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headings list	keywords list	title stringlengths 20 281	id stringlengths 20 20	toc stringlengths 57 522 ⌀	sections list	abstract list	summary list	year stringclasses 13 values
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "genetics", "biology", "molecular cell biology", "genetics and genomics" ]	Tsx Produces a Long Noncoding RNA and Has General Functions in the Germline, Stem Cells, and Brain	journal.pgen.1002248	null	[ [ "The X-inactivation center ( Xic ) controls X-chromosome inactivation ( XCI ) and is enriched for genes that produce long noncoding RNAs ( ncRNA ) ( Figure 1A ) [1] , [2] , [3] .", "Several have been shown to regulate XCI .", "The 17-kb Xist RNA is induced at the onset of XCI and silences the X-chromo...	[ "The Tsx gene resides at the X-inactivation center and is thought to encode a protein expressed in testis , but its function has remained mysterious .", "Given its proximity to noncoding genes that regulate X-inactivation , here we characterize Tsx and determine its function in mice .", "We find that Tsx is act...	[ "The X-linked gene Tsx is located within the X-inactivation center and is thought to encode a protein expressed in testis , yet its function is not known .", "Here we show that Tsx is actually a noncoding RNA , a new member of the large noncoding RNA family expressed from the X . Tsx is abundantly expressed in me...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal models", "developmental biology", "developmental neuroscience", "animal genetics", "model organisms", "entomology", "gene expression", "genetics", "molecular genetics", "cellular types", "biology", "sensory systems", "molecular cell biology", "zoology", "neuroscience", "pattern...	Genetic Dissection of Photoreceptor Subtype Specification by the Drosophila melanogaster Zinc Finger Proteins Elbow and No ocelli	journal.pgen.1004210	null	[ [ "The developing retina of Drosophila melanogaster is a powerful model for studying the specification of cell fates within a retinal mosaic .", "One important aspect is the localized specification of photoreceptor cell types in response to Wg/Wnt signaling .", "Wg emanating from the head cuticle specif...	[ "The elbow/no ocelli ( elb/noc ) complex of Drosophila melanogaster encodes two paralogs of the evolutionarily conserved NET family of zinc finger proteins .", "These transcriptional repressors share a conserved domain structure , including a single atypical C2H2 zinc finger .", "In flies , Elb and Noc are impo...	[ "The eyes of many animals contain groups of photoreceptor cells with different chromatic sensitivities that can be arranged in complex patterns .", "It is of great interest to identify the genes and pathways shaping these ‘retinal mosaics’ which include stochastically distributed groups of cells , versus highly l...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "social and behavioral sciences", "immunology", "anthropology", "parasitic diseases", "helminth infection", "hookworm infection", "neglected tropical diseases", "ascariasis", "infectious diseases", "biological anthropology", "hookworm", "immune response", "trichuriasis", "cli...	Evidence for a Peak Shift in a Humoral Response to Helminths: Age Profiles of IgE in the Shuar of Ecuador, the Tsimane of Bolivia, and the U.S. NHANES	journal.pntd.0001218	null	[ [ "Age-related epidemiological patterns are thought to result from complex interactions between parasite life cycle , exposure to infection , and host-immunity [1] , [2] .", "Helminth infections show characteristic age-patterning , peaking around puberty and then declining during adulthood [3]–[5] .", "...	[ "The peak shift model predicts that the age-profile of a pathogen's prevalence depends upon its transmission rate , peaking earlier in populations with higher transmission and declining as partial immunity is acquired .", "Helminth infections are associated with increased immunoglobulin E ( IgE ) , which may conv...	[ "Infection with parasitic worms , known as helminths , alters the immune system , causing individuals to produce high levels of a type of antibody known as immunoglobulin E ( IgE ) .", "IgE is typically very low in western populations , but is many times higher where helminth infections are common , particularly ...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "mycology", "plant science", "fungi", "plant biology", "plant pathology", "botany", "biology" ]	Large-Scale Gene Disruption in Magnaporthe oryzae Identifies MC69, a Secreted Protein Required for Infection by Monocot and Dicot Fungal Pathogens	journal.ppat.1002711	null	[ [ "Rice blast , caused by an ascomycete fungus Magnaporthe oryzae , is the most severe fungal disease of rice throughout the world [1] .", "Genetic studies of this pathogen over the last two decades have made the Magnaporthe-rice pathosystem an excellent model for investigating fungus-plant interactions .",...	[ "To search for virulence effector genes of the rice blast fungus , Magnaporthe oryzae , we carried out a large-scale targeted disruption of genes for 78 putative secreted proteins that are expressed during the early stages of infection of M . oryzae .", "Disruption of the majority of genes did not affect growth ,...	[ "Magnaporthe oryzae causes the most devastating fungal disease in rice .", "M . oryzae secretes a plethora of effector proteins , including several avirulence proteins which are known to be recognized by host resistance proteins activating innate immunity .", "However , the effectors that are required for virul...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/microbial evolution and genomics", "cell biology/gene expression", "developmental biology/stem cells", "computational biology/transcriptional regulation", "genetics and genomics/gene expression", "microbiology/microbial evolution and genomics", "developmental biology/cell differen...	The Transcriptomes of Two Heritable Cell Types Illuminate the Circuit Governing Their Differentiation	journal.pgen.1001070	null	[ [ "How differentiated cell types are epigenetically maintained through repeated cell division is a topic of intensive study [1] , [2] , both for its role in basic developmental processes [3] and its relevance to the advancement of human stem cell therapeutics [4] .", "However , as a basic model of different...	[ "The differentiation of cells into distinct cell types , each of which is heritable for many generations , underlies many biological phenomena .", "White and opaque cells of the fungal pathogen Candida albicans are two such heritable cell types , each thought to be adapted to unique niches within their human host...	[ "The differentiation of cells into distinct cell-types , each of which is “remembered” for many generations , underlies the development of both healthy and cancerous tissues .", "Such differentiation , however , is not restricted to multi-cellular organisms: “white” and “opaque” cells of the unicellular fungal pa...	2010
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "morocco", "medicine and health sciences", "pathology and laboratory medicine", "geographical locations", "tropical diseases", "parasitic diseases", "parasitic protozoans", "age groups", "protozoans", "signs and symptoms", "leishmania", "neglected tropical diseases", "africa", "research an...	Epidemiological features of a recent zoonotic cutaneous leishmaniasis outbreak in Zagora province, southern Morocco	journal.pntd.0007321	null	[ [ "Leishmaniases , a spectrum of diseases that are caused by several species belonging to the genus Leishmania , are transmitted to humans and other mammals by phlebotomine sandflies .", "Although they cause relatively low mortality , they are responsible for considerable morbidity [1] .", "A dermal inf...	[ "Leishmania major is an endemic vector-borne disease in Morocco that causes zoonotic cutaneous leishmaniasis ( ZCL ) , especially in arid pre-Saharan regions where its unique vector and reservoir are Phlebotomus papatasi and Meriones shawi , respectively , and may cause epidemics .", "In late 2017 , the Zagora pr...	[ "Zoonotic cutaneous leishmaniasis ( ZCL ) caused by Leishmania major is endemic in Morocco , especially in the arid pre-Saharan regions .", "Its main characteristics are rurality and proneness to epidemics .", "Zagora province an endemic focus for ZCL has been recently the scene of an important CL outbreak .", ...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "urology", "cell motility", "medicine and health sciences", "gene regulation", "metabolic processes", "carcinomas", "cancers and neoplasms", "genitourinary tract tumors", "oxidative phosphorylation", "oncology", "prostate cancer", "adenocarcinomas", "mitochondria", "bioenergetics", "cell...	The Mitochondrial Unfoldase-Peptidase Complex ClpXP Controls Bioenergetics Stress and Metastasis	journal.pbio.1002507	Exploitation of mitochondrial protein folding quality control via the mitochondrial unfoldase-peptidase complex ClpXP is critical for tumor cell proliferation, invasion, and metastatic competence, and represents a potential therapeutic target.	[ [ "The control of protein homeostasis , or proteostasis , occupies a central , evolutionary-conserved role in organismal integrity and flexible adaptation to environmental “stress” [1] .", "This pathway involves mechanisms of chaperone-directed protein ( re ) folding [2] as well as removal of aggregated or ...	[ "Mitochondria must buffer the risk of proteotoxic stress to preserve bioenergetics , but the role of these mechanisms in disease is poorly understood .", "Using a proteomics screen , we now show that the mitochondrial unfoldase-peptidase complex ClpXP associates with the oncoprotein survivin and the respiratory c...	[ "As the powerhouse of the cell and a pivotal hub for oxidative stress , mitochondria must tightly control the state of the proteins that they contain , quickly eliminating misfolded , aggregated , or otherwise damaged proteins .", "Here , we show that tumor mitochondria manage their set of proteins by assembling ...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology/cellular microbiology and pathogenesis", "microbiology/immunity to infections", "immunology/immune response", "microbiology/innate immunity", "immunology/innate immunity", "microbiology/cellular microbiology and pathogenesis", "nephrology/dialysis and renal transplantation", "infectious di...	A Rapid Crosstalk of Human γδ T Cells and Monocytes Drives the Acute Inflammation in Bacterial Infections	journal.ppat.1000308	null	[ [ "The immune system has evolved to survey the body constantly for potentially hazardous structures .", "In order to initiate an appropriate defense , sentinel cells need to encounter ‘danger’ signals derived from invading microbes or stressed tissue [1] .", "Microbial signals comprise pathogen-associat...	[ "Vγ9/Vδ2 T cells are a minor subset of T cells in human blood and differ from other T cells by their immediate responsiveness to microbes .", "We previously demonstrated that the primary target for Vγ9/Vδ2 T cells is ( E ) -4-hydroxy-3-methyl-but-2-enyl pyrophosphate ( HMB-PP ) , an essential metabolite produced ...	[ "As antibiotic resistance is spreading and posing a significant threat in many bacterial diseases , there is a need for a better understanding of host responses to infection .", "The precise role of an enigmatic subset of human immune cells , so-called Vγ9/Vδ2 T cells , in early infection still remains to be unve...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	HIV Latency Is Established Directly and Early in Both Resting and Activated Primary CD4 T Cells	journal.ppat.1004955	null	[ [ "Once highly active antiretroviral therapy ( HAART ) became available in 1995 , HIV infection was transformed from a deadly disease into a chronic lifelong condition [1] .", "The antiretroviral drugs used in HAART target multiple stages of the viral lifecycle , which can reduce patient viremia to undetect...	[ "Highly active antiretroviral therapy ( HAART ) suppresses human immunodeficiency virus ( HIV ) replication to undetectable levels but cannot fully eradicate the virus because a small reservoir of CD4+ T cells remains latently infected .", "Since HIV efficiently infects only activated CD4+ T cells and since laten...	[ "The study of HIV latency has been hindered because there are few latently infected cells in vivo , and we cannot distinguish latently infected cells from uninfected cells prior to reactivation of the latent provirus .", "In general , HIV latency is quantitatively studied by reactivating latently infected cells a...	2015
[ "Introduction", "Results", "Discussion", "Methods and materials" ]	[ "medicine and health sciences", "reproductive system", "pathology and laboratory medicine", "immunology", "epithelial cells", "animal models", "model organisms", "signs and symptoms", "experimental organism systems", "research and analysis methods", "immune system proteins", "inflammation", ...	STING agonists enable antiviral cross-talk between human cells and confer protection against genital herpes in mice	journal.ppat.1006976	null	[ [ "Virus infections may cause acute and chronical diseases , and there is therefore a need for development of efficient treatments .", "Significant improvements have been made in the development of therapeutics that target specific viral molecules , such as the HIV reverse transcriptase and the hepatitis C ...	[ "In recent years , there has been an increasing interest in immunomodulatory therapy as a means to treat various conditions , including infectious diseases .", "For instance , Toll-like receptor ( TLR ) agonists have been evaluated for treatment of genital herpes .", "However , although the TLR7 agonist imiquim...	[ "Herpes simplex virus ( HSV ) -2 is the leading cause of genital ulcers , and HSV-2 infection has also been reported to amplify HIV-transmission .", "So far , all attempts at making an effective anti-HSV2 vaccine have failed .", "In recent years , there has been an increasing interest in immunomodulatory therap...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "acoustics", "sociology", "social sciences", "vertebrates", "animals", "mammals", "animal signaling and communication", "bonobos", "primates", "analysis of variance", "animal behavior", "mathematics", "statistics (mathematics)", "zoology", "discrete mathematics", "combinatorics", "re...	Bonobo and chimpanzee gestures overlap extensively in meaning	journal.pbio.2004825	null	[ [ "In a series of well-known children’s books , Doctor Dolittle was able to talk to nonhuman animals , but in reality , deciphering meaning in nonhuman communication presents a much bigger challenge .", "First , there is the question of whether animal signals can be said to have ‘meanings’ or merely ‘functi...	[ "Cross-species comparison of great ape gesturing has so far been limited to the physical form of gestures in the repertoire , without questioning whether gestures share the same meanings .", "Researchers have recently catalogued the meanings of chimpanzee gestures , but little is known about the gesture meanings ...	[ "Bonobos and chimpanzees are closely related members of the great ape family , and both species use gestures to communicate .", "We are able to deduce the meaning of great ape gestures by looking at the ‘Apparently Satisfactory Outcome’ ( ASO ) , which reflects how the recipient of the gesture reacts and whether ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/gene expression", "genetics and genomics/bioinformatics", "evolutionary biology/genomics" ]	Conflict between Noise and Plasticity in Yeast	journal.pgen.1001185	null	[ [ "For cellular adaptation gene expression must respond to changes in conditions .", "However , expression also varies stochastically among cells in a population .", "In the budding yeast Saccharomyces cerevisiae both variation across different conditions ( ‘expression plasticity’ , [1] ) and variation ...	[ "Gene expression responds to changes in conditions but also stochastically among individuals .", "In budding yeast , both expression responsiveness across conditions ( “plasticity” ) and cell-to-cell variation ( “noise” ) have been quantified for thousands of genes and found to correlate across genes .", "It ha...	[ "Gene expression needs to respond to changes in conditions , but also varies stochastically among cells in a homogenous environment .", "It has been argued that these two levels of expression variation may be coupled , relating to the same underlying molecular mechanisms .", "However , such a strong coupling be...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "model organisms", "genetics", "biology", "molecular cell biology", "genetics and genomics" ]	The Caenorhabditis elegans JNK Signaling Pathway Activates Expression of Stress Response Genes by Derepressing the Fos/HDAC Repressor Complex	journal.pgen.1003315	null	[ [ "Mitogen-activated protein kinase ( MAPK ) signal transduction pathways are evolutionarily conserved in eukaryotic cells and transduce signals in response to a variety of extracellular stimuli .", "Each pathway is composed of three classes of protein kinases: MAPK , MAPK kinase ( MAPKK ) and MAPK kinase k...	[ "MAP kinases are integral to the mechanisms by which cells respond to a wide variety of environmental stresses .", "In Caenorhabditis elegans , the KGB-1 JNK signaling pathway regulates the response to heavy metal stress .", "In this study , we identified FOS-1 , a bZIP transcription factor , as a target of KGB...	[ "We have investigated the mechanisms by which the soil nematode Caenorhabditis elegans regulates its response to environmental stresses .", "Previously , we showed that a conserved KGB-1 JNK mitogen-activated protein kinase ( MAPK ) pathway regulates the response to heavy metal stress in C . elegans , illustratin...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/animal genetics", "biochemistry", "cell biology/cell signaling", "neurological disorders/movement disorders", "genetics and genomics/disease models", "genetics and genomics/genetics of disease", "genetics and genomics/gene function", "neuroscience", "molecular biology", "cel...	Progressive Purkinje Cell Degeneration in tambaleante Mutant Mice Is a Consequence of a Missense Mutation in HERC1 E3 Ubiquitin Ligase	journal.pgen.1000784	null	[ [ "The cerebellum plays the role of a coordination centre , integrating peripheral sensory information on movement and position of the body parts to fine-tune gait and balance .", "Structural or functional alterations of this part of the central nervous system result in a complex syndrome , called ataxia , ...	[ "The HERC gene family encodes proteins with two characteristic domains: HECT and RCC1-like .", "Proteins with HECT domains have been described to function as ubiquitin ligases , and those that contain RCC1-like domains have been reported to function as GTPases regulators .", "These two activities are essential ...	[ "The cerebellum is a coordination center whose function is to fine-tune vertebrates' gait and balance; and for this reason , alterations or damage affecting this structure result in a complex syndrome , called ataxia , with neurological signs that are easily recognized .", "In the mouse , many mutations producing...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Type I and Type III Interferons Drive Redundant Amplification Loops to Induce a Transcriptional Signature in Influenza-Infected Airway Epithelia	journal.ppat.1003773	null	[ [ "The type I interferon family is a group of cytokines encoded by a single IFNβ gene and a tandem cluster of multiple IFNα genes that were first characterized for their ability to interfere with influenza virus replication [1] and are now recognized as powerful inducers of the host response to viral infections...	[ "Interferons ( IFNs ) are a group of cytokines with a well-established antiviral function .", "They can be induced by viral infection , are secreted and bind to specific receptors on the same or neighbouring cells to activate the expression of hundreds of IFN stimulated genes ( ISGs ) with antiviral function .", ...	[ "The response of cells to virus infection depends on Interferons ( IFNs ) , a group of cytokines which activate the expression of hundreds of genes that help control viral replication inside infected cells .", "While type I IFN was discovered in 1957 , type III IFN ( IFNλ , IL-28/29 ) was characterized recently a...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "evolutionary biology", "none", "molecular biology", "computational biology" ]	Using Phylogeny to Improve Genome-Wide Distant Homology Recognition	journal.pcbi.0030003	null	[ [ "The prediction of protein structures from sequences is becoming increasingly important , particularly as the gap between the number of experimentally determined sequences ( >6 , 000 , 000 ) and structures ( <35 , 000 ) widens .", "Knowledge of protein structure is essential to the understanding of bioche...	[ "The gap between the number of known protein sequences and structures continues to widen , particularly as a result of sequencing projects for entire genomes .", "Recently there have been many attempts to generate structural assignments to all genes on sets of completed genomes using fold-recognition methods .", ...	[ "When predicting the structure for a protein sequence , a major step is achieved when an evolutionarily related protein with a known structure is identified .", "This process is called fold recognition , and has been a major force behind improvement in structure prediction .", "Moreover , fold-recognition techn...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics", "biology", "cancer genetics" ]	Cited1 Deficiency Suppresses Intestinal Tumorigenesis	journal.pgen.1003638	null	[ [ "Inactivation of the APC ( adenomatous polyposis coli ) gene marks one of the earliest events in colorectal tumourigenesis [1] , an observation that has given rise to the concept of Apc as a ‘cellular gatekeeper’ protecting against tumourigenesis [2] .", "This role in suppressing tumour formation has been...	[ "Conditional deletion of Apc in the murine intestine alters crypt-villus architecture and function .", "This process is accompanied by multiple changes in gene expression , including upregulation of Cited1 , whose role in colorectal carcinogenesis is unknown .", "Here we explore the relevance of Cited1 to intes...	[ "Colorectal cancer is the fourth leading cause of cancer related deaths worldwide , and a key genetic change associated with this disease is mutation of the gene APC .", "APC encodes a protein which plays a regulatory role in the Wnt signalling pathway .", "To better understand the mechanisms leading to colorec...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/genomics", "genetics and genomics/gene expression", "molecular biology/dna repair", "neurological disorders", "genetics and genomics/genetics of disease", "biochemistry/replication and repair", "genetics and genomics/bioinformatics", "cardiovascular disorders/heart failure" ]	Altered Gene Expression and DNA Damage in Peripheral Blood Cells from Friedreich's Ataxia Patients: Cellular Model of Pathology	journal.pgen.1000812	null	[ [ "Friedreich's ataxia ( FRDA; OMIM# 229300 ) is the most common autosomal-recessively inherited ataxia beginning in childhood and leading to death in early adulthood .", "Patients exhibit neurodegeneration of the large sensory neurons and spinocerebellar tracts , along with variable systemic manifestations...	[ "The neurodegenerative disease Friedreich's ataxia ( FRDA ) is the most common autosomal-recessively inherited ataxia and is caused by a GAA triplet repeat expansion in the first intron of the frataxin gene .", "In this disease , transcription of frataxin , a mitochondrial protein involved in iron homeostasis , i...	[ "Friedreich's ataxia is an inherited disease that causes progressive damage to the nervous system and affects the muscles and heart .", "The disease is caused by a defect in the frataxin gene , which is involved in iron homeostasis and likely protects against reactive oxygen species .", "In order to identify me...	2010
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases/protozoal infections", "ecology/population ecology", "ecology/evolutionary ecology", "ecology/behavioral ecology" ]	Cooperative Blood-feeding and the Function and Implications of Feeding Aggregations in the Sand Fly, Lutzomyia longipalpis (Diptera: Psychodidae)	journal.pntd.0000503	null	[ [ "Phlebotomine sand flies ( Diptera: Psychodidae ) are important vectors of leishmaniasis , a parasitic disease affecting an estimated 1–1 . 5 millions people and causing over 50'000 deaths worldwide each year [1] .", "Medical entomologists have long noticed that some sand fly species tend to arrive in wav...	[ "Given the importance that the evolution of cooperation bears in evolutionary biology and the social sciences , extensive theoretical work has focused on identifying conditions that promote cooperation among individuals .", "In insects , cooperative or altruistic interactions typically occur amongst social insect...	[ "Understanding the processes that promote cooperation amongst animals in nature is a fundamental question in evolutionary biology with ramifications in the social sciences .", "In insects , cooperative or altruistic interactions are usually observed amongst genetically related social insects ( kin selection ) .",...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "biomacromolecule-ligand interactions", "algorithms", "computer science", "protein structure", "biology", "computational biology", "biophysics", "macromolecular structure analysis" ]	Combinatorial Clustering of Residue Position Subsets Predicts Inhibitor Affinity across the Human Kinome	journal.pcbi.1003087	null	[ [ "The protein kinases constitute the largest enzyme family encoded by the human genome , with currently 518 known sequences , making up 1 . 7% of all human genes [1] , [2] .", "Because these protein kinases are intimately involved in cellular communication and regulation networks , the loss of normal kinas...	[ "The protein kinases are a large family of enzymes that play fundamental roles in propagating signals within the cell .", "Because of the high degree of binding site similarity shared among protein kinases , designing drug compounds with high specificity among the kinases has proven difficult .", "However , com...	[ "The kinases are a group of essential signaling proteins within the cell and are the largest family of enzymes encoded by the human genome .", "The high degree of binding site similarity shared across the protein kinases has made them difficult targets for which to design highly selective inhibitors , but kinome-...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Pregnancy Outcomes after a Mass Vaccination Campaign with an Oral Cholera Vaccine in Guinea: A Retrospective Cohort Study	journal.pntd.0004274	null	[ [ "Cholera represents a risk of complications for pregnant women and their fetus .", "Published literature reports fetal loss rates during cholera episodes of between 2% and 36% [1–7] .", "However , comparison of pregnancy outcomes among different reports is difficult , due to differences in inclusion c...	[ "Since 2010 , WHO has recommended oral cholera vaccines as an additional strategy for cholera control .", "During a cholera episode , pregnant women are at high risk of complications , and the risk of fetal death has been reported to be 2–36% .", "Due to a lack of safety data , pregnant women have been excluded...	[ "Pregnant women are at high risk of complications and fetal deaths when ill with cholera .", "However , they have been excluded in most cholera vaccination campaigns because of the lack of safety data on oral cholera vaccines during pregnancy .", "This study aimed to determine if the risk of pregnancy loss chan...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "immunodeficiency viruses", "medicine", "infectious diseases", "adaptive immunity", "immune cells", "immunity", "virology", "t cells", "immunity to infections", "immunology", "host-pathogen interaction", "biology", "microbiology", "infectious disease control", "immune response" ]	Rapid Perturbation in Viremia Levels Drives Increases in Functional Avidity of HIV-specific CD8 T Cells	journal.ppat.1003423	null	[ [ "CD8 T cells play a critical role in antiviral immunity and a large number of studies in both human and murine models indicate that virus-specific CD8 T cells are directly involved in the control of virus replication and disease progression [1] , [2] , [3] , [4] , [5] , [6] , [7] .", "Functional avidity o...	[ "The factors determining the functional avidity and its relationship with the broad heterogeneity of antiviral T cell responses remain partially understood .", "We investigated HIV-specific CD8 T cell responses in 85 patients with primary HIV infection ( PHI ) or chronic ( progressive and non-progressive ) infect...	[ "CD8 T cells directed against virus are complex and functionally heterogeneous .", "One relevant component of CD8 T cells is their functional avidity which reflects their sensitivity to cognate antigens , i . e . how prone T cells are to respond when they encounter low doses of antigens .", "In patients with ch...	2013
[ "Introduction", "Methods", "Results", "Discussion", "Conclusions" ]	[ "invertebrates", "medicine and health sciences", "behavioral and social aspects of health", "african trypanosomiasis", "tropical diseases", "geographical locations", "social sciences", "south sudan", "parasitic diseases", "animals", "health care", "glossina", "research design", "neglected ...	Knowledge, attitudes and practices about human African trypanosomiasis and their implications in designing intervention strategies for Yei county, South Sudan	journal.pntd.0006826	null	[ [ "Human African trypanosomiasis ( HAT ) , also known as sleeping sickness , is a parasitic neglected tropical disease of public health significance that mostly afflicts poor populations in endemic areas of rural Africa [1] .", "It is caused by two species of Trypanosoma: T . brucei rhodesiense , mostly fou...	[ "A clear understanding of the knowledge , attitudes and practices ( KAP ) of a particular community is necessary in order to improve control of human African trypanosomiasis ( HAT ) .", "New screening and diagnostic tools and strategies were introduced into South Sudan , as part of integrated delivery of primary ...	[ "Misconceptions about sleeping sickness , a neglected tropical disease transmitted by tsetse flies , can be a hindrance to effective implementation of control interventions especially in the face of accelerating work to eliminate the disease .", "Understanding community knowledge , attitudes and practices about s...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "action potentials", "neurochemistry", "medicine and health sciences", "chemical compounds", "engineering and technology", "electronics", "depolarization", "membrane potential", "electrophysiology", "neuroscience", "organic compounds", "hormones", "receptor potentials", "amines", "neurot...	Dopamine Neurons Change the Type of Excitability in Response to Stimuli	journal.pcbi.1005233	null	[ [ "Midbrain dopamine ( DA ) neurons predominantly fire in a low frequency , metronomic manner ( i . e . tonic ) and display occasional , yet functionally important , high frequency , burst-like episodes [1 , 2] .", "While regular tonic firing is observed in isolated preparations ( i . e . slices ) , tonic f...	[ "The dynamics of neuronal excitability determine the neuron’s response to stimuli , its synchronization and resonance properties and , ultimately , the computations it performs in the brain .", "We investigated the dynamical mechanisms underlying the excitability type of dopamine ( DA ) neurons , using a conducta...	[ "Dopamine neurons play a central role in guiding motivated behaviors .", "However , complete understanding of computations these neurons perform to encode rewarding and salient stimuli is still forthcoming .", "Network connectivity influences neural responses to stimuli , but so do intrinsic excitability proper...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "demography", "immunology", "tropical diseases", "geographical locations", "vertebrates", "australia", "dogs", "animals", "mammals", "preventive medicine", "rabies", "animal behavior", "neglected tropical diseases", "infectious disease control", "vaccina...	A Survey of Dog Owners in Remote Northern Australian Indigenous Communities to Inform Rabies Incursion Planning	journal.pntd.0004649	null	[ [ "Rabies is an acute viral zoonosis that causes approximately 60 , 000 human deaths annually , despite being preventable [1] .", "The disease occurs worldwide , with half of the annual deaths occurring in Asia [1 , 2] .", "Although Australia is one of the few countries free of canine rabies [3] , the i...	[ "Australia is underprepared for a rabies incursion due to a lack of information about how a rabies outbreak would spread within the susceptible canine populations and which control strategies would be best to control it .", "The aim of this study was to collect information to parameterize a recently developed dog...	[ "Australia is underprepared for a rabies incursion due to limited information about how a rabies outbreak would behave and which control strategies would be best to control it .", "A disease spread model of rabies has been developed to help policy-makers decide on the best response to a rabies incursion .", "Ho...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "immunology/immunity to infections" ]	BAFF Mediates Splenic B Cell Response and Antibody Production in Experimental Chagas Disease	journal.pntd.0000679	null	[ [ "Chagas disease is a chronic disease caused by infection with Trypanosoma cruzi .", "Initially , the disease goes through an acute episode which is characterized by circulating parasites and immunological disturbances that , at the level of B cell compartment , are mature and immature B cell apoptosis [1]...	[ "B cells and antibodies are involved not only in controlling the spread of blood circulating Trypanosoma cruzi , but also in the autoreactive manifestations observed in Chagas disease .", "Acute infection results in polyclonal B cell activation associated with hypergammaglobulinemia , delayed specific humoral imm...	[ "Chagas disease , caused by the protozoan Trypanosoma cruzi , is endemic in Central and South America .", "It affects 20 million people and about 100 million people are at risk of infection in endemic areas .", "Some cases have been identified in non-endemic countries as a consequence of blood transfusion and o...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "kinesins", "rna interference", "pathology and laboratory medicine", "microtubules", "gene regulation", "pathogens", "microbiology", "viral structure", "viruses", "dyneins", "molecular motors", "dna viruses", "epigenetics", "cellular structures and organel...	Role of kinesins in directed adenovirus transport and cytoplasmic exploration	journal.ppat.1007055	null	[ [ "Viruses generally depend on active transport inside host cells as the crowded cytoplasm restricts their ability to diffuse [1 , 2] .", "Viruses have evolved mechanisms to hijack microtubule motor proteins for this purpose during cell entry and egress [3] .", "Adenovirus [4 , 5] , herpesvirus [6] , va...	[ "Many viruses , including adenovirus , exhibit bidirectional transport along microtubules following cell entry .", "Cytoplasmic dynein is responsible for microtubule minus end transport of adenovirus capsids after endosomal escape .", "However , the identity and roles of the opposing plus end-directed motor ( s...	[ "The role of plus-end directed microtubule motors in virus entry into host cells is a long-standing question .", "In this study , the authors identify the kinesins responsible for adenovirus plus end-directed transport along microtubules , the mechanism for kinesin recruitment , and both directed and motor-based ...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "sequencing techniques", "invertebrates", "organismal evolution", "medicine and health sciences", "microbiology", "animals", "glossina", "genome sequencing", "microbial evolution", "molecular biology techniques", "tsetse fly", "epidemiology", "molecular biology", "disease vectors", "inse...	Presence of Extensive Wolbachia Symbiont Insertions Discovered in the Genome of Its Host Glossina morsitans morsitans	journal.pntd.0002728	null	[ [ "The genus Wolbachia encompasses intracellular maternally inherited Gram-negative bacteria estimated to infect over 40% of insect species , in addition to filarial nematodes , crustaceans , and arachnids [1] , [2] .", "Wolbachia interactions with its host can have diverse outcomes that range from mutualis...	[ "Tsetse flies ( Glossina spp . ) are the cyclical vectors of Trypanosoma spp .", ", which are unicellular parasites responsible for multiple diseases , including nagana in livestock and sleeping sickness in humans in Africa .", "Glossina species , including Glossina morsitans morsitans ( Gmm ) , for which the W...	[ "African trypanosomes are transmitted to man and animals by tsetse fly , a blood sucking insect .", "Tsetse flies include all Glossina species with the genome of Glossina morsitans morsitans ( Gmm ) being sequenced under the International Glossina Genome Initiative .", "The endosymbionts Wigglesworthia glossini...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "oncology", "medicine", "computer science", "computer modeling", "mathematics", "applied mathematics" ]	Patterns of Proliferative Activity in the Colonic Crypt Determine Crypt Stability and Rates of Somatic Evolution	journal.pcbi.1003082	null	[ [ "Colorectal cancer is the third most prevalent cancer type for both men and women in the United States , accounting for 9% of all cancer deaths [1] .", "This large incidence can be partially attributed to the rapid cell divisions that continuously replenish the colonic epithelium , as this large amount of...	[ "Epithelial cells in the colon are arranged in cylindrical structures called crypts in which cellular proliferation and migration are tightly regulated .", "We hypothesized that the proliferation patterns of cells may determine the stability of crypts as well as the rates of somatic evolution towards colorectal t...	[ "Mathematical and computational models have a long and rich history in enhancing our understanding of intestinal epithelial cells .", "A plethora of models have been proposed to describe different aspects of cellular behavior , including cell proliferation , migration , differentiation , and mutation accumulation...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics", "biochemistry", "biology and life sciences", "molecular biology" ]	Tpz1-Ccq1 and Tpz1-Poz1 Interactions within Fission Yeast Shelterin Modulate Ccq1 Thr93 Phosphorylation and Telomerase Recruitment	journal.pgen.1004708	null	[ [ "Telomeres are protective nucleoprotein structures found at the natural ends of eukaryotic linear chromosomes [1] .", "In most eukaryotes , telomeric DNA consists of GT-rich repeat sequences , primarily double-stranded but terminating in a single-stranded 3′ overhang , known as G-tail [1] .", "Telomer...	[ "In both fission yeast and humans , the shelterin complex plays central roles in regulation of telomerase recruitment , protection of telomeres against DNA damage response factors , and formation of heterochromatin at telomeres .", "While shelterin is essential for limiting activation of the DNA damage checkpoint...	[ "Proper maintenance of telomeres is essential for maintaining genomic stability , and genomic instability caused by dysfunctional telomeres could lead to accumulation of mutations that may drive tumor formation .", "Telomere dysfunction has also been linked to premature aging caused by depletion of stem cells .",...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "immunology", "biology", "molecular cell biology" ]	High Affinity Nanobodies against the Trypanosome brucei VSG Are Potent Trypanolytic Agents that Block Endocytosis	journal.ppat.1002072	null	[ [ "Trypanosomatid protozoan parasites cause many important diseases , including African sleeping sickness in humans and Nagana in domestic livestock in sub-Saharan Africa [1] , [2] .", "These organisms , like many other successful pathogens , have evolved sophisticated mechanisms for immune evasion [3] .", ...	[ "The African trypanosome Trypanosoma brucei , which persists within the bloodstream of the mammalian host , has evolved potent mechanisms for immune evasion .", "Specifically , antigenic variation of the variant-specific surface glycoprotein ( VSG ) and a highly active endocytosis and recycling of the surface coa...	[ "Haemoparasites , such as African trypanosomes , have developed potent immune evasion mechanisms to avoid antibody-mediated elimination .", "Consequently , trypanosome surface antigen-specific immunoglobulins in the absence of complement are non-trypanocidal .", "In contrast , certain monovalent nanobodies ( Nb...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "computational biology/macromolecular structure analysis", "virology/vaccines", "virology/virion structure, assembly, and egress", "virology/immunodeficiency viruses", "infectious diseases/hiv infection and aids", "infectious diseases/viral infections", "biochemistry/macromolecular assemblies and machin...	Molecular Architectures of Trimeric SIV and HIV-1 Envelope Glycoproteins on Intact Viruses: Strain-Dependent Variation in Quaternary Structure	journal.ppat.1001249	null	[ [ "About 2 . 5 million individuals are newly infected with human immunodeficiency virus ( HIV ) each year , and over 2 million deaths result annually from HIV/AIDS ( http://www . unaids . org ) .", "HIV-1 and the closely related simian immunodeficiency virus ( SIV ) bind to target cells by the interaction o...	[ "The initial step in target cell infection by human , and the closely related simian immunodeficiency viruses ( HIV and SIV , respectively ) occurs with the binding of trimeric envelope glycoproteins ( Env ) , composed of heterodimers of the viral transmembrane glycoprotein ( gp41 ) and surface glycoprotein ( gp120...	[ "HIV and SIV contact and infect target T-cells following the binding of trimeric Env spikes displayed on the viral membrane with cellular receptors .", "The conformational changes in trimeric Env that are triggered by the interaction between trimeric Env and cell surface receptors lead ultimately to fusion of the...	2010
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "invertebrates", "dengue virus", "medicine and health sciences", "body fluids", "pathology and laboratory medicine", "pathogens", "geographical locations", "microbiology", "tropical diseases", "saliva", "animals", "viruses", "rna viruses", "neglected tropical diseases", "insect vectors",...	Potential for sylvatic and urban Aedes mosquitoes from Senegal to transmit the new emerging dengue serotypes 1, 3 and 4 in West Africa	journal.pntd.0007043	null	[ [ "Dengue fever ( DEN ) is the most common arboviral disease in the world and is caused by four genetically distinct serotypes of virus ( DENV-1 , DENV-2 , DENV-3 , DENV-4 ) belonging to the genus Flavivirus of the family Flaviviridae .", "Among the 390 million annual infections estimated around the world ,...	[ "Dengue fever ( DEN ) is the most common arboviral disease in the world and dengue virus ( DENV ) causes 390 million annual infections around the world , of which 240 million are inapparent and 96 million are symptomatic .", "During the past decade a changing epidemiological pattern has been observed in Africa , ...	[ "Dengue fever remains a major public health problem in all tropical regions of the world and causes 390 million infections each year .", "In Africa , while dengue outbreaks were rare during the last century , recurrent urban epidemic have been reported in all regions the last decade .", "Serotype 3 , never repo...	2019
[ "Introduction", "Results", "Conclusions and Prospects", "Materials and Methods" ]	[ "genome evolution", "population genetics", "genome sequencing", "genome databases", "model organisms", "genetic polymorphism", "comparative genomics", "biology", "evolutionary genetics", "haplotypes", "natural selection", "genetics", "gene flow", "genomics", "evolutionary biology", "ge...	Population Genomics of Sub-Saharan Drosophila melanogaster: African Diversity and Non-African Admixture	journal.pgen.1003080	null	[ [ "Drosophila melanogaster has a well known history and ongoing role as a model organism in classical and molecular genetics .", "Its well-annotated genome [1] , [2] and genetic toolkit have also made it an important model organism in the field of population genetics , in many cases motivating the developme...	[ "Drosophila melanogaster has played a pivotal role in the development of modern population genetics .", "However , many basic questions regarding the demographic and adaptive history of this species remain unresolved .", "We report the genome sequencing of 139 wild-derived strains of D . melanogaster , represen...	[ "Improvements in DNA sequencing technology have allowed genetic variation to be studied at the level of fully sequenced genomes .", "We have sequenced more than 100 D . melanogaster genomes originating from sub-Saharan Africa , which is thought to contain the ancestral range of this model organism .", "We found...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "medicine and health sciences", "neurodegenerative diseases", "cell processes", "neuroscience", "animals", "animal models", "drosophila melanogaster", "model organisms", "experimental organism systems", "mitochondria", "bioenergetics", "cellular structures and organelles", ...	Lrrk promotes tau neurotoxicity through dysregulation of actin and mitochondrial dynamics	journal.pbio.2006265	null	[ [ "Parkinson disease is the second most common neurodegenerative disorder , following Alzheimer disease .", "Parkinson disease has a prevalence of approximately 1% at age 65 , which rises to nearly 5% by age 85 [1 , 2] .", "Particularly given the increasing age of the United States population , Parkinso...	[ "Mutations in leucine-rich repeat kinase 2 ( LRRK2 ) are the most common cause of familial Parkinson disease .", "Genetics and neuropathology link Parkinson disease with the microtubule-binding protein tau , but the mechanism of action of LRRK2 mutations and the molecular connection between tau and Parkinson dise...	[ "Parkinson disease is a common and debilitating neurodegenerative disorder .", "Family and larger population-based studies have revealed a number of genes important in the development and progression of the disease , but specific mechanisms linking these seemingly unrelated genes and proteins with specific cellul...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell binding", "cell physiology", "medicine and health sciences", "pathology and laboratory medicine", "viral transmission and infection", "pathogens", "drugs", "microbiology", "viral structure", "retroviruses", "viruses", "rna viruses", "pharmacology", "glycosylation", "heparin", "re...	Sensing of cell-associated HTLV by plasmacytoid dendritic cells is regulated by dense β-galactoside glycosylation	journal.ppat.1007589	null	[ [ "Human T-Lymphotropic Virus type 1 ( HTLV-1 ) infects over an estimation of 5–10 million people .", "HTLV-1 is mainly present in Japan , central Africa , Caribbean and South America [1 , 2] .", "After a long period of clinical latency , HTLV-1 infection leads , in a fraction of infected individuals , ...	[ "Human T Lymphotropic virus ( HTLV ) infection can persist in individuals resulting , at least in part , from viral escape of the innate immunity , including inhibition of type I interferon response in infected T-cells .", "Plasmacytoid dendritic cells ( pDCs ) are known to bypass viral escape by their robust typ...	[ "Human T Lymphotropic virus type ( HTLV ) establishes persistent infections , leading to adult T-cell Leukemia , a life-threatening cancer in chronically-infected individuals .", "Viral persistence likely results from a failure of immune responses to eradicate viral replication , a least in part , by viral escape...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "infectious diseases", "gastroenterology and hepatology", "immunology", "microbiology", "mus (mouse)" ]	Salmonella enterica Serovar Typhimurium Exploits Inflammation to Compete with the Intestinal Microbiota	journal.pbio.0050244	Inducing inflammation is key to the ability of the virulent pathogen Salmonella enterica serovar Typhimurium to outcompete the protective resident microbiota in a race to colonize the gut.	[ [ "The evolution of pathogenic microorganisms has been shaped to a great extent by their interaction with cognate host species .", "Colonization is the first step of any infection .", "For enteropathogenic bacteria , this poses a formidable task as the target host organ is already colonized by a dense m...	[ "Most mucosal surfaces of the mammalian body are colonized by microbial communities ( “microbiota” ) .", "A high density of commensal microbiota inhabits the intestine and shields from infection ( “colonization resistance” ) .", "The virulence strategies allowing enteropathogenic bacteria to successfully compet...	[ "A dense microbial community colonizes the intestinal tract of mammals , contributing to health and nutrition and conferring efficient protection against most pathogenic intruders .", "Intestinal pathogens can overcome this colonization resistance and cause disease; however , the mechanisms used to do this are st...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "microbiology", "dna replication", "dna recombination", "dna", "chromosome biology", "dna amplification", "biology", "molecular biology", "biochemistry", "cell biology", "nucleic acids", "genetics", "genomics", "molecular cell biology", "genetics and genomics" ]	Rtt109 Prevents Hyper-Amplification of Ribosomal RNA Genes through Histone Modification in Budding Yeast	journal.pgen.1003410	null	[ [ "The ribosome is an abundant macromolecular protein-RNA complex that translates mRNA into protein .", "In Saccharomyces cerevisiae , ribosomal proteins ( RP ) account for approximately 50% of total protein and ribosomal RNA ( RNA ) represents approximately 80% of total RNA [1] .", "While the amount of...	[ "The genes encoding ribosomal RNA are the most abundant in the eukaryotic genome .", "They reside in tandem repetitive clusters , in some cases totaling hundreds of copies .", "Due to their repetitive structure , ribosomal RNA genes ( rDNA ) are easily lost by recombination events within the repeated cluster ."...	[ "Gene amplification is one of the major strategies used by cells to increase the abundance of gene products .", "We have been studying amplification of the ribosomal RNA genes cluster , also known as rDNA ( ribosomal DNA ) , in yeast and found that unequal sister-chromatid recombination increased copy number foll...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology", "genetics and genomics", "molecular biology", "saccharomyces" ]	Genome-Wide Analysis of Rad52 Foci Reveals Diverse Mechanisms Impacting Recombination	journal.pgen.0030228	null	[ [ "Homologous recombination ( HR ) , a repair mechanism that depends on DNA sequence homology , underlies a number of important DNA processes that act to both stabilize and diversify a genome .", "In mitotic cells , HR functions to maintain the integrity of the genome through such processes as the repair of...	[ "To investigate the DNA damage response , we undertook a genome-wide study in Saccharomyces cerevisiae and identified 86 gene deletions that lead to increased levels of spontaneous Rad52 foci in proliferating diploid cells .", "More than half of the genes are conserved across species ranging from yeast to humans ...	[ "Homologous recombination ( HR ) is a cellular process that permits efficient repair of both endogenous and exogenous DNA damage .", "Although the principal players in HR have been well characterized , the interplay of diverse processes with the HR pathway remains mysterious .", "Traditionally , genetic screens...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/post-translational regulation of gene expression", "molecular biology/histone modification", "molecular biology/transcription initiation and activation", "genetics and genomics/gene expression", "physiology/cardiovascular physiology and circulation", "molecular biology/bioinformatics", ...	The Cardiac Transcription Network Modulated by Gata4, Mef2a, Nkx2.5, Srf, Histone Modifications, and MicroRNAs	journal.pgen.1001313	null	[ [ "It is long known that an evolutionary conserved orchestra of transcription factors controls cardiac development and function .", "More recently the contribution of epigenetic and post-transcriptional mechanisms has been identified .", "Many successful studies have focused on these different aspects i...	[ "The transcriptome , as the pool of all transcribed elements in a given cell , is regulated by the interaction between different molecular levels , involving epigenetic , transcriptional , and post-transcriptional mechanisms .", "However , many previous studies investigated each of these levels individually , and...	[ "An evolutionary conserved orchestra of transcription factors controls cardiac development and function .", "More recently the contributions of epigenetic and post-transcriptional mechanisms like histone modifications and microRNAs have been identified .", "The interplay between these regulatory mechanisms is s...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "biophysics/experimental biophysical methods", "biophysics/theory and simulation" ]	Evidence of Functional Protein Dynamics from X-Ray Crystallographic Ensembles	journal.pcbi.1000911	null	[ [ "It has been suggested that at temperatures below the protein dynamical transition temperature , TD , there is a dominant native basin in which a protein's dynamics is largely controlled by harmonic motions [1] .", "Above this temperature , a sudden activation of new anharmonic protein motions that are th...	[ "It is widely recognized that representing a protein as a single static conformation is inadequate to describe the dynamics essential to the performance of its biological function .", "We contrast the amino acid displacements below and above the protein dynamical transition temperature , TD∼215K , of hen egg whit...	[ "There is a well-recognized gap between the dynamical motions of proteins required to execute function and the experimental techniques capable of capturing that motion at the atomic level .", "We show that much experimental detail of dynamical motion is already present in X-ray crystallographic data , which arise...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "cereals", "crops", "wheats", "plant growth and development", "genetics", "biology", "plant genetics", "crop genetics", "wheat", "plant biology", "genetics and genomics", "agriculture" ]	Wheat TILLING Mutants Show That the Vernalization Gene VRN1 Down-Regulates the Flowering Repressor VRN2 in Leaves but Is Not Essential for Flowering	journal.pgen.1003134	null	[ [ "The temperate grasses , which include economically important species such as wheat , barley , rye , and oats , are well-adapted to cold winters .", "Most of these species require a prolonged period of cold treatment for timely flowering , a process referred to as vernalization .", "This requirement d...	[ "Most of the natural variation in wheat vernalization response is determined by allelic differences in the MADS-box transcription factor VERNALIZATION1 ( VRN1 ) .", "Extended exposures to low temperatures during the winter ( vernalization ) induce VRN1 expression and promote the transition of the apical meristem ...	[ "Crop yields are strongly associated with flowering time , therefore a precise understanding of the mechanisms involved in the regulation of flowering is required to engineer varieties adapted to new or changing environments .", "In wheat , most of the natural variation in flowering time is determined by VERNALIZ...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biomacromolecule-ligand interactions", "biochemistry", "signal transduction", "cell biology", "medical microbiology", "microbial pathogens", "biology and life sciences", "microbiology" ]	Multivalent Adhesion Molecule 7 Clusters Act as Signaling Platform for Host Cellular GTPase Activation and Facilitate Epithelial Barrier Dysfunction	journal.ppat.1004421	null	[ [ "Vibrio parahaemolyticus is an emerging food- and waterborne bacterial pathogen .", "It is predominantly associated with gastroenteritis but occasionally manifests as wound infection [1]–[3] .", "Although infections are self-limiting in immunocompetent patients , in rare cases , usually occurring in p...	[ "Vibrio parahaemolyticus is an emerging bacterial pathogen which colonizes the gastrointestinal tract and can cause severe enteritis and bacteraemia .", "During infection , V . parahaemolyticus primarily attaches to the small intestine , where it causes extensive tissue damage and compromises epithelial barrier i...	[ "Vibrio parahaemolyticus is a bacterial pathogen which occurs in marine and estuarine environments .", "It is a main cause of gastrointestinal illness following the consumption of raw or undercooked seafood .", "In immunocompromised people , the bacteria can sometimes enter the bloodstream and cause septicemia ...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "skin", "invertebrates", "medicine and health sciences", "integumentary system", "electrophoretic mobility shift assay", "gene regulation", "animals", "animal models", "developmental biology", "drosophila melanogaster", "model organisms", "experimental organism systems", "epidermis", "mole...	The Zic family homologue Odd-paired regulates Alk expression in Drosophila	journal.pgen.1006617	null	[ [ "During embryogenesis , the Anaplastic Lymphoma Kinase ( Alk ) receptor tyrosine kinase ( RTK ) is dynamically expressed predominantly in the primordia of the visceral mesoderm ( VM ) , the developing CNS , the amnioserosa ( AS ) and in a restricted manner in the epidermis [1] .", "Alk plays a critical ro...	[ "The Anaplastic Lymphoma Kinase ( Alk ) receptor tyrosine kinase ( RTK ) plays a critical role in the specification of founder cells ( FCs ) in the Drosophila visceral mesoderm ( VM ) during embryogenesis .", "Reporter gene and CRISPR/Cas9 deletion analysis reveals enhancer regions in and upstream of the Alk locu...	[ "The Alk receptor tyrosine kinase is employed repeatedly during Drosophila development to drive signaling events in a variety of tissues .", "The spatial and temporal expression pattern of the Alk gene is tightly regulated .", "Identifying factors that influence the expression of Alk is important to better unde...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "pathology", "biochemistry/protein folding", "infectious diseases", "pathology/histopathology" ]	Mouse Senile Amyloid Fibrils Deposited in Skeletal Muscle Exhibit Amyloidosis-Enhancing Activity	journal.ppat.1000914	null	[ [ "Amyloidosis refers to a group of protein folding disorders .", "Various proteins that are harmless and soluble under normal physiological conditions can undergo marked conformational changes and subsequent self-assembly outside of the cell into highly stable , insoluble amyloid fibrils with a high conten...	[ "Amyloidosis describes a group of protein folding diseases in which amyloid proteins are abnormally deposited in organs and/or tissues as fine fibrils .", "Mouse senile amyloidosis is a disorder in which apolipoprotein A-II ( apoA-II ) deposits as amyloid fibrils ( AApoAII ) and can be transmitted from one animal...	[ "“Amyloidosis” , a group of protein folding diseases characterized by deposition of fine fibrils in tissues , is a common disorder of protein metabolism and can be acquired , inherited and/or age-associated .", "Recently , prion-like transmission has been found in various amyloidoses .", "AApoAII amyloid fibril...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "pathology", "in vitro", "immunology", "microbiology", "vertebrates", "molecular biology", "genetics and genomics", "eubacteria" ]	Molecular Basis of Resistance to Muramidase and Cationic Antimicrobial Peptide Activity of Lysozyme in Staphylococci	journal.ppat.0030102	null	[ [ "In humans , lysozyme is found in a wide variety of fluids , such as tears , breast milk , and respiratory and saliva secretions , as well as in cells of the innate immune system , including neutrophils , monocytes , macrophages , and epithelial cells [1 , 2] .", "Lysozyme is an important protein in the i...	[ "It has been shown recently that modification of peptidoglycan by O-acetylation renders pathogenic staphylococci resistant to the muramidase activity of lysozyme .", "Here , we show that a Staphylococcus aureus double mutant defective in O-acetyltransferase A ( OatA ) , and the glycopeptide resistance-associated ...	[ "In humans , lysozyme plays an important role in the suppression of bacterial infections .", "However , some bacterial pathogens , such as Staphylococcus aureus , are completely resistant to lysozyme .", "Here we demonstrate that lysozyme acts on S . aureus in two ways: as a muramidase ( cell wall lytic enzyme ...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Deciphering Transcriptional Dynamics In Vivo by Counting Nascent RNA Molecules	journal.pcbi.1004345	null	[ [ "Transcription is a multi-step process that leads to the production of messenger RNA ( mRNA ) molecules from its DNA template .", "Genetic experiments on cells have identified the key molecular components of transcription , while biochemical studies with purified components have uncovered the basic mechan...	[ "Deciphering how the regulatory DNA sequence of a gene dictates its expression in response to intra and extracellular cues is one of the leading challenges in modern genomics .", "The development of novel single-cell sequencing and imaging techniques , as well as a better exploitation of currently available singl...	[ "Gene expression starts with transcription , a multi-step process that produces an RNA molecule that is complementary to the gene .", "Cells often control the amount of gene expression by controlling the amount of RNA produced through interactions between regulatory DNA and proteins involved in transcription .", ...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "deletion mutation", "insertion mutation", "euchromatin", "mutation", "substitution mutation", "fungi", "model organisms", "experimental organism systems", "mismatch repair", "epigenetics", "dna", "chromatin", "research and analysis methods", "heterochromatin", "saccharomyces", "chromo...	Involvement of DNA mismatch repair in the maintenance of heterochromatic DNA stability in Saccharomyces cerevisiae	journal.pgen.1007074	null	[ [ "Mutations fuel evolution and are also the basis of numerous diseases including cancer [1] .", "Base substitutions , 1-bp deletions , and 1-bp insertions are the most common mutations in the cell .", "Mutations are formed as a result of DNA damage and replication errors .", "Cells have evolved mul...	[ "Heterochromatin contains a significant part of nuclear DNA .", "Little is known about the mechanisms that govern heterochromatic DNA stability .", "We show here that in the yeast Saccharomyces cerevisiae", "( i ) DNA mismatch repair ( MMR ) is required for the maintenance of heterochromatic DNA stability ,",...	[ "Eukaryotic mismatch repair is an important intracellular process that defends DNA against mutations .", "Inactivation of mismatch repair in human cells strongly increases the risk of cancer initiation and development .", "Although significant progress has been made in understanding mismatch repair at euchromat...	2017
[ "Introduction", "Methods", "Results and Discussion" ]	[ "ecology/plant-environment interactions", "microbiology/environmental microbiology", "ecology/evolutionary ecology", "ecology/behavioral ecology", "infectious diseases/neglected tropical diseases", "ecology", "ecology/environmental microbiology", "ecology/spatial and landscape ecology", "infectious ...	Ecology and Transmission of Buruli Ulcer Disease: A Systematic Review	journal.pntd.0000911	null	[ [ "Buruli ulcer ( BU ) is a serious necrotizing cutaneous infection caused by Mycobacterium ulcerans [1]–[7] .", "Before the causative agent was specifically identified , it was clinically given geographic designations such as Bairnsdale , Searles , and Kumasi ulcer , depending on the country [8]–[11] .", ...	[ "Buruli ulcer is a neglected emerging disease that has recently been reported in some countries as the second most frequent mycobacterial disease in humans after tuberculosis .", "Cases have been reported from at least 32 countries in Africa ( mainly west ) , Australia , Southeast Asia , China , Central and South...	[ "Buruli ulcer ( BU ) is a serious necrotizing cutaneous infection caused by Mycobacterium ulcerans .", "It is a neglected emerging disease that has recently been reported in some countries as the second most frequent mycobacterial disease in humans after tuberculosis ( TB ) .", "Cases have been reported from at...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "togaviruses", "chikungunya infection", "maternal health", "obstetrics and gynecology", "pathogens", "tropical diseases", "microbiology", "alphaviruses", "viruses", "developmental biology", "chikungunya virus", "rna virus...	Mother-to-child transmission of Chikungunya virus: A systematic review and meta-analysis	journal.pntd.0006510	null	[ [ "Chikungunya virus ( CHIKV ) is a remerging arbovirus[1–5] in the family of Togaviridae , genus Alphavirus that is transmitted by the Aedes spp .", "mosquitos A . aegyptii and A . albopictus[6] causing a crippling musculoskeletal inflammatory disease in humans characterized by fever , polyarthralgia , mya...	[ "Chikungunya virus ( CHIKV ) is an emerging arboviral infection with a global distribution and may cause fetal and neonatal infections after maternal CHIKV-infections during gestation .", "We performed a systematic review to evaluate the risk for:", "a ) mother-to-child transmission ( MTCT ) ,", "b ) antepart...	[ "Chikungunya virus ( CHIKV ) is an emerging arboviral infection with a global distribution and can cause infections of the fetus and newborn after maternal CHIKV-infections during gestation .", "In this systematic review , we evaluated the risk for mother-to-child transmission ( MTCT ) , antepartum fetal deaths (...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "body weight", "medicine and health sciences", "neurochemistry", "pervasive developmental disorders", "brain", "vertebrates", "autism", "social sciences", "developmental psychology", "animals", "neuroscience", "dna-binding proteins", "hormones", "animal models", "osteichthyes", "model ...	MYT1L mutations cause intellectual disability and variable obesity by dysregulating gene expression and development of the neuroendocrine hypothalamus	journal.pgen.1006957	null	[ [ "Intellectual disability ( ID ) is defined by having a full-scale intelligence quota ( IQ ) of under 70 , causing difficulties with day to day functioning [1] .", "ID affects 2–3% of people and is a significant public health concern as it is associated with substantial morbidity and mortality [1] .", ...	[ "Deletions at chromosome 2p25 . 3 are associated with a syndrome consisting of intellectual disability and obesity .", "The smallest region of overlap for deletions at 2p25 . 3 contains PXDN and MYT1L .", "MYT1L is expressed only within the brain in humans .", "We hypothesized that single nucleotide variants ...	[ "Intellectual disability is defined by having an intelligence quotient of less than 70 points , and it affects about 2–3 people in every 100 .", "Obesity is defined as having a body mass index of over 30 in adults or over the 95th centile in children .", "Both of these conditions are major public health concern...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "viral replication", "genome complexity", "functional genomics", "rna viruses", "genome evolution", "virology", "viral classification", "viral enzymes", "comparative genomics", "biology", "genomics", "evolutionary biology", "genomic evolution", "microbiology", "computational biology", ...	The Footprint of Genome Architecture in the Largest Genome Expansion in RNA Viruses	journal.ppat.1003500	null	[ [ "Genome size is the net result of evolution driven by the environment , mutation , and the genetics of a given organism [1] , [2] .", "Particularly mutation rate is a powerful evolutionary factor [3] .", "The relation between mutation rate and genome size is inversely proportional for a range of life ...	[ "The small size of RNA virus genomes ( 2-to-32 kb ) has been attributed to high mutation rates during replication , which is thought to lack proof-reading .", "This paradigm is being revisited owing to the discovery of a 3′-to-5′ exoribonuclease ( ExoN ) in nidoviruses , a monophyletic group of positive-stranded ...	[ "RNA viruses include many major pathogens .", "The adaptation of viruses to their hosts is facilitated by fast mutation and constrained by small genome sizes , which are both due to the extremely high error rate of viral polymerases .", "Using an innovative computational approach , we now provide evidence for a...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "neuroscience", "biology", "computational neuroscience" ]	Optimal Recall from Bounded Metaplastic Synapses: Predicting Functional Adaptations in Hippocampal Area CA3	journal.pcbi.1003489	null	[ [ "The hippocampus , together with associated medial temporal-lobe structures , plays a critical role in memory storage and retrieval .", "A venerable line of classical theoretical work has shaped our understanding of how different hippocampal subfields subserve this function [1] , [2] .", "At the core ...	[ "A venerable history of classical work on autoassociative memory has significantly shaped our understanding of several features of the hippocampus , and most prominently of its CA3 area , in relation to memory storage and retrieval .", "However , existing theories of hippocampal memory processing ignore a key bio...	[ "Memory is central to nervous system function and has been a particular focus for studies of the hippocampus .", "However , despite many clues , we understand little about how memory storage and retrieval is implemented in neural circuits .", "In particular , while many previous studies considered the amount of...	2014
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[]	Beyond the Whole-Genome Duplication: Phylogenetic Evidence for an Ancient Interspecies Hybridization in the Baker's Yeast Lineage	journal.pbio.1002220	The ancient whole-genome duplication in the Saccharomyces cerevisiae lineage has been a paradigm for the study of genome duplications in eukaryotes. This article presents evidence for the existence of an interspecies hybridization event shortly before the duplication, with deep implications for the functional and evolu...	[ [ "Ancient whole-genome duplications ( WGDs ) are major evolutionary events that have impacted several eukaryotic lineages , including plants , animals , and fungi [1] .", "Among plants , ancestral WGDs have been identified in monocots and core eudicots [2] , and more recent events are apparent in many line...	[ "Whole-genome duplications have shaped the genomes of several vertebrate , plant , and fungal lineages .", "Earlier studies have focused on establishing when these events occurred and on elucidating their functional and evolutionary consequences , but we still lack sufficient understanding of how genome duplicati...	[ "Genome duplication is a major evolutionary process that has shaped the genomes of several eukaryotic lineages including vertebrates , plants , and fungi .", "The sequencing of the baker's yeast Saccharomyces cerevisiae in the 1990s revealed the presence of conserved blocks of duplicated genes , indicating an anc...	2015
[ "Introduction", "Materials and methods", "Results and discussion" ]	[ "engineering and technology", "biomechanics", "simulation and modeling", "viscosity", "materials science", "materials physics", "cell nucleus", "cell mechanics", "cellular structures and organelles", "cytoskeleton", "physical chemistry", "microfluidics", "fluidics", "research and analysis ...	Probing eukaryotic cell mechanics via mesoscopic simulations	journal.pcbi.1005726	null	[ [ "Cell mechanics has proved to be a widely used label-free biomarker to discern phenotypes , detect pathologies and more importantly , monitor existence or progression of a disease [1–3] .", "The most prominent example is the changes in cell biology and morphology when it evolves from a healthy to a cancer...	[ "Cell mechanics has proven to be important in many biological processes .", "Although there is a number of experimental techniques which allow us to study mechanical properties of cell , there is still a lack of understanding of the role each sub-cellular component plays during cell deformations .", "We present...	[ "Predictive simulations of cell flow in microfluidic devices and capillary networks may help to quantify the impact of different cell components on its behavior .", "Cells have complex mechanical properties and can undergo significant deformations , requiring detailed models to give an insight into the cell rheol...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "aging", "cell death", "developmental biology", "fungi", "model organisms", "organism development", "cell biology", "yeast", "biology and life sciences", "yeast and fungal models", "cell processes", "saccharomyces cerevisiae", "molecular cell biology", "saccharomyces", "population biolog...	Lifespan Extension by Methionine Restriction Requires Autophagy-Dependent Vacuolar Acidification	journal.pgen.1004347	null	[ [ "Methionine restriction ( MetR ) has been long known to enhance lifespan in various organisms , including mammals [1] , [2] .", "Nevertheless , the mechanisms underlying this phenomenon are poorly understood .", "Previous studies have mainly focused on MetR-induced alterations of the function and comp...	[ "Reduced supply of the amino acid methionine increases longevity across species through an as yet elusive mechanism .", "Here , we report that methionine restriction ( MetR ) extends yeast chronological lifespan in an autophagy-dependent manner .", "Single deletion of several genes essential for autophagy ( ATG...	[ "Health- or lifespan-prolonging regimes would be beneficial at both the individual and the social level .", "Nevertheless , up to date only very few experimental settings have been proven to promote longevity in mammals .", "Among them is the reduction of food intake ( caloric restriction ) or the pharmacologic...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal models", "medicine", "model organisms", "neurological disorders", "neurology", "biology", "mouse", "migraine" ]	Increased Susceptibility to Cortical Spreading Depression in the Mouse Model of Familial Hemiplegic Migraine Type 2	journal.pgen.1002129	null	[ [ "Migraine is a clinically heterogeneous disorder affecting more than 10% of the general population .", "It generally occurs with unilateral and pulsating severe headache often accompanied by nausea , photophobia and phonophobia .", "In approximately one third of migraineurs , the headache attack is pr...	[ "Familial hemiplegic migraine type 2 ( FHM2 ) is an autosomal dominant form of migraine with aura that is caused by mutations of the α2-subunit of the Na , K-ATPase , an isoform almost exclusively expressed in astrocytes in the adult brain .", "We generated the first FHM2 knock-in mouse model carrying the human W...	[ "We previously reported that mutations of the α2 subunit of the Na , K-ATPase cause familial hemiplegic migraine type 2 ( FHM2 ) , a dominant form of migraine with aura .", "This paper describes the first animal model of FHM2 and represents the further proceeding in this disease investigation .", "Homozygous kn...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "biotechnology", "medicine and health sciences", "pathology and laboratory medicine", "plant growth and development", "gene regulation", "pathogens", "microbiology", "tobamoviruses", "viruses", "developmental biology", "plant science", "micrornas", "rna viruses", "genetically modified plan...	A role for small RNA in regulating innate immunity during plant growth	journal.ppat.1006756	null	[ [ "Plant nucleotide-binding leucine-rich repeat receptors ( NLR ) recognize specific pathogen effectors and trigger effective defenses against invading pathogens that are usually accompanied by a hypersensitive response ( HR ) in infected tissues [1] .", "Plant genomes usually encode hundreds of NLRs that a...	[ "Plant genomes encode large numbers of nucleotide-binding ( NB ) leucine-rich repeat ( LRR ) immune receptors ( NLR ) that mediate effector triggered immunity ( ETI ) and play key roles in protecting crops from diseases caused by devastating pathogens .", "Fitness costs are associated with plant NLR genes and reg...	[ "In plants , nucleotide-binding ( NB ) leucine-rich repeat ( LRR ) receptors ( NLR ) mediate pathogen-specific effector triggered immunity and are widely used in breeding to generate pathogen-resistant crops .", "However , dysregulation of NLR expression can inhibit plant growth and how NLR expression and functio...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome-wide association studies", "animal types", "medicine and health sciences", "cancers and neoplasms", "vertebrates", "pets and companion animals", "dogs", "animals", "mammals", "oncology", "neurological tumors", "genome analysis", "mammalian genomics", "molecular biology techniques",...	Utilizing the Dog Genome in the Search for Novel Candidate Genes Involved in Glioma Development—Genome Wide Association Mapping followed by Targeted Massive Parallel Sequencing Identifies a Strongly Associated Locus	journal.pgen.1006000	null	[ [ "Gliomas are the most common form of malignant primary brain tumors in humans , characterized by rapid growth and the invasion of neoplastic cells into healthy brain .", "Despite aggressive therapy , malignant gliomas are rarely curable .", "In the USA , the yearly mortality rates for primary malignan...	[ "Gliomas are the most common form of malignant primary brain tumors in humans and second most common in dogs , occurring with similar frequencies in both species .", "Dogs are valuable spontaneous models of human complex diseases including cancers and may provide insight into disease susceptibility and oncogenesi...	[ "Gliomas are devastating malignant brain tumors that are very rarely curable .", "Despite extensive research to define pathways and genes involved in the development of disease , there is still an urgent need to improve therapy .", "Some dog breeds have a considerable elevated risk of glioma , making the dog a ...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Surveillance and Control of Aedes albopictus in the Swiss-Italian Border Region: Differences in Egg Densities between Intervention and Non-intervention Areas	journal.pntd.0004315	null	[ [ "Aedes ( Stegomyia ) albopictus ( Skuse , 1894 ) , the Asian tiger mosquito , originates from the tropical and subtropical regions of Southeast Asia .", "During recent decades this mosquito species has spread to North America , Europe , Latin America and Africa , primarily by the transport of dormant eggs...	[ "Aedes albopictus , the Asian tiger mosquito , originates from the tropical and subtropical regions of Southeast Asia .", "Over the recent decades it has been passively spread across the globe , primarily through the used tyre trade and passive transportation along major traffic routes .", "A . albopictus is a ...	[ "The Asian tiger mosquito ( Aedes albopictus ) has gained increased attention in public health because it is a globally spreading , highly invasive mosquito species that may transmit several viruses .", "Outside of its original range in Southeast Asia it has been increasingly implicated in local transmission of c...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "antimicrobials", "medicine and health sciences", "enzymes", "drugs", "microbiology", "enzymology", "organisms", "planar chromatography", "antibiotic resistance", "antibiotics", "pharmacology", "plants", "thin-layer chromatography", "research and analysis methods", "legumes", "polymyxi...	Defining ICR-Mo, an intrinsic colistin resistance determinant from Moraxella osloensis	journal.pgen.1007389	null	[ [ "Prevalent antibiotic resistance is posing a threat to providing safe and effective health care worldwide .", "Antimicrobial resistance ( AMR ) is associated with 700 , 000 deaths each year [1 , 2] .", "It is estimated by O’Neill and his team that AMR would claim as many as 10 , 000 , 000 deaths per y...	[ "Polymyxin is the last line of defense against severe infections caused by carbapenem-resistant gram-negative pathogens .", "The emergence of transferable MCR-1/2 polymyxin resistance greatly challenges the renewed interest in colistin ( polymyxin E ) for clinical treatments .", "Recent studies have suggested t...	[ "This work represents the first functional definition of ICR-Mo , a member of a family of MCR-1/2 like genes from Moraxella .", "As inferred by phylogeny , this is the closest family of chromosomally encoded determinants of colistin resistance .", "We show evidence that ICR-Mo exploits a possible “ping-pong” me...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/neglected tropical diseases", "infectious diseases/tropical and travel-associated diseases", "infectious diseases", "infectious diseases/viral infections" ]	Persisting Mixed Cryoglobulinemia in Chikungunya Infection	journal.pntd.0000374	null	[ [ "Chikungunya fever is an emerging arboviral disease characterized by a brief fever , headache and myalgias , occasional evanescent rash , inflammatory polyarthralgias , arthritides or tenosynovitis that can last for months to years [1]–[4] .", "Chikungunya virus ( CHIKV ) was identified in the 1950s in Af...	[ "Chikungunya virus ( CHIKV ) , an arbovirus , is responsible for a two-stage disabling disease , consisting of an acute febrile polyarthritis for the first 10 days , frequently followed by chronic rheumatisms , sometimes lasting for years .", "Up to now , the pathophysiology of the chronic stage has been elusive ...	[ "Chikungunya virus is present in tropical Africa and Asia and is transmitted by mosquito bites .", "The disease is characterized by fever , headache , severe joint pain and transient skin rash for about a week .", "Most patients experience persisting joint pain and/or stiffness for months to years .", "In rou...	2009
[ "Introduction", "Results", "Discussion" ]	[ "engineering and technology", "gene regulation", "signal processing", "cell cycle and cell division", "cell processes", "messenger rna", "dna-binding proteins", "dna transcription", "autocorrelation", "developmental biology", "mathematics", "polymerases", "statistics (mathematics)", "embry...	Precision of Readout at the hunchback Gene: Analyzing Short Transcription Time Traces in Living Fly Embryos	journal.pcbi.1005256	null	[ [ "During development the different identities of cells are determined by sequentially expressing particular subsets of genes in different parts of the embryo .", "Proper development relies on the correct spatial-temporal assignment of cell types .", "In the fly embryo , the initial information about th...	[ "The simultaneous expression of the hunchback gene in the numerous nuclei of the developing fly embryo gives us a unique opportunity to study how transcription is regulated in living organisms .", "A recently developed MS2-MCP technique for imaging nascent messenger RNA in living Drosophila embryos allows us to q...	[ "The fly embryo provides a natural laboratory to study the dynamics of transcription and its implications for the developing organism .", "Using live imaging experiments we investigate the nature of transcription regulation of the hunchback gene—the first to read out the maternal Bicoid gradient .", "While trad...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "learning", "neural networks", "social sciences", "neuroscience", "learning and memory", "cognitive psychology", "sensory deprivation", "network analysis", "thermodynamics", "computer and information sciences", "entropy", "animal cells", "human learning", "physics", "cellular neuroscienc...	The Emergence of Synaesthesia in a Neuronal Network Model via Changes in Perceptual Sensitivity and Plasticity	journal.pcbi.1004959	null	[ [ "A broad distinction made in the synaesthesia literature is between acquired and developmental forms and it is presently unclear whether a single model or mechanism can account for them both .", "Developmental forms of synaesthesia have no known triggering event .", "The typical explanation is that ge...	[ "Synaesthesia is an unusual perceptual experience in which an inducer stimulus triggers a percept in a different domain in addition to its own .", "To explore the conditions under which synaesthesia evolves , we studied a neuronal network model that represents two recurrently connected neural systems .", "The i...	[ "Synaesthesia is a remarkable form of altered perception , where one attribute of a stimulus ( e . g . sound ) leads to the conscious experience of an additional attribute ( often colour ) .", "Despite being known about for 200 years , there is no commonly agreed upon model for how and why synaesthesia emerges ."...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "systems biology", "theoretical biology", "biology and life sciences", "computational biology", "biophysics", "neuroscience" ]	Resolving Anatomical and Functional Structure in Human Brain Organization: Identifying Mesoscale Organization in Weighted Network Representations	journal.pcbi.1003712	null	[ [ "Noninvasive neuroimaging techniques provide quantitative measurements of structural and functional connectivity in the human brain .", "Functional magnetic resonance imaging ( fMRI ) indirectly resolves time dependent neural activity by measuring the blood-oxygen-level-dependent ( BOLD ) signal while the...	[ "Human brain anatomy and function display a combination of modular and hierarchical organization , suggesting the importance of both cohesive structures and variable resolutions in the facilitation of healthy cognitive processes .", "However , tools to simultaneously probe these features of brain architecture req...	[ "The human brain is a fascinating organ full of exquisite anatomical and functional detail .", "A striking feature of this detail lies in the presence of small modules nested within one another across hierarchical levels of organization .", "Here we develop and apply computational analysis tools to probe these ...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "cell death", "signaling networks", "apoptotic signaling", "signaling in cellular processes", "biochemistry simulations", "biology", "antiapoptotic signaling", "molecular biology", "systems biology", "biochemistry", "biochemical simulations", "signal transduction", "apoptotic signaling casca...	Exploring the Contextual Sensitivity of Factors that Determine Cell-to-Cell Variability in Receptor-Mediated Apoptosis	journal.pcbi.1002482	null	[ [ "Variability in the responses of tumor cells to biological stimuli is often ascribed to genetic differences .", "However , it has become increasingly clear that even genetically identical cells growing in a homogenous environment respond differently to ligands , drugs , or other stimuli .", "Non-genet...	[ "Stochastic fluctuations in gene expression give rise to cell-to-cell variability in protein levels which can potentially cause variability in cellular phenotype .", "For TRAIL ( TNF-related apoptosis-inducing ligand ) variability manifests itself as dramatic differences in the time between ligand exposure and th...	[ "Variability among members of a clonal cell population is increasingly recognized as a near-universal characteristic of prokaryotic and eukaryotic cells .", "Variability can arise from random fluctuations in the biochemical reactions that control gene transcription , protein synthesis or signal transduction netwo...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "public health and epidemiology/infectious diseases", "virology/virus evolution and symbiosis" ]	Emergence of the Asian 1 Genotype of Dengue Virus Serotype 2 in Viet Nam: In Vivo Fitness Advantage and Lineage Replacement in South-East Asia	journal.pntd.0000757	null	[ [ "Dengue viruses ( DENV ) are vector-borne RNA viruses of the family Flaviviridae and are classified as either four distinct viruses or different serotypes ( DENV-1 to DENV-4 ) , each of which can infect humans .", "Infection with DENV can cause a spectrum of outcomes , ranging from asymptomatic infection ...	[ "A better description of the extent and structure of genetic diversity in dengue virus ( DENV ) in endemic settings is central to its eventual control .", "To this end we determined the complete coding region sequence of 187 DENV-2 genomes and 68 E genes from viruses sampled from Vietnamese patients between 1995 ...	[ "Dengue virus ( DENV ) is a mosquito transmitted RNA virus .", "One of the most characteristic patterns of DENV evolution is that viral lineages , including whole genotypes , are born and die-out on a regular basis .", "However , the precise cause of such lineage turnover is unclear .", "To address this issue...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Factors Associated with Severe Human Rift Valley Fever in Sangailu, Garissa County, Kenya	journal.pntd.0003548	null	[ [ "Rift Valley fever virus ( RVFV ) is a mosquito-borne zoonotic disease that poses a significant risk to human health in endemic regions of Africa and the Middle East [1] .", "Epizootics usually precede epidemics and can result in large-scale abortion storms in local livestock populations [2] .", "Thes...	[ "Mosquito-borne Rift Valley fever virus ( RVFV ) causes acute , often severe , disease in livestock and humans .", "To determine the exposure factors and range of symptoms associated with human RVF , we performed a population-based cross-sectional survey in six villages across a 40 km transect in northeastern Ken...	[ "Rift Valley fever virus ( RVFV ) causes serious disease in both animals and humans .", "Large-scale outbreaks result in devastating economic losses and create many urgent public health concerns .", "Among humans , the symptoms of RVF are variable , having a broad spectrum of disease that ranges from mild to se...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Treatment Outcome of Patients with Buruli Ulcer Disease in Togo	journal.pntd.0004170	null	[ [ "Buruli ulcer disease ( BUD ) , caused by Mycobacterium ulcerans , is a chronic , necrotizing skin disease which has been reported from more than 30 countries worldwide with a focus in West Africa [1] .", "BUD predominantly affects impoverished inhabitants of remote rural areas , approximately 50% of the ...	[ "Following introduction of antimycobacterial treatment of Buruli ulcer disease ( BUD ) , several clinical studies evaluated treatment outcomes of BUD patients , in particular healing times , secondary lesions and functional limitations .", "Whereas recurrences were rarely observed , paradoxical reactions and func...	[ "Buruli ulcer disease ( BUD ) is a mycobacterial skin disease which leads to large ulcerations and causes disabilities in approximately 25% of the patients .", "Treatment consists of antimycobacterial drugs , complemented by surgery and physiotherapy if necessary .", "Available data on treatment outcome of BUD ...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "velocity", "classical mechanics", "dna-binding proteins", "dna transcription", "simulation and modeling", "polymerases", "research and analysis methods", "curve fitting", "mathematical functions", "proteins", "mathematical and statistical techniques", "gene expression", "torque", "physics...	A Mechanistic Model for Cooperative Behavior of Co-transcribing RNA Polymerases	journal.pcbi.1005069	null	[ [ "Transcription is the first , and often the key , step in the control of gene expression .", "The process of transcription has several important phases .", "First , an RNA polymerase ( RNAP ) binds to a promotor sequence of a gene and initiates elongation .", "Next , the RNAP elongates down the DN...	[ "In fast-transcribing prokaryotic genes , such as an rrn gene in Escherichia coli , many RNA polymerases ( RNAPs ) transcribe the DNA simultaneously .", "Active elongation of RNAPs is often interrupted by pauses , which has been observed to cause RNAP traffic jams; yet some studies indicate that elongation seems ...	[ "Transcription of DNA by RNA polymerases is the first step of gene expression .", "It has been known that multiple RNA polymerases copying the same gene help each other to move faster , but the mechanism of this interaction is not known .", "We propose that the torque imposed by polymerase on helically twisted ...	2016
[ "Introduction", "Results", "Discussion", "Material and Methods" ]	[ "neuroscience/motor systems", "neuroscience/neurodevelopment", "developmental biology/neurodevelopment" ]	Midline Signalling Systems Direct the Formation of a Neural Map by Dendritic Targeting in the Drosophila Motor System	journal.pbio.1000200	During embryonic development of the motor system of Drosophila, motorneurons target their dendrites to different regions along the body axis in response to midline guidance cues.	[ [ "Understanding the organisational logic of a neuronal network is a necessary step towards unravelling the mechanisms that underlie its specification and assembly .", "For many sensory systems , axon terminals are arranged in the central nervous system ( CNS ) to form neural representations of the topograp...	[ "A fundamental strategy for organising connections in the nervous system is the formation of neural maps .", "Map formation has been most intensively studied in sensory systems where the central arrangement of axon terminals reflects the distribution of sensory neuron cell bodies in the periphery or the sensory m...	[ "How neural networks governing locomotion are organised is less well understood than those governing sensory systems .", "In the Drosophila embryo dendrites form the input structures of motorneurons , and are arranged along the anterior-posterior axis in the central nervous system to reflect the distribution of b...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/post-translational regulation of gene expression", "genetics and genomics/gene discovery", "biochemistry", "genetics and genomics/functional genomics", "genetics and genomics/gene expression", "molecular biology/mrna stability", "computational biology/metabolic networks", "computati...	A Computational Screen for Regulators of Oxidative Phosphorylation Implicates SLIRP in Mitochondrial RNA Homeostasis	journal.pgen.1000590	null	[ [ "Mitochondrial oxidative phosphorylation ( OxPhos ) is central to energy homeostasis and human health by serving as the cell's primary generator of ATP .", "The core machinery underlying OxPhos consists of approximately 90 distinct protein subunits that form five complexes residing in the inner mitochondr...	[ "The human oxidative phosphorylation ( OxPhos ) system consists of approximately 90 proteins encoded by nuclear and mitochondrial genomes and serves as the primary cellular pathway for ATP biosynthesis .", "While the core protein machinery for OxPhos is well characterized , many of its assembly , maturation , and...	[ "Respiratory chain disorders represent the largest class of inborn errors in metabolism affecting 1 in every 5 , 000 individuals .", "Biochemically , these disorders are characterized by a breakdown in the cellular process called oxidative phosphorylation ( OxPhos ) , which is responsible for generating most of t...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal models", "drug therapy", "medicine and health sciences", "model organisms", "drug research and development", "pharmaceutics", "phenotypes", "genetics", "adverse reactions", "pharmacology", "biology and life sciences", "mouse models", "pharmacogenetics", "drug interactions", "drug...	A Novel Drug-Mouse Phenotypic Similarity Method Detects Molecular Determinants of Drug Effects	journal.pcbi.1005111	null	[ [ "A drug can modulate its targets directly or indirectly ( e . g . via modulation of the gene expression ) and only a small proportion of these protein targets are known [1–3] .", "Due to this incomplete understanding of drug mode of action , current drug treatment often suffers from unwanted effects [4] ....	[ "The molecular mechanisms that translate drug treatment into beneficial and unwanted effects are largely unknown .", "We present here a novel approach to detect gene-drug and gene-side effect associations based on the phenotypic similarity of drugs and single gene perturbations in mice that account for the polyph...	[ "In order to avoid unwanted effects of current drug interventions , it is necessary to expand the knowledge of the molecular mechanisms related to drug action .", "Side effects offer insight into drug action , as for example similar side effects of unrelated drugs can be caused by their common off-targets .", "...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "ecology/behavioral ecology", "infectious diseases/viral infections", "public health and epidemiology/infectious diseases", "ecology/spatial and landscape ecology", "ecology/population ecology", "genetics and genomics/population genetics" ]	Influence of Urban Landscapes on Population Dynamics in a Short-Distance Migrant Mosquito: Evidence for the Dengue Vector Aedes aegypti	journal.pntd.0000634	null	[ [ "Anthropogenic assisted invasions by non-indigenous insect vectors of human disease have and will continue to have profound effects on global health [1] .", "In addition , anthropogenic land use changes can represent primary drivers of infectious disease epidemics and significantly alter disease transmiss...	[ "Dengue viruses are endemic across most tropical and subtropical regions .", "Because no proven vaccines are available , dengue prevention is primarily accomplished through controlling the mosquito vector Aedes aegypti .", "While dispersal distance is generally believed to be ∼100 m , patterns of dispersion may...	[ "Worldwide , 2 . 5 billion people are at risk for dengue infection , with no vaccine or treatment available .", "Thus dengue prevention is largely focused on controlling its mosquito vector , Aedes aegypti .", "Traditional mosquito control approaches typically include insecticide applications and breeding site ...	2010
[ "Introduction", "Results and Discussion", "Methods" ]	[ "model organisms", "genetics", "biology and life sciences", "genomics", "research and analysis methods" ]	Genetic Dissection of the Drosophila melanogaster Female Head Transcriptome Reveals Widespread Allelic Heterogeneity	journal.pgen.1004322	null	[ [ "Uncovering the genetic basis of quantitative phenotypes is a central , yet unresolved problem in biology .", "There is a major discrepancy between the heritability estimates of most quantitative traits and the amount of heritable variation accounted for by all variants localized to a causative site .", ...	[ "Modern genetic mapping is plagued by the “missing heritability” problem , which refers to the discordance between the estimated heritabilities of quantitative traits and the variance accounted for by mapped causative variants .", "One major potential explanation for the missing heritability is allelic heterogene...	[ "For traits with complex genetic inheritance it has generally proven very difficult to identify the majority of the specific causative variants involved .", "A range of hypotheses have been put forward to explain this so-called “missing heritability” .", "One idea—allelic heterogeneity , where genes each harbor...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics and genomics/genomics", "genetics and genomics/genome projects", "genetics and genomics", "genetics and genomics/bioinformatics", "genetics and genomics/medical genetics" ]	Genetic Variation in an Individual Human Exome	journal.pgen.1000160	null	[ [ "Genetic variation in the protein-coding portion of genes is of significant interest in the study of human health .", "The focus on coding exons , or the ‘exome’ , is due to the common belief that the exome harbors the most functional variation [1] .", "This is based on the observation that mutations ...	[ "There is much interest in characterizing the variation in a human individual , because this may elucidate what contributes significantly to a person's phenotype , thereby enabling personalized genomics .", "We focus here on the variants in a person's ‘exome , ’ which is the set of exons in a genome , because the...	[ "Characterizing the functional variation in an individual is an important step towards the era of personalized medicine .", "Protein-coding exons are thought to be especially enriched in functional variation .", "In 2007 , we published the genome sequence of J . Craig Venter .", "Here we analyze the genetic v...	2008
[ "Introduction", "Results", "Discussion", "Material and Methods" ]	[]	Sustained Autophagy Contributes to Measles Virus Infectivity	journal.ppat.1003599	null	[ [ "Measles is a highly infectious human disease caused by infection with measles virus ( MeV ) , one of the most contagious human pathogens [1] .", "Measles infection takes place by the respiratory route and clinical symptoms include respiratory infection , fever , cough , coryza , conjunctivitis and the ap...	[ "The interplay between autophagy and intracellular pathogens is intricate as autophagy is an essential cellular response to fight against infections , whereas numerous microbes have developed strategies to escape this process or even exploit it to their own benefit .", "The fine tuned timing and/or selective mole...	[ "Autophagy is an evolutionarily conserved lysosomal dependent degradative pathway for recycling of long-lived proteins and damaged organelles .", "Autophagy is also an essential cellular response to fight infection by destroying infectious pathogens trapped within autophagosomes and plays a key role in the induct...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	The SMC Loader Scc2 Promotes ncRNA Biogenesis and Translational Fidelity	journal.pgen.1005308	null	[ [ "Cohesion between sister chromatids generates the force that holds sister chromatids together until the onset of anaphase [1] .", "Cohesion is generated by cohesin , an evolutionarily conserved multi-subunit protein complex consisting of four core subunits: Smc1 , Smc3 , the α-kleisin subunit Mcd1/Scc1/Ra...	[ "The Scc2-Scc4 complex is essential for loading the cohesin complex onto DNA .", "Cohesin has important roles in chromosome segregation , DSB repair , and chromosome condensation .", "Here we report that Scc2 is important for gene expression in budding yeast .", "Scc2 and the transcriptional regulator Paf1 co...	[ "The structure of chromosomes contributes to the production of RNAs .", "Chromosome structure is maintained in part by an evolutionarily conserved group of proteins known as structural maintenance of chromosomes proteins .", "These proteins are loaded onto chromosomes by a second evolutionarily conserved protei...	2015
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "biochemistry", "biochemistry/cell signaling and trafficking structures", "biochemistry/biomacromolecule-ligand interactions", "biochemistry/macromolecular assemblies and machines", "biophysics/protein chemistry and proteomics", "biophysics/membrane proteins and energy transduction", "infectious disease...	Structural Basis for c-di-GMP-Mediated Inside-Out Signaling Controlling Periplasmic Proteolysis	journal.pbio.1000588	X-ray crystallographic structural analyses of the bacterial transmembrane receptor LapD identify conserved molecular mechanisms that control biofilm formation in response to changes in the intracellular levels of the second messenger c-di-GMP.	[ [ "Bacterial biofilms arise from planktonic microbial cells that attach to surfaces and form sessile multicellular communities , a process relevant to their survival in hostile habitats and for bacterial pathogenesis [1] .", "Recent work has identified biofilm formation as a multiphase process with strict t...	[ "The bacterial second messenger bis- ( 3′–5′ ) cyclic dimeric guanosine monophosphate ( c-di-GMP ) has emerged as a central regulator for biofilm formation .", "Increased cellular c-di-GMP levels lead to stable cell attachment , which in Pseudomonas fluorescens requires the transmembrane receptor LapD .", "LapD...	[ "Bacteria have the ability to form surface-attached communities , so-called biofilms , in both free-living environmental habitats and during pathogenic colonization in infectious diseases .", "Many of the cellular processes contributing to biofilm formation , for example , changes in motility , cell adhesion , an...	2011
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "developmental biology/cell differentiation", "developmental biology", "developmental biology/pattern formation", "developmental biology/morphogenesis and cell biology" ]	JNK Signalling Controls Remodelling of the Segment Boundary through Cell Reprogramming during Drosophila Morphogenesis	journal.pbio.1000390	Reprogramming of a specific group of Drosophila epidermal cells allows the mixing of normally segregated populations and the release of mechanical tension that arises during morphogenesis.	[ [ "Patterning of tissue progenitors through specific gene expression precedes tissue morphogenesis .", "Once cells are committed to a particular lineage , they generally keep to it throughout development .", "Nonetheless , plasticity of segmental lineages is commonly observed during the stages of bounda...	[ "Segments are fundamental units in animal development which are made of distinct cell lineages separated by boundaries .", "Although boundaries show limited plasticity during their formation for sharpening , cell lineages make compartments that become tightly restricted as development goes on .", "Here , we cha...	[ "Multicellular organisms are assembled from different cell types , each following a particular fate depending on their history and location .", "During development , cells are organized into compartments , which are essential for the correct formation of organs .", "Within the compartments , cells follow two ge...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Signatures of Value Comparison in Ventral Striatum Neurons	journal.pbio.1002173	A study of single neurons in the ventral striatum reveals signatures of value comparison and selection during a risky choice task, suggesting that the cortex and its striatal targets make overlapping contributions to the choice process. Read the accompanying Primer.	[ [ "Making beneficial choices about rewarding options is a major function of our brains and is critical for our survival .", "Consequently , understanding the mechanisms of reward-based choice is a major goal of psychology , microeconomics , animal behavior , and psychiatry [1–7] .", "Recent empirical an...	[ "The ventral striatum ( VS ) , like its cortical afferents , is closely associated with processing of rewards , but the relative contributions of striatal and cortical reward systems remains unclear .", "Most theories posit distinct roles for these structures , despite their similarities .", "We compared respon...	[ "The neural calculations underlying reward-based choice are closely associated with a network of brain areas including the ventral striatum ( VS ) and ventromedial prefrontal cortex ( vmPFC ) .", "Most theories ascribe distinct roles to these two structures during choice , but these differences have yet to be con...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "biology and life sciences", "protozoan infections", "parasitic diseases", "parasitology", "toxoplasmosis" ]	Acidification Activates Toxoplasma gondii Motility and Egress by Enhancing Protein Secretion and Cytolytic Activity	journal.ppat.1004488	null	[ [ "Infectious microorganisms experience diverse microenvironments during infection of a host .", "Such pathogenic microbes utilize specific cues to assess the environment and trigger an appropriate response that aids in their survival .", "For example , malaria parasites ( Plasmodium spp ) sense xanthur...	[ "Pathogenic microbes rely on environmental cues to initiate key events during infection such as differentiation , motility , egress and invasion of cells or tissues .", "Earlier investigations showed that an acidic environment activates motility of the protozoan parasite T . gondii .", "Conversely , potassium i...	[ "Toxoplasma and related parasites including those that cause malaria are obligate intracellular pathogens that replicate within a specialized compartment termed the parasitophorous vacuole .", "To infect new host cells these parasites must first escape from the parasitophorous vacuole and other limiting membranes...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "genetic networks", "breast tumors", "cardiovascular anatomy", "gene regulation", "cancers and neoplasms", "random variables", "covariance", "simulation and modeling", "oncology", "mathematics", "arteries", "network analysis", "genome analysis", "research ...	Context Specific and Differential Gene Co-expression Networks via Bayesian Biclustering	journal.pcbi.1004791	null	[ [ "Cellular mechanisms tightly regulate gene transcription .", "Gene transcription is not independently regulated across genes: many of the mechanisms regulating transcription affect multiple genes simultaneously .", "Functional gene modules consist of subsets of genes that share similar expression patt...	[ "Identifying latent structure in high-dimensional genomic data is essential for exploring biological processes .", "Here , we consider recovering gene co-expression networks from gene expression data , where each network encodes relationships between genes that are co-regulated by shared biological mechanisms .",...	[ "Recovering gene co-expression networks from high-throughput experiments to measure gene expression levels is essential for understanding the genetic regulation of complex traits .", "It is often assumed for simplicity that gene co-expression networks are static across different contexts—e . g . , drug exposure ,...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "aging", "evolutionary biology", "evolutionary modeling", "biology", "computational biology" ]	How Evolving Heterogeneity Distributions of Resource Allocation Strategies Shape Mortality Patterns	journal.pcbi.1002825	null	[ [ "Aging can be generally defined as age-related changes in a set of variables , from growth rate to reproductive effort , which influence the fitness of an organism .", "Aging is a multiscale process which can be measured at almost every level of the individual organism .", "Individual metrics of aging...	[ "It is well established that individuals age differently .", "Yet the nature of these inter-individual differences is still largely unknown .", "For humans , two main hypotheses have been recently formulated: individuals may experience differences in aging rate or aging timing .", "This issue is central becau...	[ "Aging is a widespread phenomenon across the tree of life .", "From yeast to humans , mortality changes over age have been widely documented .", "Interestingly , all individuals are not equal with respect to the aging process: large variability in individual life span has been reported , even in clonal populati...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "public health and epidemiology/global health", "neurological disorders/epilepsy" ]	Accuracy of Serological Testing for the Diagnosis of Prevalent Neurocysticercosis in Outpatients with Epilepsy, Eastern Cape Province, South Africa	journal.pntd.0000562	null	[ [ "Neurocysticercosis ( NCC ) results when the central nervous system ( CNS ) is invaded by the larval stage of Taenia solium , a zoonotic cestode transmitted between humans and pigs .", "Humans infected with the adult tapeworm , a disease called taeniasis , contaminate the environment with the parasites' e...	[ "Few studies have estimated prevalence of neurocysticercosis ( NCC ) among persons with epilepsy in sub-Saharan Africa .", "While the limitations of serological testing in identification of NCC are well known , the characteristics of persons who are misdiagnosed based on serology have not been explored .", "The...	[ "Epilepsy is a significant contributor to morbidity world-wide in persons of all ages .", "Little is known , however , about its causes .", "In the developing world , parasitic infections of the brain , in particular Taenia solium neurocysticercosis ( NCC ) are thought to be important factors .", "Determining...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "skin", "cell death", "merkel cells", "medicine and health sciences", "integumentary system", "cell processes", "cell differentiation", "epithelial cells", "developmental biology", "epidermis", "research and analysis methods", "specimen preparation and treatment", "staining", "hair", "an...	Polycomb-Mediated Repression and Sonic Hedgehog Signaling Interact to Regulate Merkel Cell Specification during Skin Development	journal.pgen.1006151	null	[ [ "The skin epithelium is an excellent model system to study mechanisms of stem cell maintenance and differentiation [1] .", "During skin development , a single layer of embryonic epidermal stem cells gives rise to multiple lineages , including the interfollicular epidermis ( IFE ) , the hair follicles , an...	[ "An increasing amount of evidence indicates that developmental programs are tightly regulated by the complex interplay between signaling pathways , as well as transcriptional and epigenetic processes .", "Here , we have uncovered coordination between transcriptional and morphogen cues to specify Merkel cells , po...	[ "Merkel cells are innervated touch-receptor cells that are responsible for light touch sensations .", "They originate from embryonic epidermal stem cells and , in hairy regions of skin , are organized in touch domes .", "Touch domes are highly patterned structures that form exclusively around primary hair folli...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	West Nile Virus: High Transmission Rate in North-Western European Mosquitoes Indicates Its Epidemic Potential and Warrants Increased Surveillance	journal.pntd.0003956	null	[ [ "West Nile virus ( WNV; family Flaviviridae , genus Flavivirus ) is an important mosquito-borne human pathogen associated with febrile illness , which may develop into severe neuroinvasive disease and death [1] .", "The pathogenic isolates of WNV can be classified into two lineages .", "Lineage 1 WNV ...	[ "West Nile virus ( WNV ) is a highly pathogenic flavivirus transmitted by Culex spp .", "mosquitoes .", "In North America ( NA ) , lineage 1 WNV caused the largest outbreak of neuroinvasive disease to date , while a novel pathogenic lineage 2 strain circulates in southern Europe .", "To estimate WNV lineage 2...	[ "West Nile virus ( WNV ) is on the rise in Europe , with increasing numbers of human cases of neurological disease and death since 2010 .", "However , it is currently unknown whether or not WNV will continue to spread to north-western Europe ( NWE ) , in a fashion similar to the WNV epidemic sweep in the United S...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Type VI Secretion System Toxins Horizontally Shared between Marine Bacteria	journal.ppat.1005128	null	[ [ "The type VI secretion system ( T6SS ) is a protein secretion apparatus found in Gram-negative bacteria [1] .", "While it was originally described as a bacterial virulence determinant [2–4] , subsequent findings demonstrated that many T6SSs are used as antibacterial determinants in interbacterial competit...	[ "The type VI secretion system ( T6SS ) is a widespread protein secretion apparatus used by Gram-negative bacteria to deliver toxic effector proteins into adjacent bacterial or host cells .", "Here , we uncovered a role in interbacterial competition for the two T6SSs encoded by the marine pathogen Vibrio alginolyt...	[ "The bacterial type VI secretion system ( T6SS ) is a contact-dependent protein secretion apparatus that is emerging as a major component of interbacterial competition in the environment .", "The bacterium Vibrio alginolyticus is a pathogen of marine animals and a causal agent of wound infections , otitis , and g...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "circuit models", "physics", "mathematics", "neural networks", "computational neuroscience", "biology", "biophysics", "neuroscience" ]	How Structure Determines Correlations in Neuronal Networks	journal.pcbi.1002059	null	[ [ "Analysis of networks of interacting elements has become a tool for system analysis in many areas of biology , including the study of interacting species [1] , cell dynamics [2] and the brain [3] .", "A fundamental question is how the dynamics , and eventually the function , of the system as a whole depen...	[ "Networks are becoming a ubiquitous metaphor for the understanding of complex biological systems , spanning the range between molecular signalling pathways , neural networks in the brain , and interacting species in a food web .", "In many models , we face an intricate interplay between the topology of the networ...	[ "Many biological systems have been described as networks whose complex properties influence the behaviour of the system .", "Correlations of activity in such networks are of interest in a variety of fields , from gene-regulatory networks to neuroscience .", "Due to novel experimental techniques allowing the rec...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "innate immune system", "medicine and health sciences", "immune cells", "vesicles", "pathology and laboratory medicine", "immune physiology", "cytokines", "gene regulation", "immunology", "light microscopy", "immune receptor signaling", "developmental biology", "signs and sy...	Persistent mycobacteria evade an antibacterial program mediated by phagolysosomal TLR7/8/MyD88 in human primary macrophages	journal.ppat.1006551	null	[ [ "Both Mycobacterium tuberculosis ( Mtb ) and pathogenic non-tuberculous mycobacteria like M . avium ( Mav ) have developed mechanisms to hijack the normal trafficking of phagosomes and use macrophages as a natural habitat and tools of spread in the host [1–3] .", "However , the spatiotemporal dynamics of ...	[ "Pathogenic mycobacteria reside in macrophages where they avoid lysosomal targeting and degradation through poorly understood mechanisms proposed to involve arrest of phagosomal maturation at an early endosomal stage .", "A clear understanding of how this relates to host defenses elicited from various intracellul...	[ "Mycobacterium avium is increasingly reported as a causative agent of non-tuberculous disease in immunocompromised patients and in individuals with underlying disease or using immunosuppressant drugs , with prevalence often higher than the more pathogenic M . tuberculosis in developed countries .", "Both M . aviu...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "blood cells", "medicine and health sciences", "body fluids", "pathology and laboratory medicine", "micronuclei", "atrophy", "microbiology", "vertebrates", "dogs", "animals", "mammals", "toxicology", "toxicity", "routes of administration", "red blood cells", "metabolites", "signs and...	Preclinical toxicity and pharmacokinetics of a new orally bioavailable flubendazole formulation and the impact for clinical trials and risk/benefit to patients	journal.pntd.0007026	null	[ [ "Onchocerciasis is a neglected tropical disease caused by the parasitic worm species Onchocerca volvulus , which spreads through bites from infected black flies .", "The presence of larvae in the skin causes several symptoms , including intolerable itching .", "Larvae can migrate to the eye and cause ...	[ "Flubendazole , originally developed to treat infections with intestinal nematodes , has been shown to be efficacious in animal models of filarial infections .", "For treatment of filarial nematodes , systemic exposure is needed .", "For this purpose , an orally bioavailable amorphous solid dispersion ( ASD ) f...	[ "This article describes pharmacokinetic profiles and results of safety pharmacology , toxicity and genotoxicity studies with an oral ASD formulation of flubendazole with improved bioavailability .", "Flubendazole administered as ASD formulation has good oral bioavailability in animals ranging from 15% to more tha...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "innate immune system", "medicine and health sciences", "inflammation", "infectious diseases", "cytokines", "clinical immunology", "immunity", "molecular development", "influenza", "biology and life sciences", "immunology", "pulmonary immunology", "immunoregulation...	Late Engagement of CD86 after Influenza Virus Clearance Promotes Recovery in a FoxP3+ Regulatory T Cell Dependent Manner	journal.ppat.1004315	null	[ [ "Influenza A virus ( IAV ) infects and replicates in the respiratory tract , triggering a robust immune response .", "There is a large body of evidence to support the concept that fine control of the immune response to IAV is essential to prevent excessive tissue injury; while an immune mediated inflammat...	[ "Influenza A virus ( IAV ) infection in the respiratory tract triggers robust innate and adaptive immune responses , resulting in both virus clearance and lung inflammation and injury .", "After virus clearance , resolution of ongoing inflammation and tissue repair occur during a distinct recovery period .", "B...	[ "Influenza A virus ( IAV ) infection can cause severe inflammation and injury in the respiratory tract , which must be resolved and repaired for the host to fully recover after virus clearance .", "Evidence is emerging that host immune responses may regulate tissue repair and resolution of inflammation after IAV ...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "veterinary pathology", "veterinary diseases", "pathology", "veterinary microbiology", "microbiology", "veterinary science", "veterinary medicine" ]	A Pilot Study on Developing Mucosal Vaccine against Alveolar Echinococcosis (AE) Using Recombinant Tetraspanin 3: Vaccine Efficacy and Immunology	journal.pntd.0001570	null	[ [ "Alveolar echinococcosis ( AE ) , caused by E . multilocularis , is known as a very important zoonotic disease , which is endemic in the large areas of the Northern Hemisphere [1] and is often life-threatening .", "E . multilocularis infection of intermediate hosts ( humans and rodents ) occurs after oral...	[ "We have previously evaluated the vaccine efficacies of seven tetraspanins of Echinococcus multilocularis ( Em-TSP1–7 ) against alveolar echinococcosis ( AE ) by subcutaneous ( s . c . ) administration with Freund's adjuvant .", "Over 85% of liver cyst lesion number reductions ( CLNR ) were achieved by recombinan...	[ "Humans and rodents become infected with E . multilocularis by oral ingesting of the eggs , which then develop into cysts in the liver and progress an endless proliferation .", "Untreated AE has a fatality rate of >90% in humans .", "Tetraspanins have been identified in Schistosoma and showed potential as the p...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "evolutionary biology", "genetics and genomics/gene function", "computational biology" ]	Detecting Key Structural Features within Highly Recombined Genes	journal.pcbi.0030014	null	[ [ "Rapidly evolving genes are among the most biologically intriguing , yet they are also among the most difficult to analyze .", "The arms race between host and pathogen , fueled by strong selection pressures , can yield very high levels of sequence variation in certain microbial genes .", "Diversifying...	[ "Many microorganisms exhibit high levels of intragenic recombination following horizontal gene transfer events .", "Furthermore , many microbial genes are subject to strong diversifying selection as part of the pathogenic process .", "A multiple sequence alignment is an essential starting point for many of the ...	[ "Microbial genes that accumulate large amounts of nucleotide sequence diversity through lateral exchanges with other microorganisms are often central to understanding key interactions between the microbe and an ever-changing host or environment .", "Proper sequence alignment of multiple gene alleles is an essenti...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	IL-27 Signaling Is Crucial for Survival of Mice Infected with African Trypanosomes via Preventing Lethal Effects of CD4+ T Cells and IFN-γ	journal.ppat.1005065	null	[ [ "African trypanosomiasis is a vector-borne parasitic disease of medical and veterinary importance .", "It is estimated that 170 , 000 people contract the disease every year , and that approximately 70 million people mainly in sub-Saharan Africa are at the risk of contracting the disease [1 , 2] .", "I...	[ "African trypanosomes are extracellular protozoan parasites causing a chronic debilitating disease associated with a persistent inflammatory response .", "Maintaining the balance of the inflammatory response via downregulation of activation of M1-type myeloid cells was previously shown to be crucial to allow prol...	[ "Infection with extracellular protozoan parasites , African trypanosomes , is characterized by a persistent inflammatory immune response .", "It has been recently shown that maintaining the balance of the inflammatory responses via dampening M1-type myeloid cell activation is critical to guarantee control of the ...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "immune response", "biology and life sciences", "immunology", "immune system" ]	A Dual Drug Sensitive L. major Induces Protection without Lesion in C57BL/6 Mice	journal.pntd.0002785	null	[ [ "Cutaneous leishmaniasis ( CL ) manifests as a localized self-healing lesion ( s ) that in rare cases develops to a non-healing lesion .", "If non-healing lesions develop , they are extremely difficult to treat with current therapies [1] .", "Control measures for leishmaniasis such as vector and/or ré...	[ "Leishmaniasis is a major health problem in some endemic areas and yet , no vaccine is available against any form of the disease .", "Historically , leishmanization ( LZ ) which is an inoculation of individual with live Leishmania , is the most effective control measure at least against cutaneous leishmaniasis ( ...	[ "Leishmaniasis is still a major health problem in some endemic foci , yet no vaccine is available against any form of leishmaniasis .", "It is a general belief that recovery from cutaneous leishmaniasis ( CL ) is accompanied with long life protection .", "An inoculation of live pathogenic L . major into healthy...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "plant science", "plant biology", "genetics", "biology", "molecular cell biology", "genetics and genomics" ]	Inter-Homolog Crossing-Over and Synapsis in Arabidopsis Meiosis Are Dependent on the Chromosome Axis Protein AtASY3	journal.pgen.1002507	null	[ [ "Meiotic recombination is initiated by the formation of Spo11-catalysed DSBs during early prophase I [1] .", "Each break is resected to produce 3′ single-stranded DNA tails which then interact with the RecA homologs Rad51 and Dmc1 to form nucleoprotein filaments .", "The filament on one side of the br...	[ "In this study we have analysed AtASY3 , a coiled-coil domain protein that is required for normal meiosis in Arabidopsis .", "Analysis of an Atasy3-1 mutant reveals that loss of the protein compromises chromosome axis formation and results in reduced numbers of meiotic crossovers ( COs ) .", "Although the frequ...	[ "Homologous recombination ( HR ) during prophase I of meiosis leads to the formation of physical connections , known as chiasmata , between homologous chromosomes ( homologs ) .", "Chiasmata are essential for accurate homolog segregation at the first meiotic division .", "HR is initiated by the formation of DNA...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "innate immune system", "medicine and health sciences", "reproductive system", "rna interference", "gonads", "pathology and laboratory medicine", "gene regulation", "pathogens", "regulatory proteins", "immunology", "microbiology", "dna-binding proteins", "germ cells", "physiological proces...	Innate immunity mediated longevity and longevity induced by germ cell removal converge on the C-type lectin domain protein IRG-7	journal.pgen.1006577	null	[ [ "One of the most significant findings in the aging research field is the realization that lifespan is determined by the aging rate and by deleterious events that limit lifespan .", "Over the last few decades , a wealth of genes and signaling molecules that determine lifespan and longevity were identified ...	[ "In C . elegans , removal of the germline triggers molecular events in the neighboring intestine , which sends an anti-aging signal to the rest of the animal .", "In this study , we identified an innate immunity related gene , named irg-7 , as a novel mediator of longevity in germlineless animals .", "We consid...	[ "Increased sensitivity to pathogens is one of the hallmarks of aging .", "Thus , pathways that slow down the aging process should provide a remedy to this challenge .", "In this study , we have used the model organism C . elegans to identify a new longevity gene whose activation improves the resistance of the a...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	SHOEBOX Modulates Root Meristem Size in Rice through Dose-Dependent Effects of Gibberellins on Cell Elongation and Proliferation	journal.pgen.1005464	null	[ [ "The size of a plant , or part thereof , is determined by combined activity of cell proliferation and growth during development [1] .", "Cell proliferation in plants occurs mostly in specialized tissues known as meristems , where new cells are produced to ensure that plants continue to grow in height and ...	[ "Little is known about how the size of meristem cells is regulated and whether it participates in the control of meristem size in plants .", "Here , we report our findings on shoebox ( shb ) , a mild gibberellin ( GA ) deficient rice mutant that has a short root meristem size .", "Quantitative analysis of corti...	[ "Little is known concerning the identity of regulatory components and signaling pathways that control the growth of meristem cells in plants .", "Here , we report that rice plants deficient in the AP2/ERF family gene SHOEBOX ( SHB ) exhibited a severe reduction in the root meristem size .", "These plants had sh...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Network Analyses Reveal Novel Aspects of ALS Pathogenesis	journal.pgen.1005107	null	[ [ "Amyotrophic lateral sclerosis ( ALS ) is characterized by the degeneration of upper and lower motor neurons leading to a progressive deterioration of motor function and ultimately death , due to respiratory failure .", "Both environmental and genetic factors have been shown to contribute to ALS susceptib...	[ "Amyotrophic Lateral Sclerosis ( ALS ) is a fatal neurodegenerative disease characterized by selective loss of motor neurons , muscle atrophy and paralysis .", "Mutations in the human VAMP-associated protein B ( hVAPB ) cause a heterogeneous group of motor neuron diseases including ALS8 .", "Despite extensive r...	[ "Amyotrophic Lateral Sclerosis ( ALS ) is a neurodegenerative disease causing loss of motor neurons and consequently a progressive deterioration of motor functions .", "ALS is uniformly fatal with death occurring 5 years after onset of symptoms .", "There is currently no effective treatment for ALS .", "Sever...	2015

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