PeerJ
type: channel
link: https://peerj.com/articles/
description: Articles published in PeerJ
publisher: PeerJ Inc.
publication name: PeerJ
issn: 2167-8359
items: Short-term MRI measurements as predictors of EDSS progression in relapsing-remitting multiple sclerosis: grey matter atrophy but not lesions are predictive in a real-life setting
items: Environment and host species shape the skin microbiome of captive neotropical bats
items: In situ visualization of bacterial populations in coral tissues: pitfalls and solutions
items: Parameter estimation in tree graph metabolic networks
items: Contributions to the functional morphology of caudate skulls: kinetic and akinetic forms
items: Are sites with multiple single nucleotide variants in cancer genomes a consequence of drivers, hypermutable sites or sequencing errors?
items: A ‘post-honeymoon’ measles epidemic in Burundi: mathematical model-based analysis and implications for vaccination timing
items: Integrated analysis of ischemic stroke datasets revealed sex and age difference in anti-stroke targets
items: Bcl-2 homologue Debcl enhances α-synuclein-induced phenotypes in Drosophila
items: Progesterone influences cytoplasmic maturation in porcine oocytes developing in vitro

Short-term MRI measurements as predictors of EDSS progression in relapsing-remitting multiple sclerosis: grey matter atrophy but not lesions are predictive in a real-life setting
type: item
type: AcademicArticle
description: Background Magnetic resonance imaging (MRI) is the best biomarker of inflammatory disease activity in relapsing remitting Multiple Sclerosis (RRMS) so far but the association with disability is weak. Appearance of new MRI-lesions is used to evaluate response to immunotherapies in individual patients as well as being the most common primary outcome in phase-2 trials. Measurements of brain atrophy show promising outcomes in natural cohort studies and some phase-2 trials. From a theoretical perspective they might represent irreversible neurodegeneration and be more closely associated with disability. However, these atrophy measurements are not yet established as prognostic factors in real-life clinical routine. High field MRI has improved image quality and resolution and new methods to measure atrophy dynamics have become available. Objective To investigate the predictive value of MRI classification criteria in to high/low atrophy and inflammation groups, and to explore predictive capacity of two consecutive routine MRI scans for disability progression in RRMS in a real-life prospective cohort. Methods 82 RRMS-patients (40 untreated, 42 treated with immunotherapies, mean age 40 years, median Expanded Disability Status Scale (EDSS) of 2, underwent two clinically indicated MRI scans (3 Tesla) within 5–14 months, and EDSS assessment after a mean of 3.0 (1.5–4.2) years. We investigated the predictive value of predefined classifications in low/high inflammatory and atrophy groups for EDSS progression (≥1.5 if baseline EDSS = 0, ≥1.0 if baseline EDSS <5, ≥0.5 for other) by chi-square tests and by analysis of variance (ANOVA). The classifications were based on current scientific or clinical recommendation (e.g., treatment response criteria). Brain atrophy was assessed with three different methods (SIENA, SIENAX, and FreeSurfer). Post-hoc analyses aimed to explore clinical data and dynamics of MRI outcomes as predictors in multivariate linear and logit models. Results Progress…
format: application/pdf
format: text/html
creator: Johanna von Gumberz
creator: Mina Mahmoudi
creator: Kim Young
creator: Sven Schippling
creator: Roland Martin
creator: Christoph Heesen
creator: Susanne Siemonsen
creator: Jan-Patrick Stellmann
subject: Neurology
subject: Psychiatry and Psychology
subject: Radiology and Medical Imaging
subject: Statistics
description: doi:10.7717/peerj.2442
publisher: PeerJ Inc.
rights: © 2016 von Gumberz et al.
abstract: Background Magnetic resonance imaging (MRI) is the best biomarker of inflammatory disease activity in relapsing remitting Multiple Sclerosis (RRMS) so far but the association with disability is weak. Appearance of new MRI-lesions is used to evaluate response to immunotherapies in individual patients as well as being the most common primary outcome in phase-2 trials. Measurements of brain atrophy show promising outcomes in natural cohort studies and some phase-2 trials. From a theoretical perspective they might represent irreversible neurodegeneration and be more closely associated with disability. However, these atrophy measurements are not yet established as prognostic factors in real-life clinical routine. High field MRI has improved image quality and resolution and new methods to measure atrophy dynamics have become available. Objective To investigate the predictive value of MRI classification criteria in to high/low atrophy and inflammation groups, and to explore predictive capacity of two consecutive routine MRI scans for disability progression in RRMS in a real-life prospective cohort. Methods 82 RRMS-patients (40 untreated, 42 treated with immunotherapies, mean age 40 years, median Expanded Disability Status Scale (EDSS) of 2, underwent two clinically indicated MRI scans (3 Tesla) within 5–14 months, and EDSS assessment after a mean of 3.0 (1.5–4.2) years. We investigated the predictive value of predefined classifications in low/high inflammatory and atrophy groups for EDSS progression (≥1.5 if baseline EDSS = 0, ≥1.0 if baseline EDSS <5, ≥0.5 for other) by chi-square tests and by analysis of variance (ANOVA). The classifications were based on current scientific or clinical recommendation (e.g., treatment response criteria). Brain atrophy was assessed with three different methods (SIENA, SIENAX, and FreeSurfer). Post-hoc analyses aimed to explore clinical data and dynamics of MRI outcomes as predictors in multivariate linear and logit models. Results Progress…
bibliographic citation: von Gumberz et al. (2016) Short-term MRI measurements as predictors of EDSS progression in relapsing-remitting multiple sclerosis: grey matter atrophy but not lesions are predictive in a real-life setting. PeerJ 4:e2442 https://doi.org/10.7717/peerj.2442
date submitted: 2016-02-26
date accepted: 2016-08-13
issued: 2016-09-20
is part of: PeerJ
license: http://creativecommons.org/licenses/by/4.0/
author list: Agent
  family name: von Gumberz
  given name: Johanna
author list: Agent
  family name: Mahmoudi
  given name: Mina
author list: Agent
  family name: Young
  given name: Kim
author list: Agent
  family name: Schippling
  given name: Sven
author list: Agent
  family name: Martin
  given name: Roland
author list: Agent
  family name: Heesen
  given name: Christoph
author list: Agent
  family name: Siemonsen
  given name: Susanne
author list: Agent
  family name: Stellmann
  given name: Jan-Patrick
doi: 10.7717/peerj.2442
volume: 4
issn: 2167-8359
publication name: PeerJ
publication date: 2016-09-20
copyright: ©2016 von Gumberz et al.
attribution name: von Gumberz et al.

Environment and host species shape the skin microbiome of captive neotropical bats
type: item
type: AcademicArticle
description: Background A wide range of microorganisms inhabit animal skin. This microbial community (microbiome) plays an important role in host defense against pathogens and disease. Bats (Chiroptera: Mammalia) are an ecologically and evolutionarily diversified group with a relatively unexplored skin microbiome. The bat skin microbiome could play a role in disease resistance, for example, to white nose syndrome (WNS), an infection which has been devastating North American bat populations. However, fundamental knowledge of the bat skin microbiome is needed before understanding its role in health and disease resistance. Captive neotropical frugivorous bats Artibeus jamaicensis and Carollia perspicillataprovide a simple controlled system in which to characterize the factors shaping the bat microbiome. Here, we aimed to determine the relative importance of habitat and host species on the bat skin microbiome. Methods We performed high-throughput 16S rRNA gene sequencing of the skin microbiome of two different bat species living in captivity in two different habitats. In the first habitat, A. jamaicensis and C. perspicillata lived together, while the second habitat contained only A. jamaicensis. Results We found that both habitat and host species shape the composition and diversity of the skin microbiome, with habitat having the strongest influence. Cohabitating A. jamaicensis and C. perspicillata shared more similar skin microbiomes than members of the same species (A. jamaicensis) across two habitats. Discussion These results suggest that in captivity, the skin microbial community is homogenised by the shared environments and individual proximities of bats living together in the same habitat, at the expense of the innate host species factors. The predominant influence of habitat suggests that environmental microorganisms or pathogens might colonize bat skin. We also propose that bat populations could differ in pathogen susceptibility depending on their immediate environment and ha…
format: application/pdf
format: text/html
creator: Virginie Lemieux-Labonté
creator: Nicolas Tromas
creator: B. Jesse Shapiro
creator: François-Joseph Lapointe
subject: Ecology
subject: Microbiology
subject: Zoology
description: doi:10.7717/peerj.2430
publisher: PeerJ Inc.
rights: © 2016 Lemieux-Labonté et al.
abstract: Background A wide range of microorganisms inhabit animal skin. This microbial community (microbiome) plays an important role in host defense against pathogens and disease. Bats (Chiroptera: Mammalia) are an ecologically and evolutionarily diversified group with a relatively unexplored skin microbiome. The bat skin microbiome could play a role in disease resistance, for example, to white nose syndrome (WNS), an infection which has been devastating North American bat populations. However, fundamental knowledge of the bat skin microbiome is needed before understanding its role in health and disease resistance. Captive neotropical frugivorous bats Artibeus jamaicensis and Carollia perspicillataprovide a simple controlled system in which to characterize the factors shaping the bat microbiome. Here, we aimed to determine the relative importance of habitat and host species on the bat skin microbiome. Methods We performed high-throughput 16S rRNA gene sequencing of the skin microbiome of two different bat species living in captivity in two different habitats. In the first habitat, A. jamaicensis and C. perspicillata lived together, while the second habitat contained only A. jamaicensis. Results We found that both habitat and host species shape the composition and diversity of the skin microbiome, with habitat having the strongest influence. Cohabitating A. jamaicensis and C. perspicillata shared more similar skin microbiomes than members of the same species (A. jamaicensis) across two habitats. Discussion These results suggest that in captivity, the skin microbial community is homogenised by the shared environments and individual proximities of bats living together in the same habitat, at the expense of the innate host species factors. The predominant influence of habitat suggests that environmental microorganisms or pathogens might colonize bat skin. We also propose that bat populations could differ in pathogen susceptibility depending on their immediate environment and ha…
bibliographic citation: Lemieux-Labonté et al. (2016) Environment and host species shape the skin microbiome of captive neotropical bats. PeerJ 4:e2430 https://doi.org/10.7717/peerj.2430
date submitted: 2016-05-02
date accepted: 2016-08-10
issued: 2016-09-20
is part of: PeerJ
license: http://creativecommons.org/licenses/by/4.0/
author list: Agent
  family name: Lemieux-Labonté
  given name: Virginie
author list: Agent
  family name: Tromas
  given name: Nicolas
author list: Agent
  family name: Shapiro
  given name: B. Jesse
author list: Agent
  family name: Lapointe
  given name: François-Joseph
doi: 10.7717/peerj.2430
volume: 4
issn: 2167-8359
publication name: PeerJ
publication date: 2016-09-20
copyright: ©2016 Lemieux-Labonté et al.
attribution name: Lemieux-Labonté et al.

In situ visualization of bacterial populations in coral tissues: pitfalls and solutions
type: item
type: AcademicArticle
description: In situ visualization of microbial communities within their natural habitats provides a powerful approach to explore complex interactions between microorganisms and their macroscopic hosts. Specifically, the application of fluorescence in situ hybridization (FISH) to simultaneously identify and visualize diverse microbial taxa associated with coral hosts, including symbiotic algae (Symbiodinium), Bacteria, Archaea, Fungi and protists, could help untangle the structure and function of these diverse taxa within the coral holobiont. However, the application of FISH approaches to coral samples is constrained by non-specific binding of targeted rRNA probes to cellular structures within the coral animal tissues (including nematocysts, spirocysts, granular gland cells within the gastrodermis and cnidoglandular bands of mesenterial filaments). This issue, combined with high auto-fluorescence of both host tissues and endosymbiotic dinoflagellates (Symbiodinium), make FISH approaches for analyses of coral tissues challenging. Here we outline the major pitfalls associated with applying FISH to coral samples and describe approaches to overcome these challenges.
format: application/pdf
format: text/html
creator: Naohisa Wada
creator: Frederic J. Pollock
creator: Bette L. Willis
creator: Tracy Ainsworth
creator: Nobuhiro Mano
creator: David G. Bourne
subject: Marine Biology
subject: Microbiology
description: doi:10.7717/peerj.2424
publisher: PeerJ Inc.
rights: © 2016 Wada et al.
abstract: In situ visualization of microbial communities within their natural habitats provides a powerful approach to explore complex interactions between microorganisms and their macroscopic hosts. Specifically, the application of fluorescence in situ hybridization (FISH) to simultaneously identify and visualize diverse microbial taxa associated with coral hosts, including symbiotic algae (Symbiodinium), Bacteria, Archaea, Fungi and protists, could help untangle the structure and function of these diverse taxa within the coral holobiont. However, the application of FISH approaches to coral samples is constrained by non-specific binding of targeted rRNA probes to cellular structures within the coral animal tissues (including nematocysts, spirocysts, granular gland cells within the gastrodermis and cnidoglandular bands of mesenterial filaments). This issue, combined with high auto-fluorescence of both host tissues and endosymbiotic dinoflagellates (Symbiodinium), make FISH approaches for analyses of coral tissues challenging. Here we outline the major pitfalls associated with applying FISH to coral samples and describe approaches to overcome these challenges.
bibliographic citation: Wada et al. (2016) In situ visualization of bacterial populations in coral tissues: pitfalls and solutions. PeerJ 4:e2424 https://doi.org/10.7717/peerj.2424
date submitted: 2016-06-03
date accepted: 2016-08-09
issued: 2016-09-20
is part of: PeerJ
license: http://creativecommons.org/licenses/by/4.0/
author list: Agent
  family name: Wada
  given name: Naohisa
author list: Agent
  family name: Pollock
  given name: Frederic J.
author list: Agent
  family name: Willis
  given name: Bette L.
author list: Agent
  family name: Ainsworth
  given name: Tracy
author list: Agent
  family name: Mano
  given name: Nobuhiro
author list: Agent
  family name: Bourne
  given name: David G.
doi: 10.7717/peerj.2424
volume: 4
issn: 2167-8359
publication name: PeerJ
publication date: 2016-09-20
copyright: ©2016 Wada et al.
attribution name: Wada et al.

Parameter estimation in tree graph metabolic networks
type: item
type: AcademicArticle
description: We study the glycosylation processes that convert initially toxic substrates to nutritionally valuable metabolites in the flavonoid biosynthesis pathway of tomato (Solanum lycopersicum) seedlings. To estimate the reaction rates we use ordinary differential equations (ODEs) to model the enzyme kinetics. A popular choice is to use a system of linear ODEs with constant kinetic rates or to use Michaelis–Menten kinetics. In reality, the catalytic rates, which are affected among other factors by kinetic constants and enzyme concentrations, are changing in time and with the approaches just mentioned, this phenomenon cannot be described. Another problem is that, in general these kinetic coefficients are not always identifiable. A third problem is that, it is not precisely known which enzymes are catalyzing the observed glycosylation processes. With several hundred potential gene candidates, experimental validation using purified target proteins is expensive and time consuming. We aim at reducing this task via mathematical modeling to allow for the pre-selection of most potential gene candidates. In this article we discuss a fast and relatively simple approach to estimate time varying kinetic rates, with three favorable properties: firstly, it allows for identifiable estimation of time dependent parameters in networks with a tree-like structure. Secondly, it is relatively fast compared to usually applied methods that estimate the model derivatives together with the network parameters. Thirdly, by combining the metabolite concentration data with a corresponding microarray data, it can help in detecting the genes related to the enzymatic processes. By comparing the estimated time dynamics of the catalytic rates with time series gene expression data we may assess potential candidate genes behind enzymatic reactions. As an example, we show how to apply this method to select prominent glycosyltransferase genes in tomato seedlings.
format: application/pdf
format: text/html
creator: Laura Astola
creator: Hans Stigter
creator: Maria Victoria Gomez Roldan
creator: Fred van Eeuwijk
creator: Robert D. Hall
creator: Marian Groenenboom
creator: Jaap J. Molenaar
subject: Agricultural Science
subject: Computational Biology
subject: Food Science and Technology
subject: Mathematical Biology
subject: Plant Science
description: doi:10.7717/peerj.2417
publisher: PeerJ Inc.
rights: © 2016 Astola et al.
abstract: We study the glycosylation processes that convert initially toxic substrates to nutritionally valuable metabolites in the flavonoid biosynthesis pathway of tomato (Solanum lycopersicum) seedlings. To estimate the reaction rates we use ordinary differential equations (ODEs) to model the enzyme kinetics. A popular choice is to use a system of linear ODEs with constant kinetic rates or to use Michaelis–Menten kinetics. In reality, the catalytic rates, which are affected among other factors by kinetic constants and enzyme concentrations, are changing in time and with the approaches just mentioned, this phenomenon cannot be described. Another problem is that, in general these kinetic coefficients are not always identifiable. A third problem is that, it is not precisely known which enzymes are catalyzing the observed glycosylation processes. With several hundred potential gene candidates, experimental validation using purified target proteins is expensive and time consuming. We aim at reducing this task via mathematical modeling to allow for the pre-selection of most potential gene candidates. In this article we discuss a fast and relatively simple approach to estimate time varying kinetic rates, with three favorable properties: firstly, it allows for identifiable estimation of time dependent parameters in networks with a tree-like structure. Secondly, it is relatively fast compared to usually applied methods that estimate the model derivatives together with the network parameters. Thirdly, by combining the metabolite concentration data with a corresponding microarray data, it can help in detecting the genes related to the enzymatic processes. By comparing the estimated time dynamics of the catalytic rates with time series gene expression data we may assess potential candidate genes behind enzymatic reactions. As an example, we show how to apply this method to select prominent glycosyltransferase genes in tomato seedlings.
bibliographic citation: Astola et al. (2016) Parameter estimation in tree graph metabolic networks. PeerJ 4:e2417 https://doi.org/10.7717/peerj.2417
date submitted: 2016-05-25
date accepted: 2016-08-05
issued: 2016-09-20
is part of: PeerJ
license: http://creativecommons.org/licenses/by/4.0/
author list: Agent
  family name: Astola
  given name: Laura
author list: Agent
  family name: Stigter
  given name: Hans
author list: Agent
  family name: Gomez Roldan
  given name: Maria Victoria
author list: Agent
  family name: van Eeuwijk
  given name: Fred
author list: Agent
  family name: Hall
  given name: Robert D.
author list: Agent
  family name: Groenenboom
  given name: Marian
author list: Agent
  family name: Molenaar
  given name: Jaap J.
doi: 10.7717/peerj.2417
volume: 4
issn: 2167-8359
publication name: PeerJ
publication date: 2016-09-20
copyright: ©2016 Astola et al.
attribution name: Astola et al.

Contributions to the functional morphology of caudate skulls: kinetic and akinetic forms
type: item
type: AcademicArticle
description: A strongly ossified and rigid skull roof, which prevents parietal kinesis, has been reported for the adults of all amphibian clades. Our μ-CT investigations revealed that the Buresch’s newt (Triturus ivanbureschi) possess a peculiar cranial construction. In addition to the typical amphibian pleurokinetic articulation between skull roof and palatoquadrate associated structures, we found flexible connections between nasals and frontals (prokinesis), vomer and parasphenoid (palatokinesis), and between frontals and parietals (mesokinesis). This is the first description of mesokinesis in urodelans. The construction of the skull in the Buresch’s newts also indicates the presence of an articulation between parietals and the exocipitals, discussed as a possible kind of metakinesis. The specific combination of pleuro-, pro-, meso-, palato-, and metakinetic skull articulations indicate to a new kind of kinetic systems unknown for urodelans to this date. We discuss the possible neotenic origin of the skull kinesis and pose the hypothesis that the kinesis in T. ivanbureschi increases the efficiency of fast jaw closure. For that, we compared the construction of the skull in T. ivanbureschi to the akinetic skull of the Common fire salamander Salamandra salamandra. We hypothesize that the design of the skull in the purely terrestrial living salamander shows a similar degree of intracranial mobility. However, this mobility is permitted by elasticity of some bones and not by true articulation between them. We comment on the possible relation between the skull construction and the form of prey shaking mechanism that the species apply to immobilize their victims.
format: application/pdf
format: text/html
creator: Nikolay Natchev
creator: Stephan Handschuh
creator: Simeon Lukanov
creator: Nikolay Tzankov
creator: Borislav Naumov
creator: Ingmar Werneburg
subject: Animal Behavior
subject: Biodiversity
subject: Bioengineering
subject: Taxonomy
subject: Zoology
description: doi:10.7717/peerj.2392
publisher: PeerJ Inc.
rights: © 2016 Natchev et al.
abstract: A strongly ossified and rigid skull roof, which prevents parietal kinesis, has been reported for the adults of all amphibian clades. Our μ-CT investigations revealed that the Buresch’s newt (Triturus ivanbureschi) possess a peculiar cranial construction. In addition to the typical amphibian pleurokinetic articulation between skull roof and palatoquadrate associated structures, we found flexible connections between nasals and frontals (prokinesis), vomer and parasphenoid (palatokinesis), and between frontals and parietals (mesokinesis). This is the first description of mesokinesis in urodelans. The construction of the skull in the Buresch’s newts also indicates the presence of an articulation between parietals and the exocipitals, discussed as a possible kind of metakinesis. The specific combination of pleuro-, pro-, meso-, palato-, and metakinetic skull articulations indicate to a new kind of kinetic systems unknown for urodelans to this date. We discuss the possible neotenic origin of the skull kinesis and pose the hypothesis that the kinesis in T. ivanbureschi increases the efficiency of fast jaw closure. For that, we compared the construction of the skull in T. ivanbureschi to the akinetic skull of the Common fire salamander Salamandra salamandra. We hypothesize that the design of the skull in the purely terrestrial living salamander shows a similar degree of intracranial mobility. However, this mobility is permitted by elasticity of some bones and not by true articulation between them. We comment on the possible relation between the skull construction and the form of prey shaking mechanism that the species apply to immobilize their victims.
bibliographic citation: Natchev et al. (2016) Contributions to the functional morphology of caudate skulls: kinetic and akinetic forms. PeerJ 4:e2392 https://doi.org/10.7717/peerj.2392
date submitted: 2016-05-24
date accepted: 2016-08-01
issued: 2016-09-20
is part of: PeerJ
license: http://creativecommons.org/licenses/by/4.0/
author list: Agent
  family name: Natchev
  given name: Nikolay
author list: Agent
  family name: Handschuh
  given name: Stephan
author list: Agent
  family name: Lukanov
  given name: Simeon
author list: Agent
  family name: Tzankov
  given name: Nikolay
author list: Agent
  family name: Naumov
  given name: Borislav
author list: Agent
  family name: Werneburg
  given name: Ingmar
doi: 10.7717/peerj.2392
volume: 4
issn: 2167-8359
publication name: PeerJ
publication date: 2016-09-20
copyright: © 2016 Natchev et al.
attribution name: Natchev et al.

Are sites with multiple single nucleotide variants in cancer genomes a consequence of drivers, hypermutable sites or sequencing errors?
type: item
type: AcademicArticle
description: Across independent cancer genomes it has been observed that some sites have been recurrently hit by single nucleotide variants (SNVs). Such recurrently hit sites might be either (i) drivers of cancer that are postively selected during oncogenesis, (ii) due to mutation rate variation, or (iii) due to sequencing and assembly errors. We have investigated the cause of recurrently hit sites in a dataset of >3 million SNVs from 507 complete cancer genome sequences. We find evidence that many sites have been hit significantly more often than one would expect by chance, even taking into account the effect of the adjacent nucleotides on the rate of mutation. We find that the density of these recurrently hit sites is higher in non-coding than coding DNA and hence conclude that most of them are unlikely to be drivers. We also find that most of them are found in parts of the genome that are not uniquely mappable and hence are likely to be due to mapping errors. In support of the error hypothesis, we find that recurently hit sites are not randomly distributed across sequences from different laboratories. We fit a model to the data in which the rate of mutation is constant across sites but the rate of error varies. This model suggests that ∼4% of all SNVs are errors in this dataset, but that the rate of error varies by thousands-of-fold between sites.
format: application/pdf
format: text/html
creator: Thomas C.A. Smith
creator: Antony M. Carr
creator: Adam C. Eyre-Walker
subject: Bioinformatics
subject: Computational Biology
subject: Genetics
subject: Genomics
subject: Computational Science
description: doi:10.7717/peerj.2391
publisher: PeerJ Inc.
rights: © 2016 Smith et al.
abstract: Across independent cancer genomes it has been observed that some sites have been recurrently hit by single nucleotide variants (SNVs). Such recurrently hit sites might be either (i) drivers of cancer that are postively selected during oncogenesis, (ii) due to mutation rate variation, or (iii) due to sequencing and assembly errors. We have investigated the cause of recurrently hit sites in a dataset of >3 million SNVs from 507 complete cancer genome sequences. We find evidence that many sites have been hit significantly more often than one would expect by chance, even taking into account the effect of the adjacent nucleotides on the rate of mutation. We find that the density of these recurrently hit sites is higher in non-coding than coding DNA and hence conclude that most of them are unlikely to be drivers. We also find that most of them are found in parts of the genome that are not uniquely mappable and hence are likely to be due to mapping errors. In support of the error hypothesis, we find that recurently hit sites are not randomly distributed across sequences from different laboratories. We fit a model to the data in which the rate of mutation is constant across sites but the rate of error varies. This model suggests that ∼4% of all SNVs are errors in this dataset, but that the rate of error varies by thousands-of-fold between sites.
bibliographic citation: Smith et al. (2016) Are sites with multiple single nucleotide variants in cancer genomes a consequence of drivers, hypermutable sites or sequencing errors?. PeerJ 4:e2391 https://doi.org/10.7717/peerj.2391
date submitted: 2016-05-29
date accepted: 2016-08-01
issued: 2016-09-20
is part of: PeerJ
license: http://creativecommons.org/licenses/by/4.0/
author list: Agent
  family name: Smith
  given name: Thomas C.A.
author list: Agent
  family name: Carr
  given name: Antony M.
author list: Agent
  family name: Eyre-Walker
  given name: Adam C.
doi: 10.7717/peerj.2391
volume: 4
issn: 2167-8359
publication name: PeerJ
publication date: 2016-09-20
copyright: ©2016 Smith et al.
attribution name: Smith et al.

A ‘post-honeymoon’ measles epidemic in Burundi: mathematical model-based analysis and implications for vaccination timing
type: item
type: AcademicArticle
description: Using a mathematical model with realistic demography, we analyze a large outbreak of measles in Muyinga sector in rural Burundi in 1988–1989. We generate simulated epidemic curves and age × time epidemic surfaces, which we qualitatively and quantitatively compare with the data. Our findings suggest that supplementary immunization activities (SIAs) should be used in places where routine vaccination cannot keep up with the increasing numbers of susceptible individuals resulting from population growth or from logistical problems such as cold chain maintenance. We use the model to characterize the relationship between SIA frequency and SIA age range necessary to suppress measles outbreaks. If SIAs are less frequent, they must expand their target age range.
format: application/pdf
format: text/html
creator: Katelyn C. Corey
creator: Andrew Noymer
subject: Mathematical Biology
subject: Epidemiology
subject: Health Policy
subject: Infectious Diseases
subject: Public Health
description: doi:10.7717/peerj.2476
publisher: PeerJ Inc.
rights: © 2016 Corey and Noymer
abstract: Using a mathematical model with realistic demography, we analyze a large outbreak of measles in Muyinga sector in rural Burundi in 1988–1989. We generate simulated epidemic curves and age × time epidemic surfaces, which we qualitatively and quantitatively compare with the data. Our findings suggest that supplementary immunization activities (SIAs) should be used in places where routine vaccination cannot keep up with the increasing numbers of susceptible individuals resulting from population growth or from logistical problems such as cold chain maintenance. We use the model to characterize the relationship between SIA frequency and SIA age range necessary to suppress measles outbreaks. If SIAs are less frequent, they must expand their target age range.
bibliographic citation: Corey et al. (2016) A ‘post-honeymoon’ measles epidemic in Burundi: mathematical model-based analysis and implications for vaccination timing. PeerJ 4:e2476 https://doi.org/10.7717/peerj.2476
date submitted: 2016-06-21
date accepted: 2016-08-23
issued: 2016-09-15
is part of: PeerJ
license: http://creativecommons.org/licenses/by/4.0/
author list: Agent
  family name: Corey
  given name: Katelyn C.
author list: Agent
  family name: Noymer
  given name: Andrew
doi: 10.7717/peerj.2476
volume: 4
issn: 2167-8359
publication name: PeerJ
publication date: 2016-09-15
copyright: ©2016 Corey and Noymer
attribution name: Corey and Noymer

Integrated analysis of ischemic stroke datasets revealed sex and age difference in anti-stroke targets
type: item
type: AcademicArticle
description: Ischemic stroke is a common neurological disorder and the burden in the world is growing. This study aims to explore the effect of sex and age difference on ischemic stroke using integrated microarray datasets. The results showed a dramatic difference in whole gene expression profiles and influenced pathways between males and females, and also in the old and young individuals. Furthermore, compared with old males, old female patients showed more serious biological function damage. However, females showed less affected pathways than males in young subjects. Functional interaction networks showed these differential expression genes were mostly related to immune and inflammation-related functions. In addition, we found ARG1 and MMP9 were up-regulated in total and all subgroups. Importantly, IL1A, ILAB, IL6 and TNF and other anti-stroke target genes were up-regulated in males. However, these anti-stroke target genes showed low expression in females. This study found huge sex and age differences in ischemic stroke especially the opposite expression of anti-stroke target genes. Future studies are needed to uncover these pathological mechanisms, and to take appropriate pre-prevention, treatment and rehabilitation measures.
format: application/pdf
format: text/html
creator: Wen-Xing Li
creator: Shao-Xing Dai
creator: Qian Wang
creator: Yi-Cheng Guo
creator: Yi Hong
creator: Jun-Juan Zheng
creator: Jia-Qian Liu
creator: Dahai Liu
creator: Gong-Hua Li
creator: Jing-Fei Huang
subject: Bioinformatics
subject: Cardiology
subject: Immunology
description: doi:10.7717/peerj.2470
publisher: PeerJ Inc.
rights: © 2016 Li et al.
abstract: Ischemic stroke is a common neurological disorder and the burden in the world is growing. This study aims to explore the effect of sex and age difference on ischemic stroke using integrated microarray datasets. The results showed a dramatic difference in whole gene expression profiles and influenced pathways between males and females, and also in the old and young individuals. Furthermore, compared with old males, old female patients showed more serious biological function damage. However, females showed less affected pathways than males in young subjects. Functional interaction networks showed these differential expression genes were mostly related to immune and inflammation-related functions. In addition, we found ARG1 and MMP9 were up-regulated in total and all subgroups. Importantly, IL1A, ILAB, IL6 and TNF and other anti-stroke target genes were up-regulated in males. However, these anti-stroke target genes showed low expression in females. This study found huge sex and age differences in ischemic stroke especially the opposite expression of anti-stroke target genes. Future studies are needed to uncover these pathological mechanisms, and to take appropriate pre-prevention, treatment and rehabilitation measures.
bibliographic citation: Li et al. (2016) Integrated analysis of ischemic stroke datasets revealed sex and age difference in anti-stroke targets. PeerJ 4:e2470 https://doi.org/10.7717/peerj.2470
date submitted: 2016-07-26
date accepted: 2016-08-22
issued: 2016-09-15
is part of: PeerJ
license: http://creativecommons.org/licenses/by/4.0/
author list: Agent
  family name: Li
  given name: Wen-Xing
author list: Agent
  family name: Dai
  given name: Shao-Xing
author list: Agent
  family name: Wang
  given name: Qian
author list: Agent
  family name: Guo
  given name: Yi-Cheng
author list: Agent
  family name: Hong
  given name: Yi
author list: Agent
  family name: Zheng
  given name: Jun-Juan
author list: Agent
  family name: Liu
  given name: Jia-Qian
author list: Agent
  family name: Liu
  given name: Dahai
author list: Agent
  family name: Li
  given name: Gong-Hua
author list: Agent
  family name: Huang
  given name: Jing-Fei
doi: 10.7717/peerj.2470
volume: 4
issn: 2167-8359
publication name: PeerJ
publication date: 2016-09-15
copyright: ©2016 Li et al.
attribution name: Li et al.

Bcl-2 homologue Debcl enhances α-synuclein-induced phenotypes in Drosophila
type: item
type: AcademicArticle
description: Background Parkinson disease (PD) is a debilitating movement disorder that afflicts 1–2% of the population over 50 years of age. The common hallmark for both sporadic and familial forms of PD is mitochondrial dysfunction. Mammals have at least twenty proapoptotic and antiapoptotic Bcl-2 family members, in contrast, only two Bcl-2 family genes have been identified in Drosophila melanogaster, the proapoptotic mitochondrial localized Debcl and the antiapoptotic Buffy. The expression of the human transgene α-synuclein, a gene that is strongly associated with inherited forms of PD, in dopaminergic neurons (DA) of Drosophila, results in loss of neurons and locomotor dysfunction to model PD in flies. The altered expression of Debcl in the DA neurons and neuron-rich eye and along with the expression of α-synuclein offers an opportunity to highlight the role of Debcl in mitochondrial-dependent neuronal degeneration and death. Results The directed overexpression of Debcl using the Ddc-Gal4 transgene in the DA of Drosophila resulted in flies with severely decreased survival and a premature age-dependent loss in climbing ability. The inhibition of Debcl resulted in enhanced survival and improved climbing ability whereas the overexpression of Debcl in the α-synuclein-induced Drosophila model of PD resulted in more severe phenotypes. In addition, the co-expression of Debcl along with Buffy partially counteracts the Debcl-induced phenotypes, to improve the lifespan and the associated loss of locomotor ability observed. In complementary experiments, the overexpression of Debcl along with the expression of α-synuclein in the eye, enhanced the eye ablation that results from the overexpression of Debcl. The co-expression of Buffy along with Debcl overexpression results in the rescue of the moderate developmental eye defects. The co-expression of Buffy along with inhibition of Debcl partially restores the eye to a roughened eye phenotype. Discussion The overexpression of Debcl in DA ne…
format: application/pdf
format: text/html
creator: P. Githure M’Angale
creator: Brian E. Staveley
subject: Cell Biology
subject: Genetics
subject: Neuroscience
description: doi:10.7717/peerj.2461
publisher: PeerJ Inc.
rights: © 2016 M’Angale & Staveley
abstract: Background Parkinson disease (PD) is a debilitating movement disorder that afflicts 1–2% of the population over 50 years of age. The common hallmark for both sporadic and familial forms of PD is mitochondrial dysfunction. Mammals have at least twenty proapoptotic and antiapoptotic Bcl-2 family members, in contrast, only two Bcl-2 family genes have been identified in Drosophila melanogaster, the proapoptotic mitochondrial localized Debcl and the antiapoptotic Buffy. The expression of the human transgene α-synuclein, a gene that is strongly associated with inherited forms of PD, in dopaminergic neurons (DA) of Drosophila, results in loss of neurons and locomotor dysfunction to model PD in flies. The altered expression of Debcl in the DA neurons and neuron-rich eye and along with the expression of α-synuclein offers an opportunity to highlight the role of Debcl in mitochondrial-dependent neuronal degeneration and death. Results The directed overexpression of Debcl using the Ddc-Gal4 transgene in the DA of Drosophila resulted in flies with severely decreased survival and a premature age-dependent loss in climbing ability. The inhibition of Debcl resulted in enhanced survival and improved climbing ability whereas the overexpression of Debcl in the α-synuclein-induced Drosophila model of PD resulted in more severe phenotypes. In addition, the co-expression of Debcl along with Buffy partially counteracts the Debcl-induced phenotypes, to improve the lifespan and the associated loss of locomotor ability observed. In complementary experiments, the overexpression of Debcl along with the expression of α-synuclein in the eye, enhanced the eye ablation that results from the overexpression of Debcl. The co-expression of Buffy along with Debcl overexpression results in the rescue of the moderate developmental eye defects. The co-expression of Buffy along with inhibition of Debcl partially restores the eye to a roughened eye phenotype. Discussion The overexpression of Debcl in DA ne…
bibliographic citation: M’Angale et al. (2016) Bcl-2 homologue Debcl enhances α-synuclein-induced phenotypes in Drosophila. PeerJ 4:e2461 https://doi.org/10.7717/peerj.2461
date submitted: 2016-05-03
date accepted: 2016-08-18
issued: 2016-09-15
is part of: PeerJ
license: http://creativecommons.org/licenses/by/4.0/
author list: Agent
  family name: M’Angale
  given name: P. Githure
author list: Agent
  family name: Staveley
  given name: Brian E.
doi: 10.7717/peerj.2461
volume: 4
issn: 2167-8359
publication name: PeerJ
publication date: 2016-09-15
copyright: © 2016 M’Angale & Staveley
attribution name: M’Angale & Staveley

Progesterone influences cytoplasmic maturation in porcine oocytes developing in vitro
type: item
type: AcademicArticle
description: Progesterone (P4), an ovarian steroid hormone, is an important regulator of female reproduction. In this study, we explored the influence of progesterone on porcine oocyte nuclear maturation and cytoplasmic maturation and development in vitro. We found that the presence of P4 during oocyte maturation did not inhibit polar body extrusions but significantly increased glutathione and decreased reactive oxygen species (ROS) levels relative to that in control groups. The incidence of parthenogenetically activated oocytes that could develop to the blastocyst stage was higher (p < 0.05) when oocytes were exposed to P4 as compared to that in the controls. Cell numbers were increased in the P4-treated groups. Further, the P4-specific inhibitor mifepristone (RU486) prevented porcine oocyte maturation, as represented by the reduced incidence (p < 0.05) of oocyte first polar body extrusions. RU486 affected maturation promoting factor (MPF) activity and maternal mRNA polyadenylation status. In general, these data show that P4 influences the cytoplasmic maturation of porcine oocytes, at least partially, by decreasing their polyadenylation, thereby altering maternal gene expression.
format: application/pdf
format: text/html
creator: Bao Yuan
creator: Shuang Liang
creator: Yong-Xun Jin
creator: Jeong-Woo Kwon
creator: Jia-Bao Zhang
creator: Nam-Hyung Kim
subject: Developmental Biology
subject: Veterinary Medicine
description: doi:10.7717/peerj.2454
publisher: PeerJ Inc.
rights: © 2016 Yuan et al.
abstract: Progesterone (P4), an ovarian steroid hormone, is an important regulator of female reproduction. In this study, we explored the influence of progesterone on porcine oocyte nuclear maturation and cytoplasmic maturation and development in vitro. We found that the presence of P4 during oocyte maturation did not inhibit polar body extrusions but significantly increased glutathione and decreased reactive oxygen species (ROS) levels relative to that in control groups. The incidence of parthenogenetically activated oocytes that could develop to the blastocyst stage was higher (p < 0.05) when oocytes were exposed to P4 as compared to that in the controls. Cell numbers were increased in the P4-treated groups. Further, the P4-specific inhibitor mifepristone (RU486) prevented porcine oocyte maturation, as represented by the reduced incidence (p < 0.05) of oocyte first polar body extrusions. RU486 affected maturation promoting factor (MPF) activity and maternal mRNA polyadenylation status. In general, these data show that P4 influences the cytoplasmic maturation of porcine oocytes, at least partially, by decreasing their polyadenylation, thereby altering maternal gene expression.
bibliographic citation: Yuan et al. (2016) Progesterone influences cytoplasmic maturation in porcine oocytes developing in vitro. PeerJ 4:e2454 https://doi.org/10.7717/peerj.2454
date submitted: 2016-06-17
date accepted: 2016-08-17
issued: 2016-09-15
is part of: PeerJ
license: http://creativecommons.org/licenses/by/4.0/
author list: Agent
  family name: Yuan
  given name: Bao
author list: Agent
  family name: Liang
  given name: Shuang
author list: Agent
  family name: Jin
  given name: Yong-Xun
author list: Agent
  family name: Kwon
  given name: Jeong-Woo
author list: Agent
  family name: Zhang
  given name: Jia-Bao
author list: Agent
  family name: Kim
  given name: Nam-Hyung
doi: 10.7717/peerj.2454
volume: 4
issn: 2167-8359
publication name: PeerJ
publication date: 2016-09-15
copyright: ©2016 Yuan et al.
attribution name: Yuan et al.

PeerJ
type: Periodical
uri: PeerJ
issn: 2167-8359