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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" ]	[ "cell death", "signal transduction", "immunity", "innate immunity", "immunology", "host-pathogen interaction", "biology", "microbiology", "molecular cell biology" ]	MAVS-MKK7-JNK2 Defines a Novel Apoptotic Signaling Pathway during Viral Infection	journal.ppat.1004020	null	[ [ "The induction of innate immunity upon viral infection represents the first line of host defense against microbe invasion .", "During infection with a RNA virus , the mitochondrial antiviral signaling protein ( MAVS/VISA/Cardif/IPS-1 ) has been recently uncovered to seed a critical protein complex on the ...	[ "Viral infection induces innate immunity and apoptosis .", "Apoptosis is an effective means to sacrifice virus-infected host cells and therefore restrict the spread of pathogens .", "However , the underlying mechanisms of this process are still poorly understood .", "Here , we show that the mitochondrial anti...	[ "The mitochondrial antiviral signaling protein ( MAVS/VISA/Cardif/IPS-1 ) is critical for the innate immune response during viral infection , and its function has been well documented in mediating type I interferon production .", "In this study , we revealed the essential role of MAVS in virus-induced apoptosis ,...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "sequencing techniques", "invertebrates", "medicine and health sciences", "pathology and laboratory medicine", "enzymology", "invertebrate genomics", "animals", "toxicology", "dna transcription", "enzyme metabolism", "molecular biology techniques", "rna sequencing", "insect vectors", "enzy...	In the hunt for genomic markers of metabolic resistance to pyrethroids in the mosquito Aedes aegypti: An integrated next-generation sequencing approach	journal.pntd.0005526	null	[ [ "Mosquitoes are considered by the World Health Organization ( WHO ) as the most dangerous animals in the world , transmitting numerous infectious diseases and causing millions of death worldwide every year .", "Vector-borne diseases account for 16% of the estimated global burden of communicable diseases ....	[ "The capacity of Aedes mosquitoes to resist chemical insecticides threatens the control of major arbovirus diseases worldwide .", "Until alternative control tools are widely deployed , monitoring insecticide resistance levels and identifying resistance mechanisms in field mosquito populations is crucial for imple...	[ "The ability of mosquitoes to resist insecticides represents a serious threat to the prevention of arbovirus diseases such as dengue , zika and chikungunya .", "The detection and monitoring of the resistances developed by natural mosquito populations is essential to enabling their management in the field for as l...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "biochemistry", "medicine and health sciences", "immunochemistry", "pathology and laboratory medicine", "proteins", "immunity", "medical microbiology", "host-pathogen interactions", "biology and life sciences", "immunology", "recombinant proteins", "microbiology", "pathogenesis", "glycobio...	Recombinant Paracoccin Reproduces the Biological Properties of the Native Protein and Induces Protective Th1 Immunity against Paracoccidioides brasiliensis Infection	journal.pntd.0002788	null	[ [ "Paracoccidioides brasiliensis [1] , [2] is a thermo-dimorphic fungus that grows as a mycelium at 25°C and as a yeast at 37°C .", "P . brasiliensis infection in humans is known as paracoccidioidomycosis ( PCM ) , a systemic granulomatous disease with high prevalence in Latin America [3] .", "An estima...	[ "Paracoccin is a dual-function protein of the yeast Paracoccidioides brasiliensis that has lectin properties and N-acetylglucosaminidase activities .", "Proteomic analysis of a paracoccin preparation from P . brasiliensis revealed that the sequence matched that of the hypothetical protein encoded by PADG-3347 of ...	[ "Paracoccin is a constituent of Paracoccidioides brasiliensis , a human pathogen that causes paracoccidioidomycosis , the most prevalent systemic mycosis in Latin America .", "Paracoccin is a dual function protein with domains for lectin and N-acetylglucosaminidase activities .", "Proteomic analysis of paracocc...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "public health and epidemiology", "epidemiology", "genetics", "biology", "microbiology", "evolutionary biology", "genetics and genomics" ]	Recent, Independent and Anthropogenic Origins of Trypanosoma cruzi Hybrids	journal.pntd.0001363	null	[ [ "Trypanosoma cruzi is a single celled eukaryotic parasite , which is transmitted to vertebrate hosts via the faeces of blood-sucking triatomine bugs .", "It is the aetiological agent of Chagas disease in humans , which results in the death of ∼13 , 000 people and the loss of 649 , 000 disability-adjusted ...	[ "The single celled eukaryote Trypanosoma cruzi , a parasite transmitted by numerous species of triatomine bug in the Americas , causes Chagas disease in humans .", "T . cruzi generally reproduces asexually and appears to have a clonal population structure .", "However , two of the six major circulating genetic ...	[ "Trypanosoma cruzi is a parasite that causes Chagas disease in humans , an often fatal condition affecting at least 8 million people .", "The clinical outcome of Chagas disease is variable , which is probably partially attributable to genetic differences between T . cruzi strains .", "Differences between T . cr...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "biology" ]	Development of a Humanized Antibody with High Therapeutic Potential against Dengue Virus Type 2	journal.pntd.0001636	null	[ [ "Dengue is the most important arthropod-borne viral disease in humans and an increasing public health concern in tropical and subtropical regions of the world .", "Approximately 50–100 million cases of dengue fever ( DF ) and 500 , 000 cases of dengue hemorrhagic fever ( DHF ) occur every year , and 2 . 5...	[ "Dengue virus ( DENV ) is a significant public health threat in tropical and subtropical regions of the world .", "A therapeutic antibody against the viral envelope ( E ) protein represents a promising immunotherapy for disease control .", "We generated seventeen novel mouse monoclonal antibodies ( mAbs ) with ...	[ "Dengue virus ( DENV ) infection remains a serious health threat despite the availability of supportive care in modern medicine .", "Monoclonal antibodies ( mAbs ) of DENV would be powerful research tools for antiviral development , diagnosis and pathological investigations .", "Here we described generation and...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/bacterial infections", "microbiology/cellular microbiology and pathogenesis" ]	Capnocytophaga canimorsus: A Human Pathogen Feeding at the Surface of Epithelial Cells and Phagocytes	journal.ppat.1000164	null	[ [ "Capnocytophaga canimorsus ( formerly Centers for Disease Control group DF-2 ) has been rarely but regularly isolated from dog or cat bite infections since its discovery in 1976 [1] , [2] .", "C . canimorsus is a thin Gram-negative rod , found in the normal oral flora of dogs and cats .", "Clinical in...	[ "Capnocytophaga canimorsus , a commensal bacterium of the canine oral flora , has been repeatedly isolated since 1976 from severe human infections transmitted by dog bites .", "Here , we show that C . canimorsus exhibits robust growth when it is in direct contact with mammalian cells , including phagocytes .", ...	[ "Capnocytophaga canimorsus is a commensal bacterium of dogs/cats oral flora , which causes rare but severe infections in humans that have been bitten or simply licked by a dog/cat .", "Fulminant septicemia and peripheral gangrene are most common symptoms .", "Although splenectomy has been identified as a predis...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "computational biology/comparative sequence analysis", "plant biology/plant genomes and evolution", "computational biology/genomics" ]	Small RNAs Originated from Pseudogenes: cis- or trans-Acting?	journal.pcbi.1000449	null	[ [ "Pseudogenes are genomic sequences derived from functional genes , but are often considered non-functional due to the accumulation of various deleterious mutations over their evolutionary history [1]–[6] .", "Compared with its parental gene ( more precisely , the direct descendent of the ancestral gene th...	[ "Pseudogenes are significant components of eukaryotic genomes , and some have acquired novel regulatory roles .", "To date , no study has characterized rice pseudogenes systematically or addressed their impact on the structure and function of the rice genome .", "In this genome-wide study , we have identified 1...	[ "Pseudogenes are “defunct” copies of protein-coding genes that have been accumulated in a genome .", "They have conventionally been considered the junk byproducts of genome evolution , as they cannot code for proteins due to sequence degeneration .", "Recent important studies , however , have discovered that a ...	2009
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "atmospheric science", "pathogens", "microbiology", "cryptosporidium", "reoviruses", "parasitic protozoans", "shigella", "viruses", "diarrhea", "seasons", "protozoans", "rna viruses", "signs and symptoms", "gastroente...	The seasonality of diarrheal pathogens: A retrospective study of seven sites over three years	journal.pntd.0007211	null	[ [ "Pediatric diarrheal disease is caused by a wide variety of pathogens [1–3] .", "Various studies have found that some pathogens are seasonal , peaking at different times of the year [4–6] .", "Frequently , the seasonal periodicity of diarrheal disease is attributed to weather , which could drive incid...	[ "Pediatric diarrhea can be caused by a wide variety of pathogens , from bacteria to viruses to protozoa .", "Pathogen prevalence is often described as seasonal , peaking annually and associated with specific weather conditions .", "Although many studies have described the seasonality of diarrheal disease , thes...	[ "Diarrheal disease is one of the leading causes of death among young children in the developing world .", "It is difficult to determine which of a wide variety of pathogens are most responsible for disease , since this differs by location and time of year .", "Here , we study the seasonal prevalence of several ...	2019
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Allelic Variation of Cytochrome P450s Drives Resistance to Bednet Insecticides in a Major Malaria Vector	journal.pgen.1005618	null	[ [ "Despite the recent decrease in malaria mortality ( 47% ) [1] , the disease remains a serious public health burden in the tropical world , with 584 , 000 deaths globally in 2013 , of which 90% occurred in WHO African region , and mostly in children under the age of 5 .", "Malaria control relies heavily on...	[ "Scale up of Long Lasting Insecticide Nets ( LLINs ) has massively contributed to reduce malaria mortality across Africa .", "However , resistance to pyrethroid insecticides in malaria vectors threatens its continued effectiveness .", "Deciphering the detailed molecular basis of such resistance and designing di...	[ "Scale up of Long Lasting Insecticide Nets has massively reduced malaria mortality across Africa .", "However , resistance to pyrethroid insecticides in malaria vectors threatens its continued effectiveness .", "Here , we established that allelic variation in two CYP450s is the most important driver of pyrethro...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "enzymes", "brassica", "enzymology", "luminescent proteins", "model organisms", "plant science", "yellow fluorescent protein", "experimental organism systems", "seedlings", "molecular biology techniques", "plants", "extraction techniques", "ligases", "arabidopsis thaliana", "research and...	SCFAtPP2-B11 modulates ABA signaling by facilitating SnRK2.3 degradation in Arabidopsis thaliana	journal.pgen.1006947	null	[ [ "Abscisic acid ( ABA ) plays important roles in plant development and growth , including seed dormancy , seed germination , and postgerminative growth [1 , 2] .", "In particular , it plays an essential role in plant responses to adverse environmental stresses such as drought and salt stress [1 , 2] .", ...	[ "The phytohormone abscisic acid ( ABA ) is an essential part of the plant response to abiotic stressors such as drought .", "Upon the perception of ABA , pyrabactin resistance ( PYR ) /PYR1-like ( PYL ) /regulatory components of ABA receptor ( RCAR ) proteins interact with co-receptor protein phosphatase type 2Cs...	[ "The phytohormone ABA plays critical roles in both plant growth and development and the response to environmental stimuli .", "The SnRK2s are important components of the PYR/PYL-ABA-PP2C regulatory machine which activate a set of bZIP transcription factors and ion transporters .", "However , the regulation of S...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "enzyme-linked immunoassays", "body fluids", "immune physiology", "pathology and laboratory medicine", "statistics", "metaanalysis", "immunology", "pediatrics", "bacterial diseases", "mathematics", "signs and symptoms", "network analysis", "immunologic techn...	Comparative accuracy of typhoid diagnostic tools: A Bayesian latent-class network analysis	journal.pntd.0007303	null	[ [ "Typhoid fever ( also known as enteric fever ) is a systemic infection caused by the Gram-negative bacteria Salmonella enterica serotypes Typhi or Paratyphi A , B and C[1] , [2] .", "While rare in developed countries , the burden of typhoid remains high in developing countries .", "Recent annual estim...	[ "Typhoid fevers are infections caused by the bacteria Salmonella enterica serovar Typhi ( Salmonella Typhi ) and Paratyphi A , B and C ( Salmonella Paratyphi ) .", "Approximately 17 . 8 million incident cases of typhoid fever occur annually , and incidence is highest in children .", "The accuracy of current dia...	[ "Typhoid fever is an infection caused by the bacterium Salmonella Typhi .", "Typhoid fever is rare in developed countries but remains high in the developing world .", "Effective treatment is available but accurate diagnosis of typhoid fever is challenging as typhoid fever can be difficult to distinguish from ot...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	PPM1A Regulates Antiviral Signaling by Antagonizing TBK1-Mediated STING Phosphorylation and Aggregation	journal.ppat.1004783	null	[ [ "Innate immunity is the first line of the host defense system against invading microorganisms , including viruses .", "The detection of conserved microbial molecules , known as pathogen-associated molecular patterns ( PAMPs ) , by the host cells involves multiple pattern recognition receptors ( PRRs ) .",...	[ "Stimulator of interferon genes ( STING , also known as MITA and ERIS ) is critical in protecting the host against DNA pathogen invasion .", "However , the molecular mechanism underlying the regulation of STING remains unclear .", "Here , we show that PPM1A negatively regulates antiviral signaling by targeting ...	[ "Innate antiviral immunity is essential for the host defense system that rapidly detects and eliminates invading viruses .", "STING , an endoplasmic reticulum ( ER ) -associated protein , plays important roles in the activation of type I IFN in response to DNA virus infection .", "Whereas excessive activation o...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "gastroenterology and hepatology", "liver diseases", "medicine and health sciences" ]	Intrapulmonary Vascular Dilatation Evaluated by 99mTc-MAA Scintigraphy and Its Association with Portal Hypertension in Schistosomiasis	journal.pntd.0002881	null	[ [ "Hepatosplenic schistosomiasis ( HSS ) is characterized by the presence of liver fibrosis around the intrahepatic branches of the portal vein without damage to the hepatocyte synthesis ability [1] .", "It is estimated that schistosomiasis affects 2 . 5–6 million Brazilians [2] and about 10% of them develo...	[ "Portal hypertension is responsible for various complications in patients with schistosomiasis , among them intrapulmonary vascular dilations ( IPVD ) .", "In cirrhotic patients the presence of IPVD is a sign of poor prognosis , but in patients with hepatosplenic schistosomiasis ( HSS ) there are no studies asses...	[ "Intrapulmonary vascular dilatation ( IPVD ) is the key event in development of hepatopulmonary syndrome , an arterial oxygenation defect in patients with portal hypertension .", "IPVD diagnosis can be made by EchoDopplercardiography or 99mTc-macroaggregated albumin scintigraphy ( 99mTc-MAA ) , and ethiopatogeny ...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "gram negative bacteria", "medicine and health sciences", "pathology and laboratory medicine", "host-pathogen interactions", "medical microbiology", "microbial pathogens", "biology and life sciences", "microbiology", "pathogenesis", "bacterial pathogens" ]	A Translocated Effector Required for Bartonella Dissemination from Derma to Blood Safeguards Migratory Host Cells from Damage by Co-translocated Effectors	journal.ppat.1004187	null	[ [ "Pathogenic bacteria have evolved a multitude of virulence factors in order to manipulate the host to evade immune responses and to reach their replicative niche - a safe compartment to proliferate that is also a prerequisite for transmissibility [1] .", "Translocation of bacterial effector proteins into ...	[ "Numerous bacterial pathogens secrete multiple effectors to modulate host cellular functions .", "These effectors may interfere with each other to efficiently control the infection process .", "Bartonellae are Gram-negative , facultative intracellular bacteria using a VirB type IV secretion system to translocat...	[ "Cell migration , a fundamental feature of eukaryotic cells , plays a crucial role in mounting an effective immune response .", "However , several pathogens subvert the migratory properties of infected host cells to their benefit , such as using them as Trojan horses to disseminate within the host .", "Bartonel...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "mus (mouse)", "infectious diseases", "eubacteria" ]	Persistent Coxiella burnetii Infection in Mice Overexpressing IL-10: An Efficient Model for Chronic Q Fever Pathogenesis	journal.ppat.0040023	null	[ [ "The interaction between innate/adaptive immune system and invading bacteria is sufficient to eradicate microorganisms in the majority of bacterial infections .", "This microbicidal response is based on inflammatory cytokines , such as interferon ( IFN ) -γ and tumor necrosis factor ( TNF ) , which contro...	[ "Interleukin ( IL ) -10 increases host susceptibility to microorganisms and is involved in intracellular persistence of bacterial pathogens .", "IL-10 is associated with chronic Q fever , an infectious disease due to the intracellular bacterium Coxiella burnetii .", "Nevertheless , accurate animal models of chr...	[ "The interaction between immune system and invading bacteria is sufficient to eradicate microorganisms in the majority of bacterial infections , but the suppression of the microbicidal response leads to reactivation or chronic evolution of infections and to bacterial persistence .", "Coxiella burnetii , an obliga...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "biochemistry", "mycology", "model organisms", "proteins", "oral medicine", "yeast and fungal models", "biology", "microbiology" ]	The Novel Candida albicans Transporter Dur31 Is a Multi-Stage Pathogenicity Factor	journal.ppat.1002592	null	[ [ "The human oral cavity represents a discrete environmental niche , harboring a diverse and complex microbiome .", "In up to 80% of healthy individuals the fungus Candida albicans , and to a lesser extent other Candida spp .", "are part of this oral microbiome where they usually exist as harmless comme...	[ "Candida albicans is the most frequent cause of oral fungal infections .", "However , the exact pathogenicity mechanisms that this fungus employs are largely unknown and many of the genes expressed during oral infection are uncharacterized .", "In this study we sought to functionally characterize 12 previously ...	[ "The normally commensal yeast , Candida albicans is the leading cause of both oral and vaginal thrush , as well as life-threatening disseminated infections in the nosocomial setting .", "Treatment of such infections is hampered by the limited number of suitable antimycotics .", "Therefore , understanding how th...	2012
[ "Introduction", "Material and Methods", "Results", "Discussion" ]	[ "medicine", "viral vaccines", "infectious disease epidemiology", "flavivirus", "atmospheric science", "microbiology", "vaccines", "neglected tropical diseases", "infectious disease control", "japanese encephalitis", "climate change", "vaccination", "infectious diseases", "epidemiology", ...	The Effect of Vaccination Coverage and Climate on Japanese Encephalitis in Sarawak, Malaysia	journal.pntd.0002334	null	[ [ "Japanese encephalitis ( JE ) is a mosquito-borne disease which is the leading cause of viral encephalitis across Asia with approximately 70 , 000 cases a year and 10 , 000 to 15 , 000 deaths [1] , [2] .", "There are two transmission patterns of JEV in three climatic zones [3] , [4]: in temperate climate ...	[ "Japanese encephalitis ( JE ) is the leading cause of viral encephalitis across Asia with approximately 70 , 000 cases a year and 10 , 000 to 15 , 000 deaths .", "Because JE incidence varies widely over time , partly due to inter-annual climate variability effects on mosquito vector abundance , it becomes more co...	[ "Japanese encephalitis ( JE ) virus is a mosquito-borne virus which is the leading cause of viral encephalitis in Asia .", "The cumulative attack rate for human JE cases is seemingly low ( 2-cases/105/year ) ; however , epidemics are focal and intense , being concentrated in children 1 to 15 years of age and high...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Stochastic Computations in Cortical Microcircuit Models	journal.pcbi.1003311	null	[ [ "The question whether brain computations are inherently deterministic or inherently stochastic is obviously of fundamental importance .", "Numerous experimental data highlight inherently stochastic aspects of neurons , synapses and networks of neurons on virtually all spatial and temporal scales that have...	[ "Experimental data from neuroscience suggest that a substantial amount of knowledge is stored in the brain in the form of probability distributions over network states and trajectories of network states .", "We provide a theoretical foundation for this hypothesis by showing that even very detailed models for cort...	[ "The brain has not only the capability to process sensory input , but it can also produce predictions , imaginations , and solve problems that combine learned knowledge with information about a new scenario .", "But although these more complex information processing capabilities lie at the heart of human intellig...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/recombination", "genetics and genomics/cancer genetics", "molecular biology/dna repair" ]	Role of RecA and the SOS Response in Thymineless Death in Escherichia coli	journal.pgen.1000865	null	[ [ "Thymineless death ( TLD ) , the rapid loss of viability in cultures deprived of thymine , occurs in E . coli , yeast and human cells ( reviewed [1] ) .", "Cancer chemotherapeutic drugs methotrexate , 5-fluorouracil ( 5-FU ) , and fluorodeoxyuridine , and the antibiotic trimethoprim , work by inducing TLD...	[ "Thymineless death ( TLD ) is a classic and enigmatic phenomenon , documented in bacterial , yeast , and human cells , whereby cells lose viability rapidly when deprived of thymine .", "Despite its being the essential mode of action of important chemotherapeutic agents , and despite having been studied extensivel...	[ "A long-standing enigma in the fields of DNA repair and cancer chemotherapy is why it is that cells starved of the base thymine die rapidly .", "This process , called thymineless death ( TLD ) , is conserved in bacterial , yeast , and human cells and is the mode of action of important cancer chemotherapeutic drug...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "cytogenetic analysis", "chromosomal disorders", "genetics", "biology", "human genetics", "translocations", "cytogenetics", "chromosomal deletions and duplications", "genetics and genomics", "clinical genetics" ]	Molecular Mechanisms Generating and Stabilizing Terminal 22q13 Deletions in 44 Subjects with Phelan/McDermid Syndrome	journal.pgen.1002173	null	[ [ "Deletions involving the distal portion of chromosomes are among the most commonly observed rearrangements detected by cytogenetics [1] and result in several well-known genetic syndromes such as 1p36 monosomy ( MIM: 607872 ) , Cri-du-chat ( 5p- , MIM: 123450 ) , Miller-Dieker ( 17p- , MIM: 247200 ) , monosomy...	[ "In this study , we used deletions at 22q13 , which represent a substantial source of human pathology ( Phelan/McDermid syndrome ) , as a model for investigating the molecular mechanisms of terminal deletions that are currently poorly understood .", "We characterized at the molecular level the genomic rearrangeme...	[ "Terminal chromosome deletions are among the most commonly observed rearrangements detected by cytogenetics and may result in several well-known genetic syndromes .", "We used 22q13 deletions to study how these types of chromosome abnormalities arise .", "Children with Phelan/McDermid syndrome , caused by delet...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "epidemiology", "endocrinology", "mental health and psychiatry", "metabolic disorders", "cardiology" ]	Genome Wide Association Identifies Common Variants at the SERPINA6/SERPINA1 Locus Influencing Plasma Cortisol and Corticosteroid Binding Globulin	journal.pgen.1004474	null	[ [ "The adrenal steroid hormone cortisol plays a vital role in adaptation to environmental stress .", "In response to stressors such as starvation , infection or injury , cortisol secretion is elevated by activation of the hypothalamic-pituitary-adrenal ( HPA ) axis .", "Cortisol acts predominantly throu...	[ "Variation in plasma levels of cortisol , an essential hormone in the stress response , is associated in population-based studies with cardio-metabolic , inflammatory and neuro-cognitive traits and diseases .", "Heritability of plasma cortisol is estimated at 30–60% but no common genetic contribution has been ide...	[ "Cortisol is a steroid hormone from the adrenal glands that is essential in the response to stress .", "Most cortisol in blood is bound to corticosteroid binding globulin ( CBG ) .", "Diseases causing cortisol deficiency ( Addison's disease ) or excess ( Cushing's syndrome ) are life-threatening .", "Variatio...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "cell biology", "molecular biology", "drosophila", "genetics and genomics" ]	The Multiple Roles of Mps1 in Drosophila Female Meiosis	journal.pgen.0030113	null	[ [ "Female meiosis in Drosophila has proved to be a useful model system for studying the mechanisms of chromosome segregation and the regulation of the meiotic cell cycle .", "While the canonical mitotic cell division entails the separation of sister chromatids , at the first meiotic division homologous cent...	[ "The Drosophila gene ald encodes the fly ortholog of mps1 , a conserved kinetochore-associated protein kinase required for the meiotic and mitotic spindle assembly checkpoints .", "Using live imaging , we demonstrate that oocytes lacking Ald/Mps1 ( hereafter referred to as Ald ) protein enter anaphase I immediate...	[ "Female meiosis is the process that ensures developing eggs ( called oocytes ) receive the proper complement of chromosomes .", "The failure to accurately segregate chromosomes results in aneuploidy , which is the leading cause of birth defects in humans .", "Cells contain checkpoints that help ensure proper ch...	2007
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "cell binding", "cell physiology", "medicine and health sciences", "immune physiology", "pathology and laboratory medicine", "cd coreceptors", "viral transmission and infection", "hepacivirus", "pathogens", "biological cultures", "immunology", "microbiology", "mathematical models", "viruse...	Building a mechanistic mathematical model of hepatitis C virus entry	journal.pcbi.1006905	null	[ [ "HCV can establish a lifelong infection and is a leading cause of liver failure , resulting in 350 , 000–700 , 000 deaths annually [1] .", "A molecular understanding of the intermediate stages of viral replication ( e . g . RNA replication , protein processing ) has allowed the development of potent antiv...	[ "The mechanism by which hepatitis C virus ( HCV ) gains entry into cells is a complex one , involving a broad range of host proteins .", "Entry is a critical phase of the viral lifecycle , and a potential target for therapeutic or vaccine-mediated intervention .", "However , the mechanics of HCV entry remain po...	[ "Hepatitis C virus affects approximately 70 million people worldwide , resulting in a significant impact on human health .", "The virus initiates infection through a complex set of interactions with proteins on the surface of human cells .", "Here we combine experimental approaches with a new mathematical model...	2019
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "neuroscience/theoretical neuroscience" ]	Predictive Feedback Can Account for Biphasic Responses in the Lateral Geniculate Nucleus	journal.pcbi.1000373	null	[ [ "Cells in the LGN exhibit striking receptive field dynamics .", "Besides their well-known", "center-surround organization , LGN receptive fields are characterized by", "bright-excitatory ( dark-excitatory ) regions that become dark-excitatory", "( bright-excitatory ) over time intervals that m...	[ "Biphasic neural response properties , where the optimal stimulus for driving a", "neural response changes from one stimulus pattern to the opposite stimulus", "pattern over short periods of time , have been described in several visual areas ,", "including lateral geniculate nucleus ( LGN ) , primary visual c...	[ "For many neurons in the early visual brain the optimal stimulation for driving a", "response changes from one stimulus pattern to the opposite stimulus pattern over", "short periods of time .", "For example , many neurons in the lateral geniculate", "nucleus ( LGN ) respond to a bright stimulus initially b...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "inflammation", "viral persistence and latency", "immunity", "virology", "viruses and cancer", "biology", "microbiology" ]	Lymphotoxin Signaling Is Initiated by the Viral Polymerase in HCV-linked Tumorigenesis	journal.ppat.1003234	null	[ [ "Persistent HCV infection affects about 170 million people worldwide [1] and is one of the most common causes of chronic liver disease [2] .", "Infected individuals typically suffer from chronic liver inflammation that can last several decades and lead to progressive fibrotic liver that can culminate in h...	[ "Exposure to hepatitis C virus ( HCV ) typically results in chronic infection that leads to progressive liver disease ranging from mild inflammation to severe fibrosis and cirrhosis as well as primary liver cancer .", "HCV triggers innate immune signaling within the infected hepatocyte , a first step in mounting ...	[ "Hepatitis C affects nearly 200 million people worldwide .", "It results from the failure of the immune system to control the hepatitis C virus ( HCV ) replication and spread , leading to progressive liver disease that can culminate in fibrosis , cirrhosis and cancer .", "The inflammatory cells that infiltrate ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases", "genetics and genomics", "plasmodium", "microbiology" ]	Population Genomics of the Immune Evasion (var) Genes of Plasmodium falciparum	journal.ppat.0030034	null	[ [ "Quantifying the diversity of major surface antigens underlying immune evasion of HIV 1 and 2 and Influenza A has been central to characterizing the transmission dynamics of these important human pathogens .", "In addition , documentation of variation data has provided a basis for the development of candi...	[ "Var genes encode the major surface antigen ( PfEMP1 ) of the blood stages of the human malaria parasite Plasmodium falciparum .", "Differential expression of up to 60 diverse var genes in each parasite genome underlies immune evasion .", "We compared the diversity of the DBLα domain of var genes sampled from 3...	[ "Malaria parasites live in red blood cells of the human host for part of the life cycle , during which a family of diverse antigens known as PfEMP1 are placed on the surface .", "PfEMP1 variants switch by sequential expression of up to 60 var genes .", "This allows the parasite to evade immune detection within ...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "veterinary diseases", "genomics", "veterinary epidemiology", "mathematics", "ecology", "biology", "computational biology", "population biology", "nonlinear dynamics", "genetics and genomics", "veterinary science" ]	Whole Genome Sequencing Reveals Local Transmission Patterns of Mycobacterium bovis in Sympatric Cattle and Badger Populations	journal.ppat.1003008	null	[ [ "The application of whole genome sequencing ( WGS ) technology to infectious bacterial diseases has resulted in unprecedented advances in our ability to resolve epidemic data at the global scale [1] , [2] , provided new insights into within-host replication processes [3] , and been used to corroborate the imp...	[ "Whole genome sequencing ( WGS ) technology holds great promise as a tool for the forensic epidemiology of bacterial pathogens .", "It is likely to be particularly useful for studying the transmission dynamics of an observed epidemic involving a largely unsampled ‘reservoir’ host , as for bovine tuberculosis ( bT...	[ "Whole genome sequencing ( WGS ) offers the potential for unprecedented insight into infectious diseases spread at the individual-to-individual level .", "However , this potential can be compromised when a poorly sampled ‘reservoir’ population contributes to transmission , as strong biases in the obtained data ar...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroglial development", "developmental biology", "developmental neuroscience", "molecular neuroscience", "neurobiology of disease and regeneration", "nucleic acids", "gene expression", "biology", "molecular cell biology", "neuroscience" ]	MYRF Is a Membrane-Associated Transcription Factor That Autoproteolytically Cleaves to Directly Activate Myelin Genes	journal.pbio.1001625	Oligodendrocyte development and myelination rely on an unusual membrane-associated transcription factor that shares functional domains with bacteriophage proteins.	[ [ "Oligodendrocytes are the myelinating cells of the vertebrate CNS; their development and the ensheathment of receptive neuronal axons are vital for the rapid propagation of nerve impulses .", "Accordingly , the differentiation of oligodendrocyte progenitor cells ( OPCs ) into oligodendrocytes and their su...	[ "The myelination of axons is a crucial step during vertebrate central nervous system ( CNS ) development , allowing for rapid and energy efficient saltatory conduction of nerve impulses .", "Accordingly , the differentiation of oligodendrocytes , the myelinating cells of the CNS , and their expression of myelin g...	[ "Oligodendrocytes are a highly specialized cell type that surround axons of the vertebrate central nervous system with myelin , electrically insulating them and allowing rapid and energy-efficient propagation of nerve signals .", "We previously identified a protein , MYRF , that is required for the final stages o...	2013
[ "Introduction", "Material & methods", "Results", "Discussion" ]	[ "learning", "medicine and health sciences", "prefrontal cortex", "applied mathematics", "brain", "vertebrates", "social sciences", "problem solving", "neuroscience", "animals", "mammals", "learning and memory", "simulation and modeling", "animal models", "algorithms", "model organisms"...	Reservoir computing model of prefrontal cortex creates novel combinations of previous navigation sequences from hippocampal place-cell replay with spatial reward propagation	journal.pcbi.1006624	null	[ [ "Spatial navigation in the rat involves the replay of place-cell sub-sequences , that we refer to as snippets , during awake and sleep states in the hippocampus during sharp-wave-ripples ( SWR ) [1–4] .", "In the awake state , replay has been observed to take place in forward and reverse direction [2 , 5–...	[ "As rats learn to search for multiple sources of food or water in a complex environment , they generate increasingly efficient trajectories between reward sites .", "Such spatial navigation capacity involves the replay of hippocampal place-cells during awake states , generating small sequences of spatially relate...	[ "As rats search for multiple sources of food in a complex environment , they generate increasingly efficient trajectories between reward sites , across multiple trials .", "This spatial navigation optimization behavior can be measured in the laboratory using a traveling salesperson task ( TSP ) .", "This likely...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "microbial metabolism", "mycology", "medical microbiology", "microbial pathogens", "host-pathogen interaction", "biology", "microbiology", "pathogenesis", "fungal physiology" ]	Modulation of Phagosomal pH by Candida albicans Promotes Hyphal Morphogenesis and Requires Stp2p, a Regulator of Amino Acid Transport	journal.ppat.1003995	null	[ [ "Normally a benign commensal , Candida albicans is also the most prevalent fungal pathogen in humans .", "Common mucosal manifestations of candidiasis are oropharyngeal thrush and vaginitis , but C . albicans can infect virtually any body site [1] , [2] .", "The most serious infection – disseminated h...	[ "Candida albicans , the most important fungal pathogen of humans , has a unique interaction with macrophages in which phagocytosis induces a switch from the yeast to hyphal form , allowing it to escape by rupturing the immune cell .", "While a variety of factors induce this switch in vitro , including neutral pH ...	[ "The innate immune system represents a key barrier that fungal pathogens such as Candida albicans must overcome in order to disseminate through the host .", "C . albicans cells phagocytosed by macrophages initiate a complex program that involves a large-scale reprogramming of metabolism and transcription and resu...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/bacterial infections", "immunology/immunity to infections", "immunology/innate immunity" ]	Naturally Occurring Lipid A Mutants in Neisseria meningitidis from Patients with Invasive Meningococcal Disease Are Associated with Reduced Coagulopathy	journal.ppat.1000396	null	[ [ "Neisseria meningitidis is a major cause of bacterial meningitis and sepsis worldwide [1] .", "While it is a frequent commensal of the human upper respiratory tract , in some individuals the bacterium spreads to the bloodstream causing meningitis and/or sepsis , serious conditions with high morbidity and ...	[ "Neisseria meningitidis is a major cause of bacterial meningitis and sepsis worldwide .", "Lipopolysaccharide ( LPS ) , a major component of the Gram-negative bacterial outer membrane , is sensed by mammalian cells through Toll-like receptor 4 ( TLR4 ) , resulting in activation of proinflammatory cytokine pathway...	[ "Neisseria meningitidis is a Gram-negative bacterium that can cause the life-threatening diseases meningitis and sepsis .", "Most of the symptoms seen in these diseases are the result of excessive stimulation of the immune system by lipopolysaccharide ( LPS ) , a major component of the outer membrane of Gram-nega...	2009
[ "Introduction", "Results", "Discussion", "Methods", "Simulations" ]	[]	ConPADE: Genome Assembly Ploidy Estimation from Next-Generation Sequencing Data	journal.pcbi.1004229	null	[ [ "Complete genome de novo sequencing and assembly is a major initial step in understanding the underlying genetic architecture of important traits in any species [1–3] .", "Reliable reference genomes are pivotal for finding genetic variations such as single nucleotide polymorphisms ( SNP ) and insertions/d...	[ "As a result of improvements in genome assembly algorithms and the ever decreasing costs of high-throughput sequencing technologies , new high quality draft genome sequences are published at a striking pace .", "With well-established methodologies , larger and more complex genomes are being tackled , including po...	[ "Diploid organisms , such as human beings , have two “copies” of each chromosome , whereas polyploid organisms have multiple “copies” ( we use quotes to stress that the “copies” are not identical ) .", "A key difference between diploid and polyploid organisms is that the “copies” tend to be less similar in polypl...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "model organisms", "protein interactions", "dna replication", "nucleic acids", "proteins", "genetics", "yeast and fungal models", "dna", "biology", "saccharomyces cerevisiae", "molecular cell biology", "dna repair", "gene function" ]	Def1 Promotes the Degradation of Pol3 for Polymerase Exchange to Occur During DNA-Damage–Induced Mutagenesis in Saccharomyces cerevisiae	journal.pbio.1001771	After DNA damage, Def1 triggers degradation of the catalytic subunit of the replicative DNA polymerase at stalled replication forks, allowing special polymerases to take over DNA synthesis.	[ [ "The stalling of the replication machinery that occurs as a consequence of encountering unrepaired DNA damages is a challenging problem for cells .", "Stalled replication forks can undergo DNA breakage and recombination that can lead to chromosomal rearrangements and cell death .", "To ensure survival...	[ "DNA damages hinder the advance of replication forks because of the inability of the replicative polymerases to synthesize across most DNA lesions .", "Because stalled replication forks are prone to undergo DNA breakage and recombination that can lead to chromosomal rearrangements and cell death , cells possess d...	[ "DNA damages can lead to the stalling of the cellular replication machinery if not repaired on time , inducing DNA strand breaks , recombination that can result in gross chromosomal rearrangements , even cell death .", "In order to guard against this outcome , cells have evolved several precautionary mechanisms ....	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	An Atypical Kinase under Balancing Selection Confers Broad-Spectrum Disease Resistance in Arabidopsis	journal.pgen.1003766	null	[ [ "Pathogens are a threat for crops and natural plant populations .", "A major challenge in plant breeding and evolutionary biology is to identify the genetic and molecular bases for natural resistance variation in plant species .", "The identification of genes underlying natural resistance variation mi...	[ "The failure of gene-for-gene resistance traits to provide durable and broad-spectrum resistance in an agricultural context has led to the search for genes underlying quantitative resistance in plants .", "Such genes have been identified in only a few cases , all for fungal or nematode resistance , and encode div...	[ "During the evolution of plant-pathogen interactions , plants have evolved the capability to defend themselves from pathogen infection by different overlapping mechanisms .", "Disease resistance is constituted by an elaborate , multilayered system of defense .", "Among these responses , quantitative resistance ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "sequencing techniques", "biochemistry", "developmental biology", "embryology", "high throughput sequencing", "molecular biology", "genomic imprinting", "embryo development", "genetics", "biology and life sciences", "dna", "epigenetics", "dna modification", "molecular biology techniques", ...	Genome-Wide Analysis of DNA Methylation Dynamics during Early Human Development	journal.pgen.1004868	null	[ [ "In mammals , DNA methylation is essential for normal development and plays critical roles in repression of transposable elements , maintaining genome stability , genomic imprinting and X-chromosome inactivation .", "DNA methylation patterns are relatively stable in somatic cells but genome-wide reprogram...	[ "DNA methylation is globally reprogrammed during mammalian preimplantation development , which is critical for normal development .", "Recent reduced representation bisulfite sequencing ( RRBS ) studies suggest that the methylome dynamics are essentially conserved between human and mouse early embryos .", "RRBS...	[ "DNA methylation reprogramming after fertilization is critical for normal mammalian development .", "Early embryos are sensitive to environmental stresses and a number of reports have pointed out the increased risk of DNA methylation errors associated with assisted reproduction technologies .", "Therefore , it ...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "computer science", "computer modeling", "mathematics", "applied mathematics", "biology", "nonlinear dynamics", "zoology" ]	Dynamical Modeling of Collective Behavior from Pigeon Flight Data: Flock Cohesion and Dispersion	journal.pcbi.1002449	null	[ [ "The collective behavior exhibited by interacting individuals in a population has recently attracted interest in scientific and engineering communities .", "Many different definitions have been used to formally describe this behavior , in order to establish new theories and further advance the contributio...	[ "Several models of flocking have been promoted based on simulations with qualitatively naturalistic behavior .", "In this paper we provide the first direct application of computational modeling methods to infer flocking behavior from experimental field data .", "We show that this approach is able to infer gener...	[ "The construction of mathematical models from experimental time-series data has been considered with some success in many areas of science and engineering , using the power of computer algorithms to build model structures and suitably tuning their parameters .", "When considering complex systems with nonlinear or...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biophysics/theory and simulation", "biophysics/replication and repair", "otolaryngology/audiology", "biophysics", "physics/interdisciplinary physics" ]	Biophysical Parameters Modification Could Overcome Essential Hearing Gaps	journal.pcbi.1000161	null	[ [ "The heart of the mammalian auditory system is the hearing sensor , the cochlea .", "Acoustic signals arriving in the form of sound pressure waves are funneled by the outer ear towards the tympanic membrane , forcing the latter to oscillate .", "These oscillations are transmitted to the oval window , ...	[ "A majority of hearing defects are due to malfunction of the outer hair cells ( OHCs ) , those cells within the mammalian hearing sensor ( the cochlea ) that provide an active amplification of the incoming signal .", "Malformation of the hearing sensor , ototoxic drugs , acoustical trauma , infections , or the ef...	[ "The cochlea , the mammalian hearing sensor , is a formidable biophysical construct in many respects .", "Its task is to pick up environmental auditory information , which provides us with a sensory communication channel without which we experience great problems in our every day life .", "In its extreme form ,...	2008
[ "Introduction", "Effect of Variability: A Model Study", "Outlook", "Background" ]	[]	Regulation of Spatiotemporal Patterns by Biological Variability: General Principles and Applications to Dictyostelium discoideum	journal.pcbi.1004367	null	[ [ "Patterns in nature have attracted attention for centuries because of their complexity and regularity .", "A great leap forward in the theoretical understanding of their development from simple interacting constituents was made by Alan Turing in his classic work on morphogenesis [1] .", "The static \"...	[ "Spatiotemporal patterns often emerge from local interactions in a self-organizing fashion .", "In biology , the resulting patterns are also subject to the influence of the systematic differences between the system’s constituents ( biological variability ) .", "This regulation of spatiotemporal patterns by biol...	[ "Pattern formation is abundant in nature—from the rich ornaments of sea shells and the diversity of animal coat patterns to the myriad of fractal structures in biology and pattern-forming colonies of bacteria .", "Particularly fascinating are patterns changing with time , spatiotemporal patterns , like propagatin...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "immunology", "tropical diseases", "geographical locations", "social sciences", "parasitic diseases", "animals", "preventive medicine", "gastropods", "neglected tropical diseases", "infectious disease control", "vaccination and immunization", ...	Knowledge, attitudes and practices related to schistosomiasis transmission and control in Leyte, Philippines	journal.pntd.0007358	null	[ [ "Schistosomiasis is a chronic disease caused by trematode worms of the genus Schistosoma and transmitted by freshwater snails [1] .", "In 2013 , the World Health Organization ( WHO ) estimated 260 million people at risk for the disease [2] .", "The total burden of disease attributed to the three major...	[ "Schistosomiasis is a chronic but preventable disease that affects 260 million people worldwide .", "In the Philippines , 860 , 000 people are afflicted with Schistosoma japonicum annually , and another 6 . 7 million live in endemic areas .", "The disease’s complex epidemiology as well as the influence of pover...	[ "Schistosomiasis is a chronic tropical disease caused by parasitic worms of the genus Schistosoma .", "In the Philippines , Schistosoma japonicum afflicts over 800 , 000 people annually , and another 6 . 7 million live in endemic areas .", "The current national control program based on human mass treatment has ...	2019
[ "Introduction", "Results", "Discussion" ]	[ "genetics and genomics/complex traits", "rheumatology/bone and mineral metabolism" ]	Genome-Wide Association Meta-Analysis of Cortical Bone Mineral Density Unravels Allelic Heterogeneity at the RANKL Locus and Potential Pleiotropic Effects on Bone	journal.pgen.1001217	null	[ [ "Genome-wide association studies have identified reliable genetic associations with Dual x-ray absorptiometry ( DXA ) -derived measures related to bone mass , such as areal bone mineral density ( aBMD ) [1]–[4] .", "aBMD , is a commonly used skeletal trait measure on the basis of its ability to predict fr...	[ "Previous genome-wide association ( GWA ) studies have identified SNPs associated with areal bone mineral density ( aBMD ) .", "However , this measure is influenced by several different skeletal parameters , such as periosteal expansion , cortical bone mineral density ( BMDC ) cortical thickness , trabecular numb...	[ "Previous studies that have identified genetic polymorphisms involved in bone density have used a technique that cannot differentiate between cortical and trabecular bone .", "We have carried out the first genome-wide association study using a bone scanning method that can differentiate between the constituent pa...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "immune cells", "multiple sclerosis", "antigen-presenting cells", "immunology", "epstein-barr virus infectious mononucleosis", "demyelinating disorders", "immunomodulation", "infectious diseases", "t cells", "immune response", "immunopathology", "clinical immunology", "neurolog...	Gammaherpesvirus Latency Accentuates EAE Pathogenesis: Relevance to Epstein-Barr Virus and Multiple Sclerosis	journal.ppat.1002715	null	[ [ "Multiple sclerosis ( MS ) is a chronic inflammatory disease of the central nervous system ( CNS ) .", "In MS , the myelin sheath , that insulates and protects neurons , is attacked and destroyed by the host's immune system leading to progressive disability [1] .", "MS is considered to be the result o...	[ "Epstein-Barr virus ( EBV ) has been identified as a putative environmental trigger of multiple sclerosis ( MS ) , yet EBV's role in MS remains elusive .", "We utilized murine gamma herpesvirus 68 ( γHV-68 ) , the murine homolog to EBV , to examine how infection by a virus like EBV could enhance CNS autoimmunity ...	[ "Multiple sclerosis ( MS ) is a chronic inflammatory disease of the central nervous system ( CNS ) that leads to progressive disability .", "The causes of the disease are still unknown .", "Viral infections has been linked to MS development and Epstein-Barr virus has been shown to have a strong link to MS . Her...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "mutagenesis", "developmental biology", "genetic mutation", "molecular development", "gene expression", "genetics", "gene identification and analysis", "molecular genetics", "gene regulation", "biology", "molecular cell biology", "dna transcription", "gene function" ]	Polyethyleneimine Mediated DNA Transfection in Schistosome Parasites and Regulation of the WNT Signaling Pathway by a Dominant-Negative SmMef2	journal.pntd.0002332	null	[ [ "The use of transgenesis and other technological advances has had a powerful impact in the molecular characterization and functional analysis of gene function in model organisms [1] , [2] .", "However , like many parasitic worms , the natural characteristics of the schistosome ( its complex life cycle inv...	[ "Schistosomiasis is a serious global problem and the second most devastating parasitic disease following malaria .", "Parasitic worms of the genus Schistosoma are the causative agents of schistosomiasis and infect more than 240 million people worldwide .", "The paucity of molecular tools to manipulate schistoso...	[ "Schistosomiasis is a global disease infecting more than 240 million people worldwide and is ranked second only to malaria in global health importance .", "The causative agents of human schistosomiasis are parasitic worms that ingest red blood cells and can live for decades producing hundreds of eggs daily .", ...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "microbial metabolism", "genomics", "functional genomics", "metagenomics", "biology", "computational biology", "microbiology", "genetics and genomics" ]	Metabolic Reconstruction for Metagenomic Data and Its Application to the Human Microbiome	journal.pcbi.1002358	null	[ [ "Human-associated microbial communities interact directly with their hosts by means of metabolic products and immune modulation , and environmental communities are further responsible for a wide range of biochemical activities [1] .", "Metagenomic sequencing provides a culture-independent means of studyin...	[ "Microbial communities carry out the majority of the biochemical activity on the planet , and they play integral roles in processes including metabolism and immune homeostasis in the human microbiome .", "Shotgun sequencing of such communities' metagenomes provides information complementary to organismal abundanc...	[ "The human body is inhabited by trillions of bacteria and other microbes , which have recently been studied in many different habitats ( including gut , mouth , skin , and urogenital ) by the Human Microbiome Project ( HMP ) .", "These microbial communities were assayed using high-throughput DNA sequencing , but ...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "population modeling", "epidemiology", "infectious disease epidemiology", "disease dynamics", "population dynamics", "global health", "population biology", "infectious disease modeling", "biology", "infectious disease control", "computational biology" ]	Predicting the Impact of Vaccination on the Transmission Dynamics of Typhoid in South Asia: A Mathematical Modeling Study	journal.pntd.0002642	null	[ [ "Typhoid has a long and storied history as a public health scourge .", "Salmonella enterica serovar Typhi ( S . Typhi ) is a human-restricted bacterial pathogen transmitted via faecal contamination of food and water .", "While improvements in water and sanitation led to the elimination of typhoid from...	[ "Modeling of the transmission dynamics of typhoid allows for an evaluation of the potential direct and indirect effects of vaccination; however , relevant typhoid models rooted in data have rarely been deployed .", "We developed a parsimonious age-structured model describing the natural history and immunity to ty...	[ "We developed a mathematical model for the transmission dynamics of typhoid in order to evaluate the potential direct and indirect ( i . e . herd immunity ) effects of vaccination .", "The model was fit to data from Vellore , India and validated against the results of cluster randomized vaccine trials .", "We e...	2014
[ "Introduction", "Results and Discussion", "Conclusions", "Methods" ]	[ "invertebrates", "urea", "phytoplankton", "chemical compounds", "cell cycle and cell division", "plant cell biology", "cell processes", "chloroplasts", "animals", "organic compounds", "plant science", "mitochondria", "bioenergetics", "plants", "cellular structures and organelles", "gen...	Transcriptional Orchestration of the Global Cellular Response of a Model Pennate Diatom to Diel Light Cycling under Iron Limitation	journal.pgen.1006490	null	[ [ "Organisms in earth’s photic zone experience diurnal cycles that influence physiology , metabolism , and growth in different ways .", "Photosynthetic organisms are particularly affected by light cycles since they depend on energy acquired from light harvesting to drive the biosynthesis of macromolecules e...	[ "Environmental fluctuations affect distribution , growth and abundance of diatoms in nature , with iron ( Fe ) availability playing a central role .", "Studies on the response of diatoms to low Fe have either utilized continuous ( 24 hr ) illumination or sampled a single time of day , missing any temporal dynamic...	[ "Oceanic diatoms live in constantly fluctuating environments to which they must adapt in order to survive .", "During sunlit hours , photosynthesis occurs allowing diatoms to store energy used at night to sustain energy demands .", "Cellular and molecular mechanisms for regulation of phytoplankton growth are im...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "vegf signaling", "gene regulation", "regulatory proteins", "dna-binding proteins", "epithelial cells", "dna transcription", "transcription factors", "animal cells", "proteins", "gene expression", "biological tissue", "biochemistry", "signal transduction", ...	Population Heterogeneity in the Epithelial to Mesenchymal Transition Is Controlled by NFAT and Phosphorylated Sp1	journal.pcbi.1005251	null	[ [ "The epithelial to mesenchymal transition ( EMT ) is a broadly participating , evolutionarily conserved differentiation program essential for tissue morphogenesis , remodeling and pathological processes such as cancer [1] .", "During EMT polarized , tightly adhered epithelial cell monolayers are transform...	[ "Epithelial to mesenchymal transition ( EMT ) is an essential differentiation program during tissue morphogenesis and remodeling .", "EMT is induced by soluble transforming growth factor β ( TGF-β ) family members , and restricted by vascular endothelial growth factor family members .", "While many downstream m...	[ "Tissue formation and remodeling requires a complex and dynamic balance of interactions between epithelial cells , which reside on the surface , and mesenchymal cells that reside in the tissue interior .", "During embryonic development , wound healing , and cancer , epithelial cells transform into a mesenchymal c...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "signal processing", "biology", "genomics", "computational biology", "engineering" ]	A Self-Directed Method for Cell-Type Identification and Separation of Gene Expression Microarrays	journal.pcbi.1003189	null	[ [ "Gene-expression profiling of whole tissues is affected by the different cell types that exist in the tissue and their relative proportions .", "Thus , changes detected by differential expression analysis may reflect differences in the proportions of the cell-types between samples rather than an important...	[ "Gene expression analysis is generally performed on heterogeneous tissue samples consisting of multiple cell types .", "Current methods developed to separate heterogeneous gene expression rely on prior knowledge of the cell-type composition and/or signatures - these are not available in most public datasets .", ...	[ "Gene expression microarrays are widely used to uncover biological insights .", "Most microarray experiments profile whole tissues containing mixtures of multiple cell-types .", "As such , gene expression differences between samples may be due to different cellular compositions or biological differences , highl...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Function and Evolution of DNA Methylation in Nasonia vitripennis	journal.pgen.1003872	null	[ [ "DNA methylation is an important epigenetic modification found in many plants and animals [1]–[5] .", "In mammals , DNA methylation is associated with important epigenetic processes such as genomic imprinting [6] , histone modifications and X chromosome inactivation [7] , [8] , and plays an important role...	[ "The parasitoid wasp Nasonia vitripennis is an emerging genetic model for functional analysis of DNA methylation .", "Here , we characterize genome-wide methylation at a base-pair resolution , and compare these results to gene expression across five developmental stages and to methylation patterns reported in oth...	[ "Insects use methylation to modulate genome function in a different manner from vertebrates .", "Here , we quantified the global methylation profile in a parasitic wasp species , Nasonia vitripennis , a model with some advantages over ant and honeybee for functional and genetic analyses of methylation , such as s...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "cognitive neuroscience", "computational neuroscience", "biology", "neuroscience" ]	Measuring Granger Causality between Cortical Regions from Voxelwise fMRI BOLD Signals with LASSO	journal.pcbi.1002513	null	[ [ "The modern understanding of human cognition relies heavily on the concept of large-scale functional brain networks , and large-scale functional network analysis of Blood-Oxygenation-Level-Dependent ( BOLD ) signals from functional Magnetic Resonance Imaging ( fMRI ) is playing an increasingly important role ...	[ "Functional brain network studies using the Blood Oxygen-Level Dependent ( BOLD ) signal from functional Magnetic Resonance Imaging ( fMRI ) are becoming increasingly prevalent in research on the neural basis of human cognition .", "An important problem in functional brain network analysis is to understand direct...	[ "Modern cognitive neuroscience views cognition in terms of brain network function .", "A network is a physical system of nodes connected to each other by edges .", "From the network perspective , cognitive function depends on activity patterns involving the nodes and edges of functional brain networks .", "It...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine", "enzymes", "applied mathematics", "microbiology", "mathematical computing", "mathematics", "infectious diseases", "biology", "viral replication", "biochemistry", "virology", "viral diseases", "computational biology", "evolutionary biology" ]	HIV-1 Polymerase Inhibition by Nucleoside Analogs: Cellular- and Kinetic Parameters of Efficacy, Susceptibility and Resistance Selection	journal.pcbi.1002359	null	[ [ "Viral encoded polymerases perform essential enzymatic steps through amplification- or transformation of the viral genome during the viral life cycle [1] .", "As such , viral encoded polymerases constitute an attractive drug target for the treatment of many viral infections [2] .", "Nucleoside analogs...	[ "Nucleoside analogs ( NAs ) are used to treat numerous viral infections and cancer .", "They compete with endogenous nucleotides ( dNTP/NTP ) for incorporation into nascent DNA/RNA and inhibit replication by preventing subsequent primer extension .", "To date , an integrated mathematical model that could allow ...	[ "Nucleoside analogs ( NAs ) represent an important drug class for the treatment of viral infections and cancer .", "They inhibit DNA/RNA polymerization after being incorporated into nascent DNA/RNA , which prevents primer extension .", "Viruses are particularly versatile and frequently develop mutations enablin...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "immune physiology", "enzyme-linked immunoassays", "pathology and laboratory medicine", "pathogens", "vibrio", "immunology", "tropical diseases", "microbiology", "vaccines", "preventive medicine", "bacterial diseases", "vibrio cholerae", "neglected tropical ...	Antibody Secreting Cell Responses following Vaccination with Bivalent Oral Cholera Vaccine among Haitian Adults	journal.pntd.0004753	null	[ [ "Cholera , a diarrheal disease with epidemic potential caused by the bacterium Vibrio cholerae , remains a significant cause of morbidity and mortality , accounting for approximately 1 . 4 to 4 . 3 million cases of acute diarrhea and 28 , 000 to 142 , 000 deaths annually . [1]", "V . cholerae serogroup O1...	[ "The bivalent whole-cell ( BivWC ) oral cholera vaccine ( Shanchol ) is effective in preventing cholera .", "However , evaluations of immune responses following vaccination with BivWC have been limited .", "To determine whether BivWC induces significant mucosal immune responses , we measured V . cholerae O1 ant...	[ "The bivalent whole-cell ( BivWC ) oral cholera vaccine ( Shanchol ) is effective in preventing cholera .", "Despite its increasing use as part of comprehensive cholera prevention and control efforts , evaluations of immune responses following vaccination with BivWC have been limited .", "In this study , we mea...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "dengue virus", "medicine and health sciences", "genetic networks", "pathology and laboratory medicine", "pathogens", "protein interaction networks", "microbiology", "viruses", "rna viruses", "network analysis", "genome analysis", "research and analysis methods", "computer and information sc...	Unified feature association networks through integration of transcriptomic and proteomic data	journal.pcbi.1007241	null	[ [ "Over the last several decades , a number of multi-omic experimental methods have emerged to study host-pathogen interactions [1] and other complex biological systems .", "These studies focus on collecting a particular type of molecule from a biological system and using high throughput methods to query ab...	[ "High-throughput multi-omics studies and corresponding network analyses of multi-omic data have rapidly expanded their impact over the last 10 years .", "As biological features of different types ( e . g . transcripts , proteins , metabolites ) interact within cellular systems , the greatest amount of knowledge c...	[ "Inferring co-expression networks that combine multiple types of–omics data can lead to networks that are highly segregated with very few edges linking nodes of different–omics types .", "Here , we explored methods of improving integration in co-expression networks and found that a random forest approach , GENIE3...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Virulence Regulation with Venus Flytrap Domains: Structure and Function of the Periplasmic Moiety of the Sensor-Kinase BvgS	journal.ppat.1004700	null	[ [ "Two-component sensory transduction systems ( TCSs ) regulate various physiological processes in response to environmental changes [1] .", "They are abundant throughout the phylogenetic tree except for vertebrates and represent major bacterial signaling pathways [2 , 3] .", "TCSs notably regulate the ...	[ "Two-component systems ( TCS ) represent major signal-transduction pathways for adaptation to environmental conditions , and regulate many aspects of bacterial physiology .", "In the whooping cough agent Bordetella pertussis , the TCS BvgAS controls the virulence regulon , and is therefore critical for pathogenic...	[ "Bacteria make use of two-component transduction systems , composed of a sensor-kinase and a response regulator , to perceive environmental signals and orchestrate an appropriate response .", "The virulence regulon of the whooping cough agent Bordetella pertussis is controlled by the two-component system BvgAS ."...	2015
[ "Introduction", "Results", "Discussion", "Model" ]	[ "gene regulation", "regulatory proteins", "dna-binding proteins", "cell differentiation", "simulation and modeling", "developmental biology", "stem cells", "transcription factors", "research and analysis methods", "cell potency", "animal cells", "genetic interference", "proteins", "gene ex...	A conceptual and computational framework for modelling and understanding the non-equilibrium gene regulatory networks of mouse embryonic stem cells	journal.pcbi.1005713	null	[ [ "Our principal aim is to capture and integrate the results of multiple high-throughput experiments using a logical and transparent computational framework .", "This would allow us to model protein expression , particularly TF expression , across multiple layers of stem cell regulation .", "However , t...	[ "The capacity of pluripotent embryonic stem cells to differentiate into any cell type in the body makes them invaluable in the field of regenerative medicine .", "However , because of the complexity of both the core pluripotency network and the process of cell fate computation it is not yet possible to control th...	[ "Pluripotent stem cells possess the capacity both to renew themselves indefinitely and to differentiate to any cell type in the body .", "Thus the ability to direct stem cell differentiation would have immense potential in regenerative medicine .", "There is a massive amount of biological data relevant to stem ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "viral vaccines", "mammalogy", "viruses and cancer", "emerging viral diseases", "computational biology", "microbiology", "parasitology", "genome databases", "zoology", "veterinary science", "viral disease diagnosis", "sequence analysis", "emergence", "veterinary diseases", "veterinary ep...	The Extraordinary Evolutionary History of the Reticuloendotheliosis Viruses	journal.pbio.1001642	Reticuloendotheliosis viruses are mammalian retroviruses that were transmitted to avian hosts through inadvertent human intervention, and subsequently integrated their genetic material into the genomes of large DNA viruses, generating novel recombinant pathogens that now circulate naturally in poultry and wild birds.	[ [ "The reticuloendotheliosis viruses ( REVs ) comprise several closely related amphotropic retroviruses ( family Retroviridae ) isolated from birds [1] .", "The prototypic REV isolate was isolated from a turkey in 1957 [2] .", "Subsequently , REV infections have been reported in a diverse range of gameb...	[ "The reticuloendotheliosis viruses ( REVs ) comprise several closely related amphotropic retroviruses isolated from birds .", "These viruses exhibit several highly unusual characteristics that have not so far been adequately explained , including their extremely close relationship to mammalian retroviruses , and ...	[ "Retroviruses are characterized by their ability to insert a DNA copy of their genome into the chromosomes of infected cells .", "Occasionally , retroviruses insert into “germline” cells and are subsequently inherited as host alleles called endogenous retroviruses ( ERVs ) .", "Vertebrate genomes contain thousa...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "nutrition", "neuroscience", "developmental biology/aging" ]	Carbon Dioxide Sensing Modulates Lifespan and Physiology in Drosophila	journal.pbio.1000356	Loss of an olfactory receptor that senses carbon dioxide increases longevity and fecundity and alters overall physiology in fruit flies.	[ [ "The sensory neurons that constitute perceptual systems trigger countless decisions on a daily basis .", "By providing a viewport to the world , neurosensory systems help individuals to assess the current and future states of their surroundings and to enact appropriate responses .", "Whether to consum...	[ "For nearly all life forms , perceptual systems provide access to a host of environmental cues , including the availability of food and mates as well as the presence of disease and predators .", "Presumably , individuals use this information to assess the current and future states of the environment and to enact ...	[ "Sensory inputs , including taste and smell , can modulate lifespan in organisms such as fruit flies and nematodes .", "For example , the smell of live yeast is sufficient to accelerate aging in fruit flies that are nutrient restricted .", "However , the sensory pathways and specific olfactory cues that modulat...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Cross-Modulation of Homeostatic Responses to Temperature, Oxygen and Carbon Dioxide in C. elegans	journal.pgen.1004011	null	[ [ "To maintain a constant internal milieu animals use internal sensory receptors to monitor cues such as CO2/pH [1] , O2 [2] , temperature [3] , and osmolality [4] .", "These interoceptors counter changes in internal milieu by coordinating homeostatic responses that alter physiology and behavior [5] .", ...	[ "Different interoceptive systems must be integrated to ensure that multiple homeostatic insults evoke appropriate behavioral and physiological responses .", "Little is known about how this is achieved .", "Using C . elegans , we dissect cross-modulation between systems that monitor temperature , O2 and CO2 .", ...	[ "Many animals are either attracted or repelled by carbon dioxide .", "We show that the way C . elegans responds to CO2 depends on the temperature it has acclimated to and the oxygen tensions it is experiencing .", "The effects of acclimation temperature are mediated by a temperature-sensing neuron called AFD th...	2013
[ "Introduction", "Results", "Discussion", "Model" ]	[ "computational biology/evolutionary modeling", "computational biology/transcriptional regulation" ]	Evolution of Evolvability in Gene Regulatory Networks	journal.pcbi.1000112	null	[ [ "Gene regulatory networks ( GRNs ) have become a successful tool for understanding the organization within cells and their dynamics .", "In GRNs information from the cell state and the outside environment is translated into a correctly timed expression of genes .", "As such , one may argue that GRNs a...	[ "Gene regulatory networks are perhaps the most important organizational level in the cell where signals from the cell state and the outside environment are integrated in terms of activation and inhibition of genes .", "For the last decade , the study of such networks has been fueled by large-scale experiments and...	[ "A cell receives signals both from its internal and external environment and responds by changing the expression of genes .", "In this manner the cell adjusts to heat , osmotic pressures and other circumstances during its lifetime .", "Over long timescales , the network of interacting genes and its regulatory a...	2008
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "cell motility", "innate immune system", "medicine and health sciences", "immune physiology", "cytokines", "pathology and laboratory medicine", "immune cells", "pathogens", "immunology", "microbiology", "orthomyxoviruses", "viruses", "physiological processes", "development...	Pulmonary influenza A virus infection leads to suppression of the innate immune response to dermal injury	journal.ppat.1007212	null	[ [ "The immune system plays roles in multiple processes in the body including the response to infection , tissue repair , development , cancer immunosurveillance , and maintenance of homeostasis [1–4] .", "Dysregulation of these processes can lead to a disease state [5–8] .", "Most studies of the immune ...	[ "The innate immune system is responsible for many important functions in the body including responding to infection , clearing cancerous cells , healing wounds , and removing foreign substances .", "Although many of these functions happen simultaneously in life , most laboratory studies of the innate immune respo...	[ "In a natural setting , the innate immune system is frequently faced with multiple insults , against which it must mount overlapping inflammatory responses .", "We are interested in how the innate immune system deals with multiple , simultaneously occurring inflammatory insults , and if the response to one will t...	2018
[ "Introduction", "Results", "Discussion" ]	[ "chemical characterization", "crystal structure", "chemical compounds", "condensed matter physics", "organic compounds", "simulation and modeling", "protein structure", "crystallography", "thermodynamics", "research and analysis methods", "solid state physics", "proteins", "chemistry", "bi...	Atomic resolution mechanism of ligand binding to a solvent inaccessible cavity in T4 lysozyme	journal.pcbi.1006180	null	[ [ "Measurements of affinities of small molecules to specific binding sites in proteins have become routine , especially in the context of drug discovery studies where such experiments are often among the first to be performed .", "These thermodynamic measurements are routinely supplemented by kinetic studie...	[ "Ligand binding sites in proteins are often localized to deeply buried cavities , inaccessible to bulk solvent .", "Yet , in many cases binding of cognate ligands occurs rapidly .", "An intriguing system is presented by the L99A cavity mutant of T4 Lysozyme ( T4L L99A ) that rapidly binds benzene ( ~106 M-1s-1 ...	[ "Proteins often bind ligands in buried cavities that appear to be inaccessible based on static structures .", "The mechanisms and pathways by which ligands reach their binding sites in such cases are , thus , often unknown .", "Yet , ligand recognition by occluded cavities can happen rapidly .", "A central qu...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/histone modification", "molecular biology/transcription initiation and activation", "genetics and genomics/gene expression", "genetics and genomics/epigenetics", "molecular biology/translational regulation", "molecular biology/chromatin structure" ]	Two Chromatin Remodeling Activities Cooperate during Activation of Hormone Responsive Promoters	journal.pgen.1000567	null	[ [ "Regulation of eukaryotic gene expression implies mechanisms that permit transcription factors to gain access to chromatin packaged DNA sequences .", "The basic unit of chromatin , the nucleosome , consists of an octamer formed of two copies of each of the four core histones ( H2A , H2B , H3 , and H4 ) ar...	[ "Steroid hormones regulate gene expression by interaction of their receptors with hormone responsive elements ( HREs ) and recruitment of kinases , chromatin remodeling complexes , and coregulators to their target promoters .", "Here we show that in breast cancer cells the BAF , but not the closely related PBAF c...	[ "In order to adapt its gene expression program to the needs of the environment , the cell must access the information stored in the DNA sequence that is tightly packaged into chromatin in the cell nucleus .", "How the cell manages to do it in a selective maner is still unclear .", "Here we show that , in breast...	2009
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "bioengineering", "systems biology", "biomedical engineering", "biological systems engineering", "biology", "computational biology", "engineering" ]	Mathematical Modeling of the Phoenix Rising Pathway	journal.pcbi.1003461	null	[ [ "Apoptosis , or programmed cell death , is an important and tightly controlled process in mammalian cells [1] .", "However , not all cells in the same population undergo apoptosis when exposed to identical death signals [2] , [3] .", "This “fractional killing” phenomenon is problematic in cancer treat...	[ "Apoptosis is a tightly controlled process in mammalian cells .", "It is important for embryogenesis , tissue homoeostasis , and cancer treatment .", "Apoptosis not only induces cell death , but also leads to the release of signals that promote rapid proliferation of surrounding cells through the Phoenix Rising...	[ "Apoptosis , or programmed cell death , is known to be important for embryogenesis , tissue homoeostasis , and cancer treatment .", "Furthermore , researchers have recently observed that apoptosis may promote wound healing and tissue regeneration , and accelerate undesired solid tumor regrowth after chemotherapy/...	2014
[ "Introduction", "Results", "Discussion" ]	[]	Model of Fission Yeast Cell Shape Driven by Membrane-Bound Growth Factors and the Cytoskeleton	journal.pcbi.1003287	null	[ [ "Many cells such as fungal hyphae , pollen tubes and some bacteria grow from their tips by remodeling their cell wall [1]–[3] .", "Fission yeast ( S . pombe ) also grow this way and , as a well-studied model organism , are good for understanding tip growth and , more generally , the mechanisms of acquisit...	[ "Fission yeast serves as a model for how cellular polarization machinery consisting of signaling molecules and the actin and microtubule cytoskeleton regulates cell shape .", "In this work , we develop mathematical models to investigate how these cells maintain a tubular shape of approximately constant diameter ....	[ "Fission yeast is a rod-shaped organism that is studied , in part , as a model for how cells develop and regulate their shape .", "Despite extensive work identifying effects of genetic mutations and pharmacological treatments on the shape of these cells , there is a lack of mathematical and computational models e...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "phosphorylation", "innate immune system", "medicine and health sciences", "immune physiology", "cytokines", "cancer treatment", "immunology", "dna transcription", "simulation and modeling", "oncology", "developmental biology", "molecular development", "bioassays and physiological analysis",...	Quantitative analysis reveals crosstalk mechanisms of heat shock-induced attenuation of NF-κB signaling at the single cell level	journal.pcbi.1006130	null	[ [ "Cells have developed complex mechanisms to counteract environmental stresses such as toxins , free radicals , and extreme temperatures [1] .", "These involve specific stress response pathways , which control genes and proteins responsible for survival and adaptation but also alter the regulation of other...	[ "Elevated temperature induces the heat shock ( HS ) response , which modulates cell proliferation , apoptosis , the immune and inflammatory responses .", "However , specific mechanisms linking the HS response pathways to major cellular signaling systems are not fully understood .", "Here we used integrated comp...	[ "Hyperthermia has been considered a promising strategy to sensitize cancer cells to treatment .", "As such , it might potentially increase treatment efficacy while reducing negative side effects .", "So far , this potential has not been fully realized .", "One of the major obstacles is a lack of quantitative ...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "phosphorylation", "cell physiology", "meiosis", "rna interference", "gene regulation", "cell cycle and cell division", "cell processes", "dna-binding proteins", "invertebrate genomics", "germ cells", "epigenetics", "small interfering rnas", "animal cells", "genetic interference", "chrom...	The meiotic phosphatase GSP-2/PP1 promotes germline immortality and small RNA-mediated genome silencing	journal.pgen.1008004	null	[ [ "Animals , including humans , are comprised of two broad cell types: somatic cells and germ cells .", "Somatic cells consist of many diverse differentiated cell types , while germ cells are specialized to produce the next generation of offspring .", "An important difference between these two cell type...	[ "Germ cell immortality , or transgenerational maintenance of the germ line , could be promoted by mechanisms that could occur in either mitotic or meiotic germ cells .", "Here we report for the first time that the GSP-2 PP1/Glc7 phosphatase promotes germ cell immortality .", "Small RNA-induced genome silencing ...	[ "The germ line of an organism is considered immortal in its capacity to give rise to an unlimited number of future generations .", "To protect the integrity of the germ line , mechanisms act to suppress the accumulation of transgenerational damage to the genome or epigenome .", "Loss of germ cell immortality ca...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Proteasomes, Sir2, and Hxk2 Form an Interconnected Aging Network That Impinges on the AMPK/Snf1-Regulated Transcriptional Repressor Mig1	journal.pgen.1004968	null	[ [ "Many genetic and pharmacological interventions that affect lifespan in model organisms modulate the respiratory capacity of the mitochondria and change the metabolic status of cells .", "The conserved pro-longevity effects of caloric restriction ( CR ) have been related to optimal mitochondrial function ...	[ "Elevated proteasome activity extends lifespan in model organisms such as yeast , worms and flies .", "This pro-longevity effect might be mediated by improved protein homeostasis , as this protease is an integral module of the protein homeostasis network .", "Proteasomes also regulate cellular processes through...	[ "Advanced cellular age is associated with decreased efficiency of the proteostasis network .", "The proteasome , a protease in the cytoplasm and nuclei of eukaryotic cells , is an important component of this network .", "Recent studies demonstrate that increased proteasome capacity has a positive impact on long...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "crystal structure", "molecular dynamics", "condensed matter physics", "simulation and modeling", "multivariate analysis", "mathematics", "statistics (mathematics)", "crystallography", "research and analysis methods", "lipids", "solid state physics", "mathematical and statistical techniques", ...	A direct interaction of cholesterol with the dopamine transporter prevents its out-to-inward transition	journal.pcbi.1005907	null	[ [ "Monoamine transporters ( MATs ) [1] encompass the dopamine ( DAT ) , serotonin ( SERT ) , and norepinephrine ( NET ) transporters and belong to the solute carrier 6 ( SLC6 ) gene family [2] .", "MATs transport their respective neurotransmitters from the synaptic cleft back into the presynaptic neurons th...	[ "Monoamine transporters ( MATs ) carry out neurotransmitter reuptake from the synaptic cleft , a key step in neurotransmission , which is targeted in the treatment of neurological disorders .", "Cholesterol ( CHOL ) , a major component of the synaptic plasma membrane , has been shown to exhibit a modulatory effec...	[ "It has been revealed that the cellular membrane is an active contributor to biological processes occurring in and across it and can regulate the function of proteins embedded within it .", "Cholesterol ( CHOL ) plays a key role in these effects .", "Notably , CHOL affects neurotransmission .", "Neurotransmis...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[]	Distinct roles of two myosins in C. elegans spermatid differentiation	journal.pbio.3000211	Haploid spermatids segregate unwanted cellular contents into residual bodies before detaching. A study in the nematode Caenorhabditis elegans shows that residual body formation and cytoplasm segregation are executed by the coordinated activity of myosin II and myosin VI, and spermatids are detached via myosin VI-mediat...	[ [ "Spermatogenesis is a conserved multistep process that involves mitotic proliferation of spermatogonia , meiotic division of spermatocytes , and differentiation of haploid spermatids into mature spermatozoa .", "In C . elegans , spermatogenesis occurs in both males and hermaphrodites .", "Upon enterin...	[ "During spermatogenesis , interconnected haploid spermatids segregate undesired cellular contents into residual bodies ( RBs ) before detaching from RBs .", "It is unclear how this differentiation process is controlled to produce individual spermatids or motile spermatozoa .", "Here , we developed a live imagin...	[ "Spermatogenesis is a conserved multistep process that involves mitotic proliferation of spermatogonia , meiotic division of spermatocytes , and differentiation of haploid spermatids into mature spermatozoa .", "During spermatid differentiation , spermatids shed unwanted cellular contents in the form of a residua...	2019
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "body fluids", "tropical diseases", "vertebrates", "parasitic diseases", "dogs", "parasitic protozoans", "animals", "mammals", "protozoans", "leishmania", "neglected tropical diseases", "cellular structures and organelles", "research and analysis methods", ...	Potential animal reservoirs (dogs and bats) of human visceral leishmaniasis due to Leishmania infantum in French Guiana	journal.pntd.0007456	null	[ [ "Leishmaniasis are among of the ‘‘most neglected diseases”[1] from the group of vector-borne diseases .", "Leishmaniasis are caused by parasites belonging to the genus Leishmania ( Trypanosomatida: Trypanosomatidae ) with a worldwide distribution in large areas of the tropics , subtropics and Mediterranea...	[ "In French Guiana , cutaneous leishmaniasis is highly endemic , whereas no autochthonous case of visceral leishmaniasis have been reported so far .", "However , due to its proximity to Brazil which is highly endemic for visceral leishmaniasis , and the high transboundary population flow , an epidemiological chall...	[ "Leishmaniasis is endemic in French Guiana under its cutaneous form where Leishmania guyanensis is the principle parasite species .", "Visceral leishmaniasis is much more severe , although well known in neighbouring countries ( Brazil , Suriname , Venezuela ) , it has not been known in French Guiana until now .",...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "immunology", "microbiology", "mathematical models", "retroviruses", "viruses", "preventive medicine", "immunodeficiency viruses", "rna viruses", "sexually transmitted diseases", "network analysis", "infectio...	Cost-efficient vaccination protocols for network epidemiology	journal.pcbi.1005696	null	[ [ "Infectious disease is a major burden to global health .", "Infections spread from person to person over human contact networks .", "The propagation speed is an emergent property of both the pathogenesis in the infected individual and the contacts between people .", "By understanding the contact n...	[ "We investigate methods to vaccinate contact networks—i . e . removing nodes in such a way that disease spreading is hindered as much as possible—with respect to their cost-efficiency .", "Any real implementation of such protocols would come with costs related both to the vaccination itself , and gathering of inf...	[ "Finding methods to identify important spreaders—and consequently protocols to identify individuals to vaccinate in targeted vaccination campaigns—is one of the most important topics of network theory .", "Earlier studies typically make some assumption about what information is available about the contact network...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "keratinocytes", "medicine and health sciences", "dysplasia", "pathology and laboratory medicine", "cell differentiation", "epithelial cells", "developmental biology", "signs and symptoms", "stem cells", "infectious disease control", "basal cells", "research and analysis methods", "specimen ...	SOX2 and PI3K Cooperate to Induce and Stabilize a Squamous-Committed Stem Cell Injury State during Lung Squamous Cell Carcinoma Pathogenesis	journal.pbio.1002581	A study of tracheobronchial basal cells reveals a mechanism by which lung squamous cell carcinoma is almost universally initiated by exploitation of a stem cell injury response involving SOX2 and PI3K.	[ [ "It has been suggested that most cancers arise from normal stem cells [1 , 2] .", "Mounting evidence supports this being the case for certain leukemias , in which stem cell/progenitor-specific mechanisms are emerging that involve blocks in differentiation and enhanced self-renewal [3 , 4] .", "However...	[ "Although cancers are considered stem cell diseases , mechanisms involving stem cell alterations are poorly understood .", "Squamous cell carcinoma ( SQCC ) is the second most common lung cancer , and its pathogenesis appears to hinge on changes in the stem cell behavior of basal cells in the bronchial airways ."...	[ "Squamous cell carcinoma ( SQCC ) is a deadly and common form of lung cancer .", "How it develops from stem cells is poorly understood .", "SQCCs predominantly arise in bronchial epithelia , likely from basal cells , stem cells that normally generate mucinous and ciliated cells .", "Smoking , however , causes...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Loss of a Conserved tRNA Anticodon Modification Perturbs Plant Immunity	journal.pgen.1005586	null	[ [ "Transfer RNA ( tRNA ) is a noncoding RNA responsible for the accurate addition of an amino acid to the 3´ end of a translating protein , and therefore functions as an adapter molecule responsible for decoding mRNA into the corresponding peptide sequence .", "tRNA molecules are 75–78 nucleotides long with...	[ "tRNA is the most highly modified class of RNA species , and modifications are found in tRNAs from all organisms that have been examined .", "Despite their vastly different chemical structures and their presence in different tRNAs , occurring in different locations in tRNA , the biosynthetic pathways of the major...	[ "Numerous studies revealed the existence of nearly 110 ribonucleoside structures incorporated as post-transcriptional modifications in tRNA , with 25–30 modifications present in any one organism .", "Emerging evidence points to the critical role of tRNA modifications in various cellular responses to stimuli , inc...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	The Fanconi Anemia Pathway Protects Genome Integrity from R-loops	journal.pgen.1005674	null	[ [ "Genome instability is a cell pathology in which chromosomes undergo alterations in the form of DNA breaks , mutations , rearrangements and loss at a high rate .", "In many cases , the mechanism responsible for genome instability implies a DNA replication failure .", "For this reason , genome instabil...	[ "Co-transcriptional RNA-DNA hybrids ( R loops ) cause genome instability .", "To prevent harmful R loop accumulation , cells have evolved specific eukaryotic factors , one being the BRCA2 double-strand break repair protein .", "As BRCA2 also protects stalled replication forks and is the FANCD1 member of the Fan...	[ "R loops are co-transcriptional RNA-DNA hybrids that can have a physiological role in transcription and replication , but also may be a major threat to genome stability .", "To avoid the deleterious effects of R loops , specific factors prevent their formation or facilitate their removal .", "The double-strand ...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Inhibiting the Recruitment of PLCγ1 to Kaposi’s Sarcoma Herpesvirus K15 Protein Reduces the Invasiveness and Angiogenesis of Infected Endothelial Cells	journal.ppat.1005105	null	[ [ "Kaposi’s Sarcoma Herpesvirus ( KSHV ) , also known as human herpesvirus 8 ( HHV-8 ) , was first identified in Kaposi’s sarcoma ( KS ) tissues by representational difference analysis [1 , 2] .", "Found to be the etiological agent of KS , the virus was successively linked also to primary effusion lymphoma ...	[ "Kaposi’s sarcoma ( KS ) , caused by Kaposi’s sarcoma herpesvirus ( KSHV ) , is a highly vascularised tumour of endothelial origin .", "KSHV infected endothelial cells show increased invasiveness and angiogenesis .", "Here , we report that the KSHV K15 protein , which we showed previously to contribute to KSHV-...	[ "Kaposi’s Sarcoma ( KS ) , etiologically linked to Kaposi’s sarcoma herpesvirus ( KSHV ) , is a tumour of endothelial origin characterised by angiogenesis and invasiveness .", "In vitro , KSHV infected endothelial cells display an increased invasiveness and high angiogenicity .", "Here we report that the KSHV p...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "macroevolution", "phylogenetic analysis", "molecular biology", "evolutionary processes", "mathematical and statistical techniques", "evolutionary modeling", "bayesian method", "biology and life sciences", "molecular biology techniques", "epigenomics", "evolutionary biology", "computational bi...	Bayesian Inference of Sampled Ancestor Trees for Epidemiology and Fossil Calibration	journal.pcbi.1003919	null	[ [ "Phylogenetic analysis uses molecular sequence data to infer evolutionary relationships between organisms and to infer evolutionary parameters .", "Since the introduction of Bayesian inference in phylogenetics [1]–[3] , it has become the standard approach for fully probabilistic inference of evolutionary ...	[ "Phylogenetic analyses which include fossils or molecular sequences that are sampled through time require models that allow one sample to be a direct ancestor of another sample .", "As previously available phylogenetic inference tools assume that all samples are tips , they do not allow for this possibility .", ...	[ "A central goal of phylogenetic analysis is to estimate evolutionary relationships and the dynamical parameters underlying the evolutionary branching process ( e . g . macroevolutionary or epidemiological parameters ) from molecular data .", "The statistical methods used in these analyses require that the underly...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Signature Patterns of MHC Diversity in Three Gombe Communities of Wild Chimpanzees Reflect Fitness in Reproduction and Immune Defense against SIVcpz	journal.pbio.1002144	Wild chimpanzee populations maintain a diversity of major histocompatibility class I variants; one variant, enriched among chimpanzees infected with simian immunodeficiency virus, resembles the human variant that best impedes progression of HIV-1 infection.	[ [ "In vertebrate genomes , the major histocompatibility complex ( MHC ) is a region enriched with genes of the immune system .", "Defining the unique character of the MHC is the extreme polymorphism of the genes encoding the classical MHC class I and II molecules [1] .", "These cell-surface glycoprotein...	[ "Major histocompatibility complex ( MHC ) class I molecules determine immune responses to viral infections .", "These polymorphic cell-surface glycoproteins bind peptide antigens , forming ligands for cytotoxic T and natural killer cell receptors .", "Under pressure from rapidly evolving viruses , hominoid MHC ...	[ "Polymorphic major histocompatibility complex ( MHC ) class I molecules activate immune responses against infection and correlate with susceptibilities to disease .", "In humans , longitudinal study of how disease epidemics alter MHC frequencies has not been possible .", "We studied chimpanzees , a species havi...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "blood cells", "cell binding", "cell physiology", "innate immune system", "medicine and health sciences", "immune cells", "immune physiology", "cytokines", "chemical compounds", "sialic acids", "immunology", "cell processes", "microbiology", "carbohydrates", "parasitic diseases", "orga...	Leishmania donovani Utilize Sialic Acids for Binding and Phagocytosis in the Macrophages through Selective Utilization of Siglecs and Impair the Innate Immune Arm	journal.pntd.0004904	null	[ [ "Visceral leishmaniasis ( VL ) caused by the species Leishmania donovani , is the most severe form of leishmaniasis and is endemic in the region of Indian subcontinent .", "Due to its digenic nature , parasites multiply as an amastigote form within the phagolysosome of macrophages in the liver and spleen ...	[ "Leishmania donovani , belonging to a unicellular protozoan parasite , display the differential level of linkage-specific sialic acids on their surface .", "Sialic acids binding immunoglobulin-like lectins ( siglecs ) are a class of membrane-bound receptors present in the haematopoetic cell lineages interact with...	[ "Sialic acids are nine carbon sugars present on terminal cell surface glycoproteins and glycolipids .", "Siglec is a membrane receptor that belongs to an immunoglobulin super family present in almost all the haematopoetic cell lineages .", "There are 14 different types of siglecs present on human immune cells t...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "breast tumors", "cancer treatment", "carcinomas", "cancers and neoplasms", "oncology", "protein expression", "adenocarcinomas", "molecular biology techniques", "secondary lung tumors", "research and analysis methods", "lung and intrathoracic tumors", "gene ex...	Molecular characterization of breast and lung tumors by integration of multiple data types with functional sparse-factor analysis	journal.pcbi.1006520	null	[ [ "Cancer is a heterogeneous disease , both at the molecular level and in response to treatment .", "If we can better understand the variation between tumors , we may get a better understanding of why tumors respond differently to treatment .", "This could , in turn , lead to better treatment selection ...	[ "Effective cancer treatment is crucially dependent on the identification of the biological processes that drive a tumor .", "However , multiple processes may be active simultaneously in a tumor .", "Clustering is inherently unsuitable to this task as it assigns a tumor to a single cluster .", "In addition , t...	[ "In order to select effective cancer treatment , we need to determine which biological processes are active in a tumor .", "To this end , tumors have been quantified by high dimensional molecular measurements such as RNA sequencing and DNA copy number profiling .", "In order to support decision making , these m...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell death", "autophagic cell death", "vesicles", "molecular dynamics", "built structures", "engineering and technology", "cell processes", "membrane fusion", "membrane structures", "vesicle fusion", "cellular structures and organelles", "thermodynamics", "research and analysis methods", ...	Scaffolding the cup-shaped double membrane in autophagy	journal.pcbi.1005817	null	[ [ "Autophagy , a physiological process used by eukaryotic cells to degrade cytoplasmic materials , is initiated under stress conditions such as nutrient starvation [1–4] .", "Among other processes , autophagy is associated with cancer , cellular aging , the immune system , and infection [5–9] .", "Macro...	[ "Autophagy is a physiological process for the recycling and degradation of cellular materials .", "Forming the autophagosome from the phagophore , a cup-shaped double-membrane vesicle , is a critical step in autophagy .", "The origin of the cup shape of the phagophore is poorly understood .", "In yeast , fusi...	[ "Cells use autophagy to recycle and degrade a wide range of materials , from individual molecules to entire organelles .", "We perform simulations to study a key step in the initial stages of the autophagy pathway: how the membrane adopts the characteristic cup shape of the phagophore that then engulfs its target...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "plant biology/plant-environment interactions", "plant biology/plant genetics and gene expression", "plant biology" ]	A Systems Approach Uncovers Restrictions for Signal Interactions Regulating Genome-wide Responses to Nutritional Cues in Arabidopsis	journal.pcbi.1000326	null	[ [ "Living organisms need to integrate both internal and external signal information in order to program the appropriate responses for survival .", "Signaling pathways that respond to single nutrient or hormonal signals are on the way to being resolved [1] , [2] , [3] , [4] , [5] , [6] , [7] , [8] .", "H...	[ "As sessile organisms , plants must cope with multiple and combined variations of signals in their environment .", "However , very few reports have studied the genome-wide effects of systematic signal combinations on gene expression .", "Here , we evaluate a high level of signal integration , by modeling genome...	[ "Light ( L ) , nitrogen ( N ) , and carbon ( C ) are well known to be strong signals regulating gene expression in plants .", "But , so far , few reports have described their interactions on a genome scale .", "Here , we report the transcriptome response of the factorial combination of these three signals in le...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics and genomics/gene function", "plant biology/plant genetics and gene expression", "genetics and genomics/plant genomes and evolution", "plant biology/plant-environment interactions" ]	Evolution of Stress-Regulated Gene Expression in Duplicate Genes of Arabidopsis thaliana	journal.pgen.1000581	null	[ [ "The ability to sense and respond properly to environmental stresses , such as cold , draught , wounding and biotic interactions , is central to the survival of all living organisms .", "The selection pressures imposed by these stresses and sedate nature of plant life histories have likely led to the evol...	[ "Due to the selection pressure imposed by highly variable environmental conditions , stress sensing and regulatory response mechanisms in plants are expected to evolve rapidly .", "One potential source of innovation in plant stress response mechanisms is gene duplication .", "In this study , we examined the evo...	[ "Plants have developed a multitude of response mechanisms to survive stressful environments .", "Since the environment is highly variable , these stress response mechanisms are expected to undergo frequent innovation .", "Duplicate genes represent a potential source for such innovation .", "In this paper , we...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/histone modification", "genetics and genomics/gene expression", "molecular biology/centromeres", "genetics and genomics/epigenetics", "chemical biology/protein chemistry and proteomics", "molecular biology/chromatin structure" ]	The Schizosaccharomyces pombe JmjC-Protein, Msc1, Prevents H2A.Z Localization in Centromeric and Subtelomeric Chromatin Domains	journal.pgen.1000726	null	[ [ "Chromatin is based on a repetitive structural unit called the nucleosome .", "However the regulatory properties of chromatin are mediated by the differences between nucleosomes , due to post-translational modifications or presence of histone variants .", "Cytologically , chromatin was initially divid...	[ "Eukaryotic genomes are repetitively packaged into chromatin by nucleosomes , however they are regulated by the differences between nucleosomes , which establish various chromatin states .", "Local chromatin cues direct the inheritance and propagation of chromatin status via self-reinforcing epigenetic mechanisms...	[ "Chromatin is based on a repetitive structural unit called the nucleosome .", "However , the regulatory properties of chromatin are mediated by the differences between nucleosomes , due to post-translational modifications or the inclusion of histone variants .", "These differences are maintained by inheritance ...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "blood cells", "medicine and health sciences", "immune cells", "maternal health", "cd coreceptors", "obstetrics and gynecology", "cell cycle and cell division", "immunology", "cell processes", "parasitic diseases", "parasitic protozoans", "protozoans", "women's health", "pregnancy", "cyt...	Expression of inhibitory receptors and polyfunctional responses of T cells are linked to the risk of congenital transmission of T. cruzi	journal.pntd.0005627	null	[ [ "Chagas disease , which is caused by the protozoan Trypanosoma cruzi , is a tropical parasitic disease that affects approximately 10 million people worldwide .", "The disease is primarily transmitted by contact with the infected feces of triatomine bugs [1] .", "This parasite can also be transmitted b...	[ "Congenital T . cruzi infections involve multiple factors in which complex interactions between the parasite and the immune system of pregnant women play important roles .", "In this study , we used an experimental murine model of chronic infection with T . cruzi to evaluate the changes in the expression of inhib...	[ "Chagas disease or American trypanosomiasis is a complex parasitic disease caused by the protozoan Trypanosoma cruzi .", "This disease that affects approximately 10 million people worldwide may be mother-to-child transmitted which is an important public health problem with great relevance in endemic and non-endem...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "microbiology/innate immunity", "microbiology/parasitology" ]	Plasmodium-Induced Inflammation by Uric Acid	journal.ppat.1000013	null	[ [ "There are over 500 million clinical malaria cases and at least one million deaths annually [1] .", "The pathophysiological consequences of malaria are caused by the asexual blood stage of the Plasmodium parasite .", "The rupture of infected erythrocytes triggers an inflammatory response , which is in...	[ "Infection of erythrocytes with the Plasmodium parasite causes the pathologies associated with malaria , which result in at least one million deaths annually .", "The rupture of infected erythrocytes triggers an inflammatory response , which is induced by parasite-derived factors that still are not fully characte...	[ "Malaria , a disease that results in more than one million deaths per year , is caused by infection with the Plasmodium parasite .", "Plasmodium infects erythrocytes inducing an acute inflammatory response with high fevers and elevated levels of pro-inflammatory cytokines , which contribute to the pathology of th...	2008
[ "Introduction", "Model and Methods", "Results", "Discussion" ]	[ "medicine", "mathematics", "biology" ]	Challenges in Estimating Insecticide Selection Pressures from Mosquito Field Data	journal.pntd.0001387	null	[ [ "Mosquito-borne diseases are prevalent in the tropics and subtropics and constitute a large proportion of the health problems in developing countries .", "The major mosquito vectors occur in the genera Culex , Aedes , and Anopheles , which transmit Filaria spp , Japanese encephalitis , dengue and yellow f...	[ "Insecticide resistance has the potential to compromise the enormous effort put into the control of dengue and malaria vector populations .", "It is therefore important to quantify the amount of selection acting on resistance alleles , their contributions to fitness in heterozygotes ( dominance ) and their initia...	[ "The emergence and spread of insecticide resistance compromise the control of mosquito borne diseases such as dengue or malaria , which are responsible for millions of deaths every year in tropical and subtropical areas .", "There are currently no easily implemented methodologies to quantify the strength of selec...	2011
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "mosquitoes", "zoology", "entomology", "viral transmission and infection", "vector biology", "virology", "genetics", "host-pathogen interaction", "microbiology", "biology", "viral vectors", "viral replication", "gene function" ]	Deletion of the NSm Virulence Gene of Rift Valley Fever Virus Inhibits Virus Replication in and Dissemination from the Midgut of Aedes aegypti Mosquitoes	journal.pntd.0002670	null	[ [ "Rift Valley fever virus ( RVFV ) ( family Bunyaviridae , genus Phlebovirus ) is a zoonotic , mosquito-borne virus endemic to Africa .", "Human illness is typically febrile , but 1–2% of cases develop more severe disease including hepatitis , encephalitis , retinitis , vision loss , jaundice , severe anem...	[ "Previously , we investigated the role of the Rift Valley fever virus ( RVFV ) virulence genes NSs and NSm in mosquitoes and demonstrated that deletion of NSm significantly reduced the infection , dissemination , and transmission rates of RVFV in Aedes aegypti mosquitoes .", "The specific aim of this study was to...	[ "Rift Valley fever virus ( RVFV ) is a mosquito-borne virus endemic to Africa .", "Outbreaks of RVFV have resulted in devastating morbidity and mortality in livestock and humans .", "A novel RVFV vaccine strain has been developed in which two virulence genes , NSs and NSm , have been deleted from the RVFV genom...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal models", "biochemistry", "rna", "model organisms", "rna transport", "rna processing", "cell biology", "nucleic acids", "gene expression", "genetics", "gene regulation", "biology and life sciences", "molecular genetics", "mouse models", "molecular cell biology", "genetics of dis...	TBX3 Regulates Splicing In Vivo: A Novel Molecular Mechanism for Ulnar-Mammary Syndrome	journal.pgen.1004247	null	[ [ "TBX3 belongs to the T-box family of transcription factors .", "The crucial roles of TBX3 in development are evident in the fact that heterozygous mutations of TBX3 cause Ulnar–mammary syndrome in humans ( UMS ) .", "This syndrome includes limb malformations , apocrine and mammary gland hypoplasia , d...	[ "TBX3 is a member of the T-box family of transcription factors with critical roles in development , oncogenesis , cell fate , and tissue homeostasis .", "TBX3 mutations in humans cause complex congenital malformations and Ulnar-mammary syndrome .", "Previous investigations into TBX3 function focused on its acti...	[ "TBX3 is a protein with essential roles in development and tissue homeostasis , and is implicated in cancer pathogenesis .", "TBX3 mutations in humans cause a complex of birth defects called Ulnar-mammary syndrome ( UMS ) .", "Despite the importance of TBX3 and decades of investigation , few TBX3 partner protei...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "computer science", "computer modeling", "theoretical biology", "biology", "computerized simulations" ]	Smart Swarms of Bacteria-Inspired Agents with Performance Adaptable Interactions	journal.pcbi.1002177	null	[ [ "Many organisms exhibit complex group behavior [1]–[10] , including collective navigation observed in the flight of birds [11] , trail organization in ants [12] , and swarming of locust [13] , fish [14] and bacteria [15] , among others .", "The aggregation results in highly complex collective behavior , w...	[ "Collective navigation and swarming have been studied in animal groups , such as fish schools , bird flocks , bacteria , and slime molds .", "Computer modeling has shown that collective behavior of simple agents can result from simple interactions between the agents , which include short range repulsion , interme...	[ "Many groups of organisms , from colonies of bacteria and social insects through schools of fish and flocks of birds to herds of mammals exhibit advanced collective navigation .", "Identifying the minimal features of biologically-inspired interacting agents that can lead to emergence of “intelligent” like collect...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "fungal genetics", "dna-binding proteins", "plasmid construction", "fungi", "dna construction", "molecular biology techniques", "fungal reproduction", "fungal sporulation", "research and analysis methods", "pheromone receptors", "mycology", "proteins", "molecular biology", "genetic loci", ...	Genetic Dissection of Sexual Reproduction in a Primary Homothallic Basidiomycete	journal.pgen.1006110	null	[ [ "The ability to reproduce sexually is a widespread trait in all eukaryotic lineages and it is pervasive in fungi , where key regulators of sexual behavior are encoded in specialized chromosomal regions named MAT loci [1] .", "Mating in fungi is governed by mechanisms of self/non-self recognition , and it ...	[ "In fungi belonging to the phylum Basidiomycota , sexual compatibility is usually determined by two genetically unlinked MAT loci , one of which encodes one or more pheromone receptors ( P/R ) and pheromone precursors , and the other comprehends at least one pair of divergently transcribed genes encoding homeodomai...	[ "Some fungi are capable of sexual reproduction without the need for a sexually compatible partner , a behavior called homothallism .", "For some of these fungi , it was observed that they carried in a single individual all the genes normally determining sexual identity in two distinct sexually compatible individu...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "public health and epidemiology", "pathology", "drugs and devices", "immunology", "microbiology", "global health", "veterinary science", "veterinary medicine", "infectious diseases", "veterinary diseases", "veterinary microbiology", "biology", "public health", "veterinary pat...	AMP-Activated Kinase Restricts Rift Valley Fever Virus Infection by Inhibiting Fatty Acid Synthesis	journal.ppat.1002661	null	[ [ "Emerging and re-emerging arthropod-borne viral pathogens have lead to significant world-wide morbidity and mortality in humans and domestic animals , and are of medical and agricultural concern .", "Bunyaviruses are an important group of insect-borne RNA viruses that include disease causing members such ...	[ "The cell intrinsic innate immune responses provide a first line of defense against viral infection , and often function by targeting cellular pathways usurped by the virus during infection .", "In particular , many viruses manipulate cellular lipids to form complex structures required for viral replication , man...	[ "RNA viruses represent an important worldwide source of infection and disease in both humans and animals .", "While individual viruses have unique characteristics , some stages of infection are conserved and must be completed in order to successfully infect and grow .", "Viruses must undergo genome replication ...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "influenza", "immunology", "biology", "viral diseases", "immune response", "immunoglobulins" ]	Influenza Human Monoclonal Antibody 1F1 Interacts with Three Major Antigenic Sites and Residues Mediating Human Receptor Specificity in H1N1 Viruses	journal.ppat.1003067	null	[ [ "The hemagglutinin ( HA ) protein of influenza viruses binds to sialic acid receptors on host cells and is the major target of neutralizing antibodies .", "Amino-acid changes in the immunodominant HA antigenic sites that arise in response to immune selective pressure ( antigenic drift ) enable seasonal in...	[ "Most monoclonal antibodies ( mAbs ) to the influenza A virus hemagglutinin ( HA ) head domain exhibit very limited breadth of inhibitory activity due to antigenic drift in field strains .", "However , mAb 1F1 , isolated from a 1918 influenza pandemic survivor , inhibits select human H1 viruses ( 1918 , 1943 , 19...	[ "Influenza infection kills thousands of people every year and causes major pandemics every few decades .", "The most lethal outbreak of influenza known was the 1918 H1N1 influenza pandemic that killed an estimated 20 to 100 million people .", "The 1918 virus was likely introduced into the human population from ...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Evidence for a Common Origin of Blacksmiths and Cultivators in the Ethiopian Ari within the Last 4500 Years: Lessons for Clustering-Based Inference	journal.pgen.1005397	null	[ [ "Different ethnic groups in present-day Ethiopia show a substantial amount of cultural [1] and genetic [2] diversity .", "Some of this diversity falls along societal divisions , e . g . across distinct groups that are segregated through social barriers to interaction and co-operation [1] .", "Marginal...	[ "The Ari peoples of Ethiopia are comprised of different occupational groups that can be distinguished genetically , with Ari Cultivators and the socially marginalised Ari Blacksmiths recently shown to have a similar level of genetic differentiation between them ( FST ≈ 0 . 023 − 0 . 04 ) as that observed among mult...	[ "While it is widely recognized that DNA patterns vary across world-wide human populations , the primary features that drive these differences are less well understood .", "As an example , the Ari peoples of Ethiopia are presently socially divided according to occupation , with Ari Blacksmiths marginalised relativ...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "body fluids", "pathology and laboratory medicine", "pathogens", "microbiology", "parasitic diseases", "parasitic protozoans", "trypanosoma brucei", "bacterial diseases", "protozoans", "enterobacteriaceae", "serratia", "insect vectors", "bacteria", "bacter...	Colonization of the tsetse fly midgut with commensal Kosakonia cowanii Zambiae inhibits trypanosome infection establishment	journal.ppat.1007470	null	[ [ "Insects transmit numerous vertebrate pathogens that cause devastating disease throughout tropical and subtropical regions around the globe .", "The lack of effective and affordable vaccines , coupled with insect and pathogen resistance to pesticides and drug treatments , respectively , severely limits di...	[ "Tsetse flies ( Glossina spp . ) vector pathogenic trypanosomes ( Trypanosoma spp . ) in sub-Saharan Africa .", "These parasites cause human and animal African trypanosomiases , which are debilitating diseases that inflict an enormous socio-economic burden on inhabitants of endemic regions .", "Current disease ...	[ "Tsetse flies transmit pathogenic African trypanosomes , which are the causative agents of socio-economically devastating human and animal African trypanosomiases .", "These diseases are currently controlled in large part by reducing the population size of tsetse vectors through the use of insecticides , traps an...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "entomology", "biology", "zoology" ]	Male Mating Competitiveness of a Wolbachia-Introgressed Aedes polynesiensis Strain under Semi-Field Conditions	journal.pntd.0001271	null	[ [ "Lymphatic filariasis ( LF ) is a mosquito-borne disease that can lead to gross disfigurement ( lymphedema and elephantiasis ) and disability .", "In addition to the severe pain that often accompanies LF , many affected individuals suffer psychological distress due to associated social stigmas .", "In...	[ "Lymphatic filariasis ( LF ) , a global public health problem affecting approximately 120 million people worldwide , is a leading cause of disability in the developing world including the South Pacific .", "Despite decades of ongoing mass drug administration ( MDA ) in the region , some island nations have not ye...	[ "Aedes polynesiensis is the primary mosquito vector of lymphatic filariasis ( LF ) in the island nations of the South Pacific .", "Control of LF in this region of the world is difficult due to the unique biology of the mosquito vector .", "A proposed method to control LF in the Pacific is through the release of...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome sequencing", "genome-wide association studies", "genome analysis tools", "genomics", "genetics", "biology", "computational biology", "genetics and genomics", "human genetics" ]	Efficiency and Power as a Function of Sequence Coverage, SNP Array Density, and Imputation	journal.pcbi.1002604	null	[ [ "High coverage whole genome sequencing gives maximum information about individual-level genetic variation for use in disease gene mapping [1]–[6] or population genetics [7]–[12] .", "However , due to cost limitations , most population-based studies have estimated sample genome sequences through incomplete...	[ "High coverage whole genome sequencing provides near complete information about genetic variation .", "However , other technologies can be more efficient in some settings by", "( a ) reducing redundant coverage within samples and", "( b ) exploiting patterns of genetic variation across samples .", "To chara...	[ "In this work we address a series of questions prompted by the rise of next-generation sequencing as a data collection strategy for genetic studies .", "How does low coverage sequencing compare to traditional microarray based genotyping ?", "Do studies increase sensitivity by collecting both sequencing and arra...	2012
[ "Introduction", "Results", "Discussion", "Material and Methods" ]	[ "infectious diseases", "genetics and genomics/population genetics" ]	Genetic Association and Expression Studies Indicate a Role of Toll-Like Receptor 8 in Pulmonary Tuberculosis	journal.pgen.1000218	null	[ [ "Although one-third of the world's population is infected with M .", "tuberculosis", "[1] , fewer", "than 10% of infected –otherwise immunocompetent- individuals", "will develop clinical disease during their lifetime [2] .", "The immunological", "mechanisms that distinguish the majorit...	[ "Despite high rates of exposure , only 5–10% of people", "infected with Mycobacterium tuberculosis will develop active", "tuberculosis ( TB ) disease , suggesting a significant role for genetic variation", "in the human immune response to this infection .", "Here , we studied TB association", "and express...	[ "One third of the world population is infected with Mycobacterium", "tuberculosis , the bacterium that causes tuberculosis; however , only", "5–10% of those infected will develop active disease .", "Difference in polymorphisms within genes involved in host immune response has", "been proposed as a plausible...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	MicroRNA-155 Promotes Autophagy to Eliminate Intracellular Mycobacteria by Targeting Rheb	journal.ppat.1003697	null	[ [ "Mycobacterium tuberculosis ( M . tuberculosis ) is a hard-to-eradicate intracellular pathogen [1] that infects approximately one-third of the global population , and causes 1 . 5 million deaths annually [2] .", "However , only 10% of latent infections lead to active tuberculosis , indicating the importan...	[ "Mycobacterium tuberculosis is a hard-to-eradicate intracellular pathogen that infects one-third of the global population .", "It can live within macrophages owning to its ability to arrest phagolysosome biogenesis .", "Autophagy has recently been identified as an effective way to control the intracellular myco...	[ "microRNA-155 ( miR-155 ) plays an essential role in regulating the host immune response by post-transcriptionally repressing the expression of target genes .", "However , little is known regarding its activity in modulating autophagy , an important host defense mechanism against intracellular bacterial infection...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "ecology and environmental sciences", "water resources", "education", "helminths", "sociology", "tropical diseases", "hookworms", "social sciences", "geographical locations", "parasitic diseases", "animals", "health care", "pharmaceutics",...	The associations between water and sanitation and hookworm infection using cross-sectional data from Togo's national deworming program	journal.pntd.0006374	null	[ [ "The burden of soil-transmitted helminths ( STHs ) remains a major public health concern in many parts of the world [1] .", "The most prevalent STH species in human infections include the roundworm ( Ascaris lumbricoides ) , whipworm ( Trichuris trichiura ) and hookworm ( Necator americanus and Ancylostom...	[ "Sustainable control of soil-transmitted helminths requires a combination of chemotherapy treatment and environmental interventions , including access to safe drinking water , sufficient water for hygiene , use of clean sanitation facilities , and handwashing ( WASH ) .", "We quantified associations between home-...	[ "Preventive chemotherapy plays a critical role in breaking transmission of soil-transmitted helminths but it is likely that sustainable control of soil-transmitted helminths will require environmental improvements such as access to water for hygiene and hygienic sanitation , access to and use of a clean toilet faci...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "mathematics", "biology", "neuroscience", "probability theory" ]	Impact of Network Structure and Cellular Response on Spike Time Correlations	journal.pcbi.1002408	null	[ [ "New multielectrode and imaging techniques are revealing the simultaneous activity of neural ensembles and , in some cases , entire neural populations [1]–[4] .", "This has thrust upon the computational biology community the challenge of characterizing a potentially complex set of interactions – or correl...	[ "Novel experimental techniques reveal the simultaneous activity of larger and larger numbers of neurons .", "As a result there is increasing interest in the structure of cooperative – or correlated – activity in neural populations , and in the possible impact of such correlations on the neural code .", "A funda...	[ "Is neural activity more than the sum of its individual parts ?", "What is the impact of cooperative , or correlated , spiking among multiple cells ?", "We can start addressing these questions , as rapid advances in experimental techniques allow simultaneous recordings from ever-increasing populations .", "Ho...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "leptospira", "microbiology", "bacterial pathogens", "veterinary science", "animal models of infection", "infectious diseases", "veterinary diseases", "zoonoses", "proteins", "medical microbiology", "lipoproteins", "microbial pathogens", "proteomics", "vet...	Post-translational Modification of LipL32 during Leptospira interrogans Infection	journal.pntd.0003280	null	[ [ "Pathogenic Leptospira spp .", "are the causative agents of leptospirosis , which is considered to be the world's most widespread zoonotic disease [1]–[4] .", "Recent data shows the incidence of leptospirosis is increasing , with outbreaks frequently occurring within urban slum settings [5]–[8] , an e...	[ "Leptospirosis , a re-emerging disease of global importance caused by pathogenic Leptospira spp .", ", is considered the world's most widespread zoonotic disease .", "Rats serve as asymptomatic carriers of pathogenic Leptospira and are critical for disease spread .", "In such reservoir hosts , leptospires col...	[ "Leptospirosis , caused by pathogenic Leptospira spp .", ", constitutes an increasing global public health threat .", "Humans are accidental hosts , and acquire the disease primarily from contact with water sources that have been contaminated with urine from infected animals .", "Rats are asymptomatic carrier...	2014

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