarantees their safe use in the clinic. Embryonic stem cells (ESCs) present a fast cell cycle with a short G1 phase. This is due to the lack of expression of cell cycle inhibitors, which ultimately determines naïve pluripotency by holding back differentiation. The canonical Wnt/β-catenin pathway controls mESC pluripotency via the Wnt-effector Tcf3. However, if the activity of the Wnt/β-catenin controls the cell cycle of mESCs remains unknown. Here we show that the Wnt-effector Tcf1 is recruited to and triggers transcription of the Ink4/Arf tumor suppressor locus. Thereby, the activation of the Wnt pathway, a known mitogenic pathway in somatic tissues, restores G1 phase and drastically reduces proliferation of mESCs without perturbing pluripotency. Tcf1, but not Tcf3, is recruited to a palindromic motif enriched in the promoter of cell cycle repressor genes, such as p15Ink4b, p16Ink4a and p19Arf, which mediate the Wnt-dependent anti-proliferative effect in mESCs. Consistently, ablation of β-catenin or Tcf1 expression impairs Wnt-dependent cell cycle regulation. All together, here we showed that Wnt signaling controls mESC pluripotency and proliferation through non-overlapping functions of distinct Tcf factors.
ORIGINAL
De Jaime-Soguero et al.pdf
De Jaime-Soguero et al.pdf
Open Access publication
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oai:hzi.openrepository.com:10033/621221
2019-08-30 11:35:13.962
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6213412019-08-30T11:34:22Zcom_10033_620659com_10033_620601col_10033_620661col_10033_620603
Samir, M
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500
Hamed, M
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500
Abdallah, F
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500
Kinh Nguyen, V
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500
Hernandez-Vargas, E A
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500
Seehusen, F
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500
Baumgärtner, W
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Hussein, A
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Ali, A A H
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Pessler,, F
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TWINCORE, Zentrum für experimentelle uns klinische Ifektionsforschung GmbH, Feodor-Lynen-Str. 7, 30625 Hannover, Germany.
2018-04-10T08:09:30Z
2018-04-10T08:09:30Z
2018-01-24
An Egyptian HPAI H5N1 isolate from clade 2.2.1.2 is highly pathogenic in an experimentally infected domestic duck breed (Sudani duck). 2018 Transbound Emerg Dis
1865-1682
29363279
10.1111/tbed.12816
http://hdl.handle.net/10033/621341
Transboundary and emerging diseases
The highly pathogenic avian influenza (HPAI) H5N1 viruses continue to cause major problems in poultry and can, although rarely, cause human infection. Being enzootic in domestic poultry, Egyptian isolates are continuously evolving, and novel clades vary in their pathogenicity in avian hosts. Considering the importance of domestic ducks as natural hosts of HPAI H5N1 viruses and their likelihood of physical contact with other avian hosts and humans, it is of utmost importance to characterize the pathogenicity of newly emerged HPAI strains in the domestic duck. The most recently identified Egyptian clade 2.2.1.2 HPAI H5N1 viruses have been isolated from naturally infected pigeons, turkeys and humans. However, essentially nothing is known about their pathogenicity in domestic ducks. We therefore characterized the pathogenicity of an Egyptian HPAI H5N1 isolate A/chicken/Faquos/amn12/2011 (clade 2.2.1.2) in Sudani duck, a domestic duck breed commonly reared in Egypt. While viral transcription (HA mRNA) was highest in lung, heart and kidney peaking between 40 and 48 hpi, lower levels were detected in brain. Weight loss of infected ducks started at 16 hpi and persisted until 120 hpi. The first severe clinical signs were noted by 32 hpi and peaked in severity at 72 and 96 hpi. Haematological analyses showed a decline in total leucocytes, granulocytes, platelets and granulocyte/lymphocyte ratio, but lymphocytosis. Upon necropsy, lesions were obvious in heart, liver, spleen and pancreas and consisted mainly of necrosis and petechial haemorrhage. Histologically, lungs were the most severely affected organs, whereas brain only showed mild neuronal degeneration and gliosis at 48 hpi despite obvious neurological clinical signs. Taken together, our results provide first evidence that this HPAI H5N1 isolate (clade 2.2.1.2) is highly pathogenic to Sudani ducks and highlight the importance of this breed as potential reservoir and disseminator of HPAI strains from this clade.
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
An Egyptian HPAI H5N1 isolate from clade 2.2.1.2 is highly pathogenic in an experimentally infected domestic duck breed (Sudani duck).
Article
The highly pathogenic avian influenza (HPAI) H5N1 viruses continue to cause major problems in poultry and can, although rarely, cause human infection. Being enzootic in domestic poultry, Egyptian isolates are continuously evolving, and novel clades vary in their pathogenicity in avian hosts. Considering the importance of domestic ducks as natural hosts of HPAI H5N1 viruses and their likelihood of physical contact with other avian hosts and humans, it is of utmost importance to characterize the pathogenicity of newly emerged HPAI strains in the domestic duck. The most recently identified Egyptian clade 2.2.1.2 HPAI H5N1 viruses have been isolated from naturally infected pigeons, turkeys and humans. However, essentially nothing is known about their pathogenicity in domestic ducks. We therefore characterized the pathogenicity of an Egyptian HPAI H5N1 isolate A/chicken/Faquos/amn12/2011 (clade 2.2.1.2) in Sudani duck, a domestic duck breed commonly reared in Egypt. While viral transcription (HA mRNA) was highest in lung, heart and kidney peaking between 40 and 48 hpi, lower levels were detected in brain. Weight loss of infected ducks started at 16 hpi and persisted until 120 hpi. The first severe clinical signs were noted by 32 hpi and peaked in severity at 72 and 96 hpi. Haematological analyses showed a decline in total leucocytes, granulocytes, platelets and granulocyte/lymphocyte ratio, but lymphocytosis. Upon necropsy, lesions were obvious in heart, liver, spleen and pancreas and consisted mainly of necrosis and petechial haemorrhage. Histologically, lungs were the most severely affected organs, whereas brain only showed mild neuronal degeneration and gliosis at 48 hpi despite obvious neurological clinical signs. Taken together, our results provide first evidence that this HPAI H5N1 isolate (clade 2.2.1.2) is highly pathogenic to Sudani ducks and highlight the importance of this breed as potential reservoir and disseminator of HPAI strains from this clade.
ORIGINAL
Samir et al.pdf
Samir et al.pdf
original manuscript
application/pdf
409262
https://hzi.openrepository.com/bitstream/10033/621341/1/Samir%20et%20al.pdf
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oai:repository.helmholtz-hzi.de:10033/6213492019-08-30T11:25:11Zcom_10033_620601com_10033_311308col_10033_620721col_10033_620603
Kuhn, Maike
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Sühs, Kurt-Wolfram
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Klawonn, Frank
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TWINCORE, Zentrum für experimentelle und klinischeInfektionsforschung GmbH, Feodor-Lynen-Str. 7, 30625 Hannover, Germany.
2018-04-12T13:50:11Z
2018-04-12T13:50:11Z
2018-01-17
Mass-spectrometric profiling of cerebrospinal fluid reveals metabolite biomarkers for CNS involvement in varicella zoster virus reactivation. 2018, 15 (1):20 J Neuroinflammation
1742-2094
29343258
10.1186/s12974-017-1041-0
http://hdl.handle.net/10033/621349
Journal of neuroinflammation
Varicella zoster virus (VZV) reactivation spans the spectrum from uncomplicated segmental herpes zoster to life-threatening disseminated CNS infection. Moreover, in the absence of a small animal model for this human pathogen, studies of pathogenesis at the organismal level depend on analysis of human biosamples. Changes in cerebrospinal fluid (CSF) metabolites may reflect critical aspects of host responses and end-organ damage in neuroinfection and neuroinflammation. We therefore applied a targeted metabolomics screen of CSF to three clinically distinct forms of VZV reactivation and infectious and non-infectious disease controls in order to identify biomarkers for CNS involvement in VZV reactivation.
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
Mass-spectrometric profiling of cerebrospinal fluid reveals metabolite biomarkers for CNS involvement in varicella zoster virus reactivation.
Article
2018-06-12T22:25:01Z
Varicella zoster virus (VZV) reactivation spans the spectrum from uncomplicated segmental herpes zoster to life-threatening disseminated CNS infection. Moreover, in the absence of a small animal model for this human pathogen, studies of pathogenesis at the organismal level depend on analysis of human biosamples. Changes in cerebrospinal fluid (CSF) metabolites may reflect critical aspects of host responses and end-organ damage in neuroinfection and neuroinflammation. We therefore applied a targeted metabolomics screen of CSF to three clinically distinct forms of VZV reactivation and infectious and non-infectious disease controls in order to identify biomarkers for CNS involvement in VZV reactivation.
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oai:repository.helmholtz-hzi.de:10033/6213732019-08-30T11:33:29Zcom_10033_620601col_10033_620603
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Abdelilah-Seyfried, Salim
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TWINCORE, Zentrum für experimentelle und klinischeInfektionsforschung GmbH, Feodor-Lynen-Str. 7, 30625 Hannover, Germany.
2018-05-16T12:56:46Z
2018-05-16T12:56:46Z
2018-05-08
Differentiation of Human Pluripotent Stem Cells into Functional Endothelial Cells in Scalable Suspension Culture. 2018, 10 (5):1657-1672 Stem Cell Reports
2213-6711
29681541
10.1016/j.stemcr.2018.03.017
http://hdl.handle.net/10033/621373
Stem cell reports
Endothelial cells (ECs) are involved in a variety of cellular responses. As multifunctional components of vascular structures, endothelial (progenitor) cells have been utilized in cellular therapies and are required as an important cellular component of engineered tissue constructs and in vitro disease models. Although primary ECs from different sources are readily isolated and expanded, cell quantity and quality in terms of functionality and karyotype stability is limited. ECs derived from human induced pluripotent stem cells (hiPSCs) represent an alternative and potentially superior cell source, but traditional culture approaches and 2D differentiation protocols hardly allow for production of large cell numbers. Aiming at the production of ECs, we have developed a robust approach for efficient endothelial differentiation of hiPSCs in scalable suspension culture. The established protocol results in relevant numbers of ECs for regenerative approaches and industrial applications that show in vitro proliferation capacity and a high degree of chromosomal stability.
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
Differentiation of Human Pluripotent Stem Cells into Functional Endothelial Cells in Scalable Suspension Culture.
Article
2018-06-13T01:32:37Z
Endothelial cells (ECs) are involved in a variety of cellular responses. As multifunctional components of vascular structures, endothelial (progenitor) cells have been utilized in cellular therapies and are required as an important cellular component of engineered tissue constructs and in vitro disease models. Although primary ECs from different sources are readily isolated and expanded, cell quantity and quality in terms of functionality and karyotype stability is limited. ECs derived from human induced pluripotent stem cells (hiPSCs) represent an alternative and potentially superior cell source, but traditional culture approaches and 2D differentiation protocols hardly allow for production of large cell numbers. Aiming at the production of ECs, we have developed a robust approach for efficient endothelial differentiation of hiPSCs in scalable suspension culture. The established protocol results in relevant numbers of ECs for regenerative approaches and industrial applications that show in vitro proliferation capacity and a high degree of chromosomal stability.
ORIGINAL
Olmer et al.pdf
Olmer et al.pdf
Open Access publication
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TEXT
Olmer et al.pdf.txt
Olmer et al.pdf.txt
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10033/621373
oai:hzi.openrepository.com:10033/621373
2019-08-30 11:33:29.854
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6213922019-08-30T11:26:37Zcom_10033_620626com_10033_620601col_10033_620629col_10033_620603
Loof, Torsten G
5ccc458d47dd25c581ef1056936cbd9f
500
Sohail, Aaqib
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500
Bahgat, Mahmoud M
733d5af7dfe4c1b455a00d45c5481fd2
500
Tallam, Aravind
f23db3bfec9bcaf1aa09fcff084bf8b1
500
Arshad, Haroon
62d0f7bd97fe5b70c3fe3157de7533d1
500
Akmatov, Manas K
f25542d4bdb5e606e67498dbc23d9a20
500
Pils, Marina C
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500
Heise, Ulrike
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500
Beineke, Andreas
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Pessler, Frank
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TWINCORE, Zentrum für experimentelle und klinischeInfektionsforschung GmbH, Feodor-Lynen-Str. 7, 30625 Hannover, Germany.
2018-06-05T12:52:50Z
2018-06-05T12:52:50Z
29707522
http://hdl.handle.net/10033/621392
Group A streptococci may induce lymphopenia, but the value of lymphocyte loss as early biomarkers for systemic spread and severe infection has not been examined systematically. We evaluated peripheral blood cell indices as biomarkers for severity and spread of infection in a mouse model of skin infection, using two isolates of greatly differing virulence. Internal organs were examined histologically. After subcutaneous inoculation, strain AP1 disseminated rapidly to peripheral blood and internal organs, causing frank sepsis. In contrast, seeding of internal organs by 5448 was mild, this strain could not be isolated from blood, and infection remained mostly localized to skin. Histopathologic examination of liver revealed microvesicular fatty change (steatosis) in AP1 infection, and examination of spleen showed elevated apoptosis and blurring of the white pulp/red pulp border late (40 h post infection) in AP1 infection. Both strains caused profound lymphopenia, but lymphocyte loss was more rapid early in AP1 infection, and lymphocyte count at 6 h post infection was the most accurate early marker for AP1 infection (area under the receiver operator curve [AUC] = 0.93), followed by the granulocyte/lymphocyte ratio (AUC = 0.89). The results suggest that virulence of correlates with the degree of early lymphopenia and underscore the value of peripheral blood indices to predict severity of bacterial infections in mice. Early lymphopenia and elevated granulocyte/lymphocyte ratio merit further investigation as biomarkers for systemic spread of skin infections in humans and, possibly, related pyogenic streptococci in humans and animals.
Attribution-NonCommercial-ShareAlike 3.0 United States
http://creativecommons.org/licenses/by-nc-sa/3.0/us/
Streptococcus pyogenes
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biomarker
70f08e35-e592-4e2c-9878-0131aae20a5e
leukocytes
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lymphopenia
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sepsis
15aed29f-8bf1-43d1-84c1-bcb5274bf7c1
skin infection
d4c2420a-bbcc-4eb2-8ba9-919f7cd07559
Early Lymphocyte Loss and Increased Granulocyte/Lymphocyte Ratio Predict Systemic Spread of in a Mouse Model of Acute Skin Infection.
Article
2018-06-05T12:52:51Z
ORIGINAL
Loof et al.pdf
Loof et al.pdf
Open Access publication
application/pdf
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https://hzi.openrepository.com/bitstream/10033/621392/1/Loof%20et%20al.pdf
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CC-LICENSE
license_rdf
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LICENSE
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license.txt
text/plain
1685
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cb598eeb10bfed09d26fd8d285172ad4
MD5
3
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TEXT
Loof et al.pdf.txt
Loof et al.pdf.txt
Extracted text
text/plain
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https://hzi.openrepository.com/bitstream/10033/621392/4/Loof%20et%20al.pdf.txt
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THUMBNAIL
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10033/621392
oai:hzi.openrepository.com:10033/621392
2019-08-30 11:26:37.209
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6214532019-08-30T11:29:14Zcom_10033_620601col_10033_620603
Petersen, Henning
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500
Mostafa, Ahmed
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500
Tantawy, Mohamed A
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500
Iqbal, Azeem A
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500
Hoffmann, Donata
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500
Tallam, Aravind
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500
Selvakumar, Balachandar
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500
Pessler, Frank
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500
Beer, Martin
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500
Rautenschlein, Silke
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500
Pleschka, Stephan
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500
TWINCORE, Zentrum für experimentelle und klinischeInfektionsforschung GmbH, Feodor-Lynen-Str. 7, 30625 Hannover, Germany.
2018-08-27T08:47:40Z
2018-08-27T08:47:40Z
2018-01-01
1664-302X
29623073
10.3389/fmicb.2018.00526
http://hdl.handle.net/10033/621453
The 2009 pandemic influenza A virus (IAV) H1N1 strain (H1N1pdm09) has widely spread and is circulating in humans and swine together with other human and avian IAVs. This fact raises the concern that reassortment between H1N1pdm09 and co-circulating viruses might lead to an increase of H1N1pdm09 pathogenicity in different susceptible host species. Herein, we explored the potential of different NS segments to enhance the replication dynamics, pathogenicity and host range of H1N1pdm09 strain A/Giessen/06/09 (Gi-wt). The NS segments were derived from (i) human H1N1- and H3N2 IAVs, (ii) highly pathogenic- (H5- or H7-subtypes) or (iii) low pathogenic avian influenza viruses (H7- or H9-subtypes). A significant increase of growth kinetics in A549 (human lung epithelia) and NPTr (porcine tracheal epithelia) cells was only noticed
Attribution-NonCommercial-ShareAlike 3.0 United States
http://creativecommons.org/licenses/by-nc-sa/3.0/us/
H1N1pdm09
e2ae942a-e65a-4500-8df4-d24f16fbbf06
NS segment
5480d95e-b9ab-4289-898a-c6de98c5a62b
influenza virus
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innate immunity
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500
reassortment
afd81f34-c7f9-4920-88b4-65b90e639392
NS Segment of a 1918 Influenza A Virus-Descendent Enhances Replication of H1N1pdm09 and Virus-Induced Cellular Immune Response in Mammalian and Avian Systems.
Article
Frontiers in microbiology
2018-08-27T08:47:40Z
THUMBNAIL
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Petersen et al.pdf.txt
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Petersen_supplemental_Presentation_1.PDF.txt
Petersen_supplemental_Presentation_1.PDF.txt
Extracted text
text/plain
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https://hzi.openrepository.com/bitstream/10033/621453/9/Petersen_supplemental_Presentation_1.PDF.txt
d694219f3f36b0b0538930d3e982e3cc
MD5
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LICENSE
license.txt
license.txt
text/plain
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https://hzi.openrepository.com/bitstream/10033/621453/6/license.txt
cb598eeb10bfed09d26fd8d285172ad4
MD5
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CC-LICENSE
license_rdf
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application/rdf+xml; charset=utf-8
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MD5
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ORIGINAL
Petersen et al.pdf
Petersen et al.pdf
Open Access publication
application/pdf
1516473
https://hzi.openrepository.com/bitstream/10033/621453/2/Petersen%20et%20al.pdf
7356fdd34cce7355eb73f9c0f2d7666d
MD5
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true
Petersen_supplemental_Presentation_1.PDF
Petersen_supplemental_Presentation_1.PDF
supplemental materials
application/pdf
439818
https://hzi.openrepository.com/bitstream/10033/621453/3/Petersen_supplemental_Presentation_1.PDF
a2e9c53242e03bb053af79f4d642e7e3
MD5
3
false
Petersen_supplemental_Presentation_1.PDF
Petersen_supplemental_Presentation_1.PDF
supplemental material
application/pdf
439818
https://hzi.openrepository.com/bitstream/10033/621453/4/Petersen_supplemental_Presentation_1.PDF
a2e9c53242e03bb053af79f4d642e7e3
MD5
4
false
10033/621453
oai:hzi.openrepository.com:10033/621453
2019-08-30 11:29:14.528
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6214672019-08-30T11:30:30Zcom_10033_211390com_10033_620601col_10033_211409col_10033_620603
Filomena, Angela
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Akmatov, Manas K
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http://orcid.org/0000-0003-2310-3179
Krause, Gérard
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Duffy, Darragh
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Gärtner, Barbara
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Gerhard, Markus
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Albert, Matthew L
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Joos, Thomas O
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Schneiderhan-Marra, Nicole
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Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.
2018-09-04T12:07:08Z
2018-09-04T12:07:08Z
2017-10-30
2571-5135
29855458
10.3390/ht6040014
http://hdl.handle.net/10033/621467
The spread of infectious diseases and vaccination history are common subjects of epidemiological and immunological research studies. Multiplexed serological assays are useful tools for assessing both current and previous infections as well as vaccination efficacy. We developed a serological multi-pathogen assay for hepatitis A, B and C virus, cytomegalovirus (CMV),
Attribution-NonCommercial-ShareAlike 3.0 United States
http://creativecommons.org/licenses/by-nc-sa/3.0/us/
Helicobacter pylori
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Toxoplasma gondii
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cytomegalovirus (CMV)
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hepatitis
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multi-pathogen assay
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multiplex
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seroprevalence
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Development of a Bead-Based Multiplex Assay for the Analysis of the Serological Response against the Six Pathogens HAV, HBV, HCV, CMV, T. gondii, and H. pylori.
Article
High-throughput
2018-09-04T12:07:08Z
THUMBNAIL
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oai:hzi.openrepository.com:10033/621467
2019-08-30 11:30:30.634
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6215902019-08-30T11:29:44Zcom_10033_620626com_10033_620601com_10033_620618col_10033_620629col_10033_620603col_10033_620621
Strehlitz, Anja
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Goldmann, Oliver
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Pils, Marina C
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Pessler, Frank
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Medina, Eva
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http://orcid.org/0000-0001-9073-0223
HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.; TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.
2018-11-28T10:27:41Z
2018-11-28T10:27:41Z
2018-01-01
1664-3224
29988532
10.3389/fimmu.2018.01424
http://hdl.handle.net/10033/621590
Streptococcus pneumoniae is the most common cause of community-acquired pneumonia (CAP). Despite the low prevalence of CAP caused by methicillin-resistant Staphylococcus aureus (MRSA), CAP patients often receive empirical antibiotic therapy providing coverage for MRSA such as vancomycin or linezolid. An early differentiation between S. pneumoniae and S. aureus pneumonia can help to reduce the use of unnecessary antibiotics. The objective of this study was to identify candidate biomarkers that can discriminate pneumococcal from staphylococcal pneumonia. A genome-wide transcriptional analysis of lung and peripheral blood performed in murine models of S. pneumoniae and S. aureus lung infection identified an interferon signature specifically associated with S. pneumoniae infection. Prediction models built using a support vector machine and Monte Carlo cross-validation, identified the combination of the interferon-induced chemokines CXCL9 and CXCL10 serum concentrations as the set of biomarkers with best sensitivity, specificity, and predictive power that enabled an accurate discrimination between S. pneumoniae and S. aureus pneumonia. The predictive performance of these biomarkers was further validated in an independent cohort of mice. This study highlights the potential of serum CXCL9 and CXCL10 biomarkers as an adjunctive diagnostic tool that could facilitate prompt and correct pathogen-targeted therapy in CAP patients.
Frontiers
Attribution-NonCommercial-ShareAlike 3.0 United States
http://creativecommons.org/licenses/by-nc-sa/3.0/us/
Staphylococcus aureus
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Streptococcus pneumoniae
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biomarkers
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interferon
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pneumonia
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transcriptome
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An Interferon Signature Discriminates Pneumococcal From Staphylococcal Pneumonia.
Article
Frontiers in immunology
2018-11-28T10:27:41Z
THUMBNAIL
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LICENSE
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ORIGINAL
Strehlitz et al.pdf
Strehlitz et al.pdf
Open Access publication
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10033/621590
oai:hzi.openrepository.com:10033/621590
2019-08-30 11:29:44.076
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6216912019-11-21T12:02:26Zcom_10033_620601col_10033_620603
Ratuszny, Dominica
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Sühs, Kurt-Wolfram
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Novoselova, Natalia
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Kuhn, Maike
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Kaever, Volkhard
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Skripuletz, Thomas
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TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.
2019-02-15T13:11:44Z
2019-02-15T13:11:44Z
2019-01-15
1422-0067
30650575
10.3390/ijms20020337
http://hdl.handle.net/10033/621691
International journal of molecular sciences
Enteroviruses are among the most common causes of viral meningitis. Enteroviral meningitis continues to represent diagnostic challenges, as cerebrospinal fluid (CSF) cell numbers (a well validated diagnostic screening tool) may be normal in up to 15% of patients. We aimed to identify potential CSF biomarkers for enteroviral meningitis, particularly for cases with normal CSF cell count. Using targeted liquid chromatography-mass spectrometry, we determined metabolite profiles from patients with enteroviral meningitis (n = 10), and subdivided them into those with elevated (n = 5) and normal (n = 5) CSF leukocyte counts. Non-inflamed CSF samples from patients with Bell’s palsy and normal pressure hydrocephalus (n = 19) were used as controls. Analysis of 91 metabolites revealed considerable metabolic reprogramming in the meningitis samples. It identified phosphatidylcholine PC.ae.C36.3, asparagine, and glycine as an accurate (AUC, 0.92) combined classifier for enterovirus meningitis overall, and kynurenine as a perfect biomarker for enteroviral meningitis with an increased CSF cell count (AUC, 1.0). Remarkably, PC.ae.C36.3 alone emerged as a single accurate (AUC, 0.87) biomarker for enteroviral meningitis with normal cell count, and a combined classifier comprising PC.ae.C36.3, PC.ae.C36.5, and PC.ae.C38.5 achieved nearly perfect classification (AUC, 0.99). Taken together, this analysis reveals the potential of CSF metabolites as additional diagnostic tools for enteroviral meningitis, and likely other central nervous system (CNS) infections.
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metabolomics
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phosphatidylcholines
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Identification of Cerebrospinal Fluid Metabolites as Biomarkers for Enterovirus Meningitis.
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oai:repository.helmholtz-hzi.de:10033/6216932019-02-16T01:23:08Zcom_10033_620601col_10033_620603
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TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.
2019-02-15T13:56:34Z
2019-02-15T13:56:34Z
2019-01-01
PLoS Negl Trop Dis. 2019 Jan 24;13(1):e0007131. doi:10.1371/journal.pntd.0007131
1935-2735
30677033
10.1371/journal.pntd.0007131
http://hdl.handle.net/10033/621693
Plos neglected tropical diseases
Leptospirosis is the most common zoonotic disease worldwide. The diagnostic performance of a serological test for human leptospirosis is mainly influenced by the antigen used in the test assay. An ideal serological test should cover all serovars of pathogenic leptospires with high sensitivity and specificity and use reagents that are relatively inexpensive to produce and can be used in tropical climates. Peptide-based tests fulfil at least the latter two requirements, and ORFeome phage display has been successfully used to identify immunogenic peptides from other pathogens. Two ORFeome phage display libraries of the entire Leptospira spp. genomes from five local strains isolated in Malaysia and seven WHO reference strains were constructed. Subsequently, 18 unique Leptospira peptides were identified in a screen using a pool of sera from patients with acute leptospirosis. Five of these were validated by titration ELISA using different pools of patient or control sera. The diagnostic performance of these five peptides was then assessed against 16 individual sera from patients with acute leptospirosis and 16 healthy donors and was compared to that of two recombinant reference proteins from L. interrogans. This analysis revealed two peptides (SIR16-D1 and SIR16-H1) from the local isolates with good accuracy for the detection of acute leptospirosis (area under the ROC curve: 0.86 and 0.78, respectively; sensitivity: 0.88 and 0.94; specificity: 0.81 and 0.69), which was close to that of the reference proteins LipL32 and Loa22 (area under the ROC curve: 0.91 and 0.80; sensitivity: 0.94 and 0.81; specificity: 0.75 and 0.75). This analysis lends further support for using ORFeome phage display to identify pathogen-associated immunogenic peptides, and it suggests that this technique holds promise for the development of peptide-based diagnostics for leptospirosis and, possibly, of vaccines against this pathogen.
en
PLOS
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
Discovery of Leptospira spp. seroreactive peptides using ORFeome phage display.
Article
PLoS neglected tropical diseases
2019-02-15T13:56:35Z
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oai:repository.helmholtz-hzi.de:10033/6217012019-08-30T11:32:40Zcom_10033_620601col_10033_620603
Ramli, Siti Roszilawati
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Novoselova, Natalia
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TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.
2019-02-20T10:50:29Z
2019-02-20T10:50:29Z
2019-01-01
1935-2735
30677033
10.1371/journal.pntd.0007131
http://hdl.handle.net/10033/621701
Plos neglected tropical diseases
Leptospirosis is the most common zoonotic disease worldwide. The diagnostic performance of a serological test for human leptospirosis is mainly influenced by the antigen used in the test assay. An ideal serological test should cover all serovars of pathogenic leptospires with high sensitivity and specificity and use reagents that are relatively inexpensive to produce and can be used in tropical climates. Peptide-based tests fulfil at least the latter two requirements, and ORFeome phage display has been successfully used to identify immunogenic peptides from other pathogens. Two ORFeome phage display libraries of the entire Leptospira spp. genomes from five local strains isolated in Malaysia and seven WHO reference strains were constructed. Subsequently, 18 unique Leptospira peptides were identified in a screen using a pool of sera from patients with acute leptospirosis. Five of these were validated by titration ELISA using different pools of patient or control sera. The diagnostic performance of these five peptides was then assessed against 16 individual sera from patients with acute leptospirosis and 16 healthy donors and was compared to that of two recombinant reference proteins from L. interrogans. This analysis revealed two peptides (SIR16-D1 and SIR16-H1) from the local isolates with good accuracy for the detection of acute leptospirosis (area under the ROC curve: 0.86 and 0.78, respectively; sensitivity: 0.88 and 0.94; specificity: 0.81 and 0.69), which was close to that of the reference proteins LipL32 and Loa22 (area under the ROC curve: 0.91 and 0.80; sensitivity: 0.94 and 0.81; specificity: 0.75 and 0.75). This analysis lends further support for using ORFeome phage display to identify pathogen-associated immunogenic peptides, and it suggests that this technique holds promise for the development of peptide-based diagnostics for leptospirosis and, possibly, of vaccines against this pathogen.
PLOS
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
Discovery of Leptospira spp. seroreactive peptides using ORFeome phage display.
Article
PLoS neglected tropical diseases
2019-02-20T10:50:29Z
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Helmholtz Zentrum für Infektionsforschung Repository
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oai:repository.helmholtz-hzi.de:10033/6217252019-08-30T11:35:13Zcom_10033_620601col_10033_620603
Sühs, Kurt-Wolfram
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Novoselova, Natalia
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Seegers, Lena
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Kaever, Volkhard
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Müller-Vahl, Kirsten
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Trebst, Corinna
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Skripuletz, Thomas
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Stangel, Martin
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Pessler, Frank
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TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH, Feodor-Lynen-Str.7,30625 Hannover, Germany.
2019-03-18T15:08:45Z
2019-03-18T15:08:45Z
2019-02-05
J Infect Dis. 2019 Feb 5. pii: 5307059. doi: 10.1093/infdis/jiz048.
1537-6613
30721966
10.1093/infdis/jiz048
http://hdl.handle.net/10033/621725
Journal of infectious diseases
The tryptophan-kynurenine-NAD+ pathway is closely associated with regulation of immune cells toward less inflammatory phenotypes and may exert neuroprotective effects. Investigating its regulation in CNS infections would improve our understanding of pathophysiology and end-organ damage, and, furthermore, open doors to its evaluation as a source of diagnostic and/or prognostic biomarkers. We measured concentrations of kynurenine (Kyn) and tryptophan (Trp) in 220 cerebrospinal fluid samples from patients with bacterial and viral (herpes simplex, varicella zoster, enteroviruses) meningitis/encephalitis, neuroborreliosis, autoimmune neuroinflammation (anti-NMDA-R encephalitis, multiple sclerosis), and noninflamed controls (Bell's palsy, normal pressure hydrocephalus, Tourette syndrome). Kyn concentrations correlated strongly with CSF markers of neuroinflammation (leukocyte count, lactate, and blood-CSF-barrier dysfunction) and were highly increased in bacterial and viral CNS infections, but were low or undetectable in anti-NMDA-R encephalitis, multiple sclerosis, and controls. Trp was decreased mostly in viral CNS infections and neuroborreliosis. Multiple logistic regression analysis revealed combinations of Kyn, Trp and Kyn/Trp ratio with leukocyte count or lactate as accurate classifiers for the clinically important differentiation between neuroborreliosis, viral CNS infections, and autoimmune neuroinflammation. The Trp-Kyn-NAD+ pathway is activated in CNS infections and provides highly accurate CSF biomarkers, particularly when combined with standard CSF indices of neuroinflammation.
en
Oxford University Press
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
Kynurenine is a cerebrospinal fluid biomarker for bacterial and viral CNS infections.
Article
The Journal of infectious diseases
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2020-02-05
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2020-02-05
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2019-08-30 11:35:13.759
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6217842019-08-30T11:33:26Zcom_10033_620601col_10033_620603
Wawro, Nina
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Amann, Ute
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Butt, Julia
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Meisinger, Christa
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Akmatov, Manas K
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http://orcid.org/0000-0003-2310-3179
Pessler, Frank
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Peters, Annette
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Rathmann, Wolfgang
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Kääb, Stefan
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Waterboer, Tim
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Linseisen, Jakob
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HZI, Helmholtz Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.
2019-05-20T11:36:36Z
2019-05-20T11:36:36Z
2019-01-01
Front Public Health. 2019 Apr 24;7:96. doi: 10.3389/fpubh.2019.00096. eCollection 2019.
2296-2565
31069210
10.3389/fpubh.2019.00096
http://hdl.handle.net/10033/621784
Frontiers in Public Health
Introduction:Helicobacter pylori (H. pylori) is a common infection and known risk factor for gastric cancer. We assessed cross-sectional and longitudinal associations to study the impact of H. pylori seropositivity on metabolic diseases. Methods:Helicobacter pylori seropositivity in serum samples of the KORA study was analyzed by multiplex serology. We calculated sex-specific prevalence of H. pylori seropositivity for the year 2007 based on the first follow-up survey (termed F4) of the KORA study S4. We identified factors associated with H. pylori seropositivity in the F4 survey. Further, we assessed relative risks of incident metabolic diseases/risk factors at the time of the second follow-up survey of S4 (termed FF4) and H. pylori seropositivity at the F4 survey as a determinant. Models were adjusted for age, sex, overweight status, physical activity, smoking status, education level, alcohol intake, and other metabolic diseases. Results: Based on 3,037 persons aged 32 to 82 years, the H. pylori prevalence for 2007 was 30.2% in men (n = 1,465) and 28.1% in women (n = 1,572). Increasing age, current smoking, low education and no alcohol intake were significantly associated with H. pylori seropositivity in the F4 survey. However, no association between H. pylori seropositivity and BMI, metabolic diseases (type 2 diabetes, hypertension and dyslipidemia, gout or increased uric acid) and gastrointestinal diseases (gastritis, inflammatory bowel disease, and gastric or duodenal ulcer) was observed. No significant associations between H. pylori seropositivity and one of the five investigated incident metabolic diseases/risk factors were detected in the longitudinal analysis. Conclusion: We identified associations between age, smoking, education and alcohol intake and H. pylori seropositivity but no impact of H. pylori seropositivity on incident metabolic diseases/risk factors.
en
Frontiers
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
Helicobacter pylori
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infection
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metabolic diseases
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multiplex serology
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prevalence
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Helicobacter pylori seropositivity: Prevalence, Associations, and the Impact on Incident Metabolic Diseases/Risk Factors in the Population-Based KORA Study.
Article
Frontiers in public health
2019-05-20T11:36:36Z
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Wawro et al.pdf
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oai:hzi.openrepository.com:10033/621784
2019-08-30 11:33:26.005
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6219142019-08-30T11:27:14Zcom_10033_620601col_10033_620603
Akmatov, Manas K
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http://orcid.org/0000-0003-2310-3179
Riese, Peggy
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600
http://orcid.org/0000-0001-6796-6780
Trittel, Stephanie
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May, Marcus
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Prokein, Jana
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Illig, Thomas
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Schindler, Christoph
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Guzmán, Carlos A
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Pessler, Frank
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TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.
2019-08-21T10:41:11Z
2019-08-21T10:41:11Z
2019-07-23
BMC Infect Dis. 2019 Jul 23;19(1):656. doi: 10.1186/s12879-019-4214-x.
1471-2334
31337344
10.1186/s12879-019-4214-x
http://hdl.handle.net/10033/621914
BMC Infectious Diseases
BACKGROUND:
The immune response to seasonal influenza vaccines decreases with advancing age. Therefore, an adjuvanted inactivated trivalent influenza vaccine (Fluad®) exists for elderly individuals. Fluad® is more immunogenic and efficacious than conventional influenza vaccines. However, the immune response varies and may still result in high frequencies of poor responders. Therefore, we aimed to a) examine the prevalence of a weak response to Fluad® and b) identify potential risk factors.
METHODS:
A prospective population-based study among individuals 65-80 years old was conducted in 2015/2016 in Hannover, Germany (n = 200). Hemagglutination-inhibition titers 21 days after vaccination with Fluad® served as indicator of vaccine responsiveness.
RESULTS:
The percentage of vaccinees with an inadequate vaccine response varied depending on the influenza strain: it was lowest for H3N2 (13.5%; 95% CI, 9.4-18.9%), intermediate for B strain (37.0%; 30.6-43.9%), and highest for H1N1 (49.0%; 42.2-55.9%). The risk of a weak response to the influenza A H1N1 strain was independently associated with self-reported diabetes (AOR, 4.64; 95% CI, 1.16-18.54), a history of herpes zoster (2.27; 1.01-5.10) and, to a much lesser extent, increasing age (change per year, 1.08; 0.99-1.16). In addition, herpes zoster was the only risk factor for a weak response to the H3N2 antigen (AOR, 3.12; 1.18-8.23). We found no significant association between sex, Body Mass Index, cancer, hypertension, heart attack and CMV seropositivity and a weak response to these two influenza A antigens. Despite its occurence in over one third of vaccinees, none of the variables examined proved to be risk factors for a weak response to the B antigen.
CONCLUSIONS:
A considerable proportion of elderly individuals displayed a weak vaccine response to this adjuvanted seasonal influenza vaccine and further efforts are thus needed to improve immune responses to influenza vaccination among the elderly. Diabetes and herpes zoster were identified as potentially modifiable risk factors for a poor vaccine response against influenza A antigens, but the results also reveal the need for broader investigations to identify risk factors for inadequate responses to influenza B antigens.
en
BioMedCentral
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
Diabetes
Elderly
Fluad®
Herpes zoster
Influenza vaccination
Self-reported diabetes and herpes zoster are associated with a weak humoral response to the seasonal influenza A H1N1 vaccine antigen among the elderly.
Article
BMC infectious diseases
2019-08-21T10:41:12Z
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2019-08-30 11:27:14.76
Helmholtz Zentrum für Infektionsforschung Repository
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oai:repository.helmholtz-hzi.de:10033/6219642019-10-05T11:57:51Zcom_10033_620601col_10033_620603
Chen, Fangfang
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Lukat, Peer
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Iqbal, Azeem Ahmed
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Saile, Kyrill
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Kaever, Volkhard
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van den Heuvel, Joop
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Blankenfeldt, Wulf
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http://orcid.org/0000-0001-9886-9668
Büssow, Konrad
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Pessler, Frank
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HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany; TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.
2019-10-04T13:45:05Z
2019-10-04T13:45:05Z
2019-09-23
Proc Natl Acad Sci U S A. 2019 Sep 23. pii: 1908770116. doi:10.1073/pnas.1908770116.
1091-6490
31548418
10.1073/pnas.1908770116
http://hdl.handle.net/10033/621964
Proceedings of the National Academy of sciences
cis-Aconitate decarboxylase (CAD, also known as ACOD1 or Irg1) converts cis-aconitate to itaconate and plays central roles in linking innate immunity with metabolism and in the biotechnological production of itaconic acid by Aspergillus terreus We have elucidated the crystal structures of human and murine CADs and compared their enzymological properties to CAD from A. terreus Recombinant CAD is fully active in vitro without a cofactor. Murine CAD has the highest catalytic activity, whereas Aspergillus CAD is best adapted to a more acidic pH. CAD is not homologous to any known decarboxylase and appears to have evolved from prokaryotic enzymes that bind negatively charged substrates. CADs are homodimers, the active center is located in the interface between 2 distinct subdomains, and structural modeling revealed conservation in zebrafish and Aspergillus We identified 8 active-site residues critical for CAD function and rare naturally occurring human mutations in the active site that abolished CAD activity, as well as a variant (Asn152Ser) that increased CAD activity and is common (allele frequency 20%) in African ethnicity. These results open the way for 1) assessing the potential impact of human CAD variants on disease risk at the population level, 2) developing therapeutic interventions to modify CAD activity, and 3) improving CAD efficiency for biotechnological production of itaconic acid.
en
National Academy of Sciences
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
cis-aconitate
decarboxylase
enzymology
itaconic acid
macrophage
Crystal structure of -aconitate decarboxylase reveals the impact of naturally occurring human mutations on itaconate synthesis.
Article
Proceedings of the National Academy of Sciences of the United States of America
2019-10-04T13:45:07Z
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Helmholtz Zentrum für Infektionsforschung Repository
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oai:repository.helmholtz-hzi.de:10033/6219842019-10-19T01:32:04Zcom_10033_620601col_10033_620603
Ali, Jafar
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300
Sohail, Aaqib
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Wang, Lei
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Rizwan Haider, Muhammad
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Mulk, Shahi
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TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.
2019-10-18T13:14:10Z
2019-10-18T13:14:10Z
2018-07-12
1996-1073
10.3390/en11071822
http://hdl.handle.net/10033/621984
Energies
Microbial electrochemical technologies provide sustainable wastewater treatment and energy production. Despite significant improvements in the power output of microbial fuel cells (MFCs), this technology is still far from practical applications. Extracting electrical energy and harvesting valuable products by electroactive bacteria (EAB) in bioelectrochemical systems (BESs) has emerged as an innovative approach to address energy and environmental challenges. Thus, maximizing power output and resource recovery is highly desirable for sustainable systems. Insights into the electrode-microbe interactions may help to optimize the performance of BESs for envisioned applications, and further validation by bioelectrochemical techniques is a prerequisite to completely understand the electro-microbiology. This review summarizes various extracellular electron transfer mechanisms involved in BESs. The significant role of characterization techniques in the advancement of the electro-microbiology field is discussed. Finally, diverse applications of BESs, such as resource recovery, and contributions to the pursuit of a more sustainable society are also highlighted.
en
MDPI AG
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
Electro-Microbiology as a Promising Approach Towards Renewable Energy and Environmental Sustainability
Article
11
7
1822
2019-10-18T13:14:11Z
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2019-10-19 01:32:04.829
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6220332019-11-28T01:59:48Zcom_10033_620601col_10033_620603
Arshad, Haroon
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Alfonso, Juan Carlos López
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Franke, Raimo
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500
Michaelis, Katina
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Araujo, Leonardo
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Habib, Aamna
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Zboromyrska, Yuliya
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Lücke, Eva
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300
Strungaru, Emilia
57f752ea933c865306b03abbeedf6414
300
Akmatov, Manas K
f26d950190b2dc77e795c6dd0385578b
600
http://orcid.org/0000-0003-2310-3179
Hatzikirou, Haralampos
55f01b39e1256e18f124c4fc74c4e0de
500
Meyer-Hermann, Michael
cb429b7c1163ff90763035deb8eff488
600
http://orcid.org/0000-0002-4300-2474
Petersmann, Astrid
55afed0705cbe85e1f2d7beff3d5519c
500
Nauck, Matthias
bed9d9dd9042c3a33426dce5b20eb70b
500
Brönstrup, Mark
23ad6d5459084164050826384a0e6d43
600
http://orcid.org/0000-0002-8971-7045
Bilitewski, Ursula
d5bc3ba6da794cd7e729a4121719b336
500
Abel, Laurent
31c276ee0922d3d7601704b0a69aa33c
300
Sievers, Jorg
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300
Vila, Jordi
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500
Illig, Thomas
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500
Schreiber, Jens
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Pessler, Frank
9fc33677a3eea5c4e77542200bd20f05
HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
2019-11-27T09:16:59Z
2019-11-27T09:16:59Z
2019-11-11
J Transl Med. 2019 Nov 11;17(1):365. doi: 10.1186/s12967-019-2112-z.
1479-5876
31711507
10.1186/s12967-019-2112-z
http://hdl.handle.net/10033/622033
Journal of translational medicine
BACKGROUND:
There continues to be a great need for better biomarkers and host-directed treatment targets for community-acquired pneumonia (CAP). Alterations in phospholipid metabolism may constitute a source of small molecule biomarkers for acute infections including CAP. Evidence from animal models of pulmonary infections and sepsis suggests that inhibiting acid sphingomyelinase (which releases ceramides from sphingomyelins) may reduce end-organ damage.
METHODS:
We measured concentrations of 105 phospholipids, 40 acylcarnitines, and 4 ceramides, as well as acid sphingomyelinase activity, in plasma from patients with CAP (n = 29, sampled on admission and 4 subsequent time points), chronic obstructive pulmonary disease exacerbation with infection (COPD, n = 13) as a clinically important disease control, and 33 age- and sex-matched controls.
RESULTS:
Phospholipid concentrations were greatly decreased in CAP and normalized along clinical improvement. Greatest changes were seen in phosphatidylcholines, followed by lysophosphatidylcholines, sphingomyelins and ceramides (three of which were upregulated), and were least in acylcarnitines. Changes in COPD were less pronounced, but also differed qualitatively, e.g. by increases in selected sphingomyelins. We identified highly accurate biomarkers for CAP (AUC ≤ 0.97) and COPD (AUC ≤ 0.93) vs. Controls, and moderately accurate biomarkers for CAP vs. COPD (AUC ≤ 0.83), all of which were phospholipids. Phosphatidylcholines, lysophosphatidylcholines, and sphingomyelins were also markedly decreased in S. aureus-infected human A549 and differentiated THP1 cells. Correlations with C-reactive protein and procalcitonin were predominantly negative but only of mild-to-moderate extent, suggesting that these markers reflect more than merely inflammation. Consistent with the increased ceramide concentrations, increased acid sphingomyelinase activity accurately distinguished CAP (fold change = 2.8, AUC = 0.94) and COPD (1.75, 0.88) from Controls and normalized with clinical resolution.
CONCLUSIONS:
The results underscore the high potential of plasma phospholipids as biomarkers for CAP, begin to reveal differences in lipid dysregulation between CAP and infection-associated COPD exacerbation, and suggest that the decreases in plasma concentrations are at least partially determined by changes in host target cells. Furthermore, they provide validation in clinical blood samples of acid sphingomyelinase as a potential treatment target to improve clinical outcome of CAP
en
Wiley
info:eu-repo/grantAgreement/EC/FP7/115523
openAccess
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
Biomarkers
Chronic obstructive pulmonary disease
Community-acquired pneumonia
Glycerophospholipids
Infection
Lipidomics
Lung disease
Mass spectrometry
Metabolism
Metabolomics
Sphingomyelinase
Decreased plasma phospholipid concentrations and increased acid sphingomyelinase activity are accurate biomarkers for community-acquired pneumonia.
Article
Journal of translational medicine
2019-11-27T09:16:59Z
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oai:repository.helmholtz-hzi.de:10033/622033
2019-11-28 01:59:48.553
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6220522019-12-20T01:59:12Zcom_10033_620601com_10033_620636col_10033_620603col_10033_620638
de Araujo, Leonardo Silva
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Ribeiro-Alves, Marcelo
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Leal-Calvo, Thyago
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Leung, Janaína
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Durán, Verónica
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Samir, Mohamed
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Talbot, Steven
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Tallam, Aravind
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Mello, Fernanda Carvalho de Queiroz
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Geffers, Robert
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Saad, Maria Helena Féres
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Pessler, Frank
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TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.
2019-12-19T14:28:25Z
2019-12-19T14:28:25Z
2019-12-03
MBio. 2019 Dec 3;10(6). pii: mBio.01037-19. doi: 10.1128/mBio.01037-19.
2150-7511
31796535
10.1128/mBio.01037-19
http://hdl.handle.net/10033/622052
mBIO
In tuberculosis (TB), as in other infectious diseases, studies of small noncoding RNAs (sncRNA) in peripheral blood have focused on microRNAs (miRNAs) but have neglected the other major sncRNA classes in spite of their potential functions in host gene regulation. Using RNA sequencing of whole blood, we have therefore determined expression of miRNA, PIWI-interacting RNA (piRNA), small nucleolar RNA (snoRNA), and small nuclear RNA (snRNA) in patients with TB (n = 8), latent TB infection (LTBI; n = 21), and treated LTBI (LTBItt; n = 6) and in uninfected exposed controls (ExC; n = 14). As expected, sncRNA reprogramming was greater in TB than in LTBI, with the greatest changes seen in miRNA populations. However, substantial dynamics were also evident in piRNA and snoRNA populations. One miRNA and 2 piRNAs were identified as moderately accurate (area under the curve [AUC] = 0.70 to 0.74) biomarkers for LTBI, as were 1 miRNA, 1 piRNA, and 2 snoRNAs (AUC = 0.79 to 0.91) for accomplished LTBI treatment. Logistic regression identified the combination of 4 sncRNA (let-7a-5p, miR-589-5p, miR-196b-5p, and SNORD104) as a highly sensitive (100%) classifier to discriminate TB from all non-TB groups. Notably, it reclassified 8 presumed LTBI cases as TB cases, 5 of which turned out to have features of Mycobacterium tuberculosis infection on chest radiographs. SNORD104 expression decreased during M. tuberculosis infection of primary human peripheral blood mononuclear cells (PBMC) and M2-like (P = 0.03) but not M1-like (P = 0.31) macrophages, suggesting that its downregulation in peripheral blood in TB is biologically relevant. Taken together, the results demonstrate that snoRNA and piRNA should be considered in addition to miRNA as biomarkers and pathogenesis factors in the various stages of TB.IMPORTANCE Tuberculosis is the infectious disease with the worldwide largest disease burden and there remains a great need for better diagnostic biomarkers to detect latent and active M. tuberculosis infection. RNA molecules hold great promise in this regard, as their levels of expression may differ considerably between infected and uninfected subjects. We have measured expression changes in the four major classes of small noncoding RNAs in blood samples from patients with different stages of TB infection. We found that, in addition to miRNAs (which are known to be highly regulated in blood cells from TB patients), expression of piRNA and snoRNA is greatly altered in both latent and active TB, yielding promising biomarkers. Even though the functions of many sncRNA other than miRNA are still poorly understood, our results strongly suggest that at least piRNA and snoRNA populations may represent hitherto underappreciated players in the different stages of TB infection.
America Society of Microbiology (ASM)
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
RNA
biomarkers
biosignature
incipient tuberculosis
miRNA
piRNA
snRNA
sncRNA
snoRNA
subclinical tuberculosis
transcriptome
tuberculosis
Reprogramming of Small Noncoding RNA Populations in Peripheral Blood Reveals Host Biomarkers for Latent and Active Mycobacterium tuberculosis Infection.
Article
mBio
2019-12-19T14:28:25Z
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oai:repository.helmholtz-hzi.de:10033/622052
2019-12-20 01:59:12.383
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6220912020-01-18T02:09:10Zcom_10033_620601col_10033_620603
de Araujo, Leonardo Silva
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500
Pessler, Kevin
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300
Sühs, Kurt-Wolfram
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500
Novoselova, Natalia
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500
Klawonn, Frank
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500
Kuhn, Maike
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500
Kaever, Volkhard
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500
Müller-Vahl, Kirsten
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500
Trebst, Corinna
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Skripuletz, Thomas
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Stangel, Martin
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Pessler, Frank
9fc33677a3eea5c4e77542200bd20f05
TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.
2020-01-17T13:46:03Z
2020-01-17T13:46:03Z
2020-01-07
J Transl Med. 2020 Jan 7;18(1):9. doi: 10.1186/s12967-019-02179-w.
1479-5876
31910875
10.1186/s12967-019-02179-w
http://hdl.handle.net/10033/622091
l: Journal of Translational Medicine
BACKGROUND: The timely diagnosis of bacterial meningitis is of utmost importance due to the need to institute antibiotic treatment as early as possible. Moreover, the differentiation from other causes of meningitis/encephalitis is critical because of differences in management such as the need for antiviral or immunosuppressive treatments. Considering our previously reported association between free membrane phospholipids in cerebrospinal fluid (CSF) and CNS involvement in neuroinfections we evaluated phosphatidylcholine PC ae C44:6, an integral constituent of cell membranes, as diagnostic biomarker for bacterial meningitis.
METHODS: We used tandem mass spectrometry to measure concentrations of PC ae C44:6 in cell-free CSF samples (n = 221) from patients with acute bacterial meningitis, neuroborreliosis, viral meningitis/encephalitis (herpes simplex virus, varicella zoster virus, enteroviruses), autoimmune neuroinflammation (anti-NMDA-receptor autoimmune encephalitis, multiple sclerosis), facial nerve and segmental herpes zoster (shingles), and noninflammatory CNS disorders (Bell's palsy, Tourette syndrome, normal pressure hydrocephalus).
RESULTS: PC ae C44:6 concentrations were significantly higher in bacterial meningitis than in all other diagnostic groups, and were higher in patients with a classic bacterial meningitis pathogen (e.g. Streptococcus pneumoniae, Neisseria meningitidis, Staphylococcus aureus) than in those with less virulent or opportunistic pathogens as causative agents (P = 0.026). PC ae C44:6 concentrations were only moderately associated with CSF cell count (Spearman's ρ = 0.45; P = 0.009), indicating that they do not merely reflect neuroinflammation. In receiver operating characteristic curve analysis, PC ae C44:6 equaled CSF cell count in the ability to distinguish bacterial meningitis from viral meningitis/encephalitis and autoimmune CNS disorders (AUC 0.93 both), but had higher sensitivity (91% vs. 41%) and negative predictive value (98% vs. 89%). A diagnostic algorithm comprising cell count, lactate and PC ae C44:6 had a sensitivity of 97% (specificity 87%) and negative predictive value of 99% (positive predictive value 61%) and correctly diagnosed three of four bacterial meningitis samples that were misclassified by cell count and lactate due to low values not suggestive of bacterial meningitis.
CONCLUSIONS: Increased CSF PC ae C44:6 concentrations in bacterial meningitis likely reflect ongoing CNS cell membrane stress or damage and have potential as additional, sensitive biomarker to diagnose bacterial meningitis in patients with less pronounced neuroinflammation.
en
BioMed Central (BMC)
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
Biomarker
Brain
Diagnosis
Encephalitis
Infection
Lecithin
Lipidomics
Lipids
Meningitis
Metabolomics
Phosphatidylcholine PC ae C44:6 in cerebrospinal fluid is a sensitive biomarker for bacterial meningitis.
Article
Journal of translational medicine
2020-01-17T13:46:04Z
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10033/622091
oai:repository.helmholtz-hzi.de:10033/622091
2020-01-18 02:09:10.529
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6222032020-03-14T02:00:44Zcom_10033_620601col_10033_620603
Reinke, Sören
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Linge, Mary
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300
Diebner, Hans H
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300
Luksch, Hella
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300
Glage, Silke
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500
Gocht, Anne
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300
Robertson, Avril A B
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Cooper, Matthew A
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Hofmann, Sigrun R
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Naumann, Ronald
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Sarov, Mihail
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Behrendt, Rayk
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Roers, Axel
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Pessler, Frank
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Roesler, Joachim
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Rösen-Wolff, Angela
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Winkler, Stefan
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TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.
2020-03-13T09:15:40Z
2020-03-13T09:15:40Z
Cell Rep. 2020 Feb 25;30(8):2501-2511.e5. doi: 10.1016/j.celrep.2020.01.090.
32101731
10.1016/j.celrep.2020.01.090
http://hdl.handle.net/10033/622203
2211-1247
Cell reports
Pro-inflammatory caspase-1 is a key player in innate immunity. Caspase-1 processes interleukin (IL)-1β and IL-18 to their mature forms and triggers pyroptosis. These caspase-1 functions are linked to its enzymatic activity. However, loss-of-function missense mutations in CASP1 do not prevent autoinflammation in patients, despite decreased IL-1β production. In vitro data suggest that enzymatically inactive caspase-1 drives inflammation via enhanced nuclear factor κB (NF-κB) activation, independent of IL-1β processing. Here, we report two mouse models of enzymatically inactive caspase-1-C284A, demonstrating the relevance of this pathway in vivo. In contrast to Casp1-/- mice, caspase-1-C284A mice show pronounced hypothermia and increased levels of the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α) and IL-6 when challenged with lipopolysaccharide (LPS). Caspase-1-C284A signaling is RIP2 dependent and mediated by TNF-α but independent of the NLRP3 inflammasome. LPS-stimulated whole blood from patients carrying loss-of-function missense mutations in CASP1 secretes higher amounts of TNF-α. Taken together, these results reveal non-canonical caspase-1 signaling in vivo.
en
Elsevier/ Cell Press
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
NF-κB
Rip2
TNF-α
caspase-1
enzymatic activity
non-canonical caspase-1 signaling
Non-canonical Caspase-1 Signaling Drives RIP2-Dependent and TNF-α-Mediated Inflammation In Vivo.
Article
30
8
2501
2511.e5
Cell reports
United States
2020-03-13T09:15:42Z
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10033/622203
oai:repository.helmholtz-hzi.de:10033/622203
2020-03-14 02:00:44.205
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6222552020-05-12T02:36:12Zcom_10033_620601col_10033_620603
Chen, Yu-Lan
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500
Jing, Jun
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500
Mo, Ying-Qian
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500
Ma, Jian-Da
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500
Yang, Li-Juan
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500
Chen, Le-Feng
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500
Zhang, Xiang
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500
Yan, Tao
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500
Zheng, Dong-Hui
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500
Pessler, Frank
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Dai, Lie
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500
TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.
2020-05-11T14:53:34Z
2020-05-11T14:53:34Z
2018-06-19
Arthritis Res Ther. 2018 Jun 19;20(1):130. doi: 10.1186/s13075-018-1623-y.
29921328
10.1186/s13075-018-1623-y
http://hdl.handle.net/10033/622255
1478-6362
Arthritis research & therapy
BACKGROUND:
Previous studies have revealed that hepatitis B virus (HBV) infection may be related to rheumatoid arthritis (RA), but there are no studies on the presence of HBV antigens or nucleic acid in synovium from patients with RA with HBV infection. In the present study, we investigated the presence of HBV in the synovium and its clinical significance in RA.
METHODS:
Fifty-seven consecutive patients with active RA (Disease Activity Score 28-joint assessment based on C-reactive protein ≥ 2.6) and available synovial tissue who had completed 1 year of follow-up were recruited from a prospective cohort. The patients were divided into chronic HBV infection (CHB, n = 11) and non-CHB groups according to baseline HBV infection status. Clinical data were collected at baseline and at 1-, 3-, 6-, and 12-month follow-up. Radiographic changes of hand/wrist at baseline and month 12 were assessed with the Sharp/van der Heijde-modified Sharp score (mTSS). HBV in synovium was determined by immunohistochemical staining for hepatitis B virus surface antigen and hepatitis B virus core antigen (HBcAg) and by nested PCR for the HBV S gene.
RESULTS:
HBcAg was found in the synovium of patients with RA with CHB (7 of 11, 64%), which was confirmed by PCR for the HBV S gene. Compared with the non-CHB group, more CD68-positive macrophages, CD20-positive B cells, and CD15-positive neutrophils infiltrated the synovium in the CHB group (all p < 0.05). There were smaller improvements from baseline in most disease activity indicators mainly at month 12, and a significantly higher percentage of CHB patients experienced 1-year radiographic progression (ΔmTSS ≥ 0.5 unit/yr, 64% vs. 26%, p = 0.024). Multivariate logistic regression analysis showed that CHB status (OR 14.230, 95% CI 2.213-95.388; p = 0.006) and the density of synovial CD68-positive macrophages (OR 1.002, 95% CI 1.001-1.003; p = 0.003) were independently associated with 1-year radiographic progression.
CONCLUSIONS:
The presence of HBV in RA synovium may be involved in the pathogenesis of local lesions and exacerbate disease progression in RA.
en
BMC
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
Hepatitis B virus
Radiographic progression
Rheumatoid arthritis
Synovial biopsy
Synovium
Presence of hepatitis B virus in synovium and its clinical significance in rheumatoid arthritis.
Article
Other
20
1
130
Arthritis research & therapy
England
2020-05-11T14:53:35Z
THUMBNAIL
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Chen et al.pdf
Chen et al.pdf
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10033/622255
oai:repository.helmholtz-hzi.de:10033/622255
2020-05-12 02:36:12.014
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6222542020-05-12T02:36:04Zcom_10033_620601col_10033_620603
Chen, Yu-Lan
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Jing, Jun
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Mo, Ying-Qian
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Ma, Jian-Da
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Yang, Li-Juan
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Chen, Le-Feng
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Zhang, Xiang
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Yan, Tao
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Zheng, Dong-Hui
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Pessler, Frank
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Dai, Lie
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TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.
2020-05-11T14:46:10Z
2020-05-11T14:46:10Z
2018-06-19
Arthritis Res Ther. 2018 Jun 19;20(1):130. doi: 10.1186/s13075-018-1623-y.
29921328
10.1186/s13075-018-1623-y
http://hdl.handle.net/10033/622254
1478-6362
Arthritis research & therapy
Previous studies have revealed that hepatitis B virus (HBV) infection may be related to rheumatoid arthritis (RA), but there are no studies on the presence of HBV antigens or nucleic acid in synovium from patients with RA with HBV infection. In the present study, we investigated the presence of HBV in the synovium and its clinical significance in RA.
METHODS: Fifty-seven consecutive patients with active RA (Disease Activity Score 28-joint assessment based on C-reactive protein ≥ 2.6) and available synovial tissue who had completed 1 year of follow-up were recruited from a prospective cohort. The patients were divided into chronic HBV infection (CHB, n = 11) and non-CHB groups according to baseline HBV infection status. Clinical data were collected at baseline and at 1-, 3-, 6-, and 12-month follow-up. Radiographic changes of hand/wrist at baseline and month 12 were assessed with the Sharp/van der Heijde-modified Sharp score (mTSS). HBV in synovium was determined by immunohistochemical staining for hepatitis B virus surface antigen and hepatitis B virus core antigen (HBcAg) and by nested PCR for the HBV S gene.
RESULTS: HBcAg was found in the synovium of patients with RA with CHB (7 of 11, 64%), which was confirmed by PCR for the HBV S gene. Compared with the non-CHB group, more CD68-positive macrophages, CD20-positive B cells, and CD15-positive neutrophils infiltrated the synovium in the CHB group (all p < 0.05). There were smaller improvements from baseline in most disease activity indicators mainly at month 12, and a significantly higher percentage of CHB patients experienced 1-year radiographic progression (ΔmTSS ≥ 0.5 unit/yr, 64% vs. 26%, p = 0.024). Multivariate logistic regression analysis showed that CHB status (OR 14.230, 95% CI 2.213-95.388; p = 0.006) and the density of synovial CD68-positive macrophages (OR 1.002, 95% CI 1.001-1.003; p = 0.003) were independently associated with 1-year radiographic progression.
CONCLUSIONS:
The presence of HBV in RA synovium may be involved in the pathogenesis of local lesions and exacerbate disease progression in RA.
en
BMC
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
Hepatitis B virus
Radiographic progression
Rheumatoid arthritis
Synovial biopsy
Synovium
Presence of hepatitis B virus in synovium and its clinical significance in rheumatoid arthritis.
Article
Other
20
1
130
Arthritis research & therapy
England
2020-05-11T14:46:11Z
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oai:repository.helmholtz-hzi.de:10033/622254
2020-05-12 02:36:04.901
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6222572020-05-13T11:39:03Zcom_10033_620601col_10033_620603
Hahn, Katharina
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300
Pollmann, Liart
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Nowak, Juliette
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Nguyen, Ariane Hai Ha
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Haake, Kathrin
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Neehus, Anna-Lena
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Waqas, Syed F Hassnain
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Pessler, Frank
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Baumann, Ulrich
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Hetzel, Miriam
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Casanova, Jean-Laurent
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Schulz, Ansgar
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Bustamante, Jacinta
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Ackermann, Mania
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Lachmann, Nico
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TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.
2020-05-12T09:36:15Z
2020-05-12T09:36:15Z
2020-04-11
2020-05-12
Mol Ther Methods Clin Dev. 2020 Apr 11;17:785-795. doi: 10.1016/j.omtm.2020.04.002. eCollection 2020 Jun 12.
2329-0501
32355867
10.1016/j.omtm.2020.04.002
http://hdl.handle.net/10033/622257
Molecular therapy. Methods & clinical development
Autosomal recessive (AR) complete interferon-γ receptor 1 (IFN-γR1) deficiency, also known as one genetic etiology of Mendelian susceptibility to mycobacterial disease (MSMD), is a life-threatening congenital disease leading to premature death. Affected patients present a pathognomonic predisposition to recurrent and severe infections with environmental mycobacteria or the Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccine. Current therapeutic options are limited to antibiotic treatment and hematopoietic stem cell transplantation, however with poor outcome. Given the clinical success of gene therapy, we introduce the first lentiviral-based gene therapy approach to restore expression and function of the human IFN-γR-downstream signaling cascade. In our study, we developed lentiviral vectors constitutively expressing the human IFN-γR1 and demonstrate stable transgene expression without interference with cell viability and proliferation in transduced human hematopoietic cells. Using an IFN-γR1-deficient HeLa cell model, we show stable receptor reconstitution and restored IFN-γR1 signaling without adverse effect on cell functionality. Transduction of both SV40-immortalized and primary fibroblasts derived from IFN-γR1-deficient MSMD patients was able to recover IFN-γR1 expression and restore type II IFN signaling upon stimulation with IFN-γ. In summary, we highlight lentiviral vectors to correct the IFN-γ mediated immunity and present the first gene therapy approach for patients suffering from AR complete IFN-γR1 deficiency.
en
Elsevier(Cell Press)
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
Gene Therapy
IFN-γR1 deficiency
Lentiviral Vectors
MSMD
Human Lentiviral Gene Therapy Restores the Cellular Phenotype of Autosomal Recessive Complete IFN-γR1 Deficiency.
Article
17
785
795
Molecular therapy. Methods & clinical development
United States
2020-05-12T09:36:16Z
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oai:repository.helmholtz-hzi.de:10033/622257
2020-05-13 11:39:03.921
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6224232020-09-03T03:10:04Zcom_10033_620601col_10033_620603
Sohail, Muhammad U
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Yassine, Hadi M
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Sohail, Aaqib
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Al Thani, Asmaa A
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TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.
2020-09-02T12:37:12Z
2020-09-02T12:37:12Z
2019-08-04
Rev Diabet Stud. 2019;15:35-48. doi:10.1900/RDS.2019.15.35.
31380886
10.1900/RDS.2019.15.35
http://hdl.handle.net/10033/622423
1614-0575
The review of diabetic studies : RDS
Background: The gastrointestinal tract (GIT) harbors a complex and diverse microbial composition that outnumbers our own body cells and their gene contents. These microbes play a significant role in host metabolism and energy homeostasis. Emerging evidence suggests that the GIT microbiome significantly contributes to host health and that impairments in the microbiome may cause the development of metabolic diseases. The microbiome architecture is shaped by several genetic and environmental factors, including nutrition and physical activity. Physical exercise has preventive or therapeutic effects in respiratory, cardiovascular, neuroendocrine, and muscular diseases. Yet, we still have little information of the beneficial effects of physical exercise on GIT health and microbial composition. Furthermore, we are not aware whether exercise-derived benefits on microbiome diversity can beneficially influence other tissues and body organs.
Objectives: The aim of this article is to review the available literature on exercise-induced microbiome changes and to explain how these changes may induce inflammatory, immune, and oxidative responses that may contribute to the improvement of metabolic disorders.
Methods: A systemic and comprehensive search of the relevant literature using MEDLINE and Google Scholar databases was conducted during fall 2018 and spring 2019. The search identified sixty-two research and review articles that discussed exercise-induced microbiome changes.
Results: The review of the relevant literature suggests that exercise-induced microbial changes affect the host's immune pathways and improve energy homeostasis. Microbes release certain neuroendocrine and immune-modulatory factors that may lower inflammatory and oxidative stress and relieve patients suffering from metabolic disorders.
Conclusions: Exercise-induced changes in microbial diversity are able to improve tissue metabolism, cardiorespiratory fitness, and insulin resistance.
en
Society for Biomedical Diabetes Research
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
Impact of Physical Exercise on Gut Microbiome, Inflammation, and the Pathobiology of Metabolic Disorders.
Review
Other
15
35
48
The review of diabetic studies : RDS
Singapore
2020-09-02T12:37:12Z
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oai:repository.helmholtz-hzi.de:10033/622423
2020-09-03 03:10:04.992
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6226482020-12-12T10:31:18Zcom_10033_620601col_10033_620603
Luo, Yi
ce47e612b42edad4229f138aae6d8f45
300
Möhn, Nora
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300
Al-Mekhlafi, Amani
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500
Schuchardt, Sven
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Skripuletz, Thomas
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Sühs, Wolfram
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Pessler, Frank
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Stangel, Martin
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HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
2020-12-11T14:38:57Z
2020-12-11T14:38:57Z
2020-11-24
PLoS One. 2020 Nov 24;15(11):e0242321. doi: 10.1371/journal.pone.0242321.
33232337
10.1371/journal.pone.0242321
http://hdl.handle.net/10033/622648
1932-6203
PloS one
Progressive multifocal leukoencephalopathy (PML), caused by JC polyomavirus, is a demyelinating disease of the central nervous system that primarily affects oligodendrocytes. It can cause significant morbidity and mortality. An early diagnosis is of high relevance as timely immune reconstitution is essential. However, diagnosis can be challenging if virus detection via cerebrospinal fluid (CSF) PCR remains negative. Hence, identifying CSF biomarkers for this disease is of crucial importance. We applied a targeted metabolomic screen to CSF from 23 PML patients and eight normal pressure hydrocephalus (NPH) patients as controls. Out of 188 potentially detectable metabolites, 48 (13 amino acids, 4 biogenic amines, 1 acylcarnitine, 21 phosphatidylcholines, 8 sphingolipids, and the sum of hexoses) passed the quality screen and were included in the analyses. Even though there was a tendency towards lower concentrations in PML (mostly of phosphatidylcholines and sphingomyelins), none of the differences between PML and controls in individual metabolite concentrations reached statistical significance (lowest p = 0.104) and there were no potential diagnostic biomarkers (highest area under the ROC curve 0.68). Thus, CSF metabolite changes in PML are likely subtle and possibly larger group sizes and broader metabolite screens are needed to identify potential CSF metabolite biomarkers for PML.
en
PLOS
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
Targeted metabolomic profiling of cerebrospinal fluid from patients with progressive multifocal leukoencephalopathy.
Article
15
11
e0242321
PloS one
United States
2020-12-11T14:38:58Z
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10033/622648
oai:repository.helmholtz-hzi.de:10033/622648
2020-12-12 10:31:18.863
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6226852021-01-16T01:44:42Zcom_10033_620601col_10033_620603
Merkert, S
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Jaboreck, M-C
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300
Engels, L
8beb4d160789e9bf0500b6a2e70087a3
Malik, M N H
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300
Göhring, G
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Pessler, F
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500
Martin, U
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Olmer, R
8dfc5eb0dde7a80bd9e255753016bdb7
TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.
2021-01-15T14:52:39Z
2021-01-15T14:52:39Z
2020-12-22
Stem Cell Res. 2020 Dec 22;50:102135. doi: 10.1016/j.scr.2020.102135. Epub ahead of print.
33383405
10.1016/j.scr.2020.102135
http://hdl.handle.net/10033/622685
1876-7753
Stem cell research
Background and aims: T cells are the main mediators of allogeneic immune responses. Specific T cell clones can be tracked by their unique T cell receptor (TCR), but specificity and function remain elusive and have not been investigated in human liver biopsies thus far.
Methods: TCR repertoire analysis of CD4+, CD8+ and regulatory T cells of the peripheral blood and liver graft was performed in seven liver transplant recipients with either stable course (non-rejector, NR), subclinical cellular rejection (SCR) or acute cellular rejection (ACR) during an observation period from pre-transplant to six years post-transplant. Furthermore, donor-reactive T cells, identified by their expression of CD154 and GARP after allogeneic activation, were tracked longitudinally in peripheral blood and within the liver allograft.
Results: While overall clonality of the TCR repertoire did not increase in peripheral blood after liver transplantation, clonality of donor-reactive CD4+ and regulatory T cells increased and these clones accumulated within the liver graft. Surprisingly, the TCR repertoires between the liver graft and the periphery were distinct and showed only little overlap. Notably, during ACR TCR repertoires aligned suggesting either graft-specific homing or release of activated T cells from the graft.
Conclusions: This is the first study comparing TCR repertoires between liver graft and blood in patients with NR, SCR and ACR. Moreover, we attribute specificity and function to a subgroup of intragraft T cell populations. Given the little overlap between peripheral blood and intragraft repertoires future studies investigating function and specificities of T cells after liver transplantation should focus on the intragraft immune response. For this purpose, protocol biopsies of patients with normal graft function and subclinical rejection have to be taken into account.
en
Elsevier
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
Generation of two human ISG15 knockout iPSC clones using CRISPR/Cas9 editing.
Article
50
102135
Stem cell research
England
2021-01-15T14:52:39Z
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Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6228742021-05-18T01:59:55Zcom_10033_620601col_10033_620603
Winterhoff, Moritz
9deae156b5b105a541085c6c2ab13532
500
Chen, Fangfang
b9ac6050614e0c543818d6f87f9e583c
500
Sahini, Nishika
c6c9d9f01a6cf6aa22e039386d470c52
300
Ebensen, Thomas
a3b4f5d380907cad14a42cded1efb3c2
600
http://orcid.org/0000-0001-8906-063X
Kuhn, Maike
4dd016215a04f28f05296829c971718b
500
Kaever, Volkhard
c2c4019ccc1ba8201e6889532568e2e9
500
Bähre, Heike
d2bb00072178ed14ef2f8d90db5dc5f6
500
Pessler, Frank
9fc33677a3eea5c4e77542200bd20f05
TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.
2021-05-17T12:21:04Z
2021-05-17T12:21:04Z
2021-04-26
Metabolites. 2021 Apr 26;11(5):270. doi: 10.3390/metabo11050270.
2218-1989
33925995
10.3390/metabo11050270
http://hdl.handle.net/10033/622874
Metabolites
Itaconate is derived from the tricarboxylic acid (TCA) cycle intermediate cis-aconitate and links innate immunity and metabolism. Its synthesis is altered in inflammation-related disorders and it therefore has potential as clinical biomarker. Mesaconate and citraconate are naturally occurring isomers of itaconate that have been linked to metabolic disorders, but their functional relationships with itaconate are unknown. We aimed to establish a sensitive high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) assay for the quantification of itaconate, mesaconate, citraconate, the pro-drug 4-octyl-itaconate, and selected TCA intermediates. The assay was validated for itaconate, mesaconate, and citraconate for intra- and interday precision and accuracy, extended stability, recovery, freeze/thaw cycles, and carry-over. The lower limit of quantification was 0.098 µM for itaconate and mesaconate and 0.049 µM for citraconate in 50 µL samples. In spike-in experiments, itaconate remained stable in human plasma and whole blood for 24 and 8 h, respectively, whereas spiked-in citraconate and mesaconate concentrations changed during incubation. The type of anticoagulant in blood collection tubes affected measured levels of selected TCA intermediates. Human plasma may contain citraconate (0.4-0.6 µM, depending on the donor), but not itaconate or mesaconate, and lipopolysaccharide stimulation of whole blood induced only itaconate. Concentrations of the three isomers differed greatly among mouse organs: Itaconate and citraconate were most abundant in lymph nodes, mesaconate in kidneys, and only citraconate occurred in brain. This assay should prove useful to quantify itaconate isomers in biomarker and pharmacokinetic studies, while providing internal controls for their effects on metabolism by allowing quantification of TCA intermediates.
en
MDPI
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
CAD
Irg1
Krebs cycle
biomarker
cis-aconitate decarboxylase
citraconate
itaconate
mass spectrometry
mesaconate
metabolism
Establishment, Validation, and Initial Application of a Sensitive LC-MS/MS Assay for Quantification of the Naturally Occurring Isomers Itaconate, Mesaconate, and Citraconate.
Article
11
5
Metabolites
Switzerland
2021-05-17T12:21:05Z
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oai:repository.helmholtz-hzi.de:10033/622874
2021-05-18 01:59:55.898
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6229452021-07-20T01:41:11Zcom_10033_311308com_10033_620601col_10033_620721col_10033_620603
Al-Mekhlafi, Amani
b0da75fc3c0aa2ef821c5d0b5176d6a6
500
Sühs, Kurt-Wolfram
3821fd0ba7a7741a1b9d45314ed9aa1b
500
Schuchardt, Sven
70ceda607c2a6aacba5e145b6ba18d28
500
Kuhn, Maike
4dd016215a04f28f05296829c971718b
500
Müller-Vahl, Kirsten
e675a8c868f41735202c9b1b6026bd06
500
Trebst, Corinna
d0259342fa43a7b1f5366e6407ed4e0f
500
Skripuletz, Thomas
519373b11b3c5c9a11c9d55211500a2a
500
Klawonn, Frank
da2644d10297b6bb437e1cce18952393
600
http://orcid.org/0000-0001-9613-182X
Stangel, Martin
c34c7db9fb99df1894fa38347613609e
500
Pessler, Frank
9fc33677a3eea5c4e77542200bd20f05
TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
2021-07-19T15:03:01Z
2021-07-19T15:03:01Z
2021-05-06
Cells. 2021 May 6;10(5):1115. doi: 10.3390/cells10051115. PMID: 34066349.
34066349
10.3390/cells10051115
http://hdl.handle.net/10033/622945
2073-4409
Cells
The identification of CSF biomarkers for bacterial meningitis can potentially improve diagnosis and understanding of pathogenesis, and the differentiation from viral CNS infections is of particular clinical importance. Considering that substantial changes in CSF metabolites in CNS infections have recently been demonstrated, we compared concentrations of 188 metabolites in CSF samples from patients with bacterial meningitis (n = 32), viral meningitis/encephalitis (n = 34), and noninflamed controls (n = 66). Metabolite reprogramming in bacterial meningitis was greatest among phosphatidylcholines, and concentrations of all 54 phosphatidylcholines were significantly (p = 1.2 × 10-25-1.5 × 10-4) higher than in controls. Indeed, all biomarkers for bacterial meningitis vs. viral meningitis/encephalitis with an AUC ≥ 0.86 (ROC curve analysis) were phosphatidylcholines. Four of the five most accurate (AUC ≥ 0.9) phosphatidylcholine biomarkers had higher sensitivity and negative predictive values than CSF lactate or cell count. Concentrations of the 10 most accurate phosphatidylcholine biomarkers were lower in meningitis due to opportunistic pathogens than in meningitis due to typical meningitis pathogens, and they correlated most strongly with parameters reflecting blood-CSF barrier dysfunction and CSF lactate (r = 0.73-0.82), less so with CSF cell count, and not with blood CRP. In contrast to the elevated phosphatidylcholine concentrations in CSF, serum concentrations remained relatively unchanged. Taken together, these results suggest that increased free CSF phosphatidylcholines are sensitive biomarkers for bacterial meningitis and do not merely reflect inflammation but are associated with local disease and a shift in CNS metabolism.
en
MDPI
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
biomarker
cell membrane
central nervous system
enterovirus
herpes simplex virus
infection
meningitis
metabolism
varicella zoster virus
Elevated Free Phosphatidylcholine Levels in Cerebrospinal Fluid Distinguish Bacterial from Viral CNS Infections.
Article
10
5
Cells
Switzerland
2021-07-19T15:03:02Z
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Al-Mekhafi et al.pdf
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Open Access publication
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https://repository.helmholtz-hzi.de/bitstream/10033/622945/1/Al-Mekhafi%20et%20al.pdf
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10033/622945
oai:repository.helmholtz-hzi.de:10033/622945
2021-07-20 01:41:11.1
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6231082021-12-02T01:59:58Zcom_10033_620601col_10033_620603
de Araujo, Leonardo S
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Ribeiro-Alves, Marcelo
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Wipperman, Matthew F
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Vorkas, Charles Kyriakos
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Pessler, Frank
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Saad, Maria Helena Féres
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TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.
2021-12-01T14:09:08Z
2021-12-01T14:09:08Z
2021-10-09
Cells. 2021 Oct 9;10(10):2704. doi: 10.3390/cells10102704.
34685683
10.3390/cells10102704
http://hdl.handle.net/10033/623108
2073-4409
Cells
External validation in different cohorts is a key step in the translational development of new biomarkers. We previously described three host mRNA whose expression in peripheral blood is significantly higher (NPC2) or lower (DOCK9 and EPHA4) in individuals with TB compared to latent TB infection (LTBI) and controls. We have now conducted an independent validation of these genes by re-analyzing publicly available transcriptomic datasets from Brazil, China, Haiti, India, South Africa, and the United Kingdom. Comparisons between TB and control/LTBI showed significant differential expression of all three genes (NPC2high p < 0.01, DOCK9low p < 0.01, and EPHA4low p < 0.05). NPC2high had the highest mean area under the ROC curve (AUROC) for the differentiation of TB vs. controls (0.95) and LTBI (0.94). In addition, NPC2 accurately distinguished TB from the clinically similar conditions pneumonia (AUROC, 0.88), non-active sarcoidosis (0.87), and lung cancer (0.86), but not from active sarcoidosis (0.66). Interestingly, individuals progressing from LTBI to TB showed a constant increase in NPC2 expression with time when compared to non-progressors (p < 0.05), with a significant change closer to manifestation of active disease (≤3 months, p = 0.003). Moreover, NPC2 expression normalized with completion of anti-TB treatment. Taken together, these results validate NPC2 mRNA as a diagnostic host biomarker for active TB independent of host genetic background. Moreover, they reveal its potential to predict progression from latent to active infection and to indicate a response to anti-TB treatment.
en
MDPI
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
Mycobacterium tuberculosis
NPC2
Niemann–Pick disease type C2
RNA
biomarkers
diagnosis
mRNA
transcription
treatment
tuberculosis
Transcriptomic Biomarkers for Tuberculosis: Validation of as a Single mRNA Biomarker to Diagnose TB, Predict Disease Progression, and Monitor Treatment Response.
Article
10
10
Cells
Switzerland
2021-12-01T14:09:09Z
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Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6231362022-01-12T01:50:58Zcom_10033_620589com_10033_620601com_10033_338554com_10033_620636col_10033_621787col_10033_620603col_10033_620590col_10033_620638
Malik, Muhammad Nasir Hayat
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500
Waqas, Syed F Hassnain
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Zeitvogel, Jana
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Cheng, Jingyuan
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Geffers, Robert
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Gouda, Zeinab Abu-Elbaha
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Elsaman, Ahmed Mahrous
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Radwan, Ahmed R
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Schefzyk, Matthias
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Braubach, Peter
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Auber, Bernd
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Olmer, Ruth
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Müsken, Mathias
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Roesner, Lennart M
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Gerold, Gisa
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500
Schuchardt, Sven
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Merkert, Sylvia
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Martin, Ulrich
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Meissner, Felix
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Werfel, Thomas
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Pessler, Frank
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HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.; TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.
2022-01-11T11:36:56Z
2022-01-11T11:36:56Z
2021-11-30
J Clin Invest. 2021 Nov 30:e141573. doi: 10.1172/JCI141573. Epub ahead of print.
34847081
10.1172/JCI141573
http://hdl.handle.net/10033/623136
1558-8238
The Journal of clinical investigation
Ulcerating skin lesions are manifestations of human ISG15 deficiency, a type I interferonopathy. However, chronic inflammation may not be their exclusive cause. We describe two siblings with recurrent skin ulcers that healed with scar formation upon corticosteroid treatment. Both had a homozygous nonsense mutation in the ISG15 gene, leading to unstable ISG15 protein lacking the functional domain. We characterized ISG15-/- dermal fibroblasts, HaCaT keratinocytes, and human induced pluripotent stem cell-derived vascular endothelial cells. ISG15-deficient cells exhibited the expected hyperinflammatory phenotype, but also dysregulated expression of molecules critical for connective tissue and epidermis integrity, including reduced collagens and adhesion molecules, but increased matrix metalloproteases. ISG15-/- fibroblasts exhibited elevated ROS levels and reduced ROS scavenger expression. As opposed to hyperinflammation, defective collagen and integrin synthesis was not rescued by conjugation-deficient ISG15. Cell migration was retarded in ISG15-/- fibroblasts and HaCaT keratinocytes, but normalized under ruxolitinib treatment. Desmosome density was reduced in an ISG15-/- 3D epidermis model. Additionally, there were loose architecture and reduced collagen and desmoglein expression, which could be reversed by treatment with ruxolitinib/doxycycline/TGF-β1. These results reveal critical roles of ISG15 in maintaining cell migration and epidermis and connective tissue homeostasis, whereby the latter likely requires its conjugation to yet unidentified targets.
en
Society of clinical investigation
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
Autoimmunity
Collagens
Monogenic diseases
Skin
Congenital deficiency reveals critical role of ISG15 in skin homeostasis.
Article
The Journal of clinical investigation
United States
2022-01-11T11:36:57Z
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Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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Ebensen, Thomas
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Schultz, Kristin
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Pessler, Frank
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TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
2022-02-15T09:24:24Z
2022-02-15T09:24:24Z
2022-01-13
PLoS Pathog. 2022 Jan 13;18(1):e1010219. doi: 10.1371/journal.ppat.1010219. Epub ahead of print.
35025971
10.1371/journal.ppat.1010219
http://hdl.handle.net/10033/623164
1553-7374
PLoS pathogens
Excessive inflammation is a major cause of morbidity and mortality in many viral infections including influenza. Therefore, there is a need for therapeutic interventions that dampen and redirect inflammatory responses and, ideally, exert antiviral effects. Itaconate is an immunomodulatory metabolite which also reprograms cell metabolism and inflammatory responses when applied exogenously. We evaluated effects of endogenous itaconate and exogenous application of itaconate and its variants dimethyl- and 4-octyl-itaconate (DI, 4OI) on host responses to influenza A virus (IAV). Infection induced expression of ACOD1, the enzyme catalyzing itaconate synthesis, in monocytes and macrophages, which correlated with viral replication and was abrogated by DI and 4OI treatment. In IAV-infected mice, pulmonary inflammation and weight loss were greater in Acod1-/- than in wild-type mice, and DI treatment reduced pulmonary inflammation and mortality. The compounds reversed infection-triggered interferon responses and modulated inflammation in human cells supporting non-productive and productive infection, in peripheral blood mononuclear cells, and in human lung tissue. Itaconates reduced ROS levels and STAT1 phosphorylation, whereas AKT phosphorylation was reduced by 4OI and DI but increased by itaconate. Single-cell RNA sequencing identified monocytes as the main target of infection and the exclusive source of ACOD1 mRNA in peripheral blood. DI treatment silenced IFN-responses predominantly in monocytes, but also in lymphocytes and natural killer cells. Ectopic synthesis of itaconate in A549 cells, which do not physiologically express ACOD1, reduced infection-driven inflammation, and DI reduced IAV- and IFNγ-induced CXCL10 expression in murine macrophages independent of the presence of endogenous ACOD1. The compounds differed greatly in their effects on cellular gene homeostasis and released cytokines/chemokines, but all three markedly reduced release of the pro-inflammatory chemokines CXCL10 (IP-10) and CCL2 (MCP-1). Viral replication did not increase under treatment despite the dramatically repressed IFN responses. In fact, 4OI strongly inhibited viral transcription in peripheral blood mononuclear cells, and the compounds reduced viral titers (4OI>Ita>DI) in A549 cells whereas viral transcription was unaffected. Taken together, these results reveal itaconates as immunomodulatory and antiviral interventions for influenza virus infection.
en
PLOS
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
Itaconate and derivatives reduce interferon responses and inflammation in influenza A virus infection.
Article
18
1
e1010219
PLoS pathogens
United States
2022-02-15T09:24:25Z
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oai:repository.helmholtz-hzi.de:10033/623164
2022-02-16 02:00:10.046
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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