Archivi categoria: PLOS

Systems analysis of subjects acutely infected with the Chikungunya virus

by Alessandra Soares-Schanoski, Natália Baptista Cruz, Luíza Antunes de Castro-Jorge, Renan Villanova Homem de Carvalho, Cliomar Alves dos Santos, Nancy da Rós, Úrsula Oliveira, Danuza Duarte Costa, Cecília Luíza Simões dos Santos, Marielton dos Passos Cunha, Maria Leonor Sarno Oliveira, Juliana Cardoso Alves, Regina Adalva de Lucena Couto Océa, Danielle Rodrigues Ribeiro, André Nicolau Aquime Gonçalves, Patricia Gonzalez-Dias, Andreas Suhrbier, Paolo Marinho de Andrade Zanotto, Inácio Junqueira de Azevedo, Dario S. Zamboni, Roque Pacheco Almeida, Paulo Lee Ho, Jorge Kalil, Milton Yutaka Nishiyama Junior, Helder I. Nakaya

The largest ever recorded epidemic of the Chikungunya virus (CHIKV) broke out in 2004 and affected four continents. Acute symptomatic infections are typically associated with the onset of fever and often debilitating polyarthralgia/polyarthritis. In this study, a systems biology approach was adopted to analyze the blood transcriptomes of adults acutely infected with the CHIKV. Gene signatures that were associated with viral RNA levels and the onset of symptoms were identified. Among these genes, the putative role of the Eukaryotic Initiation Factor (eIF) family genes and apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC3A) in the CHIKV replication process were displayed. We further compared these signatures with signatures induced by the Dengue virus infection and rheumatoid arthritis. Finally, we demonstrated that the CHIKV in vitro infection of murine bone marrow-derived macrophages induced IL-1 beta production in a mechanism that is significantly dependent on the inflammasome NLRP3 activation. The observations provided valuable insights into virus-host interactions during the acute phase and can be instrumental in the investigation of new and effective therapeutic interventions.

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Note sul Copyright: Articles and accompanying materials published by PLOS on the PLOS Sites, unless otherwise indicated, are licensed by the respective authors of such articles for use and distribution by you subject to citation of the original source in accordance with the Creative Commons Attribution (CC BY) license.

Systems analysis of subjects acutely infected with the Chikungunya virus

by Alessandra Soares-Schanoski, Natália Baptista Cruz, Luíza Antunes de Castro-Jorge, Renan Villanova Homem de Carvalho, Cliomar Alves dos Santos, Nancy da Rós, Úrsula Oliveira, Danuza Duarte Costa, Cecília Luíza Simões dos Santos, Marielton dos Passos Cunha, Maria Leonor Sarno Oliveira, Juliana Cardoso Alves, Regina Adalva de Lucena Couto Océa, Danielle Rodrigues Ribeiro, André Nicolau Aquime Gonçalves, Patricia Gonzalez-Dias, Andreas Suhrbier, Paolo Marinho de Andrade Zanotto, Inácio Junqueira de Azevedo, Dario S. Zamboni, Roque Pacheco Almeida, Paulo Lee Ho, Jorge Kalil, Milton Yutaka Nishiyama Junior, Helder I. Nakaya

The largest ever recorded epidemic of the Chikungunya virus (CHIKV) broke out in 2004 and affected four continents. Acute symptomatic infections are typically associated with the onset of fever and often debilitating polyarthralgia/polyarthritis. In this study, a systems biology approach was adopted to analyze the blood transcriptomes of adults acutely infected with the CHIKV. Gene signatures that were associated with viral RNA levels and the onset of symptoms were identified. Among these genes, the putative role of the Eukaryotic Initiation Factor (eIF) family genes and apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC3A) in the CHIKV replication process were displayed. We further compared these signatures with signatures induced by the Dengue virus infection and rheumatoid arthritis. Finally, we demonstrated that the CHIKV in vitro infection of murine bone marrow-derived macrophages induced IL-1 beta production in a mechanism that is significantly dependent on the inflammasome NLRP3 activation. The observations provided valuable insights into virus-host interactions during the acute phase and can be instrumental in the investigation of new and effective therapeutic interventions.

Tratto da: www.plos.org
Note sul Copyright: Articles and accompanying materials published by PLOS on the PLOS Sites, unless otherwise indicated, are licensed by the respective authors of such articles for use and distribution by you subject to citation of the original source in accordance with the Creative Commons Attribution (CC BY) license.

Systems analysis of subjects acutely infected with the Chikungunya virus

by Alessandra Soares-Schanoski, Natália Baptista Cruz, Luíza Antunes de Castro-Jorge, Renan Villanova Homem de Carvalho, Cliomar Alves dos Santos, Nancy da Rós, Úrsula Oliveira, Danuza Duarte Costa, Cecília Luíza Simões dos Santos, Marielton dos Passos Cunha, Maria Leonor Sarno Oliveira, Juliana Cardoso Alves, Regina Adalva de Lucena Couto Océa, Danielle Rodrigues Ribeiro, André Nicolau Aquime Gonçalves, Patricia Gonzalez-Dias, Andreas Suhrbier, Paolo Marinho de Andrade Zanotto, Inácio Junqueira de Azevedo, Dario S. Zamboni, Roque Pacheco Almeida, Paulo Lee Ho, Jorge Kalil, Milton Yutaka Nishiyama Junior, Helder I. Nakaya

The largest ever recorded epidemic of the Chikungunya virus (CHIKV) broke out in 2004 and affected four continents. Acute symptomatic infections are typically associated with the onset of fever and often debilitating polyarthralgia/polyarthritis. In this study, a systems biology approach was adopted to analyze the blood transcriptomes of adults acutely infected with the CHIKV. Gene signatures that were associated with viral RNA levels and the onset of symptoms were identified. Among these genes, the putative role of the Eukaryotic Initiation Factor (eIF) family genes and apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC3A) in the CHIKV replication process were displayed. We further compared these signatures with signatures induced by the Dengue virus infection and rheumatoid arthritis. Finally, we demonstrated that the CHIKV in vitro infection of murine bone marrow-derived macrophages induced IL-1 beta production in a mechanism that is significantly dependent on the inflammasome NLRP3 activation. The observations provided valuable insights into virus-host interactions during the acute phase and can be instrumental in the investigation of new and effective therapeutic interventions.

Tratto da: www.plos.org
Note sul Copyright: Articles and accompanying materials published by PLOS on the PLOS Sites, unless otherwise indicated, are licensed by the respective authors of such articles for use and distribution by you subject to citation of the original source in accordance with the Creative Commons Attribution (CC BY) license.

The extent, nature, and pathogenic consequences of helminth polyparasitism in humans: A meta-analysis

by Rose E. Donohue, Zoë K. Cross, Edwin Michael

Background

Individual helminth infections are ubiquitous in the tropics; geographical overlaps in endemicity and epidemiological reports suggest areas endemic for multiple helminthiases are also burdened with high prevalences of intestinal protozoan infections, malaria, tuberculosis (TB), and human immunodeficiency virus (HIV). Despite this, pathogens tend to be studied in isolation, and there remains a need for a better understanding of the community ecology and health consequences of helminth polyparasitism to inform the design of effective parasite control programs.

Methodology

We performed meta-analyses to (i) evaluate the commonality of polyparasitism for helminth-helminth, helminth-intestinal protozoa, helminth-malaria, helminth-TB, and helminth-HIV co-infections, (ii) assess the potential for interspecies interactions among helminth-helminth and helminth-intestinal protozoan infections, and (iii) determine the presence and magnitude of association between specific parasite pairs. Additionally, we conducted a review of reported health consequences of multiply-infected individuals compared to singly- or not multiply-infected individuals.

Principal findings

We found that helminth-helminth and helminth-intestinal protozoan multiple infections were significantly more common than single infections, while individuals with malaria, TB, and HIV were more likely to be singly-infected with these infections than co-infected with at least one helminth. Most observed species density distributions significantly differed from the expected distributions, suggesting the potential presence of interspecies interactions. All significant associations between parasite pairs were positive in direction, irrespective of the combination of pathogens. Polyparasitized individuals largely exhibited lower hemoglobin levels and higher anemia prevalence, while the differences in growth-related variables were mostly statistically insignificant.

Conclusions

Our findings confirm that helminth polyparasitism and co-infection with major diseases is common in the tropics. A multitude of factors acting at various hierarchical levels, such as interspecies interactions at the within-host infra-parasite community level and environmental variables at the higher host community level, could explain the observed positive associations between pathogens; there remains a need to develop new frameworks which can consider these multilevel factors to better understand the processes structuring parasite communities to accomplish their control.

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Note sul Copyright: Articles and accompanying materials published by PLOS on the PLOS Sites, unless otherwise indicated, are licensed by the respective authors of such articles for use and distribution by you subject to citation of the original source in accordance with the Creative Commons Attribution (CC BY) license.

The extent, nature, and pathogenic consequences of helminth polyparasitism in humans: A meta-analysis

by Rose E. Donohue, Zoë K. Cross, Edwin Michael

Background

Individual helminth infections are ubiquitous in the tropics; geographical overlaps in endemicity and epidemiological reports suggest areas endemic for multiple helminthiases are also burdened with high prevalences of intestinal protozoan infections, malaria, tuberculosis (TB), and human immunodeficiency virus (HIV). Despite this, pathogens tend to be studied in isolation, and there remains a need for a better understanding of the community ecology and health consequences of helminth polyparasitism to inform the design of effective parasite control programs.

Methodology

We performed meta-analyses to (i) evaluate the commonality of polyparasitism for helminth-helminth, helminth-intestinal protozoa, helminth-malaria, helminth-TB, and helminth-HIV co-infections, (ii) assess the potential for interspecies interactions among helminth-helminth and helminth-intestinal protozoan infections, and (iii) determine the presence and magnitude of association between specific parasite pairs. Additionally, we conducted a review of reported health consequences of multiply-infected individuals compared to singly- or not multiply-infected individuals.

Principal findings

We found that helminth-helminth and helminth-intestinal protozoan multiple infections were significantly more common than single infections, while individuals with malaria, TB, and HIV were more likely to be singly-infected with these infections than co-infected with at least one helminth. Most observed species density distributions significantly differed from the expected distributions, suggesting the potential presence of interspecies interactions. All significant associations between parasite pairs were positive in direction, irrespective of the combination of pathogens. Polyparasitized individuals largely exhibited lower hemoglobin levels and higher anemia prevalence, while the differences in growth-related variables were mostly statistically insignificant.

Conclusions

Our findings confirm that helminth polyparasitism and co-infection with major diseases is common in the tropics. A multitude of factors acting at various hierarchical levels, such as interspecies interactions at the within-host infra-parasite community level and environmental variables at the higher host community level, could explain the observed positive associations between pathogens; there remains a need to develop new frameworks which can consider these multilevel factors to better understand the processes structuring parasite communities to accomplish their control.

Tratto da: www.plos.org
Note sul Copyright: Articles and accompanying materials published by PLOS on the PLOS Sites, unless otherwise indicated, are licensed by the respective authors of such articles for use and distribution by you subject to citation of the original source in accordance with the Creative Commons Attribution (CC BY) license.

The extent, nature, and pathogenic consequences of helminth polyparasitism in humans: A meta-analysis

by Rose E. Donohue, Zoë K. Cross, Edwin Michael

Background

Individual helminth infections are ubiquitous in the tropics; geographical overlaps in endemicity and epidemiological reports suggest areas endemic for multiple helminthiases are also burdened with high prevalences of intestinal protozoan infections, malaria, tuberculosis (TB), and human immunodeficiency virus (HIV). Despite this, pathogens tend to be studied in isolation, and there remains a need for a better understanding of the community ecology and health consequences of helminth polyparasitism to inform the design of effective parasite control programs.

Methodology

We performed meta-analyses to (i) evaluate the commonality of polyparasitism for helminth-helminth, helminth-intestinal protozoa, helminth-malaria, helminth-TB, and helminth-HIV co-infections, (ii) assess the potential for interspecies interactions among helminth-helminth and helminth-intestinal protozoan infections, and (iii) determine the presence and magnitude of association between specific parasite pairs. Additionally, we conducted a review of reported health consequences of multiply-infected individuals compared to singly- or not multiply-infected individuals.

Principal findings

We found that helminth-helminth and helminth-intestinal protozoan multiple infections were significantly more common than single infections, while individuals with malaria, TB, and HIV were more likely to be singly-infected with these infections than co-infected with at least one helminth. Most observed species density distributions significantly differed from the expected distributions, suggesting the potential presence of interspecies interactions. All significant associations between parasite pairs were positive in direction, irrespective of the combination of pathogens. Polyparasitized individuals largely exhibited lower hemoglobin levels and higher anemia prevalence, while the differences in growth-related variables were mostly statistically insignificant.

Conclusions

Our findings confirm that helminth polyparasitism and co-infection with major diseases is common in the tropics. A multitude of factors acting at various hierarchical levels, such as interspecies interactions at the within-host infra-parasite community level and environmental variables at the higher host community level, could explain the observed positive associations between pathogens; there remains a need to develop new frameworks which can consider these multilevel factors to better understand the processes structuring parasite communities to accomplish their control.

Tratto da: www.plos.org
Note sul Copyright: Articles and accompanying materials published by PLOS on the PLOS Sites, unless otherwise indicated, are licensed by the respective authors of such articles for use and distribution by you subject to citation of the original source in accordance with the Creative Commons Attribution (CC BY) license.

Systems analysis of subjects acutely infected with the Chikungunya virus

by Alessandra Soares-Schanoski, Natália Baptista Cruz, Luíza Antunes de Castro-Jorge, Renan Villanova Homem de Carvalho, Cliomar Alves dos Santos, Nancy da Rós, Úrsula Oliveira, Danuza Duarte Costa, Cecília Luíza Simões dos Santos, Marielton dos Passos Cunha, Maria Leonor Sarno Oliveira, Juliana Cardoso Alves, Regina Adalva de Lucena Couto Océa, Danielle Rodrigues Ribeiro, André Nicolau Aquime Gonçalves, Patricia Gonzalez-Dias, Andreas Suhrbier, Paolo Marinho de Andrade Zanotto, Inácio Junqueira de Azevedo, Dario S. Zamboni, Roque Pacheco Almeida, Paulo Lee Ho, Jorge Kalil, Milton Yutaka Nishiyama Junior, Helder I. Nakaya

The largest ever recorded epidemic of the Chikungunya virus (CHIKV) broke out in 2004 and affected four continents. Acute symptomatic infections are typically associated with the onset of fever and often debilitating polyarthralgia/polyarthritis. In this study, a systems biology approach was adopted to analyze the blood transcriptomes of adults acutely infected with the CHIKV. Gene signatures that were associated with viral RNA levels and the onset of symptoms were identified. Among these genes, the putative role of the Eukaryotic Initiation Factor (eIF) family genes and apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC3A) in the CHIKV replication process were displayed. We further compared these signatures with signatures induced by the Dengue virus infection and rheumatoid arthritis. Finally, we demonstrated that the CHIKV in vitro infection of murine bone marrow-derived macrophages induced IL-1 beta production in a mechanism that is significantly dependent on the inflammasome NLRP3 activation. The observations provided valuable insights into virus-host interactions during the acute phase and can be instrumental in the investigation of new and effective therapeutic interventions.

Tratto da: www.plos.org
Note sul Copyright: Articles and accompanying materials published by PLOS on the PLOS Sites, unless otherwise indicated, are licensed by the respective authors of such articles for use and distribution by you subject to citation of the original source in accordance with the Creative Commons Attribution (CC BY) license.

Systems analysis of subjects acutely infected with the Chikungunya virus

by Alessandra Soares-Schanoski, Natália Baptista Cruz, Luíza Antunes de Castro-Jorge, Renan Villanova Homem de Carvalho, Cliomar Alves dos Santos, Nancy da Rós, Úrsula Oliveira, Danuza Duarte Costa, Cecília Luíza Simões dos Santos, Marielton dos Passos Cunha, Maria Leonor Sarno Oliveira, Juliana Cardoso Alves, Regina Adalva de Lucena Couto Océa, Danielle Rodrigues Ribeiro, André Nicolau Aquime Gonçalves, Patricia Gonzalez-Dias, Andreas Suhrbier, Paolo Marinho de Andrade Zanotto, Inácio Junqueira de Azevedo, Dario S. Zamboni, Roque Pacheco Almeida, Paulo Lee Ho, Jorge Kalil, Milton Yutaka Nishiyama Junior, Helder I. Nakaya

The largest ever recorded epidemic of the Chikungunya virus (CHIKV) broke out in 2004 and affected four continents. Acute symptomatic infections are typically associated with the onset of fever and often debilitating polyarthralgia/polyarthritis. In this study, a systems biology approach was adopted to analyze the blood transcriptomes of adults acutely infected with the CHIKV. Gene signatures that were associated with viral RNA levels and the onset of symptoms were identified. Among these genes, the putative role of the Eukaryotic Initiation Factor (eIF) family genes and apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC3A) in the CHIKV replication process were displayed. We further compared these signatures with signatures induced by the Dengue virus infection and rheumatoid arthritis. Finally, we demonstrated that the CHIKV in vitro infection of murine bone marrow-derived macrophages induced IL-1 beta production in a mechanism that is significantly dependent on the inflammasome NLRP3 activation. The observations provided valuable insights into virus-host interactions during the acute phase and can be instrumental in the investigation of new and effective therapeutic interventions.

Tratto da: www.plos.org
Note sul Copyright: Articles and accompanying materials published by PLOS on the PLOS Sites, unless otherwise indicated, are licensed by the respective authors of such articles for use and distribution by you subject to citation of the original source in accordance with the Creative Commons Attribution (CC BY) license.

Transcriptomic correlates of electrophysiological and morphological diversity within and across excitatory and inhibitory neuron classes

by Claire Bomkamp, Shreejoy J. Tripathy, Carolina Bengtsson Gonzales, Jens Hjerling-Leffler, Ann Marie Craig, Paul Pavlidis

In order to further our understanding of how gene expression contributes to key functional properties of neurons, we combined publicly accessible gene expression, electrophysiology, and morphology measurements to identify cross-cell type correlations between these data modalities. Building on our previous work using a similar approach, we distinguished between correlations which were “class-driven,” meaning those that could be explained by differences between excitatory and inhibitory cell classes, and those that reflected graded phenotypic differences within classes. Taking cell class identity into account increased the degree to which our results replicated in an independent dataset as well as their correspondence with known modes of ion channel function based on the literature. We also found a smaller set of genes whose relationships to electrophysiological or morphological properties appear to be specific to either excitatory or inhibitory cell types. Next, using data from PatchSeq experiments, allowing simultaneous single-cell characterization of gene expression and electrophysiology, we found that some of the gene-property correlations observed across cell types were further predictive of within-cell type heterogeneity. In summary, we have identified a number of relationships between gene expression, electrophysiology, and morphology that provide testable hypotheses for future studies.

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Note sul Copyright: Articles and accompanying materials published by PLOS on the PLOS Sites, unless otherwise indicated, are licensed by the respective authors of such articles for use and distribution by you subject to citation of the original source in accordance with the Creative Commons Attribution (CC BY) license.

Hierarchical Bayesian inference for concurrent model fitting and comparison for group studies

by Payam Piray, Amir Dezfouli, Tom Heskes, Michael J. Frank, Nathaniel D. Daw

Computational modeling plays an important role in modern neuroscience research. Much previous research has relied on statistical methods, separately, to address two problems that are actually interdependent. First, given a particular computational model, Bayesian hierarchical techniques have been used to estimate individual variation in parameters over a population of subjects, leveraging their population-level distributions. Second, candidate models are themselves compared, and individual variation in the expressed model estimated, according to the fits of the models to each subject. The interdependence between these two problems arises because the relevant population for estimating parameters of a model depends on which other subjects express the model. Here, we propose a hierarchical Bayesian inference (HBI) framework for concurrent model comparison, parameter estimation and inference at the population level, combining previous approaches. We show that this framework has important advantages for both parameter estimation and model comparison theoretically and experimentally. The parameters estimated by the HBI show smaller errors compared to other methods. Model comparison by HBI is robust against outliers and is not biased towards overly simplistic models. Furthermore, the fully Bayesian approach of our theory enables researchers to make inference on group-level parameters by performing HBI t-test.

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Note sul Copyright: Articles and accompanying materials published by PLOS on the PLOS Sites, unless otherwise indicated, are licensed by the respective authors of such articles for use and distribution by you subject to citation of the original source in accordance with the Creative Commons Attribution (CC BY) license.