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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", "Methods", "Results", "Discussion", "Conclusion" ]	[ "invertebrates", "livestock", "medicine and health sciences", "rift valley fever virus", "pathology and laboratory medicine", "viral transmission and infection", "pathogens", "geographical locations", "microbiology", "animals", "viral vectors", "viruses", "rna viruses", "insect vectors", ...	Distribution and abundance of key vectors of Rift Valley fever and other arboviruses in two ecologically distinct counties in Kenya	journal.pntd.0005341	null	[ [ "Rift Valley fever virus ( RVFV ) , of the genus Phlebovirus , family Bunyaviridae is a mosquito-borne virus present in Africa and the Arabian Peninsula [1] .", "It causes disease of varying severity including hemorrhagic fever , encephalitis and mortalities in humans and abortions and death among ruminan...	[ "Rift Valley fever ( RVF ) is a mosquito-borne viral zoonosis of ruminants and humans that causes outbreaks in Africa and the Arabian Peninsula with significant public health and economic consequences .", "Humans become infected through mosquito bites and contact with infected livestock .", "The virus is mainta...	[ "Rift Valley fever ( RVF ) is a mosquito-borne disease caused by the Rift Valley fever virus ( RVFV ) transmitted by diverse species of mosquitoes broadly classified into primary vectors and secondary vectors .", "Primary vectors consist of floodwater Aedes ( e . g Ae . mcintoshi , Ae . ochraceus , Ae . sudanensi...	2017
[ "Introduction", "Results/Discussion", "Methods" ]	[ "systems biology", "computer and information sciences", "network analysis", "regulatory networks", "biology and life sciences", "computational biology" ]	Agent-Based Modeling of Oxygen-Responsive Transcription Factors in Escherichia coli	journal.pcbi.1003595	null	[ [ "The bacterium Escherichia coli is a widely used model organism to study bacterial adaptation to environmental change .", "As an enteric bacterium , E . coli has to cope with an O2-starved niche in the host and an O2-rich environment when excreted .", "In order to exploit the energetic benefits that a...	[ "In the presence of oxygen ( O2 ) the model bacterium Escherichia coli is able to conserve energy by aerobic respiration .", "Two major terminal oxidases are involved in this process - Cyo has a relatively low affinity for O2 but is able to pump protons and hence is energetically efficient; Cyd has a high affinit...	[ "The model bacterium Escherichia coli has a modular electron transport chain that allows it to successfully compete in environments with differing oxygen ( O2 ) availabilities .", "It has two well-characterized terminal oxidases , Cyd and Cyo .", "Cyd has a very high affinity for O2 , whereas Cyo has a lower af...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "engineering and technology", "statistics", "electronics", "random variables", "electrophysiology", "neuroscience", "covariance", "multivariate analysis", "mathematics", "brain mapping", "membrane electrophysiology", "electrocorticography", "bioassays and ph...	Correlation Structure in Micro-ECoG Recordings is Described by Spatially Coherent Components	journal.pcbi.1006769	null	[ [ "Electrical recording from the brain surface , known as electrocorticography ( ECoG ) , is becoming more common due to technological advances that enable recording from large cortical surface area with high temporal resolution and far better spatial resolution than non-invasive EEG [1 , 2] .", "ECoG has a...	[ "Electrocorticography ( ECoG ) is becoming more prevalent due to improvements in fabrication and recording technology as well as its ease of implantation compared to intracortical electrophysiology , larger cortical coverage , and potential advantages for use in long term chronic implantation .", "Given the flexi...	[ "Electrocorticography ( ECoG ) is a type of electrophysiological monitoring that uses electrodes placed directly on the exposed surface of the brain .", "ECoG is a promising technique for studying the brain , and EcoG signals can be used to control brain-computer interfaces .", "Advances have made it possible t...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "evolutionary biology", "virology", "plant biology" ]	Dynamics of the Multiplicity of Cellular Infection in a Plant Virus	journal.ppat.1001113	null	[ [ "Intracellular interactions among co-infecting viral genomes play a central role in viral evolution and ecology as they determine three important phenomena:", "( i ) competition and selection ,", "( ii ) re-association with other genetic backgrounds through recombination , and", "( iii ) functiona...	[ "Recombination , complementation and competition profoundly influence virus evolution and epidemiology .", "Since viruses are intracellular parasites , the basic parameter determining the potential for such interactions is the multiplicity of cellular infection ( cellular MOI ) , i . e . the number of viral genom...	[ "Viruses are fast evolving organisms for which changes in fitness and virulence are driven by interactions between genomes such as recombination , functional complementation , and competition .", "Viruses being intra-cellular parasites , one basic parameter determines the potential for such interactions: the cell...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "immune physiology", "enzyme-linked immunoassays", "pathology and laboratory medicine", "pathogens", "immunology", "microbiology", "vertebrates", "rabbits", "cloning", "animals", "mammals", "retroviruses", "animal models", "immunodeficiency viruses", "vi...	Sequential and Simultaneous Immunization of Rabbits with HIV-1 Envelope Glycoprotein SOSIP.664 Trimers from Clades A, B and C	journal.ppat.1005864	null	[ [ "Multiple recombinant , soluble envelope glycoprotein ( Env ) trimers from human immunodeficiency virus type 1 ( HIV-1 ) are currently being produced as immunogens for induction of neutralizing antibody ( NAb ) responses [1–5] .", "As NAbs act by recognizing native Env trimers on the HIV-1 surface , trime...	[ "We have investigated the immunogenicity in rabbits of native-like , soluble , recombinant SOSIP . 664 trimers based on the env genes of four isolates of human immunodeficiency virus type 1 ( HIV-1 ) ; specifically BG505 ( clade A ) , B41 ( clade B ) , CZA97 ( clade C ) and DU422 ( clade C ) .", "The various trim...	[ "Native-like SOSIP trimers are a platform for development of immunogens aimed at inducing broadly neutralizing antibodies and , hence , a possible vaccine against HIV-1 infection .", "No previous study has reported on immune responses to more than one such trimer .", "Here , we assess how rabbits respond to imm...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "reproductive system", "maternal health", "obstetrics and gynecology", "brain", "vertebrates", "animals", "mammals", "hormones", "endocrine physiology", "reproductive physiology", "developmental biology", "women's health", "pregnancy", "embryos", "embryo...	Maternal care boosted by paternal imprinting in mammals	journal.pbio.2006599	null	[ [ "High-quality maternal care is vitally important for newborn survival and their behavioural and metabolic health later in life , evidenced by the catastrophic consequences when maternal care is poor or absent [1–3] ( S1 Table ) .", "Maternal care provision comes at the cost of the mother’s later reproduct...	[ "In mammals , mothers are the primary caregiver , programmed , in part , by hormones produced during pregnancy .", "High-quality maternal care is essential for the survival and lifelong health of offspring .", "We previously showed that the paternally silenced imprinted gene pleckstrin homology-like domain fami...	[ "Female mammals are primed during pregnancy for their new role as a mother caring for their newborn .", "Indirect evidence suggests that this behaviour is , in part , instructed by hormones produced by the foetally derived placenta .", "We previously reported that the Phlda2 gene controls the size of the placen...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "vertebrates", "random variables", "neuroscience", "covariance", "animals", "mammals", "primates", "regression analysis", "cognitive neuroscience", "probability distribution", "mathematics", "statistics (mathematics)", "thermodynamics", "research and analysis methods", "computer and info...	Measuring Integrated Information from the Decoding Perspective	journal.pcbi.1004654	null	[ [ "Although its neurobiological basis remains unclear , consciousness may be related to certain aspects of information processing [1 , 2] .", "In particular , Integrated Information Theory of consciousness ( IIT ) developed by Tononi and colleagues [2–9] predicts that the amount of information integrated am...	[ "Accumulating evidence indicates that the capacity to integrate information in the brain is a prerequisite for consciousness .", "Integrated Information Theory ( IIT ) of consciousness provides a mathematical approach to quantifying the information integrated in a system , called integrated information , Φ .", ...	[ "Integrated Information Theory ( IIT ) of consciousness attracts scientists who investigate consciousness owing to its explanatory and predictive powers for understanding the neural properties of consciousness .", "IIT predicts that the levels of consciousness are related to the quantity of information integrated...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "anesthetic mechanisms", "medicine", "biophysic al simulations", "general anesthesia", "anesthesiology", "biology", "computational biology", "biophysics simulations", "biophysics" ]	Exploring Volatile General Anesthetic Binding to a Closed Membrane-Bound Bacterial Voltage-Gated Sodium Channel via Computation	journal.pcbi.1003090	null	[ [ "Voltage gated sodium channels ( VGSCs ) , which mediate the upstroke of the action potential in most excitable tissues , are key targets of anesthetics .", "The binding site and molecular mechanism of action for local anesthetics have been well characterized in the last few decades , while the role of VG...	[ "Despite the clinical ubiquity of anesthesia , the molecular basis of anesthetic action is poorly understood .", "Amongst the many molecular targets proposed to contribute to anesthetic effects , the voltage gated sodium channels ( VGSCs ) should also be considered relevant , as they have been shown to be sensiti...	[ "The molecular mechanisms mediating the pharmacologically induced state of general anesthesia are , in general , poorly understood .", "Modulation of voltage gated sodium channels is thought to play a major role in anesthesia , as several members of this class of channels show a significant response to general an...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience/behavioral neuroscience", "neuroscience/sensory systems", "computational biology", "neuroscience/psychology", "neuroscience/experimental psychology" ]	The Modulation Transfer Function for Speech Intelligibility	journal.pcbi.1000302	null	[ [ "Human speech , like most animal vocalizations , is a complex signal whose amplitude envelope fluctuates timbrally in frequency and rhythmically in time .", "Horizontal cross-sections of the speech spectrogram as in Figure 1A describe the time-varying envelope for a particular frequency while vertical cro...	[ "We systematically determined which spectrotemporal modulations in speech are necessary for comprehension by human listeners .", "Speech comprehension has been shown to be robust to spectral and temporal degradations , but the specific relevance of particular degradations is arguable due to the complexity of the ...	[ "The sound signal of speech is rich in temporal and frequency patterns .", "These fluctuations of power in time and frequency are called modulations .", "Despite their acoustic complexity , spoken words remain intelligible after drastic degradations in either time or frequency .", "To fully understand the per...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "systems biology", "cell growth", "gene expression", "genetics", "biology", "computational biology", "molecular cell biology" ]	Cell-Cycle Dependence of Transcription Dominates Noise in Gene Expression	journal.pcbi.1003161	null	[ [ "At the single-cell level , mRNA and protein levels of regulable genes are often found to be highly variable [1]–[5] .", "The resulting long-tailed mRNA and protein distributions are well-described by stochastic models [1] , [5]–[7] of transcriptional bursting , where a promoter undergoes random and inter...	[ "The large variability in mRNA and protein levels found from both static and dynamic measurements in single cells has been largely attributed to random periods of transcription , often occurring in bursts .", "The cell cycle has a pronounced global role in affecting transcriptional and translational output , but ...	[ "There is an astonishing amount of variation in the number of mRNA and protein molecules generated from particular genes between genetically identical single cells grown in the same environment .", "Particularly for mRNA , the large variation seen from these “noisy” genes is consistent with the idea of transcript...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Cell Specific eQTL Analysis without Sorting Cells	journal.pgen.1005223	null	[ [ "In the past seven years , genome-wide association studies ( GWAS ) have identified thousands of genetic variants that are associated with human disease [1] .", "The realization that many of the disease-predisposing variants are non-coding and that single nucleotide polymorphisms ( SNPs ) often affect the...	[ "The functional consequences of trait associated SNPs are often investigated using expression quantitative trait locus ( eQTL ) mapping .", "While trait-associated variants may operate in a cell-type specific manner , eQTL datasets for such cell-types may not always be available .", "We performed a genome-envir...	[ "Many variants in the genome , including variants associated with disease , affect the expression of genes .", "These so-called expression quantitative trait loci ( eQTL ) can be used to gain insight in the downstream consequences of disease .", "While it has been shown that many disease-associated variants alt...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal models", "caenorhabditis elegans", "cellular stress responses", "model organisms", "biology", "molecular cell biology" ]	Regulation of Synaptic nlg-1/Neuroligin Abundance by the skn-1/Nrf Stress Response Pathway Protects against Oxidative Stress	journal.pgen.1004100	null	[ [ "Oxidative stress is generated in cells when an imbalance occurs between the production of electrophilic reactive species and the endogenous defenses against these harmful molecules [1] .", "Increased reactive oxygen species ( ROS ) can cause damage to cellular components such as lipids , DNA , and protei...	[ "The Nrf family of transcription factors mediates adaptive responses to stress and longevity , but the identities of the crucial Nrf targets , and the tissues in which they function in multicellular organisms to promote survival , are not known .", "Here , we use whole transcriptome RNA sequencing to identify 810...	[ "Organisms have evolved mechanisms to protect themselves at the cellular level in response to a variety of environmental stresses .", "Oxidative stress , caused by an imbalance in the cellular production of free radicals and endogenous antioxidant defenses , can be particularly detrimental to the nervous system ....	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "blood serum", "medicine and health sciences", "immune physiology", "body fluids", "nucleases", "molecular probe techniques", "enzymes", "immunology", "dna-binding proteins", "enzymology", "antigenic variation", "parasitic protozoans", "dna transcription", "trypanosoma brucei", "protozoa...	Ribonuclease H1-targeted R-loops in surface antigen gene expression sites can direct trypanosome immune evasion	journal.pgen.1007729	null	[ [ "The genome provides the blueprint for life and is normally protected from rapid content change by high fidelity DNA replication and a range of repair pathways .", "However , strategies for elevated rates of genome variation have evolved , some of which are genome-wide , such as in developmental chromosom...	[ "Switching of the Variant Surface Glycoprotein ( VSG ) in Trypanosoma brucei provides a crucial host immune evasion strategy that is catalysed both by transcription and recombination reactions , each operating within specialised telomeric VSG expression sites ( ES ) .", "VSG switching is likely triggered by event...	[ "All pathogens must survive eradication by the host immune response in order to continue infections and be passed on to a new host .", "Changes in the proteins expressed on the surface of the pathogen , or on the surface of the cells the pathogen infects , is a widely used strategy to escape immune elimination ."...	2018
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "infectious diseases", "public health and epidemiology", "cell biology", "pathology", "plasmodium", "in vitro", "immunology", "microbiology", "eukaryotes", "chemical biology", "hematology" ]	Microfluidic Modeling of Cell−Cell Interactions in Malaria Pathogenesis	journal.ppat.0030099	null	[ [ "Cellular events that contribute to severe malaria are multi-faceted [1] .", "Binding of malaria-infected red blood cells ( iRBCs ) to host endothelium may alter blood flow , affect blood vessel integrity , and contribute to physical blockages of narrow capillaries [2–4] .", "Loss of red blood cell ( ...	[ "The clinical outcomes of human infections by Plasmodium falciparum remain highly unpredictable .", "A complete understanding of the complex interactions between host cells and the parasite will require in vitro experimental models that simultaneously capture diverse host–parasite interactions relevant to pathoge...	[ "With over 500 million clinical cases and 1 million deaths per year , malaria presents a devastating global health problem .", "Samples from patients with severe disease suggest that binding of malaria-infected red blood cells ( iRBCs ) to host mammalian cells plays an important role in precipitating blood vessel...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Ethylene Promotes Hypocotyl Growth and HY5 Degradation by Enhancing the Movement of COP1 to the Nucleus in the Light	journal.pgen.1004025	null	[ [ "The phytohormone ethylene plays significant roles in many developmental processes and stress responses in plants .", "Molecular and genetic analyses have revealed a linear signalling pathway , which is initiated by ethylene perception at the endoplasmic reticulum membrane , resulting in transcriptional r...	[ "In the dark , etiolated seedlings display a long hypocotyl , the growth of which is rapidly inhibited when the seedlings are exposed to light .", "In contrast , the phytohormone ethylene prevents hypocotyl elongation in the dark but enhances its growth in the light .", "However , the mechanism by which light a...	[ "It is well known that light suppresses hypocotyl growth in seedlings , while the phytohormone ethylene and its precursor 1-aminocyclopropane-1-carboxylate ( ACC ) enhance hypocotyl growth in the light .", "However , the mechanism by which light and ethylene oppositely affect this process at the protein level is ...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "epidemiological statistics", "infectious diseases", "medicine and health sciences", "mathematics", "forecasting", "statistics (mathematics)", "chikungunya infection", "epidemiology", "mathematical and statistical techniques", "influenza", "neglected tropical diseases", "tropical diseases", ...	A human judgment approach to epidemiological forecasting	journal.pcbi.1005248	null	[ [ "It is perhaps unsurprising that societal advances in technology , education , and medicine are concomitant with reduced morbidity and mortality associated with infectious diseases [1] .", "This is exemplified by the staggering drop in infectious disease mortality in the United States during the 20th cent...	[ "Infectious diseases impose considerable burden on society , despite significant advances in technology and medicine over the past century .", "Advanced warning can be helpful in mitigating and preparing for an impending or ongoing epidemic .", "Historically , such a capability has lagged for many reasons , inc...	[ "Despite advanced and widely accessible health care , a large number of annual deaths in the United States are attributable to infectious diseases like influenza .", "Many of these cases could be easily prevented if sufficiently advanced warning was available .", "This is the main goal of epidemiological foreca...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "evolutionary biology/microbial evolution and genomics", "evolutionary biology/genomics", "evolutionary biology/evolutionary ecology", "evolutionary biology/evolutionary and comparative genetics" ]	Incipient Balancing Selection through Adaptive Loss of Aquaporins in Natural Saccharomyces cerevisiae Populations	journal.pgen.1000893	null	[ [ "Biologists have long sought to understand the process of natural selection and the signatures left behind in extant species .", "Finding evidence of adaptive evolution has been a holy grail for evolutionary biologists , because it can provide insights into how and why organisms evolve .", "However , ...	[ "A major goal in evolutionary biology is to understand how adaptive evolution has influenced natural variation , but identifying loci subject to positive selection has been a challenge .", "Here we present the adaptive loss of a pair of paralogous genes in specific Saccharomyces cerevisiae subpopulations .", "W...	[ "Local adaptation is thought to be a driving force in population differentiation and the formation of new species .", "Yet , there are few examples of ecologically relevant phenotypes that have been mapped to individual genes , making it difficult to know what drives the evolution of such genes and contributes to...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics and genomics/disease models", "genetics and genomics/genetics of disease", "genetics and genomics/gene discovery" ]	Tnni3k Modifies Disease Progression in Murine Models of Cardiomyopathy	journal.pgen.1000647	null	[ [ "Heart failure is the common final outcome for many forms of acute and chronic heart disease .", "The prognosis of heart failure is highly variable between patients , and the differences in phenotypic expression ( symptoms , disease progression and course , and final outcome ) create difficulties in the c...	[ "The Calsequestrin ( Csq ) transgenic mouse model of cardiomyopathy exhibits wide variation in phenotypic progression dependent on genetic background .", "Seven heart failure modifier ( Hrtfm ) loci modify disease progression and outcome .", "Here we report Tnni3k ( cardiac Troponin I-interacting kinase ) as th...	[ "Heart failure is the common final outcome of many forms of acute and chronic heart disease .", "The prognosis of heart disease is highly variable between patients , and these differences in the phenotypic expression ( symptoms , course , and final outcome ) are in part due to genetic factors that have proven dif...	2009
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "genetics and genomics/gene expression", "evolutionary biology/evolutionary ecology", "evolutionary biology/sexual behavior", "genetics and genomics/complex traits", "evolutionary biology/genomics" ]	The Sexually Antagonistic Genes of Drosophila melanogaster	journal.pbio.1000335	An association between sex-specific fitness and gene expression in the fruit fly provides an estimate of number, identity and function of sexually antagonistic genes in this species.	[ [ "Males and females differ in the optimal value for most behavioural , morphological , and physiological traits [1] , as a consequence of the different strategies they adopt to maximize their fitness [2] , [3] .", "At the genetic level , these differences trigger an evolutionary conflict between the sexes ...	[ "When selective pressures differ between males and females , the genes experiencing these conflicting evolutionary forces are said to be sexually antagonistic .", "Although the phenotypic effect of these genes has been documented in both wild and laboratory populations , their identity , number , and location rem...	[ "Males and females of many species are different: many of these differences are thought to have evolved because the sexes often have needs and strategies that do not coincide .", "For example , in fruit-flies , females may do best by concentrating their efforts in acquiring resources to be able to lay more eggs ,...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Promiscuous RNA Binding Ensures Effective Encapsidation of APOBEC3 Proteins by HIV-1	journal.ppat.1004609	null	[ [ "The apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 ( APOBEC3 , or A3 ) proteins have been identified as potent antiviral effector proteins [1 , 2] .", "There are seven family members in humans , each of which contains one ( A3A , A3C and A3H ) or two ( A3B , A3D , A3F and A3G ) charact...	[ "The apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 ( APOBEC3 ) proteins are cell-encoded cytidine deaminases , some of which , such as APOBEC3G ( A3G ) and APOBEC3F ( A3F ) , act as potent human immunodeficiency virus type-1 ( HIV-1 ) restriction factors .", "These proteins require packaging i...	[ "APOBEC3 proteins are cell-encoded restriction factors that counteract infections , particularly by retroviruses such as HIV-1 , and retrotransposons .", "When packaged into HIV-1 particles , APOBEC3G and APOBEC3F both inhibit reverse transcription and induce destructive hypermutation in viral DNA .", "The mech...	2015
[ "Introduction", "Methods", "Results", "Discussion", "Conclusion" ]	[ "schistosoma", "invertebrates", "medicine and health sciences", "body fluids", "education", "helminths", "sociology", "tropical diseases", "social sciences", "parasitic diseases", "animals", "parasitology", "urine", "physiological processes", "neglected tropical diseases", "urination",...	Rapid mapping of urinary schistosomiasis: An appraisal of the diagnostic efficacy of some questionnaire-based indices among high school students in Katsina State, northwestern Nigeria	journal.pntd.0005518	null	[ [ "Schistosomiasis , a water-borne neglected tropical disease ( NTD ) , has been reported as the second most prevalent parasitic disease after malaria [1] .", "The causative agent of human schistosomiasis is a digenetic trematode blood fluke of the genus Schistosoma with a complex , indirect life cycle invo...	[ "In sub-Saharan Africa , over 200 million individuals are estimated to be infected with urinary and intestinal schistosomiasis .", "In a bid to lay a foundation for effective future control programme , this study was carried out with the aim of assessing the diagnostic efficacy of some questionnaire-based rapid a...	[ "Schistosomiasis is a water-borne neglected infectious disease of poverty that has consistently plagued over 200 million helpless inhabitants of the tropics , particularly , sub-Sahara Africa .", "Under the auspices of different nomenclatures and affiliations , many control programmes based on Praziquantel have b...	2017
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "body weight", "medicine and health sciences", "swimming", "education", "sociology", "sports and exercise medicine", "social sciences", "physical activity", "biological locomotion", "physiological parameters", "obesity", "public and occupational health", "exercise", "climbing", "educatio...	Performing different kinds of physical exercise differentially attenuates the genetic effects on obesity measures: Evidence from 18,424 Taiwan Biobank participants	journal.pgen.1008277	null	[ [ "Obesity is one of the most challenging public health issues worldwide [1–6] .", "According to the World Health Organization , a person with a body mass index ( BMI ) of 30 kg/m2 or above is generally considered obese .", "Although BMI is easy to calculate and is commonly used to identify obesity , it...	[ "Obesity is a worldwide health problem that is closely linked to many metabolic disorders .", "Regular physical exercise has been found to attenuate the genetic predisposition to obesity .", "However , it remains unknown what kinds of exercise can modify the genetic risk of obesity .", "This study included 18...	[ "The complex interplay of genetics and lifestyle makes obesity a challenging issue .", "Previous studies have found performing regular physical exercise could blunt the genetic effects on body mass index ( BMI ) .", "However , BMI does not take into account lean body mass or identify central obesity .", "More...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "systems biology", "molecular cell biology", "cell biology", "cell growth", "biology", "computational biology", "metabolic networks", "genetics and genomics" ]	Genome-Scale Metabolic Modeling Elucidates the Role of Proliferative Adaptation in Causing the Warburg Effect	journal.pcbi.1002018	null	[ [ "The Warburg effect , a phenomenon discovered by Otto Warburg in 1924 , reflects a shift to an inefficient metabolism in cancer cells , in which an increase in the inefficient production of adenosine 5′-triphosphate ( ATP ) via glycolysis leads to the secretion of non-oxidized carbons in the form of lactate ,...	[ "The Warburg effect - a classical hallmark of cancer metabolism - is a counter-intuitive phenomenon in which rapidly proliferating cancer cells resort to inefficient ATP production via glycolysis leading to lactate secretion , instead of relying primarily on more efficient energy production through mitochondrial ox...	[ "Cancer cells , as opposed to normal cells , produce a substantial amount of energy inefficiently via aerobic glycolysis , even in the presence of sufficient oxygen to support mitochondrial respiration .", "Despite the fact that this phenomenon , called the Warburg effect , has already been discovered back in 192...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "antimicrobials", "renal cell carcinoma", "medicine and health sciences", "cancer treatment", "carcinomas", "drugs", "cancers and neoplasms", "genitourinary tract tumors", "microbiology", "alleles", "antimalarials", "oncology", "mutation", "antibiotics", "nonsense mutation", "pharmacol...	Mechanisms of acquired resistance to rapalogs in metastatic renal cell carcinoma	journal.pgen.1007679	null	[ [ "Both everolimus and temsirolimus , analogs of rapamycin termed rapalogs , are FDA-approved and in common used for treatment of metastatic RCC based on seminal randomized clinical trials [1–3] .", "However , these drugs are known to cause disease stabilization in most cases , with a 5% objective response ...	[ "The mechanistic target of rapamycin ( mTOR ) is an established therapeutic target in renal cell carcinoma ( RCC ) .", "Mechanisms of secondary resistance to rapalog therapy in RCC have not been studied previously .", "We identified six patients with metastatic RCC who initially responded to mTOR inhibitor ther...	[ "Mammalian target of rapamycin ( mTOR ) inhibitors , everolimus and temsirolimus , are FDA-approved for treatment of metastatic renal cell carcinoma ( mRCC ) , but molecular mechanisms of acquired or secondary resistance to these agents are unknown .", "We evaluated six mRCC patients with available pre-treatment ...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "innate immune system", "medicine and health sciences", "immune cells", "immune physiology", "pathology and laboratory medicine", "cytokines", "pathogens", "immunology", "microbiology", "retroviruses", "viruses", "immunodeficiency viruses", "preventive medicine", "developm...	Anti-HIV potency of T-cell responses elicited by dendritic cell therapeutic vaccination	journal.ppat.1008011	null	[ [ "Globally , an estimated 36 . 9 million people were living with Human Immunodeficiency Virus ( HIV ) in 2017 , among them 59% were accessing antiretroviral therapy [1] .", "Introduction of combination antiretroviral therapy ( cART ) since the late 1990’s decreased HIV-related morbidity and mortality [2] a...	[ "Identification and characterization of CD8+ and CD4+ T-cell epitopes elicited by HIV therapeutic vaccination is key for elucidating the nature of protective cellular responses and mechanism of the immune evasion of HIV .", "Here , we report the characterization of HIV-specific T-cell responses in cART ( combinat...	[ "Improvement of therapeutic vaccine strategies in the perspective of HIV cure is warranted and one of the determinant factors for elucidating the nature of protective cellular responses is the identification and characterization of CD8+ and CD4+ T-cell epitopes elicited by the vaccine .", "However , fine characte...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "public health and epidemiology", "diagnostic medicine", "public health" ]	Lymphatic Filariasis: A Method to Identify Subclinical Lower Limb Change in PNG Adolescents	journal.pntd.0001242	null	[ [ "The mosquito-borne parasitic disease lymphatic filariasis ( LF ) is endemic in around 81 tropical countries , has a global burden of around 120 million cases , and is classified by the World Health organization as the second most common cause of long term disability after mental illness [1] .", "Three sp...	[ "Lymphedema related to lymphatic filariasis ( LF ) is a disabling condition that commonly manifests in adolescence .", "Fifty-three adolescents , 25 LF infected and 28 LF non-infected , in age and sex-matched groups , using the Binax ICT rapid card test for filarial antigen were recruited to the study .", "None...	[ "The effects of lymphatic filariasis ( LF ) on the lymphatic system often become apparent during adolescence when the lower limb swells due to lymphedema and males develop hydrocele .", "Currently there is no simple or mobile field method to identify those at greatest risk of developing lymphedema or those with e...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "keratinocytes", "pathology and laboratory medicine", "ultraviolet radiation", "light", "electromagnetic radiation", "epithelial cells", "radiation", "animal models", "oncology", "mutation", "model organisms", "signs and symptoms", "experimental organism sys...	Beta HPV38 oncoproteins act with a hit-and-run mechanism in ultraviolet radiation-induced skin carcinogenesis in mice	journal.ppat.1006783	null	[ [ "Non-melanoma skin cancer ( NMSC ) is the most common cancer in adult Caucasian populations [1] .", "The cutaneous human papillomavirus ( HPV ) types belonging to genus beta are suspected , together with ultraviolet ( UV ) radiation , to be involved in NMSC [2 , 3] .", "The first two beta HPV types , ...	[ "Cutaneous beta human papillomavirus ( HPV ) types are suspected to be involved , together with ultraviolet ( UV ) radiation , in the development of non-melanoma skin cancer ( NMSC ) .", "Studies in in vitro and in vivo experimental models have highlighted the transforming properties of beta HPV E6 and E7 oncopro...	[ "Many epidemiological and biological findings support the hypothesis that beta HPV types cooperate with UV radiation in the induction of NMSC , the most common form of human cancer .", "We have previously shown that K14 HPV38 E6/E7 Tg mice , when exposed to long-term UV radiation , developed NMSC , whereas WT ani...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "protein interactions", "enzymes", "regulatory proteins", "enzymology", "microbiology", "basic cancer research", "oncology", "model organisms", "population modeling", "enzyme chemistry", "research and analysis methods", "infectious diseases", "proteins", "...	The Human Adenovirus E4-ORF1 Protein Subverts Discs Large 1 to Mediate Membrane Recruitment and Dysregulation of Phosphatidylinositol 3-Kinase	journal.ppat.1004102	null	[ [ "Human adenovirus type 9 ( Ad9 ) is a member of the subgroup D adenoviruses that cause eye infections in people [1] .", "In addition , infection of experimental animals with Ad9 generates estrogen-dependent mammary tumors , and the E4-ORF1 gene is the primary viral oncogenic determinant [2]–[4] .", "T...	[ "Adenoviruses infect epithelial cells lining mucous membranes to cause acute diseases in people .", "They are also utilized as vectors for vaccination and for gene and cancer therapy , as well as tools to discover mechanisms of cancer due to their tumorigenic potential in experimental animals .", "The adenoviru...	[ "Adenoviruses cause acute illnesses in people , and are additionally utilized both as vehicles to cure genetic diseases , fight cancer , and deliver vaccines , and as tools to discover how cancers develop due to a capacity to generate tumors in experimental animals .", "The adenovirus E4-ORF1 protein reprograms c...	2014
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "enzymes", "endoplasmic reticulum", "cell processes", "enzymology", "phosphatases", "physiological processes", "sequence motif analysis", "trichomonas", "cellular structures and organelles", "research and analysis methods", "sequence analysis", "sequence align...	A secreted Heat shock protein 90 of Trichomonas vaginalis	journal.pntd.0006493	null	[ [ "Trichomonas vaginalis is the causative agent of Trichomoniasis , a leading non-viral sexually transmitted disease worldwide [1] .", "The pathogen induces local inflammation of the lower genitourinary tract , can be involved in premature labor and low birth weight .", "Trichomoniasis affects both male...	[ "Trichomonas vaginalis is a causative agent of Trichomoniasis , a leading non-viral sexually transmitted disease worldwide .", "In the current study , we show Heat shock protein 90 is essential for its growth .", "Upon genomic analysis of the parasite , it was found to possess seven ORFs which could potentially...	[ "Hsp90 is an essential chaperone in eukaryotes and it is often described as a master regulator of cellular homeostasis .", "In addition to its well-known functions inside the cell , extracellular Hsp90 has also been implicated in migration and invasion of tumor cells .", "We have , for the first time , identifi...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Vesicular Stomatitis Virus-Based Vaccines Protect Nonhuman Primates against Bundibugyo ebolavirus	journal.pntd.0002600	null	[ [ "The viruses in the family Filoviridae and within the genera Ebolavirus ( EBOV ) and Marburgvirus ( MARV ) cause severe and often fatal hemorrhagic fever ( HF ) in humans and nonhuman primates ( NHPs ) [1] , [2] .", "Case fatality rates with these viruses range from 23–90% depending on the strain and/or s...	[ "Ebola virus ( EBOV ) causes severe and often fatal hemorrhagic fever in humans and nonhuman primates ( NHPs ) .", "Currently , there are no licensed vaccines or therapeutics for human use .", "Recombinant vesicular stomatitis virus ( rVSV ) -based vaccine vectors , which encode an EBOV glycoprotein in place of...	[ "Ebola viruses ( EBOV ) , of which there are five species , are categorized as Category A Priority Pathogens and Tier 1 Select Agents by several US Government agencies as a result of their high mortality rates and potential for use as agents of bioterrorism .", "Currently , there are no vaccines or therapeutics a...	2013
[ "Introduction", "Results and discussion", "Methods and materials" ]	[ "methods and resources", "enzymes", "enzymology", "parasitic protozoans", "genomic databases", "protozoans", "genome analysis", "energy-producing organelles", "mitochondria", "bioenergetics", "cellular structures and organelles", "research and analysis methods", "sequence analysis", "blast...	Extreme genome diversity in the hyper-prevalent parasitic eukaryote Blastocystis	journal.pbio.2003769	null	[ [ "Blastocystis is a genus of atypical , nonflagellated , anaerobic stramenopiles commonly inhabiting the intestinal tract of humans and other animals .", "The majority of stramenopiles , which , along with the Alveolata and Rhizaria , are members of the eukaryotic supergroup known as SAR , are marine bifla...	[ "Blastocystis is the most prevalent eukaryotic microbe colonizing the human gut , infecting approximately 1 billion individuals worldwide .", "Although Blastocystis has been linked to intestinal disorders , its pathogenicity remains controversial because most carriers are asymptomatic .", "Here , the genome seq...	[ "Blastocystis are unicellular eukaryotic organisms related to algae and some plant pathogens .", "They are common constituents of the human gut microbial community , colonizing approximately 1 billion humans worldwide .", "Whether their presence is harmful or not continues to be hotly debated .", "Part of the...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular machines", "molecular complexes", "genetic elements", "gene expression", "genetics", "biology and life sciences", "molecular genetics", "molecular biology techniques", "molecular biology" ]	Genome-Wide Mapping of Yeast RNA Polymerase II Termination	journal.pgen.1004632	null	[ [ "Termination of RNA Polymerase II ( Pol II ) transcription plays an essential role in the transcription cycle and has been the subject of several recent reviews [1] , [2] .", "Disruption of the elongation complex at terminators recycles Pol II maintaining a pool of free enzyme able to compete for unoccupi...	[ "Yeast RNA polymerase II ( Pol II ) terminates transcription of coding transcripts through the polyadenylation ( pA ) pathway and non-coding transcripts through the non-polyadenylation ( non-pA ) pathway .", "We have used PAR-CLIP to map the position of Pol II genome-wide in living yeast cells after depletion of ...	[ "Transcription termination is an important regulatory event for both non-coding and coding transcripts .", "Using high-throughput sequencing , we have mapped RNA Polymerase II's position in the genome after depletion of termination factors from the nucleus .", "We found that depletion of Ysh1 and Sen1 cause bui...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "immune cells", "immunology", "enzymology", "social sciences", "neuroscience", "immune receptor signaling", "membrane receptor signaling", "sequence motif analysis", "enzyme kinetics", "research and analysis methods", "sequence analysis", "immune system protei...	Simple biochemical networks allow accurate sensing of multiple ligands with a single receptor	journal.pcbi.1005490	null	[ [ "Cells obtain information about their environment by capturing ligand molecules with receptors on their surface and estimating the ligand concentration from the receptor activity .", "Limits on the accuracy of such estimation have been a subject of interest since the seminal work of Berg and Purcell [1] ,...	[ "Cells use surface receptors to estimate concentrations of external ligands .", "Limits on the accuracy of such estimations have been well studied for pairs of ligand and receptor species .", "However , the environment typically contains many ligands , which can bind to the same receptors with different affinit...	[ "Cells live in chemically complex environments with many different chemical ligands around them .", "Can cells estimate concentrations of more ligands than they have receptor types ?", "In this paper , we show that , surprisingly , the answer is “yes” , and the estimation can be implemented with simple biochemi...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "viral envelope", "molecular cell biology", "viral transmission and infection", "virology", "biology", "microbiology", "viral structure", "host-pathogen interaction" ]	A36-dependent Actin Filament Nucleation Promotes Release of Vaccinia Virus	journal.ppat.1003239	null	[ [ "Crossing the membrane of host cells , either during entry or escape , is a major obstacle facing prospective viral pathogens during infection .", "Enveloped viruses are released from cells by either the acquisition or loss of an outer membrane and both strategies pose unique challenges to the final separ...	[ "Cell-to-cell transmission of vaccinia virus can be mediated by enveloped virions that remain attached to the outer surface of the cell or those released into the medium .", "During egress , the outer membrane of the double-enveloped virus fuses with the plasma membrane leaving extracellular virus attached to the...	[ "Traversing the plasma membrane of the host cell is a significant challenge for many viruses during the infection cycle , and the efficiency of detachment from the host cell and subsequent release can have implications in pathogenesis .", "Vaccinia virus exits cells through the loss of an outer membrane but remai...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "developmental biology", "cell biology", "neurological disorders", "neuroscience", "homo (human)", "genetics and genomics" ]	A Genomic Pathway Approach to a Complex Disease: Axon Guidance and Parkinson Disease	journal.pgen.0030098	null	[ [ "Complex diseases occur commonly in the population and are a major source of disability and death worldwide .", "They are thought to arise from multiple predisposing factors , both genetic and nongenetic , and joint effects of those factors are thought to be of key importance [1 , 2] .", "Parkinson di...	[ "While major inroads have been made in identifying the genetic causes of rare Mendelian disorders , little progress has been made in the discovery of common gene variations that predispose to complex diseases .", "The single gene variants that have been shown to associate reproducibly with complex diseases typica...	[ "Complex diseases are common disorders that are believed to have many causes .", "Examples include Alzheimer disease , diabetes mellitus , nicotine and alcohol dependence , and several cancers .", "This study represents a paradigm shift from single gene to pathway studies of complex diseases .", "We present t...	2007
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "action potentials", "medicine and health sciences", "neural networks", "membrane potential", "sociology", "signaling networks", "social sciences", "electrophysiology", "neuroscience", "network analysis", "thermodynamics", "computer and information sciences", "entropy", "animal cells", "...	High-Degree Neurons Feed Cortical Computations	journal.pcbi.1004858	null	[ [ "Networks of cortical neurons transmit and compute information .", "Fortunately , recent research has improved our understanding of both of these tasks [1–6] .", "Progress in these two areas lets us now ask how information modification ( computation ) depends on the number of connections a neuron rece...	[ "Recent work has shown that functional connectivity among cortical neurons is highly varied , with a small percentage of neurons having many more connections than others .", "Also , recent theoretical developments now make it possible to quantify how neurons modify information from the connections they receive ."...	[ "We recorded the electrical activity of hundreds of neurons simultaneously in brain tissue from mice and we analyzed these signals using state-of-the-art tools from information theory .", "These tools allowed us to ascertain which neurons were transmitting information to other neurons and to characterize the comp...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome expression analysis", "functional genomics", "gene regulation", "microbiology", "dna transcription", "histone modification", "model organisms", "epigenetics", "molecular genetics", "chromatin", "gene expression", "biology", "molecular biology", "genetics", "yeast and fungal model...	Two Distinct Repressive Mechanisms for Histone 3 Lysine 4 Methylation through Promoting 3′-End Antisense Transcription	journal.pgen.1002952	null	[ [ "Packaging of eukaryotic DNA with histones has a generally repressive effect on transcription [1] .", "Histones themselves are subject to a variety of post-translational modifications , such as acetylation , methylation and ubiquitinylation .", "These modifications correlate with specific states of tr...	[ "Histone H3 di- and trimethylation on lysine 4 are major chromatin marks that correlate with active transcription .", "The influence of these modifications on transcription itself is , however , poorly understood .", "We have investigated the roles of H3K4 methylation in Saccharomyces cerevisiae by determining ...	[ "In eukaryotes , DNA is packaged together with histones into nucleosomes .", "This packaging has a repressive role on gene expression .", "The N-termini of histones are subject to multiple modifications that affect DNA–dependent processes .", "The histone modification that has been predominantly linked with a...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "bacterial evolution", "genomics", "biology", "computational biology", "comparative genomics", "microbiology", "salmonella", "bacterial pathogens" ]	Recombination and Population Structure in Salmonella enterica	journal.pgen.1002191	null	[ [ "Salmonella enterica subspecies enterica ( subsequently referred to simply as enterica ) is a major cause of enteric fever in humans and gastroenteritis in humans and animals .", "Its diversity has traditionally been described on the basis of serological differences following the Kauffmann-White classific...	[ "Salmonella enterica is a bacterial pathogen that causes enteric fever and gastroenteritis in humans and animals .", "Although its population structure was long described as clonal , based on high linkage disequilibrium between loci typed by enzyme electrophoresis , recent examination of gene sequences has reveal...	[ "Salmonella enterica is a species of bacteria that causes severe diseases in humans and animals .", "We sequenced about a tenth of the genome from a broadly sampled collection of S . enterica .", "By comparing these genetic sequences , we were able to partially reconstruct the ancestry of this sample .", "We ...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "invertebrates", "medicine and health sciences", "affinity chromatography", "caenorhabditis", "messenger rna", "dna-binding proteins", "animals", "dna transcription", "animal models", "physiological processes", "caenorhabditis elegans", "model organisms", "homeostasis", ...	The Nuclear Receptor HIZR-1 Uses Zinc as a Ligand to Mediate Homeostasis in Response to High Zinc	journal.pbio.2000094	null	[ [ "Zinc is an essential nutrient for all life , including plants , animals and microbes , because zinc is involved in many different cellular events .", "Zn2+ binds tightly to many proteins and thereby contributes to their tertiary structure or catalytic activity [1] , and Zn2+ has been proposed to function...	[ "Nuclear receptors were originally defined as endocrine sensors in humans , leading to the identification of the nuclear receptor superfamily .", "Despite intensive efforts , most nuclear receptors have no known ligand , suggesting new ligand classes remain to be discovered .", "Furthermore , nuclear receptors ...	[ "Zinc is an essential nutrient for all life forms , and maintaining zinc homeostasis is critical for survival .", "However , little is known about how animals sense changes in zinc availability and make adjustments to maintain homeostasis .", "In particular , logic dictates there must be a mechanism for zinc se...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "immune physiology", "enzyme-linked immunoassays", "spleen", "immunology", "animal models", "preventive medicine", "developmental biology", "model organisms", "vaccination and immunization", "immunologic techniques", "digestive system", "research and analysis ...	Oral Vaccination with Attenuated Salmonella typhimurium-Delivered TsPmy DNA Vaccine Elicits Protective Immunity against Trichinella spiralis in BALB/c Mice	journal.pntd.0004952	null	[ [ "Trichinellosis , a serious food-borne parasitic zoonosis and an important public health problem worldwide , is mainly caused by infection with the tissue-dwelling nematode Trichinella spiralis [1 , 2] .", "People develop this infection through ingestion of raw or undercooked meat contaminated with encaps...	[ "Our previous studies showed that Trichinella spiralis paramyosin ( TsPmy ) is an immunomodulatory protein that inhibits complement C1q and C8/C9 to evade host complement attack .", "Vaccination with recombinant TsPmy protein induced protective immunity against T . spiralis larval challenge .", "Due to the diff...	[ "Trichinellosis is one of the most important food-borne parasitic zoonoses , and a serious public health issue worldwide .", "Developing a vaccine is an alternative approach to control the disease .", "TsPmy is a paramyosin expressed by Trichinella spiralis to bind and neutralize human complement and a vaccine ...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "flow cytometry", "medicine and health sciences", "enzyme-linked immunoassays", "enzymes", "metabolic processes", "enzymology", "plasmid construction", "physiological processes", "dna construction", "glycosylation", "molecular biology techniques", "immunologic techniques", "research and anal...	Proteolytic Origin of the Soluble Human IL-6R In Vivo and a Decisive Role of N-Glycosylation	journal.pbio.2000080	null	[ [ "Interleukin-6 ( IL-6 ) is a pleiotropic cytokine with important functions in many physiological and pathophysiological conditions [1 , 2] .", "IL-6 activates intracellular signaling cascades through a homodimer of the ubiquitously expressed β-receptor glycoprotein 130 ( gp130 ) [3] but first has to bind ...	[ "Signaling of the cytokine interleukin-6 ( IL-6 ) via its soluble IL-6 receptor ( sIL-6R ) is responsible for the proinflammatory properties of IL-6 and constitutes an attractive therapeutic target , but how the sIL-6R is generated in vivo remains largely unclear .", "Here , we use liquid chromatography–mass spec...	[ "Interleukin-6 ( IL-6 ) is a cytokine secreted by our body upon infection or trauma to stimulate the immune system response .", "IL-6 is partially responsible for fever and triggers inflammation in many diseases .", "It activates its target cells via the membrane-bound IL-6 receptor ( IL-6R ) , and soluble form...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "infectious disease modeling", "viral diseases" ]	Real-time Transcriptional Profiling of Cellular and Viral Gene Expression during Lytic Cytomegalovirus Infection	journal.ppat.1002908	null	[ [ "Herpesviruses are large DNA viruses which cause a broad range of disease ranging from the common cold sore to cancer .", "They all share the ability to establish a life-long , latent infection , leaving the infected individual at constant risk of reactivation and subsequent disease .", "The human cyt...	[ "During viral infections cellular gene expression is subject to rapid alterations induced by both viral and antiviral mechanisms .", "In this study , we applied metabolic labeling of newly transcribed RNA with 4-thiouridine ( 4sU-tagging ) to dissect the real-time kinetics of cellular and viral transcriptional ac...	[ "Cytomegaloviruses are large DNA viruses , which establish life-long latent infections , leaving the infected individual at risk of reactivation and disease .", "Here , we applied 4-thiouridine- ( 4sU ) -tagging of newly transcribed RNA to monitor the real-time kinetics of transcriptional activity of both cellula...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "organismal evolution", "hiv infections", "medicine and health sciences", "hiv prevention", "pathology and laboratory medicine", "viral transmission and infection", "parasite evolution", "pathogens", "microbiology", "parasitology", "retroviruses", "viruses", "immunodeficiency viruses", "pr...	Conflicting Selection Pressures Will Constrain Viral Escape from Interfering Particles: Principles for Designing Resistance-Proof Antivirals	journal.pcbi.1004799	null	[ [ "Defective interfering particles ( DIPs ) are ‘cheaters’ in a viral population .", "Rather than carrying a full set of genes essential for their own replication , these deletion mutants require co-infection by replication-competent ‘helper’ viruses to provide their missing components for replication , pac...	[ "The rapid evolution of RNA-encoded viruses such as HIV presents a major barrier to infectious disease control using conventional pharmaceuticals and vaccines .", "Previously , it was proposed that defective interfering particles could be developed to indefinitely control the HIV/AIDS pandemic; in individual pati...	[ "A major obstacle to effective antimicrobial therapy campaigns is the rapid evolution of drug resistance .", "Given the static nature of current pharmaceuticals and vaccines , natural selection inevitably drives pathogens to mutate into drug-resistant variants that can resume productive replication .", "Further...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "hiv infections", "innate immune system", "medicine and health sciences", "immune cells", "immune physiology", "pathology and laboratory medicine", "cytokines", "body fluids", "immune activation", "pathogens", "antiviral therapy", "immunology", "microbiology", "retroviruse...	Loss of Function of Intestinal IL-17 and IL-22 Producing Cells Contributes to Inflammation and Viral Persistence in SIV-Infected Rhesus Macaques	journal.ppat.1005412	null	[ [ "HIV infection in humans and SIV infection in rhesus macaques ( RMs ) is characterized by the establishment of high and persistent levels of immune activation and inflammation , which are strong and independent predictors of disease progression in the natural history of infection and co-morbidities/mortalitie...	[ "In HIV/SIV-infected humans and rhesus macaques ( RMs ) , a severe depletion of intestinal CD4+ T-cells producing interleukin IL-17 and IL-22 associates with loss of mucosal integrity and chronic immune activation .", "However , little is known about the function of IL-17 and IL-22 producing cells during lentivir...	[ "Persistent immune activation and inflammation are key features and strong predictors of morbidity/mortality in HIV infection .", "A specific quantitative loss of Th17 and Th22 CD4+ T-cells , which are crucial to maintaining the mucosal immunity , has been shown to directly associate with microbial translocation ...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "plant anatomy", "quantitative trait loci", "population genetics", "developmental biology", "plant science", "plant pathology", "molecular biology techniques", "population biology", "research and analysis methods", "gene mapping", "life cycles", "leaves", "molecular biology", "genetic loci...	The genetic architecture of colonization resistance in Brachypodium distachyon to non-adapted stripe rust (Puccinia striiformis) isolates	journal.pgen.1007637	null	[ [ "An integral characteristic of plant-pathogen interactions are the several events that lead to infection of a plant by a pathogen .", "To successfully complete its life cycle , that is to colonize a plant and reproduce , a plant pathogen needs to overcome several preformed and inducible barriers [1] .", ...	[ "Multilayered defense responses ensure that plants are hosts to only a few adapted pathogens in the environment .", "The host range of a plant pathogen depends on its ability to fully overcome plant defense barriers , with failure at any single step sufficient to prevent life cycle completion of the pathogen .", ...	[ "Plants are constantly exposed to a multitude of potential pathogens but remain immune to most of these due to a multilayered immune system .", "Pathogens have specialized by adapting to certain host plants and their defense barriers .", "Most of our understanding of plant-pathogen interactions stems from these...	2018
[ "Introduction", "Results", "Discussion", "Material and methods" ]	[ "blood cells", "flow cytometry", "cell physiology", "cell binding", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "hek 293 cells", "nervous system", "immunology", "biological cultures", "electrophysiology", "neuroscience", "research and analysis metho...	Subversion of natural killer cell responses by a cytomegalovirus-encoded soluble CD48 decoy receptor	journal.ppat.1007658	null	[ [ "Natural killer ( NK ) cells are circulating lymphocytes that play a pivotal role in the rapid recognition and control of viral infections .", "NK functions are regulated by a repertoire of specific receptors that , upon engagement with their respective ligands on target cells , transmit stimulatory or in...	[ "Throughout evolution , cytomegaloviruses ( CMVs ) have been capturing genes from their hosts , employing the derived proteins to evade host immune defenses .", "We have recently reported the presence of a number of CD48 homologs ( vCD48s ) encoded by different pathogenic viruses , including several CMVs .", "H...	[ "In order to evade detection and destruction by cytotoxic lymphocytes and successfully persist within their hosts , cytomegalovirus ( CMVs ) have evolved a number of genes dedicated to block immune recognition .", "Certain CMVs and other large DNA viruses encode homologs of the cell-surface molecule CD48 , a liga...	2019
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "blood cells", "antimicrobials", "innate immune system", "medicine and health sciences", "immune cells", "immune physiology", "cytokines", "drugs", "immunology", "microbiology", "antifungals", "neuroscience", "learning and memory", "preventive medicine", "developmental biology", "cogni...	Antifungal Tc17 cells are durable and stable, persisting as long-lasting vaccine memory without plasticity towards IFNγ cells	journal.ppat.1006356	null	[ [ "Memory Th1 and Tc1 ( IFNγ+ CD8+ T cells ) cells have been well characterized .", "Following the expansion phase of an immune response , a pool of memory precursor cells ( ~10% ) survives the contraction phase , and slowly differentiates into long-lasting memory cells[1] .", "Memory Th1 and Tc1 cells ...	[ "Our understanding of persistence and plasticity of IL-17A+ memory T cells is clouded by conflicting results in models analyzing T helper 17 cells .", "We studied memory IL-17A+ CD8+ T-cell ( Tc17 ) homeostasis , persistence and plasticity during fungal vaccine immunity .", "We report that vaccine-induced memor...	[ "CD4+ T-cell deficient patients such as those with AIDS and idiopathic CD4+ T-cell lymphopenia are vulnerable to systemic fungal infections .", "We previously showed that CD8+ T cells can be exploited in CD4+ T cell deficient hosts for vaccine immunity against lethal fungal pneumonia in mice and that IL-17A produ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Automated Learning of Subcellular Variation among Punctate Protein Patterns and a Generative Model of Their Relation to Microtubules	journal.pcbi.1004614	null	[ [ "Fluorescence microscope images can provide important information about the subcellular location of proteins , and automated systems can be used to assign these proteins to major subcellular location classes with accuracy at or above that of human annotators [1 , 2] .", "However , assigning higher resolut...	[ "Characterizing the spatial distribution of proteins directly from microscopy images is a difficult problem with numerous applications in cell biology ( e . g . identifying motor-related proteins ) and clinical research ( e . g . identification of cancer biomarkers ) .", "Here we describe the design of a system t...	[ "Determining the subcellular location of all proteins is a critical but daunting task for systems biologists , especially when variation between different cell types is considered .", "Fluorescence microscopy is the main source of information about subcellular location , but large collections of fluorescence imag...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "biochemistry", "signal transduction", "infectious diseases", "medicine and health sciences", "neurochemistry", "helminth infections", "schistosomiasis", "cell biology", "membrane receptor signaling", "neurochemicals", "mechanisms of signal transduction", "neglected tropical diseases", "biol...	Functional Characterization of a Novel Family of Acetylcholine-Gated Chloride Channels in Schistosoma mansoni	journal.ppat.1004181	null	[ [ "Flatworms of the genus Schistosoma are the causative agents of the debilitating parasitic infection schistosomiasis , afflicting over 230 million people in 74 endemic countries [1] .", "The majority of human schistosomiasis can be attributed to three species- S . mansoni , S . japonicum and S . haematobi...	[ "Acetylcholine is the canonical excitatory neurotransmitter of the mammalian neuromuscular system .", "However , in the trematode parasite Schistosoma mansoni , cholinergic stimulation leads to muscle relaxation and a flaccid paralysis , suggesting an inhibitory mode of action .", "Information about the pharmac...	[ "Schistosomiasis is a widespread , chronic disease affecting over 200 million people in developing countries .", "Currently , there is no vaccine available and treatment depends on the use of a single drug , praziquantel .", "Reports of reduced praziquantel efficacy , as well as its ineffectiveness against larv...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "blood cells", "death rates", "medicine and health sciences", "body fluids", "pathology and laboratory medicine", "demography", "melioidosis", "diabetes mellitus", "bacterial diseases", "physiological processes", "sepsis", "endocrine disorders", "signs and symptoms", "platelets", "infect...	Increased Von Willebrand factor, decreased ADAMTS13 and thrombocytopenia in melioidosis	journal.pntd.0005468	null	[ [ "The soil-dwelling intracellular bacterium Burkholderia pseudomallei is an important cause of community-acquired Gram-negative sepsis in Southeast Asia and Northern Australia [1 , 2] , and the causative agent of melioidosis .", "Recently , it has been predicted that the annual burden of melioidosis is muc...	[ "Melioidosis , caused by bioterror treat agent Burkholderia pseudomallei , is an important cause of community-acquired Gram-negative sepsis in Southeast Asia and Northern Australia .", "New insights into the pathogenesis of melioidosis may help improve treatment and decrease mortality rates from this dreadful dis...	[ "Melioidosis , caused by bioterror threat agent Burkholderia pseudomallei , is an important cause of community-acquired sepsis in Southeast Asia and Northern Australia .", "Recently , it has been predicted that the annual burden of melioidosis is much higher than previously thought , with 165 . 000 human cases fr...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "antimicrobials", "medicine and health sciences", "pathology and laboratory medicine", "drugs", "fungicides", "tropical diseases", "microbiology", "light microscopy", "immunology", "antifungals", "fungal structure", "toxicology", "toxicity", "fungi", "signs and symptoms", "microscopy",...	Antifungal activity of two oxadiazole compounds for the paracoccidioidomycosis treatment	journal.pntd.0007441	null	[ [ "Paracoccidioidomycosis ( PCM ) is an endemic fungal disease in Latin American countries , which presents high prevalence in South America .", "The lung is the most affected organ , mainly during chronic form , presenting pulmonary architectural distortion , which can lead to hypoxemia and hypercapnia in ...	[ "Paracoccidioidomycosis ( PCM ) is a neglected disease present in Latin America with difficulty in treatment and occurrence of serious sequelae .", "Thus , the development of alternative therapies is imperative .", "In the current work , two oxadiazole compounds ( LMM5 and LMM11 ) presented fungicidal activity ...	[ "Paracoccidioidomycosis ( PCM ) is a granulomatous fungal infection with clinically severe forms and serious pulmonary sequelae .", "The current limited arsenal and prolonged treatment regimen demonstrate the need for new antifungals .", "This study reveals two fungicidal oxadiazole compounds for PCM treatment ...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome expression analysis", "microbiology", "gene function", "epigenetics", "molecular genetics", "mycology", "cell adhesion", "gene expression", "microbial pathogens", "biology", "pathogenesis", "cell biology", "genetics", "genomics", "molecular cell biology", "genetics and genomics...	Genetic Control of Conventional and Pheromone-Stimulated Biofilm Formation in Candida albicans	journal.ppat.1003305	null	[ [ "Candida albicans is a prevalent pathogen of humans that colonizes and infects multiple niches in the mammalian host .", "To achieve such extreme adaptability , this pathogen has evolved genetic and epigenetic mechanisms that modulate cell behavior and morphology in response to environmental signals .", ...	[ "Candida albicans can stochastically switch between two phenotypes , white and opaque .", "Opaque cells are the sexually competent form of C . albicans and therefore undergo efficient polarized growth and mating in the presence of pheromone .", "In contrast , white cells cannot mate , but are induced – under a ...	[ "Candida albicans is the predominant fungal pathogen afflicting humans , where many infections arise due to its proclivity to form biofilms .", "Biofilms are complex multicellular communities in which cells exhibit distinct properties to those grown in suspension .", "They are particularly relevant in the devel...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "primates", "viruses", "virology", "evolutionary biology", "homo (human)", "rattus (rat)" ]	Positive Selection and Increased Antiviral Activity Associated with the PARP-Containing Isoform of Human Zinc-Finger Antiviral Protein	journal.pgen.0040021	null	[ [ "Recent discoveries have highlighted the role of intrinsic immunity genes in primate host defense against viral infections [1–3] .", "These genes are predicted to be locked in ancient , ongoing genetic conflicts with an ever-changing repertoire of viral infections [4–6] .", "Consistent with this predi...	[ "Intrinsic immunity relies on specific recognition of viral epitopes to mount a cell-autonomous defense against viral infections .", "Viral recognition determinants in intrinsic immunity genes are expected to evolve rapidly as host genes adapt to changing viruses , resulting in a signature of adaptive evolution ....	[ "Host–virus interactions are a classic example of genetic conflict in which both entities try to gain an evolutionary advantage over the other .", "This “back-and-forth” evolution is predicted to result in rapid changes of both host and viral proteins , which results in an evolutionary signature of positive selec...	2008
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "innate immune system", "medicine and health sciences", "microbial mutation", "immune physiology", "cytokines", "pathology and laboratory medicine", "influenza", "pathogens", "immunology", "microbiology", "orthomyxoviruses", "animals", "animal models", "viruses", "deve...	Influenza NS1 directly modulates Hedgehog signaling during infection	journal.ppat.1006588	null	[ [ "The multifunctional Non-Structural-1 protein ( NS1 ) is one of 14 proteins encoded by influenza A virus [1–3] .", "NS1 interacts with several viral and host components to subvert cellular defense mechanisms and promote viral replication via two domains: an N-terminal RNA-binding domain ( RBD ) and an eff...	[ "The multifunctional NS1 protein of influenza A viruses suppresses host cellular defense mechanisms and subverts other cellular functions .", "We report here on a new role for NS1 in modifying cell-cell signaling via the Hedgehog ( Hh ) pathway .", "Genetic epistasis experiments and FRET-FLIM assays in Drosophi...	[ "The NS1 protein produced by influenza A viruses alters host cellular defense mechanisms .", "We report here on a new role for NS1 in modifying cell-cell communication via the Hedgehog ( Hh ) signaling pathway .", "Genetic and microscopy studies in flies indicate that NS1 alters the transcriptional read-out of ...	2017
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "sequencing techniques", "applied mathematics", "genomic library construction", "simulation and modeling", "algorithms", "genome sequencing", "genomic databases", "mathematics", "genome analysis", "copy number variation", "molecular biology techniques", "dna construction", "research and anal...	Comprehensively benchmarking applications for detecting copy number variation	journal.pcbi.1007069	null	[ [ "Copy number variation ( CNV ) is a type of genomic structural variation that contains segmental duplications or deletions of a DNA fragment; the CNV size usually ranges from 1 kb to 3 Mb[1] .", "CNVs are found widely in individual human genomes , and they seldomly lead to genetic diseases[2] .", "CNV...	[ "Motivation: Recently , copy number variation ( CNV ) has gained considerable interest as a type of genomic variation that plays an important role in complex phenotypes and disease susceptibility .", "Since a number of CNV detection methods have recently been developed , it is necessary to help investigators choo...	[ "As an important type of genomic structural variation , CNVs are associated with complex phenotypes because they change the number of copies of genes in cells , affecting coding sequences and playing an important role in the susceptibility or resistance to human diseases .", "To identify CNVs , several experiment...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Cortical and Hippocampal Correlates of Deliberation during Model-Based Decisions for Rewards in Humans	journal.pcbi.1003387	null	[ [ "Model-based decisions stand in contrast to a simpler sort of learned decision making whose neural instantiation is better understood: simply learning to repeat rewarded behaviors [4]–[6] .", "To explain the former , more knowledge-driven path to decisions , researchers have long argued that the brain mai...	[ "How do we use our memories of the past to guide decisions we've never had to make before ?", "Although extensive work describes how the brain learns to repeat rewarded actions , decisions can also be influenced by associations between stimuli or events not directly involving reward — such as when planning routes...	[ "We are always learning regularities in the world around us: where things are , and in what order we might find them .", "Our knowledge of these contingencies can be relied upon if we later want to use them to make decisions .", "However , there is little agreement about the neurobiological mechanism by which l...	2013
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "split-decomposition method", "pathogens", "microbiology", "retroviruses", "viruses", "immunodeficiency viruses", "multiple alignment calculation", "rna viruses", "protein structure", "sequence motif analysis", "glycosylati...	Motif-Aware PRALINE: Improving the alignment of motif regions	journal.pcbi.1006547	null	[ [ "Sequence motifs are commonly described as relatively short conserved regions within a protein or DNA sequence [1] .", "These regions are of functional importance: they serve as binding sites for ligands or transcription factors , and as catalytic sites or structural elements .", "The presence of sequ...	[ "Protein or DNA motifs are sequence regions which possess biological importance .", "These regions are often highly conserved among homologous sequences .", "The generation of multiple sequence alignments ( MSAs ) with a correct alignment of the conserved sequence motifs is still difficult to achieve , due to t...	[ "The most important functional parts of proteins are often small—but very specific—sequence motifs .", "Moreover , these motifs tend to be strongly conserved during evolution due to their functional role .", "Nevertheless , when trying to align protein sequences of the same family , it is often very difficult t...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "livestock", "medicine and health sciences", "animal diseases", "foot and mouth disease", "ruminants", "immunology", "vertebrates", "animals", "mammals", "simulation and modeling", "preventive medicine", "infectious disease control", "vaccination and immunization", "zoology", "research a...	Real-time decision-making during emergency disease outbreaks	journal.pcbi.1006202	null	[ [ "The responsibilities of policymakers during infectious disease outbreaks include the difficult task of choosing between multiple control interventions based on an uncertain future .", "Mathematical and simulation models have proved a useful tool to aid decision-making during disease outbreaks by both gen...	[ "In the event of a new infectious disease outbreak , mathematical and simulation models are commonly used to inform policy by evaluating which control strategies will minimize the impact of the epidemic .", "In the early stages of such outbreaks , substantial parameter uncertainty may limit the ability of models ...	[ "Mathematical and simulation models may be used to inform policy in the early stages of an infectious disease outbreak by evaluating which control strategies will minimize the impact of the epidemic .", "In these early stages , significant uncertainty can limit the ability of models to provide accurate prediction...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "cognitive neurology", "medicine and health sciences", "maternal health", "obstetrics and gynecology", "united nations", "tropical diseases", "social sciences", "parasitic diseases", "neuroscience", "political science", "health care", "research design", "cognitive neuroscience", "women's h...	Provision of deworming intervention to pregnant women by antenatal services in countries endemic for soil-transmitted helminthiasis	journal.pntd.0007406	null	[ [ "Soil-transmitted helminthiasis ( STH ) are caused by the intestinal worms Ascaris lumbricoides ( roundworm , ) Trichuris trichiura ( whipworm ) , Necator americanus and Ancylostoma duodenale ( hookworm ) .", "STH are transmitted when individuals come in contact with environment contaminated by faeces con...	[ "The World Health Organization has recently reemphasized the importance of providing preventive chemotherapy to women of reproductive age in countries endemic for soil-transmitted helminthiasis as they are at heightened risk of associated morbidity .", "The Demographic and Health Surveys ( DHS ) Program is respon...	[ "Soil-transmitted helminths are intestinal worms that cause significant suffering among the poorest communities in the world .", "They are transmitted via contaminated water , food or soil , all of which result from poor sanitation .", "Children and women of reproductive age are at heightened risk of related mo...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "signal transduction", "molecular cell biology", "viral immune evasion", "immunity", "virology", "innate immunity", "biology", "microbiology", "molecular biology" ]	Vaccinia Virus Protein C6 Is a Virulence Factor that Binds TBK-1 Adaptor Proteins and Inhibits Activation of IRF3 and IRF7	journal.ppat.1002247	null	[ [ "Mammalian cells respond to viral infection by producing pro-inflammatory cytokines and chemokines and also interferons ( IFNs ) , of which type I IFNs , consisting of IFN-β and several IFNα proteins , are particularly important .", "IFN-α and IFN-β then act in an autocrine and paracrine manner to switch ...	[ "Recognition of viruses by pattern recognition receptors ( PRRs ) causes interferon-β ( IFN-β ) induction , a key event in the anti-viral innate immune response , and also a target of viral immune evasion .", "Here the vaccinia virus ( VACV ) protein C6 is identified as an inhibitor of PRR-induced IFN-β expressio...	[ "A key event in the innate immune response to virus infection is the detection of pathogen-associated molecular patterns ( PAMPs ) such as viral DNA and RNA by cellular pattern recognition receptors ( PRRs ) .", "This leads to expression of interferon-β ( IFN-β ) by an infected cell .", "Many viruses have evolv...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "medicine and health sciences", "rna interference", "neuroscience", "biological locomotion", "animals", "motor neurons", "animal models", "drosophila melanogaster", "model organisms", "experimental organism systems", "mitochondria", "epigenetics", "bioenergetics", "molec...	Ras-ERK-ETS inhibition alleviates neuronal mitochondrial dysfunction by reprogramming mitochondrial retrograde signaling	journal.pgen.1007567	null	[ [ "The use of ATP as a universal currency of energy transfer makes this molecule essential for life .", "ATP is generated either by glycolysis in the cytosol , or through the action of the tricarboxylic acid ( TCA ) cycle and β-oxidation of fatty acids coupled to oxidative phosphorylation ( OXPHOS ) in mito...	[ "Mitochondrial dysfunction activates the mitochondrial retrograde signaling pathway , resulting in large scale changes in gene expression .", "Mitochondrial retrograde signaling in neurons is poorly understood and whether retrograde signaling contributes to cellular dysfunction or is protective is unknown .", "...	[ "Loss of mitochondrial function activates the mitochondrial retrograde signaling pathway resulting in large scale changes in nuclear gene transcription .", "Very little is known about retrograde signaling in the nervous system and how the transcriptional changes affect neuronal function .", "Here we identify Ra...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "animal diseases", "medicine and health sciences", "molecular probe techniques", "cell cycle and cell division", "cell processes", "immunoblotting", "light microscopy", "cell disruption", "fungi", "animal prion diseases", "microscopy", "molecular biology techniques", "zoology", "research a...	A dominant-negative mutant inhibits multiple prion variants through a common mechanism	journal.pgen.1007085	null	[ [ "Alternative , self-replicating protein conformations have emerged as bona fide parallel protein-folding trajectories with significant biological consequences [1] .", "In most cases , these alternative conformations are β-sheet-rich and self-assembling , forming linear amyloid aggregates [2] .", "Thes...	[ "Prions adopt alternative , self-replicating protein conformations and thereby determine novel phenotypes that are often irreversible .", "Nevertheless , dominant-negative prion mutants can revert phenotypes associated with some conformations .", "These observations suggest that , while intervention is possible...	[ "Prion proteins adopt alternative conformations and assemble into amyloid fibers , which have been associated with human disease .", "These fibers are highly stable and self-replicate , leading to their persistence and resulting in a set of progressive and often fatal disorders .", "Inhibitors have been shown t...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biochemistry", "developmental biology", "caenorhabditis", "molecular biology", "genetics and genomics" ]	A Role for Autophagy in the Extension of Lifespan by Dietary Restriction in C. elegans	journal.pgen.0040024	null	[ [ "Dietary restriction , the reduced intake of food without malnutrition , increases the lifespan of many organisms , from yeast to mammals [1] .", "Dietary restriction increases lifespan , at least in part , by reducing the activities of pathways involved in growth and nutrient processing , including the T...	[ "In many organisms , dietary restriction appears to extend lifespan , at least in part , by down-regulating the nutrient-sensor TOR ( Target Of Rapamycin ) .", "TOR inhibition elicits autophagy , the large-scale recycling of cytoplasmic macromolecules and organelles .", "In this study , we asked whether autopha...	[ "Dietary restriction ( limited food intake ) increases lifespan in many organisms .", "However , the cellular processes underlying this fascinating phenomenon are still poorly understood .", "When an animal is starved , it degrades and recycles its organelles and other cellular components in a process called au...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology" ]	The Rad4TopBP1 ATR-Activation Domain Functions in G1/S Phase in a Chromatin-Dependent Manner	journal.pgen.1002801	null	[ [ "The DNA damage checkpoint is an elaborate signal transduction pathway that monitors the integrity of the DNA , prevents cell cycle progression and promotes appropriate DNA metabolism [1] reviewed in [2] .", "The DNA damage sensors associated with checkpoint activation define two separate DNA structure-de...	[ "DNA damage checkpoint activation can be subdivided in two steps: initial activation and signal amplification .", "The events distinguishing these two phases and their genetic determinants remain obscure .", "TopBP1 , a mediator protein containing multiple BRCT domains , binds to and activates the ATR/ATRIP com...	[ "DNA structure–dependent checkpoint activation and the amplification of checkpoint signals are carefully modulated to allow the checkpoint kinases to delay mitosis and regulate DNA metabolism .", "While much work has gone into understanding how this checkpoint functions , the mechanism by which the checkpoint sig...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "microbiology/plant-biotic interactions", "pathology/molecular pathology" ]	The Nuclear Protein Sge1 of Fusarium oxysporum Is Required for Parasitic Growth	journal.ppat.1000637	null	[ [ "The fungus Fusarium oxysporum is found in both agricultural and non-cultivated soils throughout the world .", "The species consists of non-pathogenic and pathogenic isolates , both known as efficient colonizers of the root rhizosphere .", "The pathogenic isolates , grouped into formae specialis depen...	[ "Dimorphism or morphogenic conversion is exploited by several pathogenic fungi and is required for tissue invasion and/or survival in the host .", "We have identified a homolog of a master regulator of this morphological switch in the plant pathogenic fungus Fusarium oxysporum f .", "sp .", "lycopersici .", ...	[ "Plant pathogenic fungi have evolved many ways to infect their hosts and can have devastating effects on commercial crop production .", "Dissecting their infection strategies and understanding the molecular pathways involved in pathogenesis have been and continue to be the subject of intensive research .", "New...	2009
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "parasitic cell cycles", "enzymes", "cell cycle and cell division", "cell processes", "microbiology", "enzymology", "parasitic protozoans", "protozoan life cycles", "parasitology", "developmental biology", "trypomastigotes", "protozoans", "epimastigotes", "cellular structures and organelle...	Aurora kinase protein family in Trypanosoma cruzi: Novel role of an AUK-B homologue in kinetoplast replication	journal.pntd.0007256	null	[ [ "Cell cycle in eukaryotic cells involves the sequential transition between G1 , S , G2 and M phases and this progression is tightly regulated by protein kinases and phosphatases [1] .", "During the M phase , the cell divides its nucleus to originate two daughter cells with the same genetic content .", ...	[ "Aurora kinases constitute a family of enzymes that play a key role during metazoan cells division , being involved in events like centrosome maturation and division , chromatin condensation , mitotic spindle assembly , control of kinetochore-microtubule attachments , and cytokinesis initiation .", "In this work ...	[ "The cell cycle is a complex and highly regulated cellular process in which different checkpoints are coordinated and a unique pattern of protein activities is present .", "In trypanosomatids , this process is even more complex because of the presence of the kinetoplast , a network of circular DNA inside a large ...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "green fluorescent protein", "fungi", "luminescent proteins", "model organisms", "fungal evolution", "experimental organism systems", "sequence motif analysis", "saccharomyces", "research and analysis methods", "sequence analysis", "mycology", "bioinformatics", "proteins", "molecular evolu...	Parallel reorganization of protein function in the spindle checkpoint pathway through evolutionary paths in the fitness landscape that appear neutral in laboratory experiments	journal.pgen.1006735	null	[ [ "Gene duplication and sub-/neo-functionalization are processes that both increase genomic complexity and are thought to be the major sources of genetic novelty in organisms [1] .", "Models seeking to explain the retention of paralog genes include relaxation of selection constraints leading to functional n...	[ "Regulatory networks often increase in complexity during evolution through gene duplication and divergence of component proteins .", "Two models that explain this increase in complexity are:", "1 ) adaptive changes after gene duplication , such as resolution of adaptive conflicts , and", "2 ) non-adaptive pro...	[ "Parallel evolution of protein domain organization following gene duplication has been demonstrated in the spindle checkpoint pathway leading to the hypothesis that this organization is likely to be adaptive .", "We test this hypothesis by reconstructing budding yeast strains with a spindle checkpoint pathway con...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "species colonization", "ecology and environmental sciences", "demography", "population genetics", "aquatic environments", "phylogenetic analysis", "speciation", "bodies of water", "molecular biology techniques", "population biology", "research and analysis methods", "lakes", "marine and aqu...	Multispecies Outcomes of Sympatric Speciation after Admixture with the Source Population in Two Radiations of Nicaraguan Crater Lake Cichlids	journal.pgen.1006157	null	[ [ "Understanding how populations can diverge and become distinct species in the presence of gene flow is a central objective in evolutionary biology [1–3] .", "That gene flow poses a problem for speciation has for long been known [4–6] .", "Gene flow and recombination homogenize the genomes of diverging...	[ "The formation of species in the absence of geographic barriers ( i . e . sympatric speciation ) remains one of the most controversial topics in evolutionary biology .", "While theoretical models have shown that this most extreme case of primary divergence-with-gene-flow is possible , only a handful of accepted e...	[ "Speciation is the main driver of biological diversity and how species arise is a central question in evolutionary biology .", "For speciation to occur in sexually reproducing organisms the exchange of genetic material ( gene flow ) between populations has to be reduced .", "Ultimately this has to be due to gen...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "protein transport", "innate immune system", "medicine and health sciences", "immune physiology", "cytokines", "chemical compounds", "particle physics", "energy transfer", "cell processes", "immunology", "organic compounds", "developmental biology", "photons", "molecular development", "b...	Simulation of single-protein nanopore sensing shows feasibility for whole-proteome identification	journal.pcbi.1007067	null	[ [ "Modern DNA sequencing techniques have revolutionized genomics [1] , but extending these methods to routine proteome analysis , and specifically to single-cell proteomics , remains a global unmet challenge .", "This is attributed to the fundamental complexity of the proteome: protein expression level span...	[ "Single-molecule techniques for protein sequencing are making headway towards single-cell proteomics and are projected to propel our understanding of cellular biology and disease .", "Yet , single cell proteomics presents a substantial unmet challenge due to the unavailability of protein amplification techniques ...	[ "Macromolecules identification methods are central for most biological and biomedical studies , and while the field of genomics advanced to single-molecule resolution , the proteomic field still relies on bulk and costly techniques .", "We describe a solution for single protein identification , based on the analy...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Genome Wide Analysis Reveals Zic3 Interaction with Distal Regulatory Elements of Stage Specific Developmental Genes in Zebrafish	journal.pgen.1003852	null	[ [ "Early embryonic patterning is achieved through a process involving the determination of body axes and defining which cell types develop at each coordinate .", "The Zic family of transcription factors ( TFs ) is involved in such process [1]–[4] .", "Zic genes are the vertebrate homologues of the odd-p...	[ "Zic3 regulates early embryonic patterning in vertebrates .", "Loss of Zic3 function is known to disrupt gastrulation , left-right patterning , and neurogenesis .", "However , molecular events downstream of this transcription factor are poorly characterized .", "Here we use the zebrafish as a model to study t...	[ "The Zic3 transcription factor regulates early embryonic patterning , and the loss of its function leads to defects in left-right body asymmetry .", "Previous studies have only identified a small number of Zic3 targets , which renders the molecular mechanism underlying its activity insufficiently understood .", ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome-wide association studies", "genome evolution", "microbiology", "genome sequencing", "prokaryotic models", "model organisms", "molecular cell biology", "microbial evolution", "molecular genetics", "microbial pathogens", "comparative genomics", "biology", "pathogenesis", "evolutionar...	Distributive Conjugal Transfer in Mycobacteria Generates Progeny with Meiotic-Like Genome-Wide Mosaicism, Allowing Mapping of a Mating Identity Locus	journal.pbio.1001602	We find that genome-wide DNA transfer by conjugation in mycobacteria affords bacteria that reproduce by binary fission the same advantages of sexual reproduction, and may explain the genomic evolution of Mycobacterium tuberculosis.	[ [ "Sexual reproduction in eukaryotes promotes genetic diversity by increasing gene flow through a population , permitting both the loss of mutant genes and the acquisition of functionally distinct gene alleles .", "The diversifying potential is further enhanced by crossover events that create new mosaic rec...	[ "Horizontal gene transfer ( HGT ) in bacteria generates variation and drives evolution , and conjugation is considered a major contributor as it can mediate transfer of large segments of DNA between strains and species .", "We previously described a novel form of chromosomal conjugation in mycobacteria that does ...	[ "Bacteria reproduce by binary fission , generating two clones of the original; this restricts the genomic diversity of the population , which brings with it inherent evolutionary drawbacks .", "This problem can be eased by conjugation , which transfers DNA from a donor to a recipient bacterium .", "Understandin...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases", "genetics and genomics", "microbiology/microbial evolution and genomics" ]	Autophagy Gene Variant IRGM −261T Contributes to Protection from Tuberculosis Caused by Mycobacterium tuberculosis but Not by M. africanum Strains	journal.ppat.1000577	null	[ [ "Autophagy is induced by the formation of intracellular double-membrane structures which form autophagosomes to sequester and , after further maturation to autolysosomes , degrade cytosolic protein aggregates and corrupted cellular organelles .", "Thereby , it allows a re-cycling of amino acids , which is...	[ "The human immunity-related GTPase M ( IRGM ) has been shown to be critically involved in regulating autophagy as a means of disposing cytosolic cellular structures and of reducing the growth of intracellular pathogens in vitro .", "This includes Mycobacterium tuberculosis , which is in agreement with findings in...	[ "Autophagy is a process in which cell components are degraded by the lysosomal machinery .", "It has recently been described that activation of autophagy reduces the viability of M . tuberculosis in phagosomes due to an intimate autophagy-phagocytosis interaction .", "M . tuberculosis may also be directly acces...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "systems biology", "regulatory networks", "population genetics", "biology", "computational biology" ]	Learning Gene Networks under SNP Perturbations Using eQTL Datasets	journal.pcbi.1003420	null	[ [ "Recent advances in the next-generation sequencing and other high-throughput technology has allowed researchers to collect various types of genome-scale datasets , providing unprecedented opportunities to discover detailed gene regulation processes in cells via analysis of the massive data .", "The standa...	[ "The standard approach for identifying gene networks is based on experimental perturbations of gene regulatory systems such as gene knock-out experiments , followed by a genome-wide profiling of differential gene expressions .", "However , this approach is significantly limited in that it is not possible to pertu...	[ "A complete understanding of how gene regulatory networks are wired in a biological system is important in many areas of biology and medicine .", "The most popular method for investigating a gene network has been based on experimental perturbation studies , where the expression of a gene is experimentally manipul...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell death", "invertebrates", "redox signaling", "cell processes", "animals", "animal models", "developmental biology", "drosophila melanogaster", "model organisms", "organism development", "experimental organism systems", "morphogenesis", "drosophila", "research and analysis methods", ...	Ask1 and Akt act synergistically to promote ROS-dependent regeneration in Drosophila	journal.pgen.1007926	null	[ [ "Organisms are continuously exposed to a wide variety of environmental stressors that can cause deterioration and cell death .", "Tissues overcome the effect of those stressors by replacing damaged cells to restore homeostasis .", "Therefore , understanding the early signals that initiate the response...	[ "How cells communicate to initiate a regenerative response after damage has captivated scientists during the last few decades .", "It is known that one of the main signals emanating from injured cells is the Reactive Oxygen Species ( ROS ) , which propagate to the surrounding tissue to trigger the replacement of ...	[ "One of the early events that occur after tissue damage consists on the production of Reactive Oxygen Species ( ROS ) , that signal to the surrounding tissue to initiate wound healing and regeneration .", "Many signaling pathways , such as JNK and p38 , respond to oxidative stress and are necessary for regenerati...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "game theory", "computer science", "evolutionary ecology", "computer modeling", "animal behavior", "mathematics", "theoretical biology", "ecology", "evolutionary biology", "applied mathematics", "theoretical ecology", "biology", "behavioral ecology" ]	The Effects of Dominance on Leadership and Energetic Gain: A Dynamic Game between Pairs of Social Foragers	journal.pcbi.1002252	null	[ [ "Animals can gain many benefits from associating in groups [1] , but there are disadvantages that need to be considered as well .", "Competition for resources that cannot easily be shared equally ( such as food , security , or access to mates ) can lead to conflict between the members of the group [2] .",...	[ "Although social behaviour can bring many benefits to an individual , there are also costs that may be incurred whenever the members of a social group interact .", "The formation of dominance hierarchies could offer a means of reducing some of the costs of social interaction , but individuals within the hierarchy...	[ "Dominance hierarchies could offer interacting animals a quick way to settle disputes without having to use too much effort .", "However , individuals may pay a price for acknowledging their position within the hierarchy , which could influence how they choose to behave within the group .", "Consequently , the ...	2011
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "animal types", "livestock", "morocco", "medicine and health sciences", "pathology and laboratory medicine", "tropical diseases", "geographical locations", "vertebrates", "parasitic diseases", "dogs", "mammals", "animals", "pets and companion animals", "surgical and invasive medical proced...	Human cystic echinococcosis in Morocco: Ultrasound screening in the Mid Atlas through an Italian-Moroccan partnership	journal.pntd.0005384	null	[ [ "Cystic Echinococcosis ( CE ) is a globally distributed parasitic zoonosis , caused by the larval stage of the dog tapeworm Echinococcus granulosus sensu lato .", "Its life cycle develops between the dog ( and other canids ) , which is the definitive host harbouring the adult parasites in the intestine , ...	[ "Cystic echinococcosis ( CE ) is a neglected parasitic zoonosis with considerable socioeconomic impact on affected pastoral communities .", "CE is endemic throughout the Mediterranean , including Morocco , where the Mid Atlas is the most prevalent area for both human and animal infection .", "The highest hospit...	[ "Cystic Echinococcosis ( CE ) is a parasitic infection whose natural domestic cycle develops between dogs and sheep ( and other livestock ) .", "Human infection is endemic in pastoral communities , where close contact with the dog-sheep cycle occurs .", "In humans , as well as in livestock , the parasite develo...	2017
[ "Introduction", "Methods", "Results and discussion" ]	[ "medicine and health sciences", "enzymology", "microbiology", "parasitic protozoans", "protozoans", "sequence motif analysis", "pharmacology", "enzyme inhibitors", "research and analysis methods", "sequence analysis", "bioinformatics", "biological databases", "drug discovery", "trypanosoma...	Essential multimeric enzymes in kinetoplastid parasites: A host of potentially druggable protein-protein interactions	journal.pntd.0005720	null	[ [ "Infections caused by the kinetoplastid parasites Leishmania spp .", ", Trypanosoma brucei , and Trypanosoma cruzi are estimated collectively to put at risk one billion people , resulting in tens of millions of infections and upwards of ten thousand deaths per year [1] .", "Neglected tropical diseases...	[ "Parasitic diseases caused by kinetoplastid parasites of the genera Trypanosoma and Leishmania are an urgent public health crisis in the developing world .", "These closely related species possess a number of multimeric enzymes in highly conserved pathways involved in vital functions , such as redox homeostasis a...	[ "Neglected tropical diseases caused by parasites of the genera Trypanosoma and Leishmania affect millions of people , primarily in the developing world .", "Due to a historical lack of incentive or interest , few new drugs have been developed to treat these conditions .", "Numerous efforts have targeted the met...	2017
[ "Introduction", "Materials and Methods", "Results and Discussion" ]	[]	Genomic Characterisation of Invasive Non-Typhoidal Salmonella enterica Subspecies enterica Serovar Bovismorbificans Isolates from Malawi	journal.pntd.0002557	null	[ [ "Invasive Non-typhoidal Salmonella ( iNTS ) are a major cause of morbidity and mortality in sub-Saharan Africa .", "Especially in young children , iNTS are either the first or second most common cause of bacteraemia [1] , [2] , meningitis and septic arthritis [3] , [4] with high morbidity .", "HIV inf...	[ "Invasive Non-typhoidal Salmonella ( iNTS ) are an important cause of bacteraemia in children and HIV-infected adults in sub-Saharan Africa .", "Previous research has shown that iNTS strains exhibit a pattern of gene loss that resembles that of host adapted serovars such as Salmonella Typhi and Paratyphi A . Salm...	[ "Bacteraemia and meningitis caused by non-typhoidal Salmonella ( including serovars Typhimurium , Enteritidis and Bovismorbificans ) are a serious health issue in sub-Saharan Africa , particularly in young children and HIV-infected adults .", "Previous work has indicated that a distinct S . Typhimurium sequence t...	2013
[ "Introduction", "Methods", "Results/Discussion" ]	[ "protein structure comparison", "biochemistry", "proteins", "protein structure", "protein structure databases", "biology and life sciences", "protein domains" ]	ECOD: An Evolutionary Classification of Protein Domains	journal.pcbi.1003926	null	[ [ "The billions of proteins in extant species constitute a bewilderingly diverse protein world .", "To understand this world , systematic classifications are needed to reduce its complexity and to bring order to its relationships .", "As proteins are the products of evolution , their phylogeny provides ...	[ "Understanding the evolution of a protein , including both close and distant relationships , often reveals insight into its structure and function .", "Fast and easy access to such up-to-date information facilitates research .", "We have developed a hierarchical evolutionary classification of all proteins with ...	[ "Protein structural domain databases offer a vital resource for structural bioinformatics .", "These databases provide functional inference for homologous structures , supply templates for structural prediction experiments , and differentiate between homologs and analogs .", "The rate of structure determination...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "learning", "medicine and health sciences", "diagnostic radiology", "functional magnetic resonance imaging", "reaction time", "brain electrophysiology", "social sciences", "electrophysiology", "neuroscience", "learning and memory", "magnetic resonance imaging", "cognitive neuroscience", "cog...	Human Inferences about Sequences: A Minimal Transition Probability Model	journal.pcbi.1005260	null	[ [ "From bird song to music , sea waves , or traffic lights , many processes in real life unfold across time and generate time series of events .", "Sequences of observations are therefore often underpinned by some regularity that depends on the underlying generative process .", "The ability to detect su...	[ "The brain constantly infers the causes of the inputs it receives and uses these inferences to generate statistical expectations about future observations .", "Experimental evidence for these expectations and their violations include explicit reports , sequential effects on reaction times , and mismatch or surpri...	[ "We explore the possibility that the computation of time-varying transition probabilities may be a core building block of sequence knowledge in humans .", "Humans may then use these estimates to predict future observations .", "Expectations derived from such a model should conform to several properties .", "W...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Performance of Kala-Azar Surveillance in Gaffargaon Subdistrict of Mymensingh, Bangladesh	journal.pntd.0003531	null	[ [ "Visceral leishmaniasis ( VL ) , caused by protozoan parasites transmitted by sandflies , is a systemic illness characterized by fever and splenomegaly .", "The disease is endemic in impoverished tropical areas globally [1–3] , and in South Asia is known as kala-azar ( black-fever ) and only affects human...	[ "Elimination of kala-azar is planned for South Asia requiring good surveillance along with other strategies .", "We assessed surveillance in Gaffargaon upazila ( a subdistrict of 13 unions ) of Mymensingh district , Bangladesh highly endemic for kala-azar .", "In 4703 randomly sampled households , within nine r...	[ "Visceral leishmaniasis , a parasitic disease transmitted by sandflies , is known as kala-azar in South Asia , and has been targeted for elimination in that region .", "The aim is to reduce its incidence to a low level so that it is no longer a public health problem .", "Elimination strategies include good surv...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "mutagenesis", "biochemistry", "mitochondrial genetics", "medicine and health sciences", "dna polymerase", "polymerases", "dna replication", "proteins", "mitochondrial dna", "forms of dna", "genetics", "biology and life sciences", "dna", "dna-binding proteins", "mitochondrial diseases", ...	MMS Exposure Promotes Increased MtDNA Mutagenesis in the Presence of Replication-Defective Disease-Associated DNA Polymerase γ Variants	journal.pgen.1004748	null	[ [ "Mitochondrial DNA ( mtDNA ) maintenance is necessary for the majority of ATP production in eukaryotic cells .", "The inability to properly replicate mtDNA potentially impacts human health in several ways .", "The premature aging phenotype of POLG exonuclease deficient mice indicates that increased mt...	[ "Mitochondrial DNA ( mtDNA ) encodes proteins essential for ATP production .", "Mutant variants of the mtDNA polymerase cause mutagenesis that contributes to aging , genetic diseases , and sensitivity to environmental agents .", "We interrogated mtDNA replication in Saccharomyces cerevisiae strains with disease...	[ "Thousands of mitochondrial DNA ( mtDNA ) per cell are necessary to maintain energy required for cellular survival in humans .", "Interfering with the mtDNA polymerase can result in mitochondrial diseases and mitochondrial toxicity .", "Therefore , it is important to explore new genetic and environmental mechan...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "biology and life sciences", "medical microbiology", "microbiology" ]	Nitric Oxide from IFNγ-Primed Macrophages Modulates the Antimicrobial Activity of β-Lactams against the Intracellular Pathogens Burkholderia pseudomallei and Nontyphoidal Salmonella	journal.pntd.0003079	null	[ [ "B . pseudomallei are endemic in tropical areas of Southeast Asia , Northern Australia and equatorial countries [1] .", "This Gram-negative , opportunistic pathogen is a saprophyte that inhabits water and soil , becoming infectious to humans and animals if inoculated through cutaneous abrasions , ingested...	[ "Our investigations show that nonlethal concentrations of nitric oxide ( NO ) abrogate the antibiotic activity of β-lactam antibiotics against Burkholderia pseudomallei , Escherichia coli and nontyphoidal Salmonella enterica serovar Typhimurium .", "NO protects B . pseudomallei already exposed to β-lactams , sugg...	[ "β-lactam drugs that inhibit peptidoglycan biosynthesis are often used in the treatment of bacterial infections , including melioidosis .", "Independent of their antibiotic activity , we have noted that submicromolar concentrations of β-lactams potentiate the killing of intracellular B . pseudomallei supported by...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology" ]	The Histone Demethylase Jarid1b Ensures Faithful Mouse Development by Protecting Developmental Genes from Aberrant H3K4me3	journal.pgen.1003461	null	[ [ "Embryonic development is characterized by a coordinated program of proliferation and differentiation that is tightly regulated by transcription factors and chromatin-associated proteins .", "As embryonic cells differentiate , certain genes are activated while others are repressed , resulting in a unique ...	[ "Embryonic development is tightly regulated by transcription factors and chromatin-associated proteins .", "H3K4me3 is associated with active transcription and H3K27me3 with gene repression , while the combination of both keeps genes required for development in a plastic state .", "Here we show that deletion of...	[ "Histone modifications are involved in transcriptional regulation and thus affect cellular identity , differentiation , and development .", "We study the histone demethylase Jarid1b ( Kdm5b/Plu1 ) , as it has been reported to be highly expressed in several human cancers and therefore might present a novel target ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cancer genetics", "genetics", "molecular genetics", "biology", "genetics of disease", "genetics and genomics" ]	Global Chromosomal Structural Instability in a Subpopulation of Starving Escherichia coli Cells	journal.pgen.1002223	null	[ [ "Copy number variations ( CNVs ) are regions of DNA either deleted or duplicated/amplified relative to a reference genome .", "CNVs constitute the most ubiquitous differences between individual or personal human genomes [1] , can be associated with many Mendelian and complex human diseases [2] because de ...	[ "Copy-number variations ( CNVs ) constitute very common differences between individual humans and possibly all genomes and may therefore be important fuel for evolution , yet how they form remains elusive .", "In starving Escherichia coli , gene amplification is induced by stress , controlled by the general stres...	[ "Much of the difference between individual humans is in the number of copies of genes and lengths of genome .", "The mechanisms by which copy number variation arises are not well understood .", "We sought information on copy number change mechanisms by extensive use of array comparative genomic hybridization of...	2011
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "in situ hybridization", "molecular probe techniques", "pathogens", "microbiology", "vertebrates", "animals", "mammals", "xenarthra", "fungi", "materials science", "speciation", "paracoccidioides brasiliensis", "amniote...	Environmental Mapping of Paracoccidioides spp. in Brazil Reveals New Clues into Genetic Diversity, Biogeography and Wild Host Association	journal.pntd.0004606	null	[ [ "The study of biological and ecological aspects of Paracoccidioides brasiliensis [1 , 2] and Paracoccidioides lutzii [3] has been developed by several research groups in recent years .", "In particular , investigators have been seeking to isolate and/or detect those pathogens in clinical and environmental...	[ "Paracoccidioides brasiliensis and Paracoccidioides lutzii are the etiological agents of Paracoccidioidomycosis ( PCM ) , and are easily isolated from human patients .", "However , due to human migration and a long latency period , clinical isolates do not reflect the spatial distribution of these pathogens .", ...	[ "Paracoccidioides brasiliensis and Paracoccidioides lutzii are the fungal species responsible for one of the most important mycoses of Latin America , Paracoccidioidomycosis ( PCM ) .", "These fungi can grow in soil from forests , deforested areas , sugarcane , coffee , and rice plantations , as well as pasturela...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology and life sciences", "cell fate determination", "developmental biology" ]	Integration of Signals along Orthogonal Axes of the Vertebrate Neural Tube Controls Progenitor Competence and Increases Cell Diversity	journal.pbio.1001907	FGF gates competence to generate Floor Plate and Neural Crest in response to Shh and BMP signals by controlling expression of the transcription factor Nkx1.2.	[ [ "A large array of distinct cell types is generated during embryonic development in response to a relatively small number of inductive signals .", "A mechanism to explain this was described by C . H . Waddington in his influential book “Organizers and Genes” [1] .", "In this work he proposed that the s...	[ "A relatively small number of signals are responsible for the variety and pattern of cell types generated in developing embryos .", "In part this is achieved by exploiting differences in the concentration or duration of signaling to increase cellular diversity .", "In addition , however , changes in cellular co...	[ "During embryonic development different cell types arise at different times and places .", "This diversity is produced by a relatively small number of signals and depends , at least in part , on changes in the way cells respond to each signal .", "One example of this so-called change in “competence” is found in...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/bacterial infections", "microbiology/cellular microbiology and pathogenesis", "biochemistry/biocatalysis" ]	The Haemophilus influenzae HMW1C Protein Is a Glycosyltransferase That Transfers Hexose Residues to Asparagine Sites in the HMW1 Adhesin	journal.ppat.1000919	null	[ [ "Glycosylation of proteins is an essential process that plays an important role in protein structure and function and represents a strategy to fine tune cell-cell recognition and signaling .", "For a long period of time , glycosylation of proteins was believed to be restricted to eukaryotes .", "Howev...	[ "The Haemophilus influenzae HMW1 adhesin is a high-molecular weight protein that is secreted by the bacterial two-partner secretion pathway and mediates adherence to respiratory epithelium , an essential early step in the pathogenesis of H . influenzae disease .", "In recent work , we discovered that HMW1 is a gl...	[ "Decoration of proteins with carbohydrates has an important impact on protein function throughout biology and has been recognized increasingly in pathogenic bacteria .", "Haemophilus influenzae is a common cause of both bacterial respiratory tract disease and bacterial invasive disease and initiates infection by ...	2010
[ "Introduction", "Model", "Results", "Discussion" ]	[ "developmental biology/embryology", "developmental biology/stem cells", "developmental biology/morphogenesis and cell biology", "computational biology/transcriptional regulation", "biophysics/theory and simulation" ]	Simulating the Mammalian Blastocyst - Molecular and Mechanical Interactions Pattern the Embryo	journal.pcbi.1001128	null	[ [ "How a complete embryo emerges starting from a single fertilized egg is an intriguing process in developmental biology , understanding of which has important clinical implications [1] .", "Recent advances in live imaging have allowed for the tracking of single cells as they grow and divide and subsequentl...	[ "Mammalian embryogenesis is a dynamic process involving gene expression and mechanical forces between proliferating cells .", "The exact nature of these interactions , which determine the lineage patterning of the trophectoderm and endoderm tissues occurring in a highly regulated manner at precise periods during ...	[ "We elucidate by computational means the processes by which the development of the mammalian embryo during its first four to five days occurs , as it is transformed from a single stem cell into hundreds of cells of different tissue types .", "We are interested in understanding the fundamental processes of how gen...	2011
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Comparisons of Allergenic and Metazoan Parasite Proteins: Allergy the Price of Immunity	journal.pcbi.1004546	null	[ [ "Allergy is a hypersensitive immune reaction to environmental antigens from diverse sources such as foods , plants and innocuous organisms .", "The mechanism responsible for eliciting the allergic reaction involves components of the immune system , in particular the IgE antibody isotype , which also media...	[ "Allergic reactions can be considered as maladaptive IgE immune responses towards environmental antigens .", "Intriguingly , these mechanisms are observed to be very similar to those implicated in the acquisition of an important degree of immunity against metazoan parasites ( helminths and arthropods ) in mammali...	[ "Allergy is an increasingly widespread clinical problem that leads to various conditions such as allergic asthma and susceptibility to anaphylactic shock .", "These conditions arise from exposure to a range of environmental and food proteins ( ‘allergens’ ) that are recognised by a form of immune system antibody ...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "genetics of disease", "trait locus", "heredity", "genetics", "biology", "evolutionary biology", "evolutionary selection", "genetic determinism", "evolutionary processes", "genetics and genomics" ]	Effects of Cu/Zn Superoxide Dismutase (sod1) Genotype and Genetic Background on Growth, Reproduction and Defense in Biomphalaria glabrata	journal.pntd.0001701	null	[ [ "Although vector-borne diseases account for approximately one-sixth of the global human disease burden [1] , [2] , we still lack effective drugs and vaccines for many of these diseases .", "Even when effective drugs are available , high-risk populations often cannot be adequately treated due to a lack of ...	[ "Resistance of the snail Biomphalaria glabrata to the trematode Schistosoma mansoni is correlated with allelic variation at copper-zinc superoxide dismutase ( sod1 ) .", "We tested whether there is a fitness cost associated with carrying the most resistant allele in three outbred laboratory populations of snails ...	[ "Driving resistance genes into vector populations remains a promising but underused method for reducing transmission of vector-borne diseases .", "Understanding the genetic mechanisms governing resistance and how resistance is maintained in vector populations is essential for the development of resistant vectors ...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/gene discovery", "genetics and genomics", "molecular biology" ]	A Microarray-Based Genetic Screen for Yeast Chronological Aging Factors	journal.pgen.1000921	null	[ [ "Model eukaryotic organisms such as Drosophila and C . elegans have played important roles in the identification of genes and the molecular characterization of cellular and biochemical pathways that affect the aging process [1] .", "For example , large-scale systematic RNAi knockdown screens for lifespan ...	[ "Model organisms have played an important role in the elucidation of multiple genes and cellular processes that regulate aging .", "In this study we utilized the budding yeast , Saccharomyces cerevisiae , in a large-scale screen for genes that function in the regulation of chronological lifespan , which is define...	[ "The aging process is associated with the onset of several age-associated diseases including diabetes and cancer .", "In rodent model systems , the dietary regimen known as caloric restriction ( CR ) is known to delay or prevent these diseases and to extend lifespan .", "As a result , there is a great deal of i...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "infectious diseases", "public health and epidemiology", "mathematics", "none", "science policy", "neurological disorders", "gastroenterology and hepatology", "in vitro", "mus (mouse)", "mammals" ]	Oral Transmissibility of Prion Disease Is Enhanced by Binding to Soil Particles	journal.ppat.0030093	null	[ [ "Bovine spongiform encephalopathy , human Creutzfeldt-Jakob disease and kuru , sheep scrapie , and chronic wasting disease of deer , elk , and moose belong to the class of fatal , infectious neurodegenerative diseases known as transmissible spongiform encephalopathies ( TSEs ) or prion diseases [1 , 2] .", ...	[ "Soil may serve as an environmental reservoir for prion infectivity and contribute to the horizontal transmission of prion diseases ( transmissible spongiform encephalopathies [TSEs] ) of sheep , deer , and elk .", "TSE infectivity can persist in soil for years , and we previously demonstrated that the disease-as...	[ "Transmissible spongiform encephalopathies ( TSEs ) are a group of incurable neurological diseases likely caused by a misfolded form of the prion protein .", "TSEs include scrapie in sheep , bovine spongiform encephalopathy ( “mad cow” disease ) in cattle , chronic wasting disease in deer and elk , and Creutzfeld...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "computational neuroscience", "biology", "computational biology", "neuroscience" ]	Attracting Dynamics of Frontal Cortex Ensembles during Memory-Guided Decision-Making	journal.pcbi.1002057	null	[ [ "To fully understand how neural processes give rise to cognitive operations , it is essential to reconstruct the underlying neural network dynamics from electrophysiological or neuroimaging measurements in relation to behavior .", "A common theoretical idea is that these dynamical properties of the nervou...	[ "A common theoretical view is that attractor-like properties of neuronal dynamics underlie cognitive processing .", "However , although often proposed theoretically , direct experimental support for the convergence of neural activity to stable population patterns as a signature of attracting states has been spars...	[ "For understanding how neural processes give rise to cognitive operations , it is essential to understand how aspects of the underlying neural network dynamics reconstructed from neurophysiological measurements relate to behavior .", "For instance , different actions may be represented by neural states characteri...	2011
[ "Introduction", "Results", "Discussion" ]	[ "action potentials", "medicine and health sciences", "neural networks", "applied mathematics", "population dynamics", "membrane potential", "electrophysiology", "random variables", "neuroscience", "covariance", "simulation and modeling", "algorithms", "mathematics", "population biology", ...	Approximate Inference for Time-Varying Interactions and Macroscopic Dynamics of Neural Populations	journal.pcbi.1005309	null	[ [ "Activity patterns of neuronal populations are constrained by biological mechanisms such as biophysical properties of each neuron ( e . g . , synaptic integration and spike generation [1 , 2] ) and their anatomical connections [3] .", "The characteristic correlations among neurons imposed by the biologica...	[ "The models in statistical physics such as an Ising model offer a convenient way to characterize stationary activity of neural populations .", "Such stationary activity of neurons may be expected for recordings from in vitro slices or anesthetized animals .", "However , modeling activity of cortical circuitries...	[ "Simultaneous analysis of large-scale neural populations is necessary to understand coding principles of neurons because they concertedly process information .", "Methods of thermodynamics and statistical mechanics are useful to understand collective phenomena of the interacting elements , and they have been succ...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "public health and epidemiology", "immunology", "bacterial diseases", "test evaluation", "clinical epidemiology", "global health", "neglected tropical diseases", "immunologic techniques", "infectious diseases", "epidemiology", "immunoassays", "biology", "leptospirosis", "diag...	Accuracy of a Dual Path Platform (DPP) Assay for the Rapid Point-of-Care Diagnosis of Human Leptospirosis	journal.pntd.0001878	null	[ [ "Leptospirosis , caused by >200 pathogenic serovars of Leptospira interrogans , is an increasingly important cause of morbidity worldwide with >500 , 000 cases annually [1] , [2] .", "Most urban infections in Brazil and other emerging economy countries occur in densely populated , resource-poor slums that...	[ "Diagnosis of leptospirosis by the gold standard serologic assay , the microscopic agglutination test ( MAT ) , requires paired sera and is not widely available .", "We developed a rapid assay using immunodominant Leptospira immunoglobulin-like ( Lig ) proteins in a Dual Path Platform ( DPP ) .", "This study ai...	[ "Leptospirosis is an important cause of acute fever in the tropics and the mortality rate may exceed 15% in patients with severe disease manifestations .", "The gold standard serological test for diagnosing leptospirosis , the microagglutination test or MAT , requires significant laboratory resources and results ...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "circuit models", "computational neuroscience", "biology", "neuroscience" ]	Network Self-Organization Explains the Statistics and Dynamics of Synaptic Connection Strengths in Cortex	journal.pcbi.1002848	null	[ [ "The computations performed by cortical circuits depend on their detailed patterns of synaptic connection strengths .", "While the gross patterning of connections across different cortical layers has been well described in some cases [1] , [2] , the detailed connectivity structure between groups of cells ...	[ "The information processing abilities of neural circuits arise from their synaptic connection patterns .", "Understanding the laws governing these connectivity patterns is essential for understanding brain function .", "The overall distribution of synaptic strengths of local excitatory connections in cortex and...	[ "The computations that brain circuits can perform depend on their wiring .", "While a wiring diagram is still out of reach for major brain structures such as the neocortex and hippocampus , data on the overall distribution of synaptic connection strengths and the temporal fluctuations of individual synapses have ...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "oleic acid", "gene regulation", "rna extraction", "microbiology", "viral structure", "viruses", "rna viruses", "extraction techniques", "research and analysis methods", "small interfering rnas", "lipids", "gene expression", "viral replication", "virions", "biochemistry", "rna", "nuc...	Stearoly-CoA desaturase 1 differentiates early and advanced dengue virus infections and determines virus particle infectivity	journal.ppat.1007261	null	[ [ "Phospholipids are critical for membrane structure , function and stability of eukaryotic cells .", "Specific distributions of lipids within these membranes define their characteristics such as curvature , fluidity , leakiness and the interactions between membranes and membrane-bound protein complexes .",...	[ "Positive strand RNA viruses , such as dengue virus type 2 ( DENV2 ) expand and structurally alter ER membranes to optimize cellular communication pathways that promote viral replicative needs .", "These complex rearrangements require significant protein scaffolding as well as changes to the ER chemical compositi...	[ "Dengue viruses are aggressive mosquito-borne viruses causing over 350 million infections annually .", "There are no antivirals to combat infection and the only vaccine available is suboptimal .", "Here , we have investigated how these viruses hijack critical metabolic pathways in cells to convert the host envi...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "protein transport", "b vitamins", "cell physiology", "plant anatomy", "medicine and health sciences", "vesicles", "chemical compounds", "cell processes", "green fluorescent protein", "organic compounds", "cholines", "physiological processes", "plant science", "luminescent proteins", "ho...	A new vesicle trafficking regulator CTL1 plays a crucial role in ion homeostasis	journal.pbio.2002978	null	[ [ "The root is highly specified and well organized for the uptake and transport of water and mineral nutrients from the highly heterogeneous soil environment .", "Plants have evolved complex gene networks to fine tune the activities of different transporters , as well as the functions of different cell wall...	[ "Ion homeostasis is essential for plant growth and environmental adaptation , and maintaining ion homeostasis requires the precise regulation of various ion transporters , as well as correct root patterning .", "However , the mechanisms underlying these processes remain largely elusive .", "Here , we reported t...	[ "Ion transporters play a key role in mineral nutrients uptake and transport of plants .", "Their cellular and subcellular localization is essential for fulfilling their functions and are therefore generally fine-tuned .", "However , the molecular mechanisms underlying this process remain largely unclear .", "...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome expression analysis", "genomics", "functional genomics", "molecular cell biology", "molecular biology", "gene regulation", "gene expression", "molecular genetics", "biology", "computational biology", "chromatin", "genetics and genomics", "histone modification" ]	In Vivo Effects of Histone H3 Depletion on Nucleosome Occupancy and Position in Saccharomyces cerevisiae	journal.pgen.1002771	null	[ [ "Twenty-five years ago , Michael Grunstein's laboratory began a series of experiments in which histones H2B or H4 were depleted in vivo in S . cerevisiae ( yeast ) .", "After histone gene silencing , the yeast cells complete a single round of DNA replication , reducing their histone-DNA ratio by a factor ...	[ "Previous studies in Saccharomyces cerevisiae established that depletion of histone H4 results in the genome-wide transcriptional de-repression of hundreds of genes .", "To probe the mechanism of this transcriptional de-repression , we depleted nucleosomes in vivo by conditional repression of histone H3 transcrip...	[ "Chromatin is formed by wrapping 146 bp of DNA around a disc-shaped complex of proteins called histones .", "These protein–DNA structures are known as nucleosomes .", "Nucleosomes help to regulate gene transcription , because nucleosomes compete with transcription factors for access to DNA .", "The precise po...	2012

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