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headings list	keywords list	title stringlengths 20 281	id stringlengths 20 20	toc stringlengths 57 522 ⌀	sections list	abstract list	summary list	year stringclasses 13 values
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "cardiovascular physiology", "vegf signaling", "dose prediction methods", "endothelial cells", "cancer treatment", "basic cancer research", "biomarkers", "epithelial cells", "oncology", "angiogenesis", "developmental biology", "pharmaceutics", "tumor physiol...	Mechanistic modeling quantifies the influence of tumor growth kinetics on the response to anti-angiogenic treatment	journal.pcbi.1005874	null	[ [ "Angiogenesis is the formation of new blood vessels from pre-existing vasculature and is important in both physiological and pathological conditions .", "Numerous promoters and inhibitors regulate angiogenesis .", "One key promoter of angiogenesis is the vascular endothelial growth factor-A ( VEGF-A )...	[ "Tumors exploit angiogenesis , the formation of new blood vessels from pre-existing vasculature , in order to obtain nutrients required for continued growth and proliferation .", "Targeting factors that regulate angiogenesis , including the potent promoter vascular endothelial growth factor ( VEGF ) , is therefor...	[ "One hallmark of cancer is angiogenesis , the formation of new blood capillaries from pre-existing vessels .", "Angiogenesis promotes tumor growth by enabling the tumor to obtain oxygen and nutrients from the surrounding microenvironment .", "Cancer drugs that inhibit angiogenesis ( \"anti-angiogenic therapies\...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "phosphorylation", "cellular stress responses", "gene regulation", "protein interaction networks", "regulatory proteins", "cell processes", "signaling networks", "dna-binding proteins", "network analysis", "genome analysis", "transcription factors", "computer and information sciences", "geno...	Network inference reveals novel connections in pathways regulating growth and defense in the yeast salt response	journal.pcbi.1006088	null	[ [ "Cells sense and respond to stressful situations by utilizing complex signaling networks that integrate diverse signals and coordinate what is ultimately a multi-faceted response .", "In optimal conditions , microbial cells maximize growth at the expense of stress defense by up-regulating growth related p...	[ "Cells respond to stressful conditions by coordinating a complex , multi-faceted response that spans many levels of physiology .", "Much of the response is coordinated by changes in protein phosphorylation .", "Although the regulators of transcriptome changes during stress are well characterized in Saccharomyce...	[ "Cells sense and respond to stressful environments by utilizing complex signaling networks that integrate diverse signals to coordinate a multi-faceted physiological response .", "Much of this response is controlled by post-translational protein phosphorylation .", "Although many regulators that mediate changes...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases", "veterinary diseases", "zoonoses", "medicine and health sciences", "diagnostic medicine", "african trypanosomiasis", "neglected tropical diseases", "biology and life sciences", "tropical diseases", "trypanosomiasis", "parasitic diseases", "veterinary science" ]	Performance of Parasitological and Molecular Techniques for the Diagnosis and Surveillance of Gambiense Sleeping Sickness	journal.pntd.0002954	null	[ [ "Human African trypanosomiasis ( HAT ) or sleeping sickness is caused by two subspecies of the protozoan parasite Trypanosoma brucei ( T . b . ) and transmitted through tsetse flies ( Glossina sp . ) .", "T . b . gambiense occurs from West to Central sub-Saharan Africa while T . b . rhodesiense is endemic...	[ "Recently , improvements have been made to diagnostics for gambiense sleeping sickness control but their performance remains poorly documented and may depend on specimen processing prior to examination .", "In a prospective study in the Democratic Republic of the Congo , we compared the diagnostic performance of ...	[ "Human African trypanosomiasis or sleeping sickness still causes considerable suffering in sub-Sahara Africa .", "Diagnostics for this infectious disease constantly improve but their performance in terms of accuracy and reproducibility should be evaluated prior to implementation in control activities .", "We ev...	2014
[ "Introduction", "Results", "Discussion", "Conclusions", "Materials and methods" ]	[]	The amplitude in periodic neural state trajectories underlies the tempo of rhythmic tapping	journal.pbio.3000054	Beat-based timing depends on the amplitude of periodic neural population dynamics and on the number of engaged neurons in primate medial premotor areas.	[ [ "Precise timing is a fundamental requisite for a select group of complex actions such as the execution and appreciation of music and dance [1] .", "In these behaviors , the perception of time intervals is facilitated by the presence of a regular beat in the rhythmic sequence , and individual intervals are...	[ "Our motor commands can be exquisitely timed according to the demands of the environment , and the ability to generate rhythms of different tempos is a hallmark of musical cognition .", "Yet , the neuronal underpinnings behind rhythmic tapping remain elusive .", "Here , we found that the activity of hundreds of...	[ "The ability to extract the regular pulse in music and to respond in synchrony to this pulse is called beat synchronization and is a natural human behavior exhibited during dancing and musical ensemble playing .", "A part of the brain called the medial premotor cortex has been associated with rhythmic entrainment...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "computer applications", "plant anatomy", "gene regulation", "plant physiology", "hormones", "regulator genes", "plant science", "plant hormones", "gene types", "inflorescences", "computer and information sciences", "gene expression", "biochemistry", "plant biochemistry", "flowers", "g...	The logic of the floral transition: Reverse-engineering the switch controlling the identity of lateral organs	journal.pcbi.1005744	null	[ [ "Computational approaches have become routinely used in the study of gene regulatory networks [1 , 2] .", "One of the fundamental key outcomes of gene-network activity is specification of the differentiated cell types during development that lead to different tissues and organs .", "To address this pa...	[ "Much laboratory work has been carried out to determine the gene regulatory network ( GRN ) that results in plant cells becoming flowers instead of leaves .", "However , this also involves the spatial distribution of different cell types , and poses the question of whether alternative networks could produce the s...	[ "Complex organisms develop following a genetic program specifying how their cells differentiate into organs with different specialized functions .", "Details of these mechanisms are incomplete , and aspects might not be correct .", "These genetic programs can be represented by simple computer programs processin...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "bacteriology", "biofilms", "invertebrates", "medicine and health sciences", "plagues", "body fluids", "pathology and laboratory medicine", "pathogens", "microbiology", "vertebrates", "animals", "mammals", "bacterial diseases", "yersinia", "fleas", "bacteria", "bacterial pathogens", ...	Feeding Behavior Modulates Biofilm-Mediated Transmission of Yersinia pestis by the Cat Flea, Ctenocephalides felis	journal.pntd.0004413	null	[ [ "The cat flea , Ctenocephalides felis , is a mammalian ectoparasite commonly found on domesticated animals , and , by association , humans [1] .", "C . felis is a known vector for the bacterial pathogens Rickettsia felis , R . typhi , and Bartonella spp .", "[2–4] .", "However , relatively limited...	[ "The cat flea , Ctenocephalides felis , is prevalent worldwide , will parasitize animal reservoirs of plague , and is associated with human habitations in known plague foci .", "Despite its pervasiveness , limited information is available about the cat flea’s competence as a vector for Yersinia pestis .", "It i...	[ "Although plague primarily affects wild rodents , human plague outbreaks still occur periodically in some areas of the world .", "Yersinia pestis , the bacterial agent of plague , is transmitted by fleas .", "Cat fleas are abundant worldwide , regularly infest human habitations in plague endemic areas , and rea...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular cell biology", "cell division", "cell biology", "protozoology", "biology", "microbiology", "parasitology" ]	Cell Division in Apicomplexan Parasites Is Organized by a Homolog of the Striated Rootlet Fiber of Algal Flagella	journal.pbio.1001444	Apicomplexan parasites undergo cell division using an evolutionarily conserved mechanism first described in the positioning and assembly of flagella in algae.	[ [ "Apicomplexa are protozoan parasites responsible for numerous human and veterinary diseases .", "Human pathogens in this phylum include Plasmodium , the causative agent of malaria , Toxoplasma , an opportunistic pathogen that causes encephalitis in immunocompromised individuals and congenital toxoplasmosi...	[ "Apicomplexa are intracellular parasites that cause important human diseases including malaria and toxoplasmosis .", "During host cell infection new parasites are formed through a budding process that parcels out nuclei and organelles into multiple daughters .", "Budding is remarkably flexible in output and can...	[ "Malaria , toxoplasmosis , and related diseases are caused by infection with unicellular parasites called Apicomplexa .", "Their name refers to the elaborate invasion machinery that occupies the apical end of the parasite cell .", "This apparatus allows the parasite to force its way into the cells of its host ,...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "cell death", "innate immune system", "medicine and health sciences", "autophagic cell death", "immune physiology", "cytokines", "pathology and laboratory medicine", "intracellular pathogens", "immune cells", "pathogens", "antigen-presenting cells", "immunology", "cell proce...	HDAC6 controls innate immune and autophagy responses to TLR-mediated signalling by the intracellular bacteria Listeria monocytogenes	journal.ppat.1006799	null	[ [ "Histone deacetylase 6 ( HDAC6 ) is a cytoplasmic deacetylase involved in the regulation of several biological processes , including migration , transport , angiogenesis , and tumour progression [1–5] .", "This enzyme is able to deacetylate α-tubulin and cortactin , regulating not only the microtubule cyt...	[ "Recent evidence on HDAC6 function underlines its role as a key protein in the innate immune response to viral infection .", "However , whether HDAC6 regulates innate immunity during bacterial infection remains unexplored .", "To assess the role of HDAC6 in the regulation of defence mechanisms against intracell...	[ "Listeria monocytogenes ( Lm ) is a food-borne intracellular bacterium that causes listeriosis to 1 . 600 people each year , being responsible of approximately 260 deaths .", "This pathogen mostly affects immunocompromised individuals and pregnant women .", "It is particularly dangerous for the later due to its...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "ecology" ]	Fish Invasions in the World's River Systems: When Natural Processes Are Blurred by Human Activities	journal.pbio.0060028	Mapping worldwide freshwater fish invasions allowed the identification of major invasion hot spots and demonstrated that economic activity is the main determinant of freshwater fish invasions at the global scale.	[ [ "The deliberate or accidental introduction of species outside their native range is a key component of the human-induced biodiversity crisis , harming native species and disturbing ecosystems processes [1–3] .", "The greater the introduction of non-natives in a region , the higher the probability that som...	[ "Because species invasions are a principal driver of the human-induced biodiversity crisis , the identification of the major determinants of global invasions is a prerequisite for adopting sound conservation policies .", "Three major hypotheses , which are not necessarily mutually exclusive , have been proposed t...	[ "As one of the major threats to biodiversity , the detrimental consequences of biological invasions are widely recognised .", "Despite this , a global view of invasion patterns and their determinants is still lacking in aquatic ecosystems , reducing our ability to initiate practical actions .", "Here we report ...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology", "microbiology" ]	Control of Virulence by Small RNAs in Streptococcus pneumoniae	journal.ppat.1002788	null	[ [ "Gene regulation and intercellular communication are fundamental aspects of bacterial adaptation to dynamic environments .", "As such , bacteria have evolved numerous strategies to facilitate tight control of genetic networks in response to diverse extracellular stimuli .", "Roles have been described ...	[ "Small noncoding RNAs ( sRNAs ) play important roles in gene regulation in both prokaryotes and eukaryotes .", "Thus far , no sRNA has been assigned a definitive role in virulence in the major human pathogen Streptococcus pneumoniae .", "Based on the potential coding capacity of intergenic regions , we hypothes...	[ "Pneumonia is a leading cause of childhood mortality worldwide , resulting in more deaths in young children than any other infectious disease .", "One of the leading causes of pneumonia is the human pathogen , Streptococcus pneumoniae , the causative agent of over six million infections each year in the United St...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "computational biology/macromolecular structure analysis", "biophysics/theory and simulation", "molecular biology/bioinformatics", "biophysics/rna structure", "mathematics/statistics", "computational biology/molecular dynamics" ]	A Probabilistic Model of RNA Conformational Space	journal.pcbi.1000406	null	[ [ "Non-coding RNA is of crucial importance for the functioning of the living cell , where it plays key catalytic , regulatory and structural roles [1] , [2] .", "Understanding the exact mechanisms behind these functions is therefore of great importance for both biology and medicine .", "In many cases , ...	[ "The increasing importance of non-coding RNA in biology and medicine has led to a growing interest in the problem of RNA 3-D structure prediction .", "As is the case for proteins , RNA 3-D structure prediction methods require two key ingredients: an accurate energy function and a conformational sampling procedure...	[ "The importance of RNA in biology and medicine has increased immensely over the last several years , due to the discovery of a wide range of important biological processes that are under the guidance of non-coding RNA .", "As is the case with proteins , the function of an RNA molecule is encoded in its three-dime...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "clinical laboratory sciences", "immune physiology", "body fluids", "pathology and laboratory medicine", "nervous system", "pathogens", "immunology", "tropical diseases", "microbiology", "saliva", "viruses", "preventive medicine", "rabies", "rna viruses", ...	Utility of rabies neutralizing antibody detection in cerebrospinal fluid and serum for ante-mortem diagnosis of human rabies	journal.pntd.0007128	null	[ [ "Rabies is an acute progressive , fatal encephalomyelitis caused by viruses of the Lyssavirus genus ( Order Mononegavirales , Family Rhabdoviridae ) .", "Rabies lyssavirus ( RABV ) , the prototype virus of the Lyssavirus genus is the most common causative agent of rabies , usually transmitted through the ...	[ "Early ante-mortem laboratory confirmation of human rabies is essential to aid patient management and institute public health measures .", "Few studies have highlighted the diagnostic value of antibody detection in CSF/serum in rabies , and its utility is usually undermined owing to the late seroconversion and sh...	[ "Ante-mortem diagnosis of human rabies is essential for patient management and public health measures .", "The detection of virus specific antibodies in the CSF/serum of patients with suspected rabies is thought to have a limited diagnostic role owing to late seroconversion and short survival in rabies .", "We ...	2019
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[]	The Universal Statistical Distributions of the Affinity, Equilibrium Constants, Kinetics and Specificity in Biomolecular Recognition	journal.pcbi.1004212	null	[ [ "Experiments on random sequence protein folding [11] and protein design [12] , have implied the statistical distributions of physical observable .", "Experimental and computational studies on biomolecular binding have also shown evidences of distribution of physical relevant quantities such as binding equ...	[ "We uncovered the universal statistical laws for the biomolecular recognition/binding process .", "We quantified the statistical energy landscapes for binding , from which we can characterize the distributions of the binding free energy ( affinity ) , the equilibrium constants , the kinetics and the specificity b...	[ "Uncovering the principles and underlying mechanisms of biomolecular recognition and molecular binding process is crucial for understanding the function and evolution , yet challenging .", "We meet the challenge by quantifying the statistical natures of the relevant physical variables of biomolecular recognition ...	2015
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "genetics", "biology", "microbiology", "evolutionary biology", "genetics and genomics" ]	Selection-Driven Gene Loss in Bacteria	journal.pgen.1002787	null	[ [ "A central biological question is how genomes evolve with respect to size and gene content and which factors affect and constrain this evolution .", "Clearly many bacterial genomes are in continuous flux with respect to genome size and a number of processes , including gene loss , gene duplications , gene...	[ "Gene loss by deletion is a common evolutionary process in bacteria , as exemplified by bacteria with small genomes that have evolved from bacteria with larger genomes by reductive processes .", "The driving force ( s ) for genome reduction remains unclear , and here we examined the hypothesis that gene loss is s...	[ "The mechanisms and driving forces involved in reductive evolution and loss of non-used gene functions are still largely unknown .", "Since most deletions are thought to have a negative effect on fitness , it is thought that deletions accumulate by chance , via non-adaptive genetic drift combined with an associat...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "developmental biology", "in vitro", "eukaryotes", "vertebrates", "mammals" ]	Functional Modulation of Cardiac Form through Regionally Confined Cell Shape Changes	journal.pbio.0050053	Cardiac function depends upon properly shaped heart chambers. Here the authors show that blood flow and contractility independently regulate cell shape changes in the emerging ventricle.	[ [ "Embryonic organs acquire a characteristic size and shape during their development .", "Cell division and cell growth control are known to influence organ size ( reviewed in [1–4] ) .", "Organ shape , on the other hand , is not simply a consequence of accumulated cell number and mass; organ shaping is...	[ "Developing organs acquire a specific three-dimensional form that ensures their normal function .", "Cardiac function , for example , depends upon properly shaped chambers that emerge from a primitive heart tube .", "The cellular mechanisms that control chamber shape are not yet understood .", "Here , we demo...	[ "As organs develop , they acquire a characteristic shape; the factors governing this complex process , however , are not understood .", "Shape may be sculpted by cell movement , cell division , or changes in cell size and shape , all of which can be influenced by the local environment .", "Here we investigate h...	2007
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "ears", "immunology", "parasitic diseases", "animal models", "otology", "model organisms", "ear infections", "signs and symptoms", "experimental organism systems", "inflammasomes", "cytoto...	CD8+ T cell cytotoxicity mediates pathology in the skin by inflammasome activation and IL-1β production	journal.ppat.1006196	null	[ [ "Granule mediated cytotoxicity is required for the clearance of several viral pathogens , as well as the killing of tumor cells [1] .", "However , cytotoxicity can also provoke a detrimental inflammatory response in several diseases , including experimental cerebral malaria , Trypanosoma cruzi-elicited ca...	[ "Deregulated CD8+ T cell cytotoxicity plays a central role in enhancing disease severity in several conditions .", "However , we have little understanding of the mechanisms by which immunopathology develops as a consequence of cytotoxicity .", "Using murine models of inflammation induced by the protozoan parasi...	[ "Leishmaniasis is a neglected tropical disease endemic in 98 countries and approximately 1 million new cases occur each year .", "Disease caused by Leishmania braziliensis , the main causative agent of leishmaniasis in South America , leads to skin ulcers that are difficult to heal with drugs that target the para...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Decay-Initiating Endoribonucleolytic Cleavage by RNase Y Is Kept under Tight Control via Sequence Preference and Sub-cellular Localisation	journal.pgen.1005577	null	[ [ "RNA synthesis and decay are both vital factors in the bacterial response to changing growth conditions , by starting up and shutting down cellular programs , respectively .", "RNA synthesis is determined by promoter strength , via the adherence of the RNA polymerase sigma factor to promoter motifs such a...	[ "Bacteria depend on efficient RNA turnover , both during homeostasis and when rapidly altering gene expression in response to changes .", "Nevertheless , remarkably few details are known about the rate-limiting steps in targeting and decay of RNA .", "The membrane-anchored endoribonuclease RNase Y is a virulenc...	[ "Ribonucleic acids ( RNA ) are key intermediates between the heritable genome and the expression of proteins .", "Thus the level of a specific RNA determines the capability of the cell to produce the corresponding protein .", "Bacteria maintain a very high turnover ( high production but also high decay-rate ) o...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Neorickettsia sennetsu as a Neglected Cause of Fever in South-East Asia	journal.pntd.0003908	null	[ [ "Neorickettsia sennetsu was not reported for 24 years prior to the identification of a Lao patient with sennetsu in 2009 [1] .", "This pathogen was the first documented cause of glandular fever ( infectious mononucleosis ) in Japan in 1954 , characterized by fever , weakness , anorexia , lymphadenopathy a...	[ "Neorickettsia sennetsu infection is rarely recognized , with less than 100 globally reported patients over the last 50 years .", "The disease is thought to be contracted by eating raw fish , a staple of many South-East Asian cuisines .", "In 2009 , the first patient with sennetsu was identified in the Lao PDR ...	[ "After the rediscovery of Neorickettsia sennetsu as a possible fish-borne cause of fever in 2009 , it remained unclear to what extent this pathogen was responsible for disease in Laos and South-East Asia .", "The original reports from the 1960s proposed an epidemiological link between eating raw fish and sennetsu...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology/cytoskeleton", "microbiology/cellular microbiology and pathogenesis", "cell biology/cellular death and stress responses" ]	Bim and Bmf Synergize To Induce Apoptosis in Neisseria Gonorrhoeae Infection	journal.ppat.1000348	null	[ [ "Infection with various pathogens results in the inhibition or activation of apoptotic cell death [1] .", "Whereas viral pathogens frequently inhibit host cell apoptosis , many bacteria kill immune or epithelial cells by apoptosis allowing them to subvert immune reactions or to invade tissues , respective...	[ "Bcl-2 family proteins including the pro-apoptotic BH3-only proteins are central regulators of apoptotic cell death .", "Here we show by a focused siRNA miniscreen that the synergistic action of the BH3-only proteins Bim and Bmf is required for apoptosis induced by infection with Neisseria gonorrhoeae ( Ngo ) .",...	[ "A variety of physiological death signals , as well as pathological insults , trigger apoptosis , a genetically programmed form of cell death .", "Pathogens often induce host cell apoptosis to establish a successful infection .", "Neisseria gonorrhoeae ( Ngo ) , the etiological agent of the sexually transmitted...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "pathology and laboratory medicine", "togaviruses", "chikungunya infection", "pathogens", "tropical diseases", "microbiology", "geographical locations", "panama", "animals", "alphaviruses", "viruses", "north america", "chikungunya virus", ...	Unusual pattern of chikungunya virus epidemic in the Americas, the Panamanian experience	journal.pntd.0005338	null	[ [ "The chikungunya virus ( CHIKV , Alphavirus , Togaviridae ) is an RNA single-stranded arthropod-borne pathogen that was first recognized in 1952–1953 in southeast Tanzania and northern Mozambique [1] .", "In Africa , CHIKV was associated with small outbreaks in rural areas , however , in Asia between 1960...	[ "Chikungunya virus ( CHIKV ) typically causes explosive epidemics of fever , rash and polyarthralgia after its introduction into naïve populations .", "Since its introduction in Panama in May of 2014 , few autochthonous cases have been reported; most of them were found within limited outbreaks in Panama City in 2...	[ "Chikungunya virus ( CHIKV ) is a mosquito borne pathogen that causes fever with rash and arthralgia , which are often confused with Dengue virus ( DENV ) infections .", "It has been reported that when CHIKV colonizes regions without previous circulation , it generally results in explosive human epidemics .", "...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "medicine and health sciences", "immune physiology", "immune cells", "pathology and laboratory medicine", "pathogens", "immunology", "microbiology", "cloning", "viruses", "rna viruses", "mammalian genomics", "molecular biology techniques", "antibodies", "research and analy...	Preconceptual Zika virus asymptomatic infection protects against secondary prenatal infection	journal.ppat.1006684	null	[ [ "The ongoing Zika virus ( ZIKV ) epidemic has triggered an explosion in cases of fetal death , microcephaly and other birth defects in surviving infants with congenital infection [1–4] .", "These sequelae usually occur in parallel with higher and more prolonged maternal viremia for up to 15 weeks followin...	[ "Pregnant women , and their fetal offspring , are uniquely susceptible to Zika virus and other microbial pathogens capable of congenital fetal infection .", "Unavoidable exposure to Zika virus in endemic areas underscores the need for identifying at-risk individuals , and protecting expecting mothers and their fe...	[ "Expecting mothers are uniquely susceptible to Zika virus infection that often spreads to vital tissues of the developing fetus .", "Since Zika virus infection in healthy non-pregnant individuals is mostly asymptomatic , a large proportion of reproductive age women that live in Zika endemic areas have been previo...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "gram positive bacteria", "biochemistry", "developmental biology", "dna replication", "bacterial genes", "genetics", "biology and life sciences", "dna", "microbial growth and development", "molecular genetics", "microbiology", "bacterial growth" ]	Multiple Regulatory Systems Coordinate DNA Replication with Cell Growth in Bacillus subtilis	journal.pgen.1004731	null	[ [ "DNA replication must be coordinated with the cell cycle to ensure proper genome inheritance .", "For many bacteria cellular physiology dictates the rate of growth and division .", "In nutrient-rich media that support rapid growth rates , bacteria synthesize DNA more rapidly by increasing the frequenc...	[ "In many bacteria the rate of DNA replication is linked with cellular physiology to ensure that genome duplication is coordinated with growth .", "Nutrient-mediated growth rate control of DNA replication initiation has been appreciated for decades , however the mechanism ( s ) that connects these cell cycle activ...	[ "DNA replication must be coordinated with cellular physiology to ensure proper genome inheritance .", "Model bacteria such as the soil-dwelling Bacillus subtilis can achieve a wide range of growth rates in response to nutritional and chemical signals .", "In order to match the rate of DNA synthesis to the rate ...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "chemical bonding", "medicine and health sciences", "chemical compounds", "endoplasmic reticulum", "cell processes", "organic compounds", "fibroblasts", "collagens", "animal models", "model organisms", "immunoprecipitation", "connective tissue cells", "basic amino acids", "amino acids", ...	Sc65-Null Mice Provide Evidence for a Novel Endoplasmic Reticulum Complex Regulating Collagen Lysyl Hydroxylation	journal.pgen.1006002	null	[ [ "Fibrillar collagens are abundant components of connective tissue extracellular matrix ( ECM ) [1] .", "They are formed by three polypeptides ( termed α chains ) each characterized by the presence of a long uninterrupted Gly-X-Y sequence repeat which folds into a characteristic triple-helical structure [1...	[ "Collagen is a major component of the extracellular matrix and its integrity is essential for connective tissue and organ function .", "The importance of proteins involved in intracellular collagen post-translational modification , folding and transport was recently highlighted from studies on recessive forms of ...	[ "Fibrillar collagens are major components of connective tissue extracellular matrix ( ECM ) .", "Among them , type I collagen is the most abundant protein in the human body and a large constituent of bone , dermis , tendon and ligament ECMs; type I collagen is also present in the stroma of other organs including ...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "histology", "model organisms", "physiology", "genetics", "biology", "anatomy and physiology", "molecular cell biology", "genetics and genomics" ]	Physiological Notch Signaling Maintains Bone Homeostasis via RBPjk and Hey Upstream of NFATc1	journal.pgen.1002577	null	[ [ "Notch signaling mediates communication between neighboring cells to control cell fate decisions in all metazoans [1] , [2] .", "The mammalian genome encodes four Notch receptors ( Notch1-4 ) and at least five ligands ( Jagged1 , 2 and Delta-like 1 , 3 , 4 ) [3] .", "In the canonical Notch pathway , b...	[ "Notch signaling between neighboring cells controls many cell fate decisions in metazoans both during embryogenesis and in postnatal life .", "Previously , we uncovered a critical role for physiological Notch signaling in suppressing osteoblast differentiation in vivo .", "However , the contribution of individu...	[ "Osteoporosis is a disease caused by disruption of the balance between bone formation and resorption resulting in a net loss of bone mass .", "Although anti-resorptive agents are the current mainstay of osteoporosis therapy , novel strategies to promote bone formation are critically needed for more effective prev...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Real-Time Imaging of the Intracellular Glutathione Redox Potential in the Malaria Parasite Plasmodium falciparum	journal.ppat.1003782	null	[ [ "Malaria is a major disease burden in 106 countries , causing an estimated 225 million cases and , as reported for 2010 , 665 , 000 to 1 , 133 , 000 human deaths each year in tropical and sub-tropical regions [1] .", "Despite recent progress [2] , drug resistance remains a major obstacle to the effective ...	[ "In the malaria parasite Plasmodium falciparum , the cellular redox potential influences signaling events , antioxidant defense , and mechanisms of drug action and resistance .", "Until now , the real-time determination of the redox potential in malaria parasites has been limited because conventional approaches d...	[ "In the malaria parasite Plasmodium falciparum , cellular redox reactions play important roles not only in redox-regulatory processes and antioxidant defense but also in the mechanisms of drug action and drug resistance .", "The tripeptide glutathione is present in malaria parasites in millimolar concentrations a...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases", "veterinary diseases", "zoonoses", "medicine and health sciences", "veterinary parasitology", "leishmaniasis", "parasitology", "neglected tropical diseases", "biology and life sciences", "tropical diseases", "protozoan infections", "parasitic diseases", "veterinary sci...	Distinct Leishmania Species Infecting Wild Caviomorph Rodents (Rodentia: Hystricognathi) from Brazil	journal.pntd.0003389	null	[ [ "More than 30 species within the Leishmania genus ( Trypanosomatidae , Trypanosomatida ) are recognized , including both extremely specific as well as generalist species transmitted by a variety of Phlebotomine vectors worldwide [1]–[2] In fact , several Leishmania species are multi-host parasites that infect...	[ "Caviomorph rodents , some of the oldest Leishmania spp .", "hosts , are widely dispersed in Brazil .", "Despite both experimental and field studies having suggested that these rodents are potential reservoirs of Leishmania parasites , not more than 88 specimens were analyzed in the few studies of natural infec...	[ "Leishmaniasis is a major public health problem expanding in Brazil and one of the reasons is that we still have poor knowledge of some aspects of the biology and epidemiology of Leishmania species , including the role of wild mammals .", "Caviomorph rodents , some of the oldest Leishmania spp .", "hosts , are ...	2014
[ "Introduction", "Results and Discussion", "Methods" ]	[]	Biotic and Human Vulnerability to Projected Changes in Ocean Biogeochemistry over the 21st Century	journal.pbio.1001682	Mora and colleagues show that ongoing greenhouse gas emissions are likely to have a considerable effect on several biogeochemical properties of the world's oceans, with potentially serious consequences for biodiversity and human welfare.	[ [ "As CO2 and other greenhouse gas emissions continue to rise , ocean biogeochemistry is being altered in ways that could potentially impact nature and mankind .", "Atmospheric CO2 concentrations have already risen to ∼400 ppm from ∼280 ppm in pre-industrial times and could rise to between 550 and 900 ppm b...	[ "Ongoing greenhouse gas emissions can modify climate processes and induce shifts in ocean temperature , pH , oxygen concentration , and productivity , which in turn could alter biological and social systems .", "Here , we provide a synoptic global assessment of the simultaneous changes in future ocean biogeochemi...	[ "Climate change caused by human activity could damage biological and social systems .", "Here we gathered climate , biological , and socioeconomic data to describe some of the events by which ocean biogeochemical changes triggered by ongoing greenhouse gas emissions could cascade through marine habitats and organ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "biology", "molecular cell biology" ]	Sequential Analysis of Trans-SNARE Formation in Intracellular Membrane Fusion	journal.pbio.1001243	SM proteins stabilize cis-SNARE complexes leading to a specific preferred topology for trans-SNARE formation.	[ [ "Cognate combinations of v- and t-SNAREs mediate membrane docking in every vesicular transport step in the endomembrane system .", "v- and t-SNAREs bind each other in coiled-coil complexes containing four helices [1] .", "Three of these helices ( termed Qa , Qb , and Qc ) are provided by t-SNAREs , wh...	[ "SNARE complexes are required for membrane fusion in the endomembrane system .", "They contain coiled-coil bundles of four helices , three ( Qa , Qb , and Qc ) from target ( t ) -SNAREs and one ( R ) from the vesicular ( v ) -SNARE .", "NSF/Sec18 disrupts these cis-SNARE complexes , allowing reassembly of their...	[ "Cellular components often travel between organelles in vesicular entities .", "This intracellular traffic usually involves production of a vesicle containing cargo from one organelle membrane , movement of the vesicle to its destination , and then fusion of the vesicle with the target organelle .", "Thus , mem...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "condensed matter physics", "simulation and modeling", "optimization", "mathematics", "statistics (mathematics)", "stochastic processes", "research and analysis methods", "stat signaling", "probability theory", "mesoscopic physics", "approximation methods", "physics", "biochemistry", "bioc...	Inference for Stochastic Chemical Kinetics Using Moment Equations and System Size Expansion	journal.pcbi.1005030	null	[ [ "On the single-cell level many biological processes are influenced by stochastic fluctuations [1–3] .", "This stochasticity must be accounted for when constructing quantitative mechanistic models for the behavior of cells .", "Traditionally , dynamics of stochastic biochemical processes are modeled us...	[ "Quantitative mechanistic models are valuable tools for disentangling biochemical pathways and for achieving a comprehensive understanding of biological systems .", "However , to be quantitative the parameters of these models have to be estimated from experimental data .", "In the presence of significant stocha...	[ "In this manuscript , we introduce efficient methods for parameter estimation for stochastic processes .", "The stochasticity of chemical reactions can influence the average behavior of the considered system .", "For some biological systems , a microscopic , stochastic description is computationally intractable...	2016
[ "Introduction", "Results", "Discussion" ]	[ "learning", "medicine and health sciences", "action potentials", "nervous system", "population dynamics", "membrane potential", "social sciences", "electrophysiology", "neuroscience", "learning and memory", "synaptic plasticity", "cognitive psychology", "population biology", "neuronal plas...	Oscillations via Spike-Timing Dependent Plasticity in a Feed-Forward Model	journal.pcbi.1004878	null	[ [ "It is generally believed that synaptic plasticity is the basis for learning and memory .", "According to Hebb's rule [1] , which is considered the foundation for current views on learning and memory , the interaction strength between two neurons that are co-activated potentiates .", "This rule has be...	[ "Neuronal oscillatory activity has been reported in relation to a wide range of cognitive processes including the encoding of external stimuli , attention , and learning .", "Although the specific role of these oscillations has yet to be determined , it is clear that neuronal oscillations are abundant in the cent...	[ "Oscillatory activity in the brain has been described in relation to many cognitive states and tasks , including the encoding of external stimuli , attention , learning and consolidation of memory .", "However , without tuning of synaptic weights with the preferred phase of firing the oscillatory signal may not b...	2016
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "biotechnology", "invertebrates", "medicine and health sciences", "ecology and environmental sciences", "population dynamics", "population genetics", "animals", "theoretical ecology", "population biology", "insect vectors", "genetic engineering", "infectious diseases", "population ecology", ...	Population dynamics of engineered underdominance and killer-rescue gene drives in the control of disease vectors	journal.pcbi.1006059	null	[ [ "Mosquito-borne diseases represent one of the most severe public health burdens worldwide .", "For example , dengue viruses that are primarily transmitted by Aedes aegypti mosquitoes have rapidly increased in prevalence in recent years [1] .", "One recent study estimated that around 3 . 9 billion peop...	[ "A number of different genetics-based vector control methods have been proposed .", "Two approaches currently under development in Aedes aegypti mosquitoes are the two-locus engineered underdominance and killer-rescue gene drive systems .", "Each of these is theoretically capable of increasing in frequency with...	[ "Vector-borne diseases represent a severe burden to both human and animal health worldwide .", "The methods currently being used to control a range of these diseases do not appear sufficient to address the issues at hand .", "As such , alternate methods for the control of vector-borne diseases are currently bei...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "fisheries science", "marine and aquatic sciences", "genetics", "epigenetics", "biology", "dna modification", "morphogenesis", "marine biology", "genetics and genomics", "sex determination" ]	DNA Methylation of the Gonadal Aromatase (cyp19a) Promoter Is Involved in Temperature-Dependent Sex Ratio Shifts in the European Sea Bass	journal.pgen.1002447	null	[ [ "The sex ratio is a crucial demographic parameter important for population viability that is established by the processes of sex determination and differentiation .", "The sex determination mechanisms in vertebrates include genotypic sex determination ( GSD ) , temperature-dependent sex determination ( TS...	[ "Sex ratio shifts in response to temperature are common in fish and reptiles .", "However , the mechanism linking temperature during early development and sex ratios has remained elusive .", "We show in the European sea bass ( sb ) , a fish in which temperature effects on sex ratios are maximal before the gonad...	[ "Temperature changes during early embryonic and/or larval stages are able to modify sex ratios in fish and reptiles .", "However , the underlying mechanism by which temperature is able to modify the molecular pathways that developing gonads follow to become ovaries or testes is still unknown .", "One of the mos...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology/germ cells", "developmental biology/embryology", "developmental biology", "cell biology/cell signaling", "cell biology/membranes and sorting", "biochemistry/cell signaling and trafficking structures", "cell biology/cytoskeleton" ]	Requirements for F-BAR Proteins TOCA-1 and TOCA-2 in Actin Dynamics and Membrane Trafficking during Caenorhabditis elegans Oocyte Growth and Embryonic Epidermal Morphogenesis	journal.pgen.1000675	null	[ [ "The coordination and functional cooperation between endocytic trafficking of membranes and membrane proteins with actin-based motility is required for the correct execution of many cellular phenotypes .", "These include directional cell migration , tissue morphogenesis , cell-fate determination , and the...	[ "The TOCA family of F-BAR–containing proteins bind to and remodel lipid bilayers via their conserved F-BAR domains , and regulate actin dynamics via their N-Wasp binding SH3 domains .", "Thus , these proteins are predicted to play a pivotal role in coordinating membrane traffic with actin dynamics during cell mig...	[ "Cells continuously remodel their shape especially during cell migration , differentiation , and tissues morphogenesis .", "This occurs through the dynamic reorganization of their plasma membrane and actin cytoskeleton: two processes that must therefore be intimately linked and coordinated .", "Molecules that s...	2009
[ "Introduction", "Results", "Discussion" ]	[ "taxonomy", "medicine and health sciences", "pathology and laboratory medicine", "togaviruses", "pathogens", "microbiology", "alphaviruses", "viruses", "phylogenetics", "data management", "chikungunya virus", "rna viruses", "phylogenetic analysis", "genome analysis", "research and analys...	A computational method for the identification of Dengue, Zika and Chikungunya virus species and genotypes	journal.pntd.0007231	null	[ [ "In the recent years , an increasing number of outbreaks of Dengue ( DENV ) , Chikungunya ( CHIKV ) and Zika ( ZIKV ) viruses have been reported in Asia and the Americas [1–3] .", "The predominant mosquito species transmitting DENV , CHIKV and ZIKV , are Aedes aegypti and Aedes Albopictus , which are wide...	[ "In recent years , an increasing number of outbreaks of Dengue , Chikungunya and Zika viruses have been reported in Asia and the Americas .", "Monitoring virus genotype diversity is crucial to understand the emergence and spread of outbreaks , both aspects that are vital to develop effective prevention and treatm...	[ "Dengue ( DENV ) , Chikungunya ( CHIKV ) and Zika ( ZIKV ) are considered major public health challenges .", "In addition to the epidemic caused by DENV , which has been described in many tropical countries , the introduction of CHIKV and ZIKV in these countries is a major public health concern .", "These arbov...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/gene discovery", "infectious diseases/fungal infections", "genetics and genomics/gene function", "microbiology/microbial growth and development", "molecular biology" ]	Transcription Factors Mat2 and Znf2 Operate Cellular Circuits Orchestrating Opposite- and Same-Sex Mating in Cryptococcus neoformans	journal.pgen.1000953	null	[ [ "Many fungi undergo dramatic morphological differentiation during their life cycles .", "The morphological transition between the yeast form and the pseudohyphal form during mating and invasive growth in Saccharomyces cerevisiae has served as a paradigm for developmental biology due to the well-characteri...	[ "Cryptococcus neoformans is a human fungal pathogen that undergoes a dimorphic transition from a unicellular yeast to multicellular hyphae during opposite sex ( mating ) and unisexual reproduction ( same-sex mating ) .", "Opposite- and same-sex mating are induced by similar environmental conditions and involve ma...	[ "Although sexual reproduction typically involves partners of opposite mating type ( sexuality ) , sex can occur with just one mating type and even with single individuals ( parthenogenesis , homothallism ) .", "For example , Cryptococcus neoformans , a fungal pathogen that causes cryptococcal meningitis , can und...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "public health and epidemiology", "epidemiology", "gastroenterology and hepatology", "inflammatory bowel disease" ]	A Genome-Wide Scan of Ashkenazi Jewish Crohn's Disease Suggests Novel Susceptibility Loci	journal.pgen.1002559	null	[ [ "Ashkenazi Jews ( AJs ) comprise a single genetic community of individuals of Eastern and Central European descent .", "Several lines of evidence suggest genetic differences between the Jewish and non-Jewish peoples of Europe ( NJ ) .", "It has been demonstrated that the genomes of individuals with on...	[ "Crohn's disease ( CD ) is a complex disorder resulting from the interaction of intestinal microbiota with the host immune system in genetically susceptible individuals .", "The largest meta-analysis of genome-wide association to date identified 71 CD–susceptibility loci in individuals of European ancestry .", ...	[ "Crohn's disease causes inflammation of the digestive tract resulting from the interaction of normal gut bacteria with the host immune system in genetically predisposed individuals .", "People of Jewish heritage have an increased risk of developing Crohn's disease compared to non-Jewish Europeans .", "So far , ...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "test evaluation", "diagnostic medicine", "african trypanosomiasis", "neglected tropical diseases", "malaria", "parasitic diseases" ]	False Positivity of Non-Targeted Infections in Malaria Rapid Diagnostic Tests: The Case of Human African Trypanosomiasis	journal.pntd.0002180	null	[ [ "Traditional diagnosis of malaria relies on microscopic detection of Plasmodium in thick blood films , which is labour-intensive , time-consuming and requires technical skills .", "Malaria rapid diagnostic tests ( RDT ) offer an attractive alternative for microscopy .", "They detect parasite antigens ...	[ "In endemic settings , diagnosis of malaria increasingly relies on the use of rapid diagnostic tests ( RDTs ) .", "False positivity of such RDTs is poorly documented , although it is especially relevant in those infections that resemble malaria , such as human African trypanosomiasis ( HAT ) .", "We therefore e...	[ "Rapid diagnostic tests ( RDT ) for malaria are currently rolled-out as the backbone of parasite-based diagnosis , and their diagnostic accuracy is sufficiently high to substitute microscopy .", "One decade ago , attention has been given to occurrence of limited false positivity in a number of malaria RDTs , but ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cellular structures", "cell biology", "synapses", "biology", "molecular cell biology", "neuroscience", "neurophysiology", "cytoskeleton" ]	Drosophila cyfip Regulates Synaptic Development and Endocytosis by Suppressing Filamentous Actin Assembly	journal.pgen.1003450	null	[ [ "To establish functional neural circuits , synapses must form at specific locations and grow to an appropriate size and strength .", "A multitude of signaling pathways are required to achieve and maintain these precise patterns of synaptic connectivity [1]–[3] .", "Many of these signals regulate local...	[ "The formation of synapses and the proper construction of neural circuits depend on signaling pathways that regulate cytoskeletal structure and dynamics .", "After the mutual recognition of a growing axon and its target , multiple signaling pathways are activated that regulate cytoskeletal dynamics to determine t...	[ "Synapses are specialized junctions at which neurons communicate with target cells .", "To establish properly wired neuronal circuits , synapses must grow in size and strength with a high degree of accuracy .", "The actin cytoskeleton plays a crucial role in the formation and function of synapses , but the unde...	2013
[ "Introduction", "Material and methods", "Results", "Discussion" ]	[ "parasite groups", "medicine and health sciences", "pathology and laboratory medicine", "plasmodium", "tropical diseases", "plasmodium falciparum", "parasitic diseases", "parasitic protozoans", "parasitology", "apicomplexa", "protozoans", "signs and symptoms", "global health", "medical eth...	Persistent transmission of Plasmodium malariae and Plasmodium ovale species in an area of declining Plasmodium falciparum transmission in eastern Tanzania	journal.pntd.0007414	null	[ [ "Since the turn of the millennium , there has been a substantial reduction in the global burden of malaria including a reduction in the clinical incidence of both Plasmodium falciparum and P . vivax malaria [1–3] .", "This reduction has largely been attributed to an increase in malaria control efforts usi...	[ "A reduction in the global burden of malaria over the past two decades has encouraged efforts for regional malaria elimination .", "Despite the need to target all Plasmodium species , current focus is mainly directed towards Plasmodium falciparum , and to a lesser extent P . vivax .", "There is a substantial la...	[ "The reduction in the global burden of malaria has encouraged efforts for elimination .", "Attempts to control and monitor transmission have mainly focused on the predominant malaria parasites Plasmodium falciparum and P . vivax .", "However , eliminating malaria requires the elimination of all human malaria pa...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "gene regulation", "population genetics", "departures from diploidy", "pediatrics", "bioassays and physiological analysis", "dna", "epigenetics", "molecular genetics", "epigenomics", "population biology", "developmental and pediatric neurology", "chromatin", ...	Mosaic Epigenetic Dysregulation of Ectodermal Cells in Autism Spectrum Disorder	journal.pgen.1004402	null	[ [ "Progress in understanding the genetic basis of ASD has been substantial in recent years , with the development of microarray technologies allowing the identification of copy number variants associated with the disorder [1] and massively-parallel sequencing focused on protein-coding exons allowing insights in...	[ "DNA mutational events are increasingly being identified in autism spectrum disorder ( ASD ) , but the potential additional role of dysregulation of the epigenome in the pathogenesis of the condition remains unclear .", "The epigenome is of interest as a possible mediator of environmental effects during developme...	[ "Older mothers have a higher than expected risk of having a child with an autism spectrum disorder ( ASD ) .", "The reason for this increased risk is unknown .", "The eggs of older mothers are more prone to abnormalities of chromosome numbers , suggesting this as one possible mechanism of the increased ASD risk...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "parasite groups", "plasmodium", "tropical diseases", "enzymology", "parasitic diseases", "parasitic protozoans", "parasitology", "apicomplexa", "metabolomics", "protozoans", "metabolites", "enzyme metabolism", "pharmacology", "drug metabolism", "thermod...	Bioenergetics-based modeling of Plasmodium falciparum metabolism reveals its essential genes, nutritional requirements, and thermodynamic bottlenecks	journal.pcbi.1005397	null	[ [ "Malaria remains a major global health care concern , with almost half of the world population at risk of infection that ultimately results in over half a million deaths each year [1] .", "Of the five Plasmodium species capable of infecting humans , P . falciparum is responsible for most malaria-related d...	[ "Novel antimalarial therapies are urgently needed for the fight against drug-resistant parasites .", "The metabolism of malaria parasites in infected cells is an attractive source of drug targets but is rather complex .", "Computational methods can handle this complexity and allow integrative analyses of cell m...	[ "Almost half of the world population is at risk of infection by malaria parasites .", "The rise in drug-resistant parasites requires better understanding and targeting of their metabolism .", "In this study , we present a genome-scale metabolic reconstruction ( iPfa ) of the deadliest malaria parasite , Plasmod...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "chemical bonding", "chemical characterization", "neurochemistry", "crystal structure", "chemical compounds", "oxygen", "condensed matter physics", "neuroscience", "organic compounds", "simulation and modeling", "acidic amino acids", "amino acids", "neurotransmitters", "crystallography", ...	Molecular Mechanisms of Glutamine Synthetase Mutations that Lead to Clinically Relevant Pathologies	journal.pcbi.1004693	null	[ [ "Glutamine synthetase ( GS , glutamate ammonia ligase , EC 6 . 3 . 1 . 2 ) catalyzes the ATP-dependent ligation of glutamate and ammonia to glutamine [1] .", "GS is ubiquitously expressed in human tissues .", "High expression levels of GS are found in astrocytes in brain tissues [2] , where it is part...	[ "Glutamine synthetase ( GS ) catalyzes ATP-dependent ligation of ammonia and glutamate to glutamine .", "Two mutations of human GS ( R324C and R341C ) were connected to congenital glutamine deficiency with severe brain malformations resulting in neonatal death .", "Another GS mutation ( R324S ) was identified i...	[ "Glutamine synthetase ( GS ) catalyzes the ATP-dependent ligation of ammonia and glutamate to glutamine , which makes the enzyme essential for human nitrogen metabolism .", "Three mutations in human GS , R324C , R324S , and R341C , had been identified previously that lead to a glutamine deficiency , resulting in ...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "obstetrics/pregnancy", "infectious diseases/helminth infections", "public health and epidemiology/infectious diseases", "infectious diseases/hiv infection and aids", "infectious diseases/tropical and travel-associated diseases" ]	Risk Factors for Helminth, Malaria, and HIV Infection in Pregnancy in Entebbe, Uganda	journal.pntd.0000473	null	[ [ "Approximately one third of the world's population is infected with helminths and , in recent years , helminth control has been the focus of renewed interest on account of the concomitant direct disease burden [1] , [2] .", "At the same time , researchers have become more interested in the effects helmint...	[ "Infections during pregnancy may have serious consequences for both mother and baby .", "Assessment of risk factors for infections informs planning of interventions and analysis of the impact of infections on health outcomes .", "To describe risk factors for helminths , malaria and HIV in pregnant Ugandan women...	[ "Infections in pregnancy can cause miscarriage , stillbirth , maternal mortality , and low birth weight and have other long-term complications for mother and baby , although the full impact of many infections , particularly worm infections , is not yet fully understood .", "There is a high burden of infectious di...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Wdpcp, a PCP Protein Required for Ciliogenesis, Regulates Directional Cell Migration and Cell Polarity by Direct Modulation of the Actin Cytoskeleton	journal.pbio.1001720	Wdpcp, a protein required for both planar cell polarity and ciliogenesis, regulates cell polarity and alignment via direct modulation of the actin cytoskeleton.	[ [ "The cilium is a microtubule-based organelle projecting from the cell surface with a variety of signaling functions .", "It plays an important role in development as indicated by the wide spectrum of birth defects associated with ciliopathy syndromes such as Bardet–Biedl ( BBS ) and Meckel–Gruber ( MKS ) ...	[ "Planar cell polarity ( PCP ) regulates cell alignment required for collective cell movement during embryonic development .", "This requires PCP/PCP effector proteins , some of which also play essential roles in ciliogenesis , highlighting the long-standing question of the role of the cilium in PCP .", "Wdpcp ,...	[ "Cilia are microscopic cell surface hair-like protrusions that can act as antennae to mediate cell signaling .", "Mutations disrupting ciliogenesis can cause many developmental anomalies associated with syndromes known as “ciliopathies . ”", "Some developmental defects , such as limb polydactyly , arise from di...	2013
[ "Introduction", "Results", "Discussion", "Materials And Methods" ]	[ "marine biology", "ecology", "biology" ]	Rare Species Support Vulnerable Functions in High-Diversity Ecosystems	journal.pbio.1001569	The most unusual, and thus irreplaceable, functions performed by species in three different species-rich ecosystems are fulfilled by only the rare species in these ecosystems.	[ [ "The vast majority of species are rare—that is , comprising few individuals—and often have restricted geographic distributions [1] .", "Although several forms of rarity have been defined with respect to the trajectories by which species become extinct [2] , [3] , rare species are all seen as highly vulner...	[ "Around the world , the human-induced collapses of populations and species have triggered a sixth mass extinction crisis , with rare species often being the first to disappear .", "Although the role of species diversity in the maintenance of ecosystem processes has been widely investigated , the role of rare spec...	[ "In ecological systems most species are rare—that is , represented by only a few individuals or restricted to particular habitats—and are vulnerable to being lost .", "Yet the ecological consequences of such biodiversity loss are often overlooked and remain controversial .", "In the best-case scenario , the fun...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Analysis of the Relationships between DNA Double-Strand Breaks, Synaptonemal Complex and Crossovers Using the Atfas1-4 Mutant	journal.pgen.1005301	null	[ [ "Histone chaperones are a family of proteins that facilitate appropriate interactions between histones and DNA by regulating the assembly and disassembly of chromatin in response to cellular requirements [1–3] .", "CAF-1 is a heterotrimeric histone chaperone complex that mediates nucleosome assembly on ne...	[ "Chromatin Assembly Factor 1 ( CAF-1 ) is a histone chaperone that assembles acetylated histones H3/H4 onto newly synthesized DNA , allowing the de novo assembly of nucleosomes during replication .", "CAF-1 is an evolutionary conserved heterotrimeric protein complex .", "In Arabidopsis , the three CAF-1 subunit...	[ "Meiosis is a special cell division common in all sexually reproducing organisms .", "It consists of two successive rounds of chromosome segregation , preceded by a single DNA replication event .", "Homologous recombination is a key process that occurs during the first meiotic division .", "It guarantees the ...	2015
[ "Introduction", "Materials and Methods", "Results and Discussion", "Software and Data Availability" ]	[]	PF2 fit: Polar Fast Fourier Matched Alignment of Atomistic Structures with 3D Electron Microscopy Maps	journal.pcbi.1004289	null	[ [ "Protein structural data is available in primarily two forms .", "Atomistic scale structures ( or atomic structures for short ) , acquired through X-ray or nuclear magnetic resonance ( NMR ) imaging , contain information fine enough to localize the position of most , if not all , the atoms of the protein ...	[ "There continue to be increasing occurrences of both atomistic structure models in the PDB ( possibly reconstructed from X-ray diffraction or NMR data ) , and 3D reconstructed cryo-electron microscopy ( 3D EM ) maps ( albeit at coarser resolution ) of the same or homologous molecule or molecular assembly , deposite...	[ "In recent years , advances in cryo-electron microscopy ( cryoEM ) and three-dimensional ( 3D ) image reconstruction have made it possible to determine the structures of molecular complexes , to sub-nanometer resolutions .", "These reconstructed 3D cryoEM maps provide a unique challenge , since the resolutions ar...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology and life sciences" ]	Activation of Focal Adhesion Kinase by Salmonella Suppresses Autophagy via an Akt/mTOR Signaling Pathway and Promotes Bacterial Survival in Macrophages	journal.ppat.1004159	null	[ [ "Serovars of Salmonella enterica are facultative intracellular Gram-negative entero-pathogens that cause a spectrum of human diseases ranging from localized gastroenteritis to typhoid fever .", "Pathogenic Salmonella strains use two Type III secretion systems ( T3SS ) , encoded within Salmonella Pathogeni...	[ "Autophagy has emerged as an important antimicrobial host defense mechanism that not only orchestrates the systemic immune response , but also functions in a cell autonomous manner to directly eliminate invading pathogens .", "Pathogenic bacteria such as Salmonella have evolved adaptations to protect themselves f...	[ "Salmonella enterica is a food- and water-borne pathogen that has evolved closely with vertebrate hosts .", "Two medically relevant serovars include S . typhimurium , which causes gastroenteritis and S . typhi , which is the causative agent of typhoid fever .", "Host cells can utilize a process called autophagy...	2014
[ "Introduction", "Mathematical and Computational Model", "Results", "Discussion" ]	[ "acoustics", "medicine and health sciences", "classical mechanics", "engineering and technology", "ears", "lasers", "inner ear", "reflection", "optical equipment", "waves", "traveling waves", "sensory physiology", "head", "physics", "sound waves", "anatomy", "cochlea", "equipment",...	The Coda of the Transient Response in a Sensitive Cochlea: A Computational Modeling Study	journal.pcbi.1005015	null	[ [ "In a sensitive cochlea , the response of the basilar membrane ( BM ) to transient external acoustic excitation consists not only of a primary impulse response but also of a coda of delayed secondary responses ( sometimes called echoes or ringing ) with varying amplitudes but similar spectral content centered...	[ "In a sensitive cochlea , the basilar membrane response to transient excitation of any kind–normal acoustic or artificial intracochlear excitation–consists of not only a primary impulse but also a coda of delayed secondary responses with varying amplitudes but similar spectral content around the characteristic freq...	[ "The fluid-structure-electrical interaction in the cochlea enable the basilar membrane , one of the most important structures in the cochlear partition , to display different dynamic patterns depending on the frequency content of the incoming sound .", "Interestingly , in a healthy cochlea the motion of the basil...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "developmental biology", "computer and information sciences", "genetic networks", "gene regulatory networks", "network analysis", "gene identification and analysis", "evolutionary processes", "genetics", "natural selection", "biology and life sciences", "gene expression", "gene regulation", ...	On the role of sparseness in the evolution of modularity in gene regulatory networks	journal.pcbi.1006172	null	[ [ "Many biological systems are modular .", "That is , their interactions occur predominantly within groups of elements and rarely between groups [1–3] .", "Modularity seems to be associated to important attributes of distinct biological systems .", "For example , theoretical and experimental efforts...	[ "Modularity is a widespread property in biological systems .", "It implies that interactions occur mainly within groups of system elements .", "A modular arrangement facilitates adjustment of one module without perturbing the rest of the system .", "Therefore , modularity of developmental mechanisms is a majo...	[ "Modular systems have performance and design advantages over non-modular systems .", "Thus , modularity is very important for the development of a wide range of new technological or clinical applications .", "Moreover , modularity is paramount to evolutionary biology since it allows adjusting one organismal fun...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "urology", "bladder and ureteric disorders", "immunity to infections", "immunology", "microbiology", "host-pathogen interaction", "parasitic diseases", "parasitology", "dna transcription", "animal models", "model organisms", "global health", "neglected tropical diseases", "ur...	Transcriptional Profiling of the Bladder in Urogenital Schistosomiasis Reveals Pathways of Inflammatory Fibrosis and Urothelial Compromise	journal.pntd.0001912	null	[ [ "Schistosomiasis , chronic infection with parasitic Schistosoma worms , affects at least 200 million people worldwide , and may rival malaria in terms of socioeconomic impact in endemic regions [1] .", "The two main forms of schistosomiasis are hepatoenteric and urogenital , caused primarily by Schistosom...	[ "Urogenital schistosomiasis , chronic infection by Schistosoma haematobium , affects 112 million people worldwide .", "S . haematobium worm oviposition in the bladder wall leads to granulomatous inflammation , fibrosis , and egg expulsion into the urine .", "Despite the global impact of urogenital schistosomias...	[ "Parasitic Schistosoma haematobium worms cause urogenital schistosomiasis in 112 million people worldwide .", "These worms lay eggs in the bladder wall , resulting in inflammation , fibrosis ( internal scarring ) , bladder cancer , and passage of eggs into the urine .", "Indeed , the International Agency for Re...	2012
[ "Introduction", "Materials and methods", "Results", "Discussion", "Conclusion" ]	[ "medicine and health sciences", "legs", "education", "sociology", "tropical diseases", "geographical locations", "limbs (anatomy)", "social sciences", "parasitic diseases", "filariasis", "neglected tropical diseases", "ethiopia", "lymphatic filariasis", "africa", "feet (anatomy)", "alu...	Soil iron and aluminium concentrations and feet hygiene as possible predictors of Podoconiosis occurrence in Kenya	journal.pntd.0005864	null	[ [ "Podoconiosis is a neglected geochemical , non-filarial , non-infectious lymphodema of the lower limb [1] .", "In Africa , countries in which non-filarial elephantiasis have been reported include: Tanzania [2] , Uganda [3] , Kenya [4] , Cameroon [5] , Sao Tome and Principe [6] , Rwanda , Burundi , Sudan ,...	[ "Podoconiosis ( mossy foot ) is a neglected non-filarial elephantiasis considered to be caused by predisposition to cumulative contact of uncovered feet to irritative red clay soil of volcanic origins in the tropical regions .", "Data from structured observational studies on occurrence of Podoconiosis and related...	[ "Podoconiosis is a neglected disease in the tropical regions of the world considered to be caused by prolonged contact of uncovered feet to irritant particles found in red clay soil from volcanic origins .", "The disease presents like filarial elephantiasis .", "Data from observational studies from Kenya are no...	2017
[ "Introduction", "Methods", "Vaccination schedules with peptide-based nanovaccines and challenge infection", "Results", "Discussion" ]	[ "blood cells", "medicine and health sciences", "immune cells", "immune physiology", "spleen", "immunology", "tropical diseases", "parasitic diseases", "drug delivery system preparation", "preventive medicine", "antigen encapsulation", "pharmaceutics", "neglected tropical diseases", "cytoto...	Identification of BALB/c Immune Markers Correlated with a Partial Protection to Leishmania infantum after Vaccination with a Rationally Designed Multi-epitope Cysteine Protease A Peptide-Based Nanovaccine	journal.pntd.0005311	null	[ [ "Leishmaniasis is an infectious diseases complex caused by protozoan parasites of the genus Leishmania .", "According to epidemiological data , visceral leishmaniasis ( VL ) is the second most common parasitic cause of death among tropical infections and is prevalent in 47 countries with about 200 million...	[ "Through their increased potential to be engaged and processed by dendritic cells ( DCs ) , nanovaccines consisting of Poly ( D , L-lactic-co-glycolic acid ) ( PLGA ) nanoparticles ( NPs ) loaded with both antigenic moieties and adjuvants are attractive candidates for triggering specific defense mechanisms against ...	[ "Leishmaniases are a wide spectrum of parasite diseases caused by different species of the genus Leishmania .", "Among them , visceral leishmaniasis is the most severe form of the disease affecting millions of people worldwide .", "Currently chemotherapeutic agents are highly toxic and suffer from extensive dru...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "microbiology/environmental microbiology", "microbiology/microbial growth and development", "biochemistry/cell signaling and trafficking structures", "biochemistry/biomacromolecule-ligand interactions" ]	A c-di-GMP Effector System Controls Cell Adhesion by Inside-Out Signaling and Surface Protein Cleavage	journal.pbio.1000587	null	[ [ "Bacteria can be exquisitely tuned to sense and respond to changes in their environment .", "A single cell may possess an immense repertoire of signal transduction systems capable of receiving sensory input and directing physiological adaptation .", "The recent groundswell of studies on the intracellu...	[ "In Pseudomonas fluorescens Pf0-1 the availability of inorganic phosphate ( Pi ) is an environmental signal that controls biofilm formation through a cyclic dimeric GMP ( c-di-GMP ) signaling pathway .", "In low Pi conditions , a c-di-GMP phosphodiesterase ( PDE ) RapA is expressed , depleting cellular c-di-GMP a...	[ "Bacteria can live as free swimming cells or attached to surfaces in communities called biofilms .", "The di-nucleotide c-di-GMP is a key cytoplasmic signal that regulates biofilm formation in a number of bacterial species .", "Our study , in combination with structural analysis described in the accompanying pa...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "rna interference", "neuroscience", "animals", "animal models", "drosophila melanogaster", "model organisms", "experimental organism systems", "nerve fibers", "epigenetics", "molecular biology techniques", "drosophila", "research and analysis methods", "chemoattractant axo...	Combinations of DIPs and Dprs control organization of olfactory receptor neuron terminals in Drosophila	journal.pgen.1007560	null	[ [ "One of the most complex biological systems in nature is the human brain , which contains an estimated 86 billion neurons wired to make approximately 100 trillion synaptic connections [1] .", "Our ability to experience the world , solve complex problems , create , and behave , all depends on the molecular...	[ "In Drosophila , 50 classes of olfactory receptor neurons ( ORNs ) connect to 50 class-specific and uniquely positioned glomeruli in the antennal lobe .", "Despite the identification of cell surface receptors regulating axon guidance , how ORN axons sort to form 50 stereotypical glomeruli remains unclear .", "H...	[ "In the human brain there are over 80 billion neurons that form approximately 100 trillion specific connections .", "How the brain organizes the axon terminals of these neurons into distinct synaptic units on such a large scale is largely unknown .", "In Drosophila , 50 classes of olfactory receptor neurons ( O...	2018
[ "Introduction", "Materials and Methods", "Results and Discussion", "Conclusions" ]	[ "medicine", "infectious diseases", "chagas disease", "neglected tropical diseases", "parasitic diseases" ]	Aptamer Based, Non-PCR, Non-Serological Detection of Chagas Disease Biomarkers in Trypanosoma cruzi Infected Mice	journal.pntd.0002650	null	[ [ "Chagas disease affects about 5 million people in Mexico , Central and South America and is caused by the parasite Trypanosoma cruzi ( T . cruzi ) .", "The parasite survives in the infected mammalian host as two distinct life cycle forms , trypomastigotes , which are terminally differentiated motile extra...	[ "Chagas disease affects about 5 million people across the world .", "The etiological agent , the intracellular parasite Trypanosoma cruzi ( T . cruzi ) , can be diagnosed using microscopy , serology or PCR based assays .", "However , each of these methods has their limitations regarding sensitivity and specific...	[ "Chagas disease , caused by the parasite Trypanosoma cruzi , is a major health concern for people living in Latin America .", "There are no vaccines to prevent this disease and only two drugs are prescribed for treatment .", "Current methods to diagnose patients are not always successful and thus new methods ne...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal diseases", "medicine and health sciences", "alloys", "chemical compounds", "metallurgy", "prions", "neurodegenerative diseases", "salts", "hypochlorites", "vertebrates", "animals", "mammals", "animal prion diseases", "stainless steel", "materials science", "zoology", "hamster...	Inactivation of Prions and Amyloid Seeds with Hypochlorous Acid	journal.ppat.1005914	null	[ [ "Prion diseases , or transmissible spongiform encephalopathies ( TSEs ) , are fatal and untreatable neurodegenerative diseases .", "In humans , prion diseases include sporadic , variant and genetic forms of Creutzfeldt-Jakob disease ( sCJD , vCJD and gCJD ) as well as a number of other disorders [1–3] .",...	[ "Hypochlorous acid ( HOCl ) is produced naturally by neutrophils and other cells to kill conventional microbes in vivo .", "Synthetic preparations containing HOCl can also be effective as microbial disinfectants .", "Here we have tested whether HOCl can also inactivate prions and other self-propagating protein ...	[ "Many serious diseases have been linked to pathogenic states of various proteins .", "These naturally occurring proteins can be corrupted to form aggregates such as prions and amyloids that propagate in and between tissues by acting as seeds that convert the normal form of the protein into more of the pathologica...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetic mutation", "heredity", "genetics", "molecular genetics", "biology", "human genetics", "population genetics", "genetics and genomics" ]	Comparison of Mitochondrial Mutation Spectra in Ageing Human Colonic Epithelium and Disease: Absence of Evidence for Purifying Selection in Somatic Mitochondrial DNA Point Mutations	journal.pgen.1003082	null	[ [ "Ageing is a stochastic process commonly defined as the progressive decline in the condition of an organism which is accompanied by a reduction in fertility and an increasing risk of death [1] .", "Ageing is unlikely to be genetically programmed as evolution theory suggests that nature would not select fo...	[ "Human ageing has been predicted to be caused by the accumulation of molecular damage in cells and tissues .", "Somatic mitochondrial DNA ( mtDNA ) mutations have been documented in a number of ageing tissues and have been shown to be associated with cellular mitochondrial dysfunction .", "It is unknown whether...	[ "Mitochondrial DNA encodes essential components of the mitochondrial respiratory chain and is strictly maternally inherited , making it vulnerable to the accumulation of deleterious mutations .", "To avoid this , mtDNA is subjected to a bottleneck phenomenon whereby only a small number of mtDNA molecules are pass...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "genetics", "biology", "genetics and genomics" ]	Specification of Drosophila Corpora Cardiaca Neuroendocrine Cells from Mesoderm Is Regulated by Notch Signaling	journal.pgen.1002241	null	[ [ "Recent work has revealed multiple features of evolutionary conservation in endocrine regulation of glucose metabolism .", "For example , in the fruit fly Drosophila melanogaster , insulin-producing cells ( IPCs ) in the brain and adipokinetic hormone-producing corpora cardiaca ( CC ) cells in the neuroen...	[ "Drosophila neuroendocrine cells comprising the corpora cardiaca ( CC ) are essential for systemic glucose regulation and represent functional orthologues of vertebrate pancreatic α-cells .", "Although Drosophila CC cells have been regarded as developmental orthologues of pituitary gland , the genetic regulation ...	[ "The requirement for glucose regulation is conserved in metazoans and crucial for metabolism , growth , and survival .", "In fruit flies and other insects , neurons secrete insulin-like hormones and neuroendocrine corpora cardiaca cells secrete adipokinetic hormone , a peptide with functional similarities to gluc...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "textbooks", "invertebrates", "chemical characterization", "rna interference", "education", "gene regulation", "sociology", "social sciences", "animals", "invertebrate genomics", "animal models", "developmental biology", "drosophila melanogaster", "model organisms", "experimental organis...	Hunchback is counter-repressed to regulate even-skipped stripe 2 expression in Drosophila embryos	journal.pgen.1007644	null	[ [ "Bifunctional transcription factors ( TFs ) that can activate or repress their target genes are critical in animal development [1 , 2] and are associated with human disease [3 , 4] .", "The function of these TFs can depend on the context of the enhancer sequences they bind [5–9] .", "To infer accurate...	[ "Hunchback is a bifunctional transcription factor that can activate and repress gene expression in Drosophila development .", "We investigated the regulatory DNA sequence features that control Hunchback function by perturbing enhancers for one of its target genes , even-skipped ( eve ) .", "While Hunchback dire...	[ "During development , animals express genes in distinct patterns to specify different cell types that are important for function .", "Enhancers are DNA sequences that generate these patterns by binding proteins that activate gene expression , repress gene expression , or both .", "We have learned how enhancers ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "biochemistry", "cell biology", "in vitro", "chemical biology" ]	Global Analysis of Posttranslational Protein Arginylation	journal.pbio.0050258	A comprehensive study indicates that protein arginylation may be a general mechanism for regulation of protein structure and function, similar to other major posttranslational modifications.	[ [ "Protein arginylation is an enigmatic posttranslational modification mediated by arginyl-tRNA-protein transferase ( ATE1 ) that transfers arginine ( Arg ) from tRNA onto proteins [1] .", "Until recently it had been believed that arginylation can only occur on the exposed N-terminus of aspartic acid ( Asp ...	[ "Posttranslational arginylation is critical for embryogenesis , cardiovascular development , and angiogenesis , but its molecular effects and the identity of proteins arginylated in vivo are largely unknown .", "Here we report a global analysis of this modification on the protein level and identification of 43 pr...	[ "A common cellular mechanism for the regulation of proteins , once they have been translated from mRNA , is the addition and removal of chemical groups via enzymatic reactions .", "The posttranslational addition of arginyl groups is critical for the embryonic development and survival of an organism , but the mole...	2007
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "inflammatory diseases", "children", "medicine and health sciences", "pathology and laboratory medicine", "chlamydia trachomatis", "pathogens", "immunology", "tropical diseases", "microbiology", "bacterial diseases", "age groups", "signs and symptoms", "eye diseases", "sexually transmitted...	Ocular immune responses, Chlamydia trachomatis infection and clinical signs of trachoma before and after azithromycin mass drug administration in a treatment naïve trachoma-endemic Tanzanian community	journal.pntd.0007559	null	[ [ "Trachoma remains the leading infectious cause of blindness worldwide , with the greatest burden in sub-Saharan Africa [1] .", "Trachomatous disease is initiated by repeated conjunctival infection with Chlamydia trachomatis , which triggers prolonged inflammatory episodes that contribute to the developmen...	[ "Trachoma , caused by Chlamydia trachomatis , remains the leading infectious cause of blindness worldwide .", "Persistence and progression of the resulting clinical disease appears to be an immunologically mediated process .", "Azithromycin , which is distributed at the community level for trachoma control , ha...	[ "Trachoma , caused by conjunctival infection with Chlamydia trachomatis , remains the leading infectious cause of blindness .", "Repeated infection during childhood can trigger prolonged inflammation , which is the main risk factor for conjunctival scarring .", "Azithromycin is distributed globally for trachoma...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immune cells", "antigen-presenting cells", "immunity to infections", "immunology", "adaptive immunity", "gene expression", "t cells", "biology", "molecular biology", "immune response", "signal transduction", "monocytes", "immunity", "innate immunity", "molecular cell biology" ]	Conditional Stat1 Ablation Reveals the Importance of Interferon Signaling for Immunity to Listeria monocytogenes Infection	journal.ppat.1002763	null	[ [ "Signal transducer and activator of transcription ( Stat1 ) is a central mediator of interferon responses in the immune system .", "Signals from type I ( IFNα/IFNβ; IFN-I ) , type II ( IFNγ; IFN-II ) and type III ( IFNλ , IFN-III ) interferons employ receptor-associated Janus kinases ( Jaks ) to activate ...	[ "Signal transducer and activator of transcription 1 ( Stat1 ) is a key player in responses to interferons ( IFN ) .", "Mutations of Stat1 cause severe immune deficiencies in humans and mice .", "Here we investigate the importance of Stat1 signaling for the innate and secondary immune response to the intracellul...	[ "Signal transducer and activator of transcription 1 ( Stat1 ) is an indispensable component of the cellular response to interferons ( IFN ) during immune reactions to pathogens .", "Stat1 deficiency leads to severe immune defects in humans and mice .", "The sensitivity of animals with complete Stat1 ablation to...	2012
[ "Introduction", "Results", "Discussion", "Material and methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "influenza", "pathogens", "immunology", "microbiology", "orthomyxoviruses", "staphylococcus aureus", "viruses", "methicillin-resistant staphylococcus aureus", "bacterial diseases", "rna viru...	Influenza-induced immune suppression to methicillin-resistant Staphylococcus aureus is mediated by TLR9	journal.ppat.1007560	null	[ [ "Influenza viruses are single-stranded RNA viruses with a segmented genome capable of undergoing mutagenesis to evade host immunity and they cause seasonal outbreaks leading to over a half million deaths per year worldwide ( World Health Organization , 2016 ) [1] .", "Influenza viruses can overcome tradit...	[ "Bacterial lung infections , particularly with methicillin-resistant Staphylococcus aureus ( MRSA ) , increase mortality following influenza infection , but the mechanisms remain unclear .", "Here we show that expression of TLR9 , a microbial DNA sensor , is increased in murine lung macrophages , dendritic cells ...	[ "Influenza-associated secondary bacterial infections , particularly with methicillin-resistant Staphylococcus aureus ( MRSA ) , are a major cause of morbidity and mortality , and better therapeutic strategies are needed .", "Stimulation of TLR2 has shown promise for improving health in influenza-bacteria dual-inf...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "dengue virus", "innate immune system", "medicine and health sciences", "immune physiology", "cytokines", "pathology and laboratory medicine", "pathogens", "immunology", "tropical diseases", "microbiology", "vertebrates", "animals", "mammals", "primates", "vaccines", "viruses", "deve...	Detection of post-vaccination enhanced dengue virus infection in macaques: An improved model for early assessment of dengue vaccines	journal.ppat.1007721	null	[ [ "Dengue viruses 1–4 ( DENV-1-4 ) are mosquito-borne flaviviruses annually responsible for 50–100 million dengue cases in humans , that have been classified as dengue fever ( DF ) , dengue hemorrhagic fever ( DHF ) and dengue shock syndrome ( DSS ) , and further re-classified as dengue ( with or without warnin...	[ "The need for improved dengue vaccines remains since the only licensed vaccine , Dengvaxia , shows variable efficacy depending on the infecting dengue virus ( DENV ) type , and increases the risk of hospitalization for severe dengue in children not exposed to DENV before vaccination .", "Here , we developed a tet...	[ "Dengue virus ( DENV ) is responsible for the most widespread arboviral disease affecting humans .", "A pre-existing suboptimal immunity to DENV is accepted as being the major risk factor for severe dengue .", "Thus , if vaccination does not elicit optimal DENV-specific immunity , a vaccine might , instead , in...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "carbohydrate metabolism", "medicine and health sciences", "forkhead box", "chemical compounds", "molecular probe techniques", "metabolic processes", "carcinomas", "cancers and neoplasms", "immunoblotting", "carbohydrates", "glucose metabolism", "gastrointestinal tumors", "liver diseases", ...	Phosphoglucomutase 1 inhibits hepatocellular carcinoma progression by regulating glucose trafficking	journal.pbio.2006483	null	[ [ "Hepatocellular carcinoma ( HCC ) is the most common type of primary liver cancer in adults and is the sixth most prevalent cancer and the third most frequent cause of cancer-related death [1] .", "Due to the rapid progression of HCC , most HCC patients are diagnosed at advanced stage , the 5-year surviva...	[ "Glycogen metabolism commonly altered in cancer is just beginning to be understood .", "Phosphoglucomutase 1 ( PGM1 ) , the first enzyme in glycogenesis that catalyzes the reversible conversion between glucose 1-phosphate ( G-1-P ) and glucose 6-phosphate ( G-6-P ) , participates in both the breakdown and synthes...	[ "Hepatocellular carcinoma ( HCC ) is the most common type of primary liver cancer in adults .", "Sorafenib is the only clinically approved systemic drug for patients with advanced HCC .", "Identification of novel targets and biomarkers will provide new therapeutic strategies for advanced HCC and better prognost...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/disease models", "genetics and genomics", "oncology/breast cancer" ]	Aneuploidy and Improved Growth Are Coincident but Not Causal in a Yeast Cancer Model	journal.pbio.1000161	Aneuploidy is a hallmark of cancer cells and is assumed to play a causative role. This relationship is dissected in a yeast, with results that show that anueploidy can be removed, but cells maintain their proliferative advantage.	[ [ "With the sequencing of cancer genome , it has been shown that the tumors of human cancer patients contain numerous genetic alterations [1] .", "Not all of the alterations promote cancer initiation or progression , the so-called driver events .", "Recent data indicate that most clonal mutations in tum...	[ "Cancer cells have acquired mutations that alter their growth .", "Aneuploidy that typify cancer cells are often assumed to contribute to the abnormal growth characteristics .", "Here we test the idea of a link between aneuploidy and mutations allowing improved growth , using Saccharomyces cerevisiae containing...	[ "Aneuploidy , an abnormality in chromosome number and structure , occurs commonly in cancers and has been suggested to be required to maintain accelerated cell proliferation .", "However , this hypothesis remains untested as it is not possible to selectively remove the acquired aneuploidy in cells that already ha...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biophysics", "biology and life sciences", "computational biology" ]	Atomistic Picture for the Folding Pathway of a Hybrid-1 Type Human Telomeric DNA G-quadruplex	journal.pcbi.1003562	null	[ [ "G-quadruplexes are high-order DNA or RNA structures formed from guanine-rich sequences , and their building blocks are G-tetrads that arise from Hoogsten hydrogen-bonding between four guanines .", "The G-tetrads stack on top of each other and form four-stranded helical structures .", "Bioinformatics ...	[ "In this work we studied the folding process of the hybrid-1 type human telomeric DNA G-quadruplex with solvent and ions explicitly modeled .", "Enabled by the powerful bias-exchange metadynamics and large-scale conventional molecular dynamic simulations , the free energy landscape of this G-DNA was obtained for ...	[ "G-quadruplexes are high-order DNA/RNA structures .", "They are involved in the regulation of telomere maintenance , DNA replication , transcription and translation , and are also attractive drug designing targets for treating cancers and promising building blocks for molecular nanodevices .", "The knowledge of...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Cellular Growth and Mitochondrial Ultrastructure of Leishmania (Viannia) braziliensis Promastigotes Are Affected by the Iron Chelator 2,2-Dipyridyl	journal.pntd.0002481	null	[ [ "Leishmania ( Viannia ) braziliensis is a protozoan parasite widely distributed in the New World .", "This species is considered the main etiological agent of American tegumentary leishmaniasis ( ATL ) [1] and has been associated with an extensive clinical polymorphism , ranging from simple cutaneous lesi...	[ "Iron is an essential element for the survival of microorganisms in vitro and in vivo , acting as a cofactor of several enzymes and playing a critical role in host-parasite relationships .", "Leishmania ( Viannia ) braziliensis is a parasite that is widespread in the new world and considered the major etiological...	[ "American tegumentary leishmaniasis ( ATL ) is a neglected disease that is widely distributed in the Americas .", "The protozoan parasite Leishmania ( Viannia ) braziliensis is one of the main causative agents of ATL , being responsible for the development of different clinical manifestations of the disease , whi...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "velocity", "acceleration", "action potentials", "medicine and health sciences", "classical mechanics", "membrane potential", "condensed matter physics", "electricity", "fibrosis", "electrophysiology", "anisotropy", "neuroscience", "geometry", "developmental biology", "mathematics", "m...	Microheterogeneity-induced conduction slowing and wavefront collisions govern macroscopic conduction behavior: A computational and experimental study	journal.pcbi.1006276	null	[ [ "Both experimental [1] and clinical [2] studies have shown that the presence of non-conducting tissue heterogeneities in the myocardium can facilitate arrhythmia induction and maintenance .", "These tissue heterogeneities vary greatly in size , shape and distribution .", "Arrhythmogenic roles of macro...	[ "The incidence of cardiac arrhythmias is known to be associated with tissue heterogeneities including fibrosis .", "However , the impact of microscopic structural heterogeneities on conduction in excitable tissues remains poorly understood .", "In this study , we investigated how acellular microheterogeneities ...	[ "It is well known that perturbations in the heart structure are associated with the initiation and maintenance of clinically significant cardiac arrhythmia .", "While previous studies have examined how single structural perturbations affect local electrical conduction , our understanding of how numerous microscop...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "influenza", "pathogens", "messenger rna", "microbiology", "orthomyxoviruses", "viruses", "virus effects on host gene expression", "protein synthesis", "rna viruses", "molecular biology techniques", "microbial genetics", ...	Specificity and functional interplay between influenza virus PA-X and NS1 shutoff activity	journal.ppat.1007465	null	[ [ "Influenza A virus is a major respiratory pathogen that frequently causes seasonal epidemics and periodic pandemics , resulting in half-a million deaths worldwide each year [1] .", "Like many other viruses , the influenza virus relies on the host cellular machinery to facilitate its replication cycle .", ...	[ "Influenza A viruses modulate host antiviral responses to promote viral growth and pathogenicity .", "Through viral PA-X and NS1 proteins , the virus is capable of suppressing host protein synthesis , termed “host shutoff . ”", "Although both proteins are known to induce general shutoff , specificity of target ...	[ "Virus infection induces a wide range of host defense responses , such as the innate immune response and inflammation .", "Some viruses express accessory proteins to induce general shutoff of host protein synthesis , which is one of the major viral strategies to counteract host antiviral activity and immune respo...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "microbiology/microbial evolution and genomics" ]	Genomic Diversity and Evolution of Mycobacterium ulcerans Revealed by Next-Generation Sequencing	journal.ppat.1000580	null	[ [ "Mycobacterium ulcerans causes Buruli ulcer ( BU ) , a necrotizing skin disease and the third most common mycobacterial disease , after tuberculosis and leprosy [1] .", "In the past decade the incidence of BU has increased dramatically in West African countries , but the disease is also found in tropical ...	[ "Mycobacterium ulcerans is the causative agent of Buruli ulcer , the third most common mycobacterial disease after tuberculosis and leprosy .", "It is an emerging infectious disease that afflicts mainly children and youths in West Africa .", "Little is known about the evolution and transmission mode of M . ulce...	[ "Mycobacterium ulcerans is the causative agent of Buruli ulcer ( BU ) , a necrotizing skin disease and the third most common mycobacterial disease after tuberculosis and leprosy .", "It is an emerging infectious disease that afflicts mainly children and youths in West Africa .", "The disease is also found in tr...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "neural networks", "computational neuroscience", "biology", "computational biology", "neuroscience" ]	Significance of Input Correlations in Striatal Function	journal.pcbi.1002254	null	[ [ "The striatum is the main input stage of the basal ganglia and plays an important role in various cognitive and motor functions [1]–[5] .", "With its involvement in multiple behavioral tasks , the computational role of the striatum is of crucial interest .", "The presence of recurrent inhibitory proje...	[ "The striatum is the main input station of the basal ganglia and is strongly associated with motor and cognitive functions .", "Anatomical evidence suggests that individual striatal neurons are unlikely to share their inputs from the cortex .", "Using a biologically realistic large-scale network model of striat...	[ "The striatum is the main input station of the basal ganglia and plays a crucial role in multiple motor and cognitive functions .", "Striatum is a recurrently connected network of GABAergic medium spiny neurons ( MSNs ) , which receive strong feedforward inhibition from the fast spiking interneurons and massive e...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "evolutionary biology", "genetics", "biology", "microbiology" ]	Chikungunya Virus 3′ Untranslated Region: Adaptation to Mosquitoes and a Population Bottleneck as Major Evolutionary Forces	journal.ppat.1003591	null	[ [ "Genetic change , which can lead to adaptation to new hosts or vectors , is a major cause of the emergence or re-emergence of arthropod-borne viral ( arboviral ) and other RNA viral diseases [1] , [2] .", "However , compared to the numerous investigations of point mutations within viral genomic open readi...	[ "The 3′ untranslated genome region ( UTR ) of arthropod-borne viruses is characterized by enriched direct repeats ( DRs ) and stem-loop structures .", "Despite many years of theoretical and experimental study , on-going positive selection on the 3′UTR had never been observed in ‘real-time , ’ and the role of the ...	[ "The 3′ untranslated genome region ( UTR ) of arbovirus ( arthropod-borne virus ) RNA genomes is characterized by enriched direct repeats ( DRs ) and stem-loop structures , which are thought to play a specific role in maintaining efficient transmission in multiple hosts .", "However , this hypothesis is vague and...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/immune evasion", "virology/host antiviral responses", "virology" ]	Rotavirus NSP1 Inhibits NFκB Activation by Inducing Proteasome-Dependent Degradation of β-TrCP: A Novel Mechanism of IFN Antagonism	journal.ppat.1000280	null	[ [ "Research into mechanisms by which viruses evade host defense has received increased attention in the past several years because of the potential to develop attenuated vaccines based on viruses with weakened evasion strategies , or antiviral therapies that target specific immune system antagonists .", "Mo...	[ "Mechanisms by which viruses counter innate host defense responses generally involve inhibition of one or more components of the interferon ( IFN ) system .", "Multiple steps in the induction and amplification of IFN signaling are targeted for inhibition by viral proteins , and many of the IFN antagonists have di...	[ "Cells respond to virus infection by inducing a pattern of gene expression regulated by interferon ( IFN ) that modulates the host immune response .", "In order to successfully replicate , viruses have evolved mechanisms to block the induction or function of IFN and IFN-regulated genes .", "Multiple proteins ar...	2009
[ "Introduction", "Methods", "Discussion" ]	[]	Improved Completion Rates and Characterization of Drug Reactions with an Intensive Chagas Disease Treatment Program in Rural Bolivia	journal.pntd.0002407	null	[ [ "Over 100 years after its discovery , there are still few effective treatment options for Chagas disease .", "Chagas disease is caused by a vector-borne parasite , Trypanosoma cruzi , and is responsible for an estimated 430 , 000 DALYs lost and a cost of $1 . 2 billion in lost productivity each year [1] ....	[ "Chagas disease treatment is limited by drug availability , adverse side effect profiles of available medications , and poor adherence .", "Adult Chagas disease patients initiating 60-days of benznidazole were randomized to weekly or twice-weekly evaluations of medication adherence and screening for adverse drug ...	[ "Treatment of Chagas disease is complicated by poor adherence and frequent adverse drug events ( ADEs ) .", "To determine the utility of pill counts and frequent monitoring to improve treatment completion and reduce ADEs , this study randomized Bolivian adults with chronic Chagas disease to either weekly or twice...	2013
[ "Introduction", "Methods", "Results", "Discussion", "Conclusion" ]	[ "invertebrates", "medicine and health sciences", "body fluids", "immunology", "tropical diseases", "geographical locations", "parasitic diseases", "animals", "nematode infections", "filariasis", "neglected tropical diseases", "onchocerciasis", "cross reactivity", "lymphatic filariasis", ...	Mapping of lymphatic filariasis in loiasis areas: A new strategy shows no evidence for Wuchereria bancrofti endemicity in Cameroon	journal.pntd.0007192	null	[ [ "Lymphatic filariasis ( LF ) is a neglected tropical disease that is targeted for elimination .", "A key intervention strategy is mass drug administration ( MDA ) in all endemic areas with a microfilaria ( Mf ) or antigen prevalence of at least 1% .", "The Global Program to Eliminate Lymphatic Filaria...	[ "Mapping of lymphatic filariasis ( LF ) caused by Wuchereria bancrofti largely relies on the detection of circulating antigen using ICT cards .", "Several studies have recently shown that this test can be cross-reactive with sera of subjects heavily infected with Loa loa and thus mapping results in loiasis endemi...	[ "High prevalence of loiasis can confound the mapping efforts for lymphatic filariasis ( LF ) that use tests for circulating filarial antigen .", "In order to develop a LF mapping strategy for loiasis endemic areas , we screened day blood samples from 5 , 001 subjects residing in 50 villages in 6 health districts ...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "biology", "microbiology", "molecular cell biology" ]	Antiviral Activity of a Small Molecule Deubiquitinase Inhibitor Occurs via Induction of the Unfolded Protein Response	journal.ppat.1002783	null	[ [ "Noroviruses are small non-enveloped viruses with positive-strand RNA genomes [1] .", "Human Norovirus ( HuNoV ) is the major cause of sporadic and epidemic non-bacterial gastroenteritis worldwide in people of all ages [2] , [3] .", "Typically these infections result in high morbidity and economic cos...	[ "Ubiquitin ( Ub ) is a vital regulatory component in various cellular processes , including cellular responses to viral infection .", "As obligate intracellular pathogens , viruses have the capacity to manipulate the ubiquitin ( Ub ) cycle to their advantage by encoding Ub-modifying proteins including deubiquitin...	[ "Deubiquitinases ( DUBs ) are enzymes , which are implicated in many cellular processes but their functions during virus infection are not well understood .", "We used WP1130 , a small molecule inhibitor of a subset of DUBs , as a probe to unravel the functions of DUBs during norovirus infections .", "We identi...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "model organisms", "genetics", "biology", "molecular cell biology", "genetics and genomics" ]	Molecular, Physiological, and Motor Performance Defects in DMSXL Mice Carrying >1,000 CTG Repeats from the Human DM1 Locus	journal.pgen.1003043	null	[ [ "Myotonic dystrophy type I ( DM1 ) is a dominantly inherited disorder , highly variable and associated with multisystemic symptoms .", "The adult onset form of the condition typically presents distal muscle weakness , myotonia , cardio-respiratory problems , presenile cataracts , hypersomnia , hyperinsuli...	[ "Myotonic dystrophy type 1 ( DM1 ) is caused by an unstable CTG repeat expansion in the 3′UTR of the DM protein kinase ( DMPK ) gene .", "DMPK transcripts carrying CUG expansions form nuclear foci and affect splicing regulation of various RNA transcripts .", "Furthermore , bidirectional transcription over the D...	[ "Myotonic dystrophy type 1 ( DM1 ) is caused by the abnormal expansion of a CTG repeat located in the DM protein kinase ( DMPK ) gene .", "DMPK transcripts carrying CUG expansions form toxic nuclear foci that affect other RNAs .", "DM1 involve multiple pathogenic pathways including changes in gene expression , ...	2012
[ "Introduction", "Materials and Methods", "Results and Discussion" ]	[ "veterinary parasitology", "biology and life sciences", "parasitology", "parasite physiology" ]	Expression Profile of the Schistosoma japonicum Degradome Reveals Differential Protease Expression Patterns and Potential Anti-schistosomal Intervention Targets	journal.pcbi.1003856	null	[ [ "Schistosomiasis is one of the most socioeconomic parasitic diseases , afflicting millions of people in many tropical and subtropical countries [1] .", "Praziquantel is the only specific remedy for the disease and no effective vaccine is available [2] .", "However , long-term , repeated mass chemother...	[ "Blood fluke proteases play pivotal roles in the processes of invasion , nutrition acquisition , immune evasion , and other host-parasite interactions .", "Hundreds of genes encoding putative proteases have been identified in the recently published schistosome genomes .", "However , the expression profiles of t...	[ "Parasite proteases play critical roles in host-parasite interactions and thus are considered to be potential anti-schistosomal targets .", "Although numerous schistosome proteases have been predicted based on recently published genomes , no systematic analysis of their expression in Schistosoma species has been ...	2014
[ "Introduction", "Methods", "Results and Discussion" ]	[ "biology" ]	An Integrated Linkage, Chromosome, and Genome Map for the Yellow Fever Mosquito Aedes aegypti	journal.pntd.0002052	null	[ [ "Mosquitoes are vectors of numerous human pathogens such as malaria parasites transmitted by the subfamily Anophelinae; lymphatic filarial worms transmitted by both Anophelinae and Culicinae subfamilies; and arboviruses whose transmission is largely associated with the subfamily Culicinae .", "Aedes aegyp...	[ "Aedes aegypti , the yellow fever mosquito , is an efficient vector of arboviruses and a convenient model system for laboratory research .", "Extensive linkage mapping of morphological and molecular markers localized a number of quantitative trait loci ( QTLs ) related to the mosquito's ability to transmit variou...	[ "About half of the human population is under risk of dengue infection .", "Because of the absence of a vaccine or drug treatment , the prevention of this disease largely relies on controlling its major vector mosquito Aedes aegypti .", "Availability of the complete genome sequence for this mosquito offers the p...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Interplay between Constraints, Objectives, and Optimality for Genome-Scale Stoichiometric Models	journal.pcbi.1004166	null	[ [ "Research in biotechnology and medicine benefits from understanding the metabolic capacity of organisms , including their sensitivities to genetic and environmental changes .", "Genome-scale stoichiometric models of metabolism [1 , 2] and the availability of annotated genome sequences have greatly acceler...	[ "High-throughput data generation and genome-scale stoichiometric models have greatly facilitated the comprehensive study of metabolic networks .", "The computation of all feasible metabolic routes with these models , given stoichiometric , thermodynamic , and steady-state constraints , provides important insights...	[ "Organisms depend on huge networks of molecular reactions for environmental sensing , information integration , gene expression , and metabolism .", "The discovery of general principles of network behavior is a major ambition of systems biology and of great interest to biotechnology and medicine .", "We present...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/genomics", "evolutionary biology/microbial evolution and genomics", "genetics and genomics/gene discovery", "genetics and genomics/comparative genomics", "evolutionary biology/evolutionary and comparative genetics", "genetics and genomics/functional genomics", "genetics and genomi...	Bacterial Genes in the Aphid Genome: Absence of Functional Gene Transfer from Buchnera to Its Host	journal.pgen.1000827	null	[ [ "The smallest known cellular genomes are those of symbiotic bacteria living in insects [1]–[4] .", "These genomes have lost many genes considered essential in other bacteria , and one proposed explanation is that certain ancestral symbiont genes have been transferred to the host genome , with their produc...	[ "Genome reduction is typical of obligate symbionts .", "In cellular organelles , this reduction partly reflects transfer of ancestral bacterial genes to the host genome , but little is known about gene transfer in other obligate symbioses .", "Aphids harbor anciently acquired obligate mutualists , Buchnera aphi...	[ "Bacterial lineages have repeatedly evolved intimate symbioses with eukaryotic hosts , the most famous cases being those of the cell organelles , mitochondria , and plastids .", "Symbiont genomes typically lose many ancestral genes , raising the question of how they function with so few genes .", "In organelles...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "immunology/antigen processing and recognition", "immunology", "immunology/immune response" ]	Urea-Mediated Cross-Presentation of Soluble Epstein-Barr Virus BZLF1 Protein	journal.ppat.1000198	null	[ [ "Cytotoxic CD8+ T lymphocytes ( CTL ) play a key role in the immunological control of persistent intracellular pathogens and tumors .", "CTL specifically target infected cells through the recognition of peptides , which are displayed by surface exposed HLA class I molecules .", "In most cell types , H...	[ "Soluble extracellular proteins usually do not enter the endogenous human leukocyte antigen ( HLA ) I–dependent presentation pathway of antigen-presenting cells , strictly impeding their applicability for the re-stimulation of protein-specific CD8+ cytotoxic T lymphocytes ( CTL ) .", "Here we present for the Epst...	[ "CD8+ T lymphocytes ( CTL ) play a key role in the immunological control of persistent intracellular pathogens and tumors .", "Thus , the development of improved technologies for the monitoring and expansion of protein-specific CTL represents a major challenge in clinical immunology .", "CTL specifically target...	2008
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "computational biology/molecular dynamics", "biophysics", "biophysics/theory and simulation" ]	Mechanical Strength of 17 134 Model Proteins and Cysteine Slipknots	journal.pcbi.1000547	null	[ [ "Atomic force microscopy , optical tweezers , and other tools of nanotechnology have enabled induction and monitoring of large conformational changes in biomolecules .", "Such studies are performed to assess structure of the biomolecules , their elastic properties , and ability to act as nanomachines in a...	[ "A new theoretical survey of proteins' resistance to constant speed stretching is performed for a set of 17 134 proteins as described by a structure-based model .", "The proteins selected have no gaps in their structure determination and consist of no more than 250 amino acids .", "Our previous studies have dea...	[ "The advances in nanotechnology have allowed for manipulation of single biomolecules and determination of their elastic properties .", "Titin was among the first proteins studied in this way .", "Its unravelling by stretching requires a 204 pN force .", "The resistance to stretching comes mostly from a locali...	2009
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "chitin", "invertebrates", "medicine and health sciences", "rna interference", "animals", "membrane proteins", "physiological processes", "developmental biology", "pupae", "materials science", "epigenetics", "macromolecules", "cellular structures and organelles", "materials by structure", ...	A chitinase with two catalytic domains is required for organization of the cuticular extracellular matrix of a beetle	journal.pgen.1007307	null	[ [ "Insect chitinases ( CHTs ) belong to family 18 glycosylhydrolases ( GH-18 superfamily , EC 3 . 2 . 1 . 14 ) that hydrolyze chitin by an endo-type cleavage to chitooligosaccharides [1–3] .", "With the availability of many complete genome sequences , it has been recognized that insect genomes encode a larg...	[ "Insect cuticle or exoskeleton is an extracellular matrix formed primarily from two different structural biopolymers , chitin and protein .", "During each molt cycle , a new cuticle is deposited simultaneously with degradation of the inner part of the chitinous procuticle of the overlying old exoskeleton by molti...	[ "Insect cuticle or exoskeleton is an extracellular matrix consisting of three major morphologically distinct layers , the water-proofing envelope , the protein-rich epicuticle and the chitin/protein-rich procuticle .", "To accommodate growth , insects must periodically replace their cuticles in a process called “...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "antimicrobials", "medicine and health sciences", "microbiology", "clinical medicine", "pharmacology", "veterinary science", "infectious diseases", "veterinary diseases", "viral replication", "drug discovery", "biochemistry", "drug research and development", "veterinary vi...	Discovery of a Novel Compound with Anti-Venezuelan Equine Encephalitis Virus Activity That Targets the Nonstructural Protein 2	journal.ppat.1004213	null	[ [ "Emergence and re-emergence of arboviruses such as alphaviruses continue to present serious health and economic threats [1] , [2] .", "New World alphaviruses , family Togaviridae , including Venezuelan ( VEEV ) , eastern ( EEEV ) , and western ( WEEV ) equine encephalitis viruses , also represent signific...	[ "Alphaviruses present serious health threats as emerging and re-emerging viruses .", "Venezuelan equine encephalitis virus ( VEEV ) , a New World alphavirus , can cause encephalitis in humans and horses , but there are no therapeutics for treatment .", "To date , compounds reported as anti-VEEV or anti-alphavir...	[ "Alphaviruses occur worldwide , causing significant diseases such as encephalitis or arthritis in humans and animals .", "In addition , some alphaviruses , such as VEEV , pose a biothreat due to their high infectivity and lack of available treatments .", "To discover small molecule inhibitors with lead developm...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "biotechnology", "small molecules", "microbiology", "chemical biology", "emerging infectious diseases", "organic synthesis", "chemistry", "biology", "drug discovery", "biochemistry", "virology", "microbial control", "antivirals", "synthetic chemistry" ]	Bispidine-Amino Acid Conjugates Act as a Novel Scaffold for the Design of Antivirals That Block Japanese Encephalitis Virus Replication	journal.pntd.0002005	null	[ [ "Japanese encephalitis virus ( JEV ) is a mosquito-borne , neurotropic RNA virus within the family Flaviviridae , which includes other pathogens of global significance such as dengue virus and West Nile virus .", "JEV is endemic to most South- and South-East Asian countries and recurring outbreaks lead to...	[ "Japanese encephalitis virus ( JEV ) is a major cause of viral encephalitis in South and South-East Asia .", "Lack of antivirals and non-availability of affordable vaccines in these endemic areas are a major setback in combating JEV and other closely related viruses such as West Nile virus and dengue virus .", ...	[ "Japanese encephalitis virus is a mosquito-borne virus , which causes encephalitis primarily in children and is a major cause of encephalitis-related deaths in South and South-East Asian countries .", "Although new and safe vaccines are available for use , it is neither affordable nor readily available in endemic...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "biochemistry", "veterinary science", "veterinary diseases", "veterinary parasitology", "proteins", "physiology", "protein structure", "biology and life sciences", "computational biology", "electrophysiology", "molecular biology", "parasitology", "macromolecular structure analysis" ]	Identification and Functional Expression of a Glutamate- and Avermectin-Gated Chloride Channel from Caligus rogercresseyi, a Southern Hemisphere Sea Louse Affecting Farmed Fish	journal.ppat.1004402	null	[ [ "Sea lice are marine ectoparasite copepods of the Caligidae family ( order Siphonostomatoida ) that attach to host marine fish and feed on their epidermal tissue , and blood .", "The Caligidae family is constituted by hundreds of species belonging to the Caligus and Lepeoptherius genera .", "Increasin...	[ "Parasitic sea lice represent a major sanitary threat to marine salmonid aquaculture , an industry accounting for 7% of world fish production .", "Caligus rogercresseyi is the principal sea louse species infesting farmed salmon and trout in the southern hemisphere .", "Most effective control of Caligus has been...	[ "Sea lice are the main parasites affecting farmed salmon and trout in the world .", "Caligus rogercresseyi is the principal sea louse species infesting farmed fish in the southern hemisphere .", "Successful control of these parasites has been achieved using macrocyclic lactones ( MLs ) , but resistance has emer...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Coupling Protein Side-Chain and Backbone Flexibility Improves the Re-design of Protein-Ligand Specificity	journal.pcbi.1004335	null	[ [ "Interactions between small molecules and proteins play critical roles in essentially all biological processes .", "Naturally occurring proteins have evolved to function as sensitive small-molecule sensors that detect and respond to changes in the extra- and intracellular environment , or as catalysts tha...	[ "Interactions between small molecules and proteins play critical roles in regulating and facilitating diverse biological functions , yet our ability to accurately re-engineer the specificity of these interactions using computational approaches has been limited .", "One main difficulty , in addition to inaccuracie...	[ "Designing new protein–ligand interactions has tremendous potential for engineering sensitive biosensors for diagnostics or new enzymes useful in biotechnology , but these applications are extremely challenging , both because of inaccuracies of the energy functions used in modeling and design , and because protein ...	2015
[ "Introduction", "Results", "Discussion", "Material and Methods" ]	[ "blood cells", "flow cytometry", "innate immune system", "medicine and health sciences", "parasite groups", "immune cells", "immune physiology", "cytokines", "plasmodium", "immunology", "tropical diseases", "parasitic diseases", "parasitic protozoans", "parasitology", "organisms", "dev...	Reduced Plasmodium Parasite Burden Associates with CD38+ CD4+ T Cells Displaying Cytolytic Potential and Impaired IFN-γ Production	journal.ppat.1005839	null	[ [ "Malaria is associated with complex multi-factorial immune responses , due in part to the multi-stage life cycle of the Plasmodium spp .", "parasite which is targeted by multiple arms of the immune system , and the existence of elaborate host-pathogen interactions and evasion mechanisms [1] .", "The e...	[ "ClinicalTrials . gov clinical trial numbers ACTRN12612000814875 , ACTRN12613000565741 and ACTRN12613001040752" ]	[ "Malaria is one of the three most deadly infectious disease worldwide , together with tuberculosis and HIV .", "The exact mechanisms underlying effective immunity to malaria remain largely unknown and there is no reliable immune correlate of protection .", "Here , we take advantage of a unique experimental huma...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "physiology/cognitive neuroscience", "neuroscience/theoretical neuroscience", "computational biology/computational neuroscience" ]	Finding the Way with a Noisy Brain	journal.pcbi.1000992	null	[ [ "For convenience and consistency with previous work , we use the term ‘navigation’ in a general sense to encompass all forms of non-random locomotion , including biological path integration ( PI ) or ‘dead reckoning’ , a process described by Charles Darwin in 1873 [1] .", "Darwin realized that documented ...	[ "Successful navigation is fundamental to the survival of nearly every animal on earth , and achieved by nervous systems of vastly different sizes and characteristics .", "Yet surprisingly little is known of the detailed neural circuitry from any species which can accurately represent space for navigation .", "P...	[ "The ability to navigate allows animals to vastly increase the action space for finding resources , mates , and to avoid predators .", "The benefits are many and it is commonly believed that modern brain functions have emerged from ancestral forms evolved for effective navigation .", "Since the time of Charles ...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/epigenetics", "plant biology/plant genetics and gene expression", "plant biology/plant-environment interactions" ]	Stress-Induced Activation of Heterochromatic Transcription	journal.pgen.1001175	null	[ [ "Chromatin can adopt conformations that were first defined cytologically as condensed heterochromatin and open euchromatin [1] .", "Subsequent genomic studies characterized euchromatin as gene rich and transcriptionally active , and heterochromatin as inert matter , mostly holding transcriptionally silent...	[ "Constitutive heterochromatin comprising the centromeric and telomeric parts of chromosomes includes DNA marked by high levels of methylation associated with histones modified by repressive marks .", "These epigenetic modifications silence transcription and ensure stable inheritance of this inert state .", "Alt...	[ "In eukaryotic cells , DNA is packaged into chromatin that is present in two different forms named euchromatin and heterochromatin .", "Gene-rich euchromatin is relaxed and permissive to transcription compared with heterochromatin that essentially contains transcriptionally inert non-coding repeated DNA .", "Th...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "schistosoma", "invertebrates", "medicine and health sciences", "body fluids", "helminths", "malacology", "tropical diseases", "geographical locations", "ponds", "parasitic diseases", "animals", "urine", "gastropods", "fresh water", "bodies of water", "neglected tropical diseases", "...	Impact of Annual Praziquantel Treatment on Urogenital Schistosomiasis in a Seasonal Transmission Focus in Central Senegal	journal.pntd.0004557	null	[ [ "Urogenital schistosomiasis is a parasitic disease caused by infection with Schistosoma haematobium , a blood fluke of the genus Schistosoma [1] .", "In Africa , urogenital schistosomiasis remains a significant public health problem and causes 150 . 000 deaths / year with approximately 112 million cases d...	[ "In Sub-Saharan Africa , urogenital schistosomiasis remains a significant public health problem , causing 150 . 000 deaths/year with approximately 112 million cases diagnosed .", "The Niakhar district is a disease hotspot in central Senegal where transmission occurs seasonally with high prevalences .", "The aim...	[ "Urogenital schistosomiasis represents a serious cause of morbidity and mortality in S . haematobium endemic countries .", "Treatment with praziquantel ( PZQ ) is effective at reducing or eliminating active infection , but does not prevent reinfection that remains a continuing problem in high-risk communities , e...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "skin", "medicine and health sciences", "integumentary system", "dysplasia", "pathology and laboratory medicine", "gene regulation", "notch signaling", "mutation", "signs and symptoms", "mutation databases", "digestive system", "research and analysis methods", "small interfering rnas", "ha...	Mutations in TSPEAR, Encoding a Regulator of Notch Signaling, Affect Tooth and Hair Follicle Morphogenesis	journal.pgen.1006369	null	[ [ "Ectodermal dysplasias refer to a large clinically and genetically heterogeneous group of disorders characterized by developmental defects affecting tissues of ectodermal origin [1] .", "These conditions therefore feature various combinations of cutaneous , nail , hair , dental or limb anomalies which dem...	[ "Despite recent advances in our understanding of the pathogenesis of ectodermal dysplasias ( EDs ) , the molecular basis of many of these disorders remains unknown .", "In the present study , we aimed at elucidating the genetic basis of a new form of ED featuring facial dysmorphism , scalp hypotrichosis and hypod...	[ "Ectodermal dysplasias refer to a large group of inherited disorders characterized by developmental defects in tissues of ectodermal origin .", "The study of these conditions has been instrumental in the discovery of biological pathways involved in the regulation of epithelial tissue morphogenesis .", "In this ...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "biochemistry", "applied chemistry", "animal behavior", "entomology", "chemical biology", "chemistry", "biology", "zoology", "neuroscience", "hormones" ]	Post-Control Surveillance of Triatoma infestans and Triatoma sordida with Chemically-Baited Sticky Traps	journal.pntd.0001822	null	[ [ "Chagas disease control remains a major public health challenge in Latin America , where ∼7 . 5 million people are estimated to be infected by Trypanosoma cruzi , its etiological agent [1] .", "T . cruzi is primarily transmitted by blood-sucking triatomine bugs [2]; in the absence of effective vaccines , ...	[ "Chagas disease prevention critically depends on keeping houses free of triatomine vectors .", "Insecticide spraying is very effective , but re-infestation of treated dwellings is commonplace .", "Early detection-elimination of re-infestation foci is key to long-term control; however , all available vector-dete...	[ "Triatoma infestans is the main vector of Chagas disease in southern South America .", "Dwelling-infesting populations are controlled through insecticide-spraying campaigns; however , dwellings are often re-infested when insecticide effects wane , and this leads to the re-establishment of disease transmission .",...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/gene discovery", "public health and epidemiology", "public health and epidemiology/epidemiology", "ophthalmology", "genetics and genomics", "ophthalmology/glaucoma", "genetics and genomics/population genetics" ]	A Genome-Wide Association Study of Optic Disc Parameters	journal.pgen.1000978	null	[ [ "The optic nerve head , or optic disc , is the place where the axons of the retinal ganglion cells leave the eye and form the optic nerve .", "Its morphology , visible by ophthalmoscopy , is important in the diagnosis and follow-up of patients with ( neuro- ) ophthalmologic diseases , such as ischemic and...	[ "The optic nerve head is involved in many ophthalmic disorders , including common diseases such as myopia and open-angle glaucoma .", "Two of the most important parameters are the size of the optic disc area and the vertical cup-disc ratio ( VCDR ) .", "Both are highly heritable but genetically largely undeterm...	[ "Morphologic characteristics of the optic nerve head are involved in many ophthalmic diseases .", "Its size , called the optic disc area , is an important measure and has been associated with e . g . myopia and open-angle glaucoma ( OAG ) .", "Another important and clinical parameter of the optic disc is the ve...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics", "genetics and genomics/cancer genetics" ]	The 5p15.33 Locus Is Associated with Risk of Lung Adenocarcinoma in Never-Smoking Females in Asia	journal.pgen.1001051	null	[ [ "To date , several large genome-wide association studies ( GWAS ) of lung cancer conducted in subjects of European background have identified susceptibility alleles on chromosomes 5p15 . 33 , 6p21 . 33 and 15q25 [1]–[8] .", "These studies have shown that statistical evidence that exceeds the threshold of ...	[ "Genome-wide association studies of lung cancer reported in populations of European background have identified three regions on chromosomes 5p15 . 33 , 6p21 . 33 , and 15q25 that have achieved genome-wide significance with p-values of 10−7 or lower .", "These studies have been performed primarily in cigarette smo...	[ "Worldwide , approximately 15% of lung cancer cases occur among nonsmokers .", "Genome-wide association studies ( GWAS ) of lung cancer conducted in populations of European background have identified three regions on chromosomes 5 , 6 , and 15 that harbor genetic variants that confer risk for lung cancer .", "P...	2010
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "dengue virus", "medicine and health sciences", "pathology and laboratory medicine", "togaviruses", "viral transmission and infection", "pathogens", "spatial epidemiology", "microbiology", "census", "alphaviruses", "viruses", "research design", "chikungunya virus", "rna viruses", "infect...	Spatio-temporal coherence of dengue, chikungunya and Zika outbreaks in Merida, Mexico	journal.pntd.0006298	null	[ [ "The unprecedented global emergence of infectious disease threats has demonstrated how ill-prepared the world is to predict , rapidly respond to , and contain pandemics [1–3] .", "Zika virus ( ZIKV ) , an emerging arthropod-borne flavivirus , has become a global public health threat since its emergence ou...	[ "Response to Zika virus ( ZIKV ) invasion in Brazil lagged a year from its estimated February 2014 introduction , and was triggered by the occurrence of severe congenital malformations .", "Dengue ( DENV ) and chikungunya ( CHIKV ) invasions tend to show similar response lags .", "We analyzed geo-coded symptoma...	[ "Over the past decades , Aedes-borne viruses ( dengue , chikungunya , Zika ) have become a major source of morbidity within urban areas .", "Worldwide , public health response to these viruses is reactive to the occurrence of symptomatic cases ( a small proportion of all infections ) .", "Here we used geocoded ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "computational biology/population genetics", "computer science/applications", "cardiovascular disorders/cardiovascular imaging", "genetics and genomics/bioinformatics", "computer science/numerical analysis and theoretical computing", "cardiovascular disorders/coronary artery disease", "mathematics/stati...	Genetic Variants and Their Interactions in the Prediction of Increased Pre-Clinical Carotid Atherosclerosis: The Cardiovascular Risk in Young Finns Study	journal.pgen.1001146	null	[ [ "A major challenge of medical genetics is to determine an optimal set of genetic markers , typically in the form of single nucleotide polymorphisms ( SNP ) , which when combined together with conventional risk factors , could be used in individual level risk prediction , classification and clinical decision-m...	[ "The relative contribution of genetic risk factors to the progression of subclinical atherosclerosis is poorly understood .", "It is likely that multiple variants are implicated in the development of atherosclerosis , but the subtle genotypic and phenotypic differences are beyond the reach of the conventional cas...	[ "Although cardiovascular events , such as myocardial infarction and stroke , usually occur at later ages , it is known that the atherogenic process begins much earlier in life .", "Detection of subclinical atherosclerosis would therefore offer the means to identify individuals who are at increased risk of develop...	2010

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