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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 and Discussion", "Materials and Methods" ]	[ "vertebrates", "animals", "systems science", "mathematics", "statistics (mathematics)", "fungal evolution", "discrete mathematics", "combinatorics", "research and analysis methods", "mycology", "evolutionary rate", "computer and information sciences", "proteins", "mathematical and statisti...	Selection on Network Dynamics Drives Differential Rates of Protein Domain Evolution	journal.pgen.1006132	null	[ [ "Over evolutionary time , every protein accumulates amino acid changes at its own characteristic rate , which Zuckerkandl and Pauling likened to the ticking of a molecular clock [1] .", "Remarkably , this evolutionary rate varies by orders of magnitude among proteins .", "Understanding the determinant...	[ "The long-held principle that functionally important proteins evolve slowly has recently been challenged by studies in mice and yeast showing that the severity of a protein knockout only weakly predicts that protein’s rate of evolution .", "However , the relevance of these studies to evolutionary changes within p...	[ "Different proteins evolve at dramatically different rates .", "To understand this variation , it is necessary to determine which characteristics of proteins are visible to natural selection and how the strength of selection depends on those characteristics .", "One protein characteristic that is evidently visi...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "chemistry/organic chemistry", "infectious diseases/neglected tropical diseases", "infectious diseases/protozoal infections", "biochemistry/small molecule chemistry", "biochemistry/drug discovery" ]	Leishmanicidal Metabolites from Cochliobolus sp., an Endophytic Fungus Isolated from Piptadenia adiantoides (Fabaceae)	journal.pntd.0000348	null	[ [ "Protozoan parasites belonging to the genera Leishmania and Trypanosoma ( order Kinetoplastida , family Trypanosomatidae ) occurs in the tropical and sub-tropical areas of the world , where they cause severe diseases with huge medical , social , and economic impact to millions of people [1] .", "All disea...	[ "Protozoan parasites belonging to genera Leishmania and Trypanosoma are the etiological agents of severe neglected tropical diseases ( NTDs ) that cause enormous social and economic impact in many countries of tropical and sub-tropical areas of the world .", "In our screening program for new drug leads from natur...	[ "Protozoans belonging to genera Leishmania and Trypanosoma are single-cell organisms that can infect humans and cause disfiguring lesions and debilitating or fatal diseases , with enormous social and economic impact in many tropical and sub-tropical areas of the world .", "The drugs currently available to treat t...	2008
[ "Introduction", "Materials and Methods", "Results and Discussion" ]	[ "infectious diseases/protozoal infections", "infectious diseases/neglected tropical diseases", "infectious diseases/skin infections" ]	Identification of Leishmania Proteins Preferentially Released in Infected Cells Using Change Mediated Antigen Technology (CMAT)	journal.pntd.0000842	null	[ [ "Leishmaniasis is a disease that affects over 12 million people in approximately 88 countries .", "It manifests as varying types of cutaneous lesions , mucocutaneous lesions or visceral disease; the type of disease presentation is dependent on both the parasite species and characteristics of the host that...	[ "Although Leishmania parasites have been shown to modulate their host cell's responses to multiple stimuli , there is limited evidence that parasite molecules are released into infected cells .", "In this study , we present an implementation of the change mediated antigen technology ( CMAT ) to identify parasite ...	[ "Leishmania are intracellular parasites that reside within parasitophorous vacuoles ( PV ) in phagocytes .", "From within these compartments parasites control the host cell's responses to multiple stimuli .", "There is limited knowledge of the molecules that Leishmania parasites elaborate in the host cell to ta...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "anatomy and physiology", "electrophysiology", "neuroscience", "motor systems", "cognitive neuroscience", "computational neuroscience", "neurological system", "coding mechanisms", "robotics", "musculoskeletal system", "biology", "systems biology", "visual system", "physiology", "sensory ...	Optimal Control of Saccades by Spatial-Temporal Activity Patterns in the Monkey Superior Colliculus	journal.pcbi.1002508	null	[ [ "Visually evoked saccades have remarkably stereotyped characteristics .", "Their two-dimensional trajectories are virtually straight , there is a near-linear relationship between movement duration and saccade amplitude , and peak eye velocity versus saccade amplitude follows a nonlinear , saturating relat...	[ "A major challenge in computational neurobiology is to understand how populations of noisy , broadly-tuned neurons produce accurate goal-directed actions such as saccades .", "Saccades are high-velocity eye movements that have stereotyped , nonlinear kinematics; their duration increases with amplitude , while pea...	[ "As the fovea is the only spot on the retina with high spatial resolution , primates need to move their eyes to peripheral targets for detailed inspection .", "Saccades are the fastest movements of the body , and theoretical studies suggest that their trajectories are optimized to bring the fovea as fast and accu...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "immune physiology", "spleen", "immunology", "developmental biology", "antibodies", "immune system proteins", "white blood cells", "animal cells", "proteins", "gene expression", "t cells", "toll-like receptors", "biochemist...	CD71+VISTA+ erythroid cells promote the development and function of regulatory T cells through TGF-β	journal.pbio.2006649	null	[ [ "Reticulocytes originate in bone marrow ( BM ) from erythroblasts by the process of nuclear extrusion and are released into the blood , where they further mature into erythrocytes ( red blood cells ) .", "Reticulocytes contain RNA , mitochondria , endoplasmic reticulum , and ribosomes .", "As reticulo...	[ "Cell-surface transferrin receptor ( CD71+ ) erythroid cells are abundant in newborns with immunomodulatory properties .", "Here , we show that neonatal CD71+ erythroid cells express significant levels of V-domain Immunoglobulin ( Ig ) Suppressor of T Cell Activation ( VISTA ) and , via constitutive production of...	[ "The primary role of the red blood cells is to transport oxygen , but we know relatively little about the other functions they perform .", "Following maturation , red blood cells exit the bone marrow and enter blood circulation .", "Their immature counterparts are normally absent or in very low frequency in the...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "bacterial diseases", "infectious diseases", "immunoassays", "neglected tropical diseases", "immunology", "biology", "immunologic techniques", "leptospirosis" ]	Prospective Evaluation of Three Rapid Diagnostic Tests for Diagnosis of Human Leptospirosis	journal.pntd.0002290	null	[ [ "Leptospirosis is caused by microorganisms of the genus Leptospira .", "It is one of the world's most wide-spread zoonoses , with a mean global incidence of endemic and epidemic leptospirosis of 5 per 100 , 000 and 14 per 100 , 000 population , respectively [1] .", "It causes an acute febrile illness ...	[ "Diagnosis of leptospirosis by the microscopic agglutination test ( MAT ) or by culture is confined to specialized laboratories .", "Although ELISA techniques are more common , they still require laboratory facilities .", "Rapid Diagnostic Tests ( RDTs ) can be used for easy point-of-care diagnosis .", "This ...	[ "Leptospirosis is one of the world's most spread zoonoses causing acute fever .", "The illness can rapidly develop into a severe , potentially fatal , form with a high mortality rate .", "Laboratory tests are needed to confirm the diagnosis .", "Culturing leptospires from patient material can take months to g...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "clinical laboratory sciences", "immunology", "microbiology", "parasitic diseases", "parasitology", "test evaluation", "neglected tropical diseases", "infectious disease control", "infectious diseases", "travel-associated diseases", "biology", "schistosomiasis", "diagnostic med...	Comparison of Schistosoma mansoni Soluble Cercarial Antigens and Soluble Egg Antigens for Serodiagnosing Schistosome Infections	journal.pntd.0001815	null	[ [ "More than 200 million people in over 70 countries world-wide are infected with schistosomes with infection-induced morbidity being particularly pronounced in sub-Saharan Africa [1] , [2] .", "Humans become infected as a result of swimming , bathing and fishing in water in which infected intermediate host...	[ "A Schistosoma mansoni cercarial antigen preparation ( cercarial transformation fluid – SmCTF ) was evaluated for detection of anti-schistosome antibodies in human sera in 4 collaborating laboratories .", "The performance of SmCTF was compared with that of S . mansoni egg antigens ( SmSEA ) in an indirect enzyme-...	[ "Diagnosis of schistosomiasis is problematic since no method is yet available that gives both 100% sensitivity and 100% specificity .", "The method traditionally used is microscopy , but because of inherent insensitivity this technique often wrongly diagnoses patients as uninfected .", "Use of serological assay...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "geographical locations", "tropical diseases", "vector-borne diseases", "parasitic diseases", "animals", "filariasis", "neglected tropical diseases", "insect vectors", "lymphatic filariasis", "infectious diseases", "geography", "wuchereria b...	Development of an urban molecular xenomonitoring system for lymphatic filariasis in the Recife Metropolitan Region, Brazil	journal.pntd.0006816	null	[ [ "Lymphatic filariasis ( LF ) is a neglected tropical disease and ranked by the World Health Organization ( WHO ) as the world’s leading cause of physical disability , the second leading cause of long-term disability overall , and the leading cause of disability due to infectious disease [1 , 2] .", "In 20...	[ "Molecular xenomonitoring ( MX ) —pathogen detection in the mosquito rather than human—is a promising tool for lymphatic filariasis ( LF ) surveillance .", "In the Recife Metropolitan Region ( RMR ) , the last LF focus in Brazil , Culex quinquefasciatus mosquitoes have been implicated in transmitting Wuchereria b...	[ "Lymphatic filariasis ( LF ) is a parasitic disease transmitted by mosquitoes , and can cause elephantiasis .", "It is the world’s leading cause of disability due to infectious diseases , affects over 120 million people globally , and is scheduled for global elimination via mass drug administration ( MDA ) and mo...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genome-wide association studies", "medicine", "population genetics", "immunology", "parasitology", "population biology", "zoology", "infectious diseases", "genetic polymorphism", "biology", "genetics of the immune system", "natural selection", "heredity", "genetics", "genomics", "evol...	Genome-Wide Association Studies Reveal a Simple Genetic Basis of Resistance to Naturally Coevolving Viruses in Drosophila melanogaster	journal.pgen.1003057	null	[ [ "Variation in susceptibility to infectious disease often has a substantial genetic component in animal and plant populations [1]–[4] .", "As pathogens are a powerful selective force in the wild , natural selection is expected to play an important role in determining the nature of this genetic variation ."...	[ "Variation in susceptibility to infectious disease often has a substantial genetic component in animal and plant populations .", "We have used genome-wide association studies ( GWAS ) in Drosophila melanogaster to identify the genetic basis of variation in susceptibility to viral infection .", "We found that th...	[ "In most animal populations , individuals vary genetically in how susceptible they are to infectious disease .", "To understand the genetic basis of this variation , we have infected a panel of inbred lines of the fruit fly D . melanogaster with viruses and have looked for genetic variants associated with resista...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell death", "medicine and health sciences", "milk", "autophagic cell death", "body fluids", "maternal health", "obstetrics and gynecology", "gene regulation", "cell processes", "diet", "reproductive physiology", "endocrine physiology", "nutrition", "women's health", "pregnancy", "pop...	Rapid autophagic regression of the milk gland during involution is critical for maximizing tsetse viviparous reproductive output	journal.pntd.0006204	null	[ [ "Tsetse are important vectors of disease caused by African trypanosomes , known as Sleeping Sickness in humans and Nagana in animals .", "An effective way to combat disease involves vector control applications , which are highly efficient due to the low reproductive output of tsetse .", "Tsetse flies ...	[ "Tsetse flies are important vectors of human and animal trypanosomiasis .", "Ability to reduce tsetse populations is an effective means of disease control .", "Lactation is an essential component of tsetse’s viviparous reproductive physiology and requires a dramatic increase in the expression and synthesis of m...	[ "Tsetse flies are vectors for trypanosomes that cause both African sleeping sickness in humans and Nagana in animals .", "The reduction of tsetse populations is the most efficient way to reduce the prevalence of this economically important disease with current control methods including pesticide application , tra...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "diagnostic radiology", "pathology and laboratory medicine", "functional magnetic resonance imaging", "brain", "social sciences", "neuroscience", "cerebral hemispheres", "left hemisphere", "magnetic resonance imaging", "signs and symptoms", "scotoma", "brain m...	Blindsight relies on a functional connection between hMT+ and the lateral geniculate nucleus, not the pulvinar	journal.pbio.2005769	null	[ [ "Damage to the primary visual cortex ( V1 ) that may occur following a stroke causes visual loss in the corresponding part of the visual field ( homonymous hemianopia , [1] ) .", "However , extensive research has shown that some patients retain an ability to respond to images inside their scotoma , even t...	[ "When the primary visual cortex ( V1 ) is damaged , the principal visual pathway is lost , causing a loss of vision in the opposite visual field .", "While conscious vision is impaired , patients can still respond to certain images; this is known as ‘blindsight’ .", "Recently , a direct anatomical connection be...	[ "When the primary visual cortex ( V1 ) is damaged in one hemisphere , we lose the ability to see one half of the world around us .", "Clinical tests show that in this blind region of vision , we cannot see even the brightest flashes of light .", "However , many years of research have shown that individuals who ...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "innate immune system", "medicine and health sciences", "immune physiology", "cytokines", "pathology and laboratory medicine", "mycetoma", "immunology", "tropical diseases", "surgical and invasive medical procedures", "developmental biology", "fungi", "signs and symptoms", "molecular develop...	Th-1, Th-2 Cytokines Profile among Madurella mycetomatis Eumycetoma Patients	journal.pntd.0004862	null	[ [ "Mycetoma is a chronic subcutaneous infection caused by certain bacteria ( actinomycetoma ) or fungi ( eumycetoma ) [1] .", "It is characterised by a slow progressive infection and a granulomatous inflammatory response that can result in severe soft tissue and muscle damage along with destruction of the u...	[ "Eumycetoma is a progressive and destructive chronic granulomatous subcutaneous inflammatory disease caused by certain fungi , the most common being Madurella mycetomatis .", "The host defence mechanisms against fungi usually range from an early non-specific immune response to activation and induction of specific...	[ "Madurella mycetomatis is the most common causative agent for eumycetoma , which is a progressive and destructive subcutaneous inflammatory disease .", "It is a neglected tropical disease affecting the population in poor and remote endemic tropical and subtropical areas .", "Currently , the susceptibility and r...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroglial development", "neurobiology of disease and regeneration", "developmental neuroscience", "cellular neuroscience", "neuronal morphology", "biology", "neuroscience" ]	Excessive Astrocyte-Derived Neurotrophin-3 Contributes to the Abnormal Neuronal Dendritic Development in a Mouse Model of Fragile X Syndrome	journal.pgen.1003172	null	[ [ "Fragile X syndrome is a form of inherited mental retardation in humans that results from expansion of a CGG repeat in the Fmr1 gene on the X chromosome [1] , [2] .", "This syndrome is characterized by low intelligence quotient , attention deficits , and anxiety [3]–[6] .", "As an mRNA binding protein...	[ "Fragile X syndrome ( FXS ) is a form of inherited mental retardation in humans that results from expansion of a CGG repeat in the Fmr1 gene .", "Recent studies suggest a role of astrocytes in neuronal development .", "However , the mechanisms involved in the regulation process of astrocytes from FXS remain unc...	[ "Fragile X syndrome is a form of inherited mental retardation in humans that results from expansion of a CGG repeat in the Fmr1 gene .", "Recent studies suggest that astrocytes play a role in neuronal growth .", "In this study , we find that astrocytes derived from a Fragile X model , the Fmr1 knockout ( KO ) m...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "inflammatory diseases", "medicine and health sciences", "body fluids", "leptospira", "pathology and laboratory medicine", "coagulation factors", "pathogens", "tropical diseases", "microbiology", "bacterial diseases", "neglected tropical diseases", "bacteria", "bacterial pathogens", "infec...	Modulation of Hemostatic and Inflammatory Responses by Leptospira Spp.	journal.pntd.0004713	null	[ [ "Leptospirosis is an infectious disease caused by pathogenic bacteria of the genus Leptospira [1 , 2] .", "In humans , infections are mainly acquired through contact with wild or domestic infected animals or exposure to contaminated soil or water [3 , 4] .", "It is estimated that more than 500 , 000 c...	[ "Leptospirosis is a worldwide spread zoonotic and neglected infectious disease of human and veterinary concern that is caused by pathogenic Leptospira species .", "In severe infections , hemostatic impairments such as coagulation/fibrinolysis dysfunction are frequently observed .", "These complications often oc...	[ "Leptospirosis is one of the most relevant and spread zoonotic and neglected infectious diseases affecting humans and other mammals , and is caused by pathogenic bacteria of the genus Leptospira .", "During infectious diseases , when bacterial pathogens control and/or modulate the host response , impaired hemosta...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology" ]	Phosphorylation-Coupled Proteolysis of the Transcription Factor MYC2 Is Important for Jasmonate-Signaled Plant Immunity	journal.pgen.1003422	null	[ [ "Plants are continuously challenged by various biotic and abiotic stresses with diverse modes of attack .", "In response to an attack , plant cells undergo dramatic transcriptional reprogramming to efficiently coordinate the activation of attacker-specific immune responses so that the optimal resistance i...	[ "As a master regulator of jasmonic acid ( JA ) –signaled plant immune responses , the basic helix-loop-helix ( bHLH ) Leu zipper transcription factor MYC2 differentially regulates different subsets of JA–responsive genes through distinct mechanisms .", "However , how MYC2 itself is regulated at the protein level ...	[ "The plant hormone jasmonic acid ( JA ) regulates a wide range of plant immune responses involving genome-wide transcriptional reprogramming that are regulated by the basic helix-loop-helix ( bHLH ) Leu zipper transcription factor MYC2 .", "As a master regulator of JA signaling , MYC2 differentially regulates the...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "brain electrophysiology", "electrophysiology", "neuroscience", "cognitive neuroscience", "brain mapping", "computational neuroscience", "bioassays and physiological analysis", "electroencephalography", "research and analysis methods", "computer and information sc...	Spectral Signatures of Reorganised Brain Networks in Disorders of Consciousness	journal.pcbi.1003887	null	[ [ "There has been considerable recent interest in the view that consciousness is a phenomenon emerging from the dynamic equilibrium between differentiated and integrated information processing in the brain [1]–[4] .", "This view has inspired research into ways of quantifying the characteristics of informati...	[ "Theoretical advances in the science of consciousness have proposed that it is concomitant with balanced cortical integration and differentiation , enabled by efficient networks of information transfer across multiple scales .", "Here , we apply graph theory to compare key signatures of such networks in high-dens...	[ "What are the neural signatures of consciousness ?", "This is an elusive yet fascinating challenge to current cognitive neuroscience , but it takes on an immediate clinical and societal significance in patients diagnosed as vegetative and minimally conscious .", "In these patients , it leads us to ask whether w...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "behavioral neuroscience", "computational neuroscience", "biology", "neuroscience", "learning and memory" ]	Modelling Individual Differences in the Form of Pavlovian Conditioned Approach Responses: A Dual Learning Systems Approach with Factored Representations	journal.pcbi.1003466	null	[ [ "Standard Reinforcement Learning ( RL ) [1] is a widely used normative framework for modelling conditioning experiments [2] , [3] .", "Different RL systems , mainly Model-Based and Model-Free systems , have often been combined to better account for a variety of observations suggesting that multiple valuat...	[ "Reinforcement Learning has greatly influenced models of conditioning , providing powerful explanations of acquired behaviour and underlying physiological observations .", "However , in recent autoshaping experiments in rats , variation in the form of Pavlovian conditioned responses ( CRs ) and associated dopamin...	[ "Acquisition of responses towards full predictors of rewards , namely Pavlovian conditioning , has long been explained using the reinforcement learning theory .", "This theory formalizes learning processes that , by attributing values to situations and actions , makes it possible to direct behaviours towards rewa...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "rna", "cellular stress responses", "molecular cell biology", "cell biology", "nucleic acids", "biology", "microbiology", "rna stability", "molecular biology", "parasitology", "parasite physiology" ]	Post-Transcriptional Regulation of the Trypanosome Heat Shock Response by a Zinc Finger Protein	journal.ppat.1003286	null	[ [ "When living organisms are exposed to temperatures above their growth optima , they respond by increased synthesis of heat-shock proteins .", "In eukaryotes as diverse as animals , ciliates and plants , heat-shock protein expression is controlled by heat-shock transcription factors , whose activation enab...	[ "In most organisms , the heat-shock response involves increased heat-shock gene transcription .", "In Kinetoplastid protists , however , virtually all control of gene expression is post-transcriptional .", "Correspondingly , Trypanosoma brucei heat-shock protein 70 ( HSP70 ) synthesis after heat shock depends o...	[ "When organisms are placed at a temperature that is higher than normal , their proteins start to unfold .", "The organisms protect themselves by increasing the synthesis of “heat-shock” proteins which can re-fold other proteins when the temperature returns to normal .", "In trypanosomes , the degradation of mRN...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "primates", "genetics and genomics" ]	Genomic Relationships and Speciation Times of Human, Chimpanzee, and Gorilla Inferred from a Coalescent Hidden Markov Model	journal.pgen.0030007	null	[ [ "The recent evolutionary history of the human species can be investigated by comparative approaches using the genomes of the great apes: chimpanzee , gorilla , and orangutan [1] .", "Nucleotide differences , accumulated by fixation of mutations , carry a wealth of information on important issues such as s...	[ "The genealogical relationship of human , chimpanzee , and gorilla varies along the genome .", "We develop a hidden Markov model ( HMM ) that incorporates this variation and relate the model parameters to population genetics quantities such as speciation times and ancestral population sizes .", "Our HMM is an a...	[ "Primate evolution is a central topic in biology and much information can be obtained from DNA sequence data .", "A key parameter is the time “when we became human , ” i . e . , the time in the past when descendents of the human–chimp ancestor split into human and chimpanzee .", "Other important parameters are ...	2007
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "lipoprotein metabolism", "body fluids", "pathology and laboratory medicine", "pathogens", "microbiology", "developmental biology", "molecular biology techniques", "bacteria", "lipoprotein structure", "bacterial pathogens", "research and analysis methods", "bo...	Genome-wide screen identifies novel genes required for Borrelia burgdorferi survival in its Ixodes tick vector	journal.ppat.1007644	null	[ [ "Lyme disease is caused by the spirochete , Borrelia burgdorferi .", "In nature , B . burgdorferi is maintained in a cycle between mammalian or bird hosts and Ixodes ticks [1] Newly hatched ticks can acquire B . burgdorferi from infected animals during their larval feeding [1] .", "After molting to th...	[ "Borrelia burgdorferi , the causative agent of Lyme disease in humans , is maintained in a complex biphasic life cycle , which alternates between tick and vertebrate hosts .", "To successfully survive and complete its enzootic cycle , B . burgdorferi adapts to diverse hosts by regulating genes required for surviv...	[ "Borrelia burgdorferi , the causative agent of Lyme disease , must adjust to environmental changes as it moves between its tick and vertebrate hosts .", "We performed a screen of a B . burgdorferi transposon library using massively parallel sequencing ( Tn-seq ) to identify fitness defects involved in survival in...	2019
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "public health and epidemiology", "epidemiology", "neglected tropical diseases", "parasitic diseases" ]	Taenia solium Infections in a Rural Area of Eastern Zambia-A Community Based Study	journal.pntd.0001594	null	[ [ "Taenia solium taeniosis/cysticercosis is a neglected parasitic zoonosis , affecting mostly developing countries [1] .", "Its occurrence is strongly associated with poverty , poor hygiene and sanitation , free-range pig management and lack of meat inspection [2]–[4] .", "Adult intestinal tapeworm infe...	[ "Taenia solium taeniosis/cysticercosis is a parasitic infection occurring in many developing countries .", "Data on the status of human infections in Zambia is largely lacking .", "We conducted a community-based study in Eastern Zambia to determine the prevalence of human taeniosis and cysticercosis in a rural ...	[ "Taenia solium taeniosis/cysticercosis is a zoonotic infection endemic in many developing countries , with humans as the definitive host ( taeniosis ) and pigs and humans as the intermediate hosts ( cysticercosis ) .", "When humans act as the intermediate host , the result can be neurocysticercosis , which is ass...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genome-wide association studies", "genome expression analysis", "genomics", "gene expression", "genetics", "biology", "human genetics", "genetics and genomics" ]	Identification, Replication, and Functional Fine-Mapping of Expression Quantitative Trait Loci in Primary Human Liver Tissue	journal.pgen.1002078	null	[ [ "Genome-wide association studies have uncovered numerous robust associations between", "common variants and complex traits , but only a minority of these can be traced to", "protein-altering polymorphisms [1] .", "It is likely that most of these associations result from", "non-coding variants ...	[ "The discovery of expression quantitative trait loci ( “eQTLs” ) can", "help to unravel genetic contributions to complex traits .", "We identified genetic", "determinants of human liver gene expression variation using two independent", "collections of primary tissue profiled with Agilent", "( n = 206 ) an...	[ "Many disease-associated genetic variants do not alter protein sequences and are", "difficult to precisely identify .", "Discovery of expression quantitative trait loci", "( eQTL ) , or correlations between genetic variants and gene expression levels ,", "offers one means of addressing this challenge .", ...	2011
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "biochemistry", "lipids", "lipid mediators", "biology and life sciences", "microbiology", "parasitology" ]	Structural and Functional Analysis of a Platelet-Activating Lysophosphatidylcholine of Trypanosoma cruzi	journal.pntd.0003077	null	[ [ "Trypanosoma cruzi is the etiological agent of Chagas disease , which is associated with myocarditis and vasculitis , accompanied by an increase in inflammatory mediators , such as cytokines , chemokines , phospholipids , and glycolipids [1]–[3] .", "There is also an increase in platelet aggregation , foc...	[ "Trypanosoma cruzi is the causative agent of the life-threatening Chagas disease , in which increased platelet aggregation related to myocarditis is observed .", "Platelet-activating factor ( PAF ) is a potent intercellular lipid mediator and second messenger that exerts its activity through a PAF-specific recept...	[ "Chagas disease , caused by the parasite Trypanosoma cruzi , was exclusively confined to Latin America but it has recently spread to other regions of the world .", "Chagas disease affects 8–10 million people and kills thousands of them every year .", "Lysophosphatidylcholine ( LPC ) is a major bioactive phospho...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Large-Scale Analysis of Kinase Signaling in Yeast Pseudohyphal Development Identifies Regulation of Ribonucleoprotein Granules	journal.pgen.1005564	null	[ [ "The pseudohyphal growth response is a complex morphogenetic program in which fungal cells transition from a yeast-like growth form to a filamentous state , with cells remaining physically connected after cytokinesis in elongated structures [1–3] .", "This growth transition is evident in several strains o...	[ "Yeast pseudohyphal filamentation is a stress-responsive growth transition relevant to processes required for virulence in pathogenic fungi .", "Pseudohyphal growth is controlled through a regulatory network encompassing conserved MAPK ( Ste20p , Ste11p , Ste7p , Kss1p , and Fus3p ) , protein kinase A ( Tpk2p ) ,...	[ "Eukaryotic cells affect precise changes in shape and growth in response to environmental and nutritional stress , enabling cell survival and wild-type function .", "The single-celled budding yeast provides a striking example , undergoing a set of changes under conditions of nitrogen or glucose limitation resulti...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Development of Recombinase Polymerase Amplification Assays for Detection of Orientia tsutsugamushi or Rickettsia typhi	journal.pntd.0003884	null	[ [ "Rickettsial pathogens are among the leading causes of morbidity and mortality during military operations .", "In recent years , emerging rickettsial diseases have been reported throughout the world and are a significant medical concern for local and deployed personnel and travelers [1–3] .", "These p...	[ "Sensitive , specific and rapid diagnostic tests for the detection of Orientia tsutsugamushi ( O . tsutsugamushi ) and Rickettsia typhi ( R . typhi ) , the causative agents of scrub typhus and murine typhus , respectively , are necessary to accurately and promptly diagnose patients and ensure that they receive prop...	[ "Historically , rickettsial pathogens are among the leading causes of morbidity and mortality during military operations .", "Rickettsial diseases , lately , are reemerging in areas of known abundance or emerging in areas of unknown existence , posing a significant medical concern for local residents and traveler...	2015
[ "Introduction", "Methods", "BAnOCC: Bayesian analysis of compositional covariance", "Choosing hyperparameters", "Software", "Results", "Simulation studies", "A microbial interaction network from the Human Microbiome Project", "Discussion" ]	[ "ecology and environmental sciences", "microbiome", "microbiology", "random variables", "covariance", "simulation and modeling", "mathematics", "theoretical ecology", "microbial genomics", "research and analysis methods", "medical microbiology", "mathematical and statistical techniques", "ba...	A Bayesian method for detecting pairwise associations in compositional data	journal.pcbi.1005852	null	[ [ "A long-standing goal of applied statistics in many fields has been identifying features associated significantly by a measure such as correlation [1 , 2] .", "When the features to be associated form a composition , inference of the correlation matrix is subject to the well-known problem of spurious corre...	[ "Compositional data consist of vectors of proportions normalized to a constant sum from a basis of unobserved counts .", "The sum constraint makes inference on correlations between unconstrained features challenging due to the information loss from normalization .", "However , such correlations are of long-stan...	[ "Data from many fields are available primarily in the form of proportions , also referred to as compositions , which impose mathematical constraints on identifying interactions among components in the underlying systems .", "In particular , correlations cannot be calculated directly from proportions or from count...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "t helper cells", "dermatology", "medicine and health sciences", "immune cells", "immunology", "parasitic diseases", "nematode infections", "skin infections", "cytotoxic t cells", "digestive system", "infectious diseases", "white blood cells", "animal cells", "t cells", ...	Atrophy of skin-draining lymph nodes predisposes for impaired immune responses to secondary infection in mice with chronic intestinal nematode infection	journal.ppat.1007008	null	[ [ "Infections with intestinal nematodes often become chronic in mammals due to both the longevity of worms and continuous reinfection .", "Worm infections , once chronically established , typically cause little overt pathology but may have implications on growth development , nutritional status and the abil...	[ "Intestinal nematodes suppress immune responses in the context of allergy , gut inflammation , secondary infection and vaccination .", "Several mechanisms have been proposed for this suppression including alterations in Th2 cell differentiation and increased Treg cell suppressive function .", "In this study , w...	[ "Infections with intestinal nematodes may be one explanation to why BCG vaccination is less effective in areas of high worm burden .", "In support of this , we recently showed that chronic intestinal nematode infection resulted in reduced immune responses and higher mycobacterial burden at distal sites .", "How...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology/genetics of the immune system", "biochemistry/replication and repair", "biochemistry" ]	The BRCT Domain of PARP-1 Is Required for Immunoglobulin Gene Conversion	journal.pbio.1000428	During affinity maturation, genomic integrity is maintained through specific targeting of DNA mutations. The DNA damage sensor PARP-1 helps determine whether a DNA lesion results in faithful or mutagenic repair.	[ [ "The generation of high affinity antibodies through affinity maturation in B cells relies on the introduction of mutations into expressed immunoglobulin ( Ig ) gene alleles by somatic hypermutation ( SHM ) or gene conversion ( GCV ) .", "These closely related processes are mediated through introduction of...	[ "Genetic variation at immunoglobulin ( Ig ) gene variable regions in B-cells is created through a multi-step process involving deamination of cytosine bases by activation-induced cytidine deaminase ( AID ) and their subsequent mutagenic repair .", "To protect the genome from dangerous , potentially oncogenic effe...	[ "To produce a limitless diversity of antibodies within the constraints of a finite genome , activated B cells introduce random mutations into antibody genes through a process of targeted DNA damage and subsequent mutagenic repair .", "At the same time , the rest of the genome must be protected from mutagenesis to...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Predicting Anticancer Drug Responses Using a Dual-Layer Integrated Cell Line-Drug Network Model	journal.pcbi.1004498	null	[ [ "Over the past two decades , substantial improvements in high-throughput profiling technologies and systems approaches have increased expectations that personalized or precision medicine will become the paradigm of future medical science [1–3] .", "In contrast to the one-size-fits-all approach that has do...	[ "The ability to predict the response of a cancer patient to a therapeutic agent is a major goal in modern oncology that should ultimately lead to personalized treatment .", "Existing approaches to predicting drug sensitivity rely primarily on profiling of cancer cell line panels that have been treated with differ...	[ "In this study , using the Cancer Cell Line Encyclopedia ( CCLE ) and Cancer Genome Project ( CGP ) studies as benchmark datasets , we explored the application of similarity information between cell lines and drugs in drug response prediction .", "We found that similar cell lines by gene expression profiles exhib...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "viruses", "virology", "evolutionary biology", "plants", "genetics and genomics" ]	Constraints to Genetic Exchange Support Gene Coadaptation in a Tripartite RNA Virus	journal.ppat.0030008	null	[ [ "Genetic exchange is , with mutation , a primary source of genetic variation and plays an important role in virus evolution .", "Viruses possess mechanisms for genetic exchange that make their reproduction “just as sexual as that in eukaryotes” [1]: whenever different genetic variants replicate in the sam...	[ "Genetic exchange by recombination , or reassortment of genomic segments , has been shown to be an important process in RNA virus evolution , resulting often in important phenotypic changes affecting host range and virulence .", "However , data from numerous systems indicate that reassortant or recombinant genoty...	[ "The exchange of genomic regions between viral strains or species is an important process in virus evolution , resulting often in dramatic changes in virulence and host range and in the emergence of new viral diseases .", "In spite of its potential importance , little is known about what factors affect the freque...	2007
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases/neglected tropical diseases", "public health and epidemiology/infectious diseases", "public health and epidemiology/screening", "infectious diseases/protozoal infections", "infectious diseases/epidemiology and control of infectious diseases" ]	Screening of Trypanosoma brucei gambiense in Domestic Livestock and Tsetse Flies from an Insular Endemic Focus (Luba, Equatorial Guinea)	journal.pntd.0000704	null	[ [ "Human African Trypanosomiasis ( HAT ) , also known as sleeping sickness , is a parasitic disease endemic of the African continent .", "HAT is caused by two subspecies of the flagellate Trypanosoma brucei; T . b .", "gambiense , spread over West and Central Africa , which is responsible for the chroni...	[ "Sleeping sickness is spread over 36 Sub-Saharan African countries .", "In West and Central Africa , the disease is caused by Trypanosoma brucei gambiense , which produces a chronic clinical manifestation .", "The Luba focus ( Bioko Island , Equatorial Guinea ) has not reported autochthonous sleeping sickness c...	[ "Sleeping sickness is a neglected disease with an important impact on public health of many countries of Sub-Saharan Africa .", "It is transmitted by tsetse fly bites ( the vector ) and mainly affects remote and rural populations .", "The chronic form , caused by Trypanosoma brucei gambiense , includes almost 9...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "genome-wide association studies", "medicine and health sciences", "gene regulation", "regulatory proteins", "dna-binding proteins", "dna transcription", "coronary heart disease", "genome analysis", "transcription factors", "cardiology", "small interfering rnas", "proteins", "gene expression...	TCF21 and the environmental sensor aryl-hydrocarbon receptor cooperate to activate a pro-inflammatory gene expression program in coronary artery smooth muscle cells	journal.pgen.1006750	null	[ [ "Genome-wide association studies ( GWAS ) have identified susceptibility loci and candidate genetic variants that predispose to atherosclerotic coronary artery disease ( CAD ) in humans .", "[1–4] Despite significant advances made in mapping the genetic contribution to CAD , there has been limited progres...	[ "Both environmental factors and genetic loci have been associated with coronary artery disease ( CAD ) , however gene-gene and gene-environment interactions that might identify molecular mechanisms of risk are not easily studied by human genetic approaches .", "We have previously identified the transcription fact...	[ "Coronary heart disease is the leading cause of death in the world .", "Both genes and the environment are important risk factors for the progression of disease , however , how genes may modulate the harmful response to the disease promoting environment is unknown and difficult to study .", "Here , we show that...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "proteins", "protein structure", "biology", "proteomics", "glycobiology", "drug discovery" ]	Structural and Functional Analysis of Laninamivir and its Octanoate Prodrug Reveals Group Specific Mechanisms for Influenza NA Inhibition	journal.ppat.1002249	null	[ [ "The 2009 pandemic swine origin influenza A H1N1 virus ( pH1N1 ) has reminded the world of the threat of pandemic influenza [1] , [2] , [3] .", "In 2009 , the total sales of Tamiflu ( oseltamivir phosphate ) increased to over 3 billion US dollars ( Annual General Meeting of Roche Holding Ltd , 2 March 201...	[ "The 2009 H1N1 influenza pandemic ( pH1N1 ) led to record sales of neuraminidase ( NA ) inhibitors , which has contributed significantly to the recent increase in oseltamivir-resistant viruses .", "Therefore , development and careful evaluation of novel NA inhibitors is of great interest .", "Recently , a highl...	[ "The influenza neuraminidase ( NA ) enzyme is the most successful drug target against the seasonal and pandemic flu .", "The 2009 H1N1 flu pandemic led to record sales of the NA inhibitors oseltamivir ( Tamiflu ) and zanamivir ( Relenza ) .", "Recently , a new drug , laninamivir ( Inavir ) , has been approved f...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "animal genetics", "model organisms", "genetic screens", "gene identification and analysis", "genetics", "biology and life sciences", "research and analysis methods", "gene function" ]	p53- and ERK7-Dependent Ribosome Surveillance Response Regulates Drosophila Insulin-Like Peptide Secretion	journal.pgen.1004764	null	[ [ "Animals coordinate tissue growth and body size with changing nutrient conditions and it is well established that insulin-like signalling has a key role in this process [1] , [2] .", "In mammals , insulin-like signalling is mediated by insulin and insulin-like growth factors through their respective recep...	[ "Insulin-like signalling is a conserved mechanism that coordinates animal growth and metabolism with nutrient status .", "In Drosophila , insulin-producing median neurosecretory cells ( IPCs ) regulate larval growth by secreting insulin-like peptides ( dILPs ) in a diet-dependent manner .", "Previous studies ha...	[ "Ribosome biogenesis is a major consumer of cellular energy and a rate-limiting process during cell growth .", "The ribosome biogenesis pathway is tightly connected with signaling pathways that regulate tissue growth .", "For example , nutrient-regulated signaling cues adjust the rate of ribosome biogenesis .",...	2014
[ "Introduction", "Materials and methods", "Results and discussion" ]	[ "medicine and health sciences", "molecular dynamics", "diagnostic radiology", "crystal structure", "enzymes", "condensed matter physics", "enzymology", "protein structure", "lyases", "crystallography", "g protein coupled receptors", "research and analysis methods", "solid state physics", "...	Exploring the inhibition mechanism of adenylyl cyclase type 5 by n-terminal myristoylated Gαi1	journal.pcbi.1005673	null	[ [ "Many proteins are involved in cell communication of which one type is the G-protein-coupled receptor ( GPCR ) , embedded in the membrane .", "GPCRs are part of a major signalling pathway , the GPCR signal transduction pathway , which enables the transfer of a signal from the extracellular region to the i...	[ "Adenylyl cyclase ( AC ) is an important messenger involved in G-protein-coupled-receptor signal transduction pathways , which is a well-known target for drug development .", "AC is regulated by activated stimulatory ( Gαs ) and inhibitory ( Gαi ) G proteins in the cytosol .", "Although experimental studies hav...	[ "Communication between cells is essential for the survival of any multicellular organism .", "When these mechanisms cannot function properly , diseases can occur such as heart failure or Parkinson’s disease .", "Understanding cell communication is therefore crucial for drug development .", "Important proteins...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "blood cells", "infographics", "medicine and health sciences", "ecology and environmental sciences", "methods and resources", "immune cells", "cluster analysis", "statistics", "hierarchical clustering", "immunology", "mathematics", "genome analysis", "cytotoxic t cells", "information techn...	Quantitative assessment of cell population diversity in single-cell landscapes	journal.pbio.2006687	null	[ [ "Single-cell sequencing technologies enable profiling of hundreds to thousands of individual cells from a tissue composed of diverse cell types [1–8] .", "The rapid advances in single-cell technologies have led to a proliferation of novel computational tools .", "Current analyses mainly focus on ident...	[ "Single-cell RNA sequencing ( scRNA-seq ) has become a powerful tool for the systematic investigation of cellular diversity .", "As a number of computational tools have been developed to identify and visualize cell populations within a single scRNA-seq dataset , there is a need for methods to quantitatively and s...	[ "Single-cell technologies generate hundreds to thousands of data points per sample , presenting a conundrum in determining similarities and differences across multiple samples .", "Currently , similarity is determined by the degree of “intermixing” of data points among samples , a local approach , but this approa...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "flow cytometry", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "pathogens", "cancer treatment", "immunology", "microbiology", "retroviruses", "viruses", "immunodeficiency viruses", "oncology", "rna viruses", "proteasome inhibitors", ...	Reiterative Enrichment and Authentication of CRISPRi Targets (REACT) identifies the proteasome as a key contributor to HIV-1 latency	journal.ppat.1007498	null	[ [ "Transcriptional silence of integrated HIV-1 proviruses in a minority of infected CD4+ T cells is a key signature of the latent viral reservoirs that necessitate a lifelong antiretroviral therapy ( ART ) to maintain their silence [1 , 2] .", "Strategies to expose the latently infected cells for immune rec...	[ "The establishment of HIV-1 latency gives rise to persistent chronic infection that requires life-long treatment .", "To reverse latency for viral eradiation , the HIV-1 Tat protein and its associated ELL2-containing Super Elongation Complexes ( ELL2-SECs ) are essential to activate HIV-1 transcription .", "Des...	[ "To cure chronic HIV-1 infection requires reversal of HIV-1 latency from latently infected CD4+ T cells .", "A key step in HIV latency reversal is the recruitment of Super Elongation Complexes ( SECs ) that contain ELL2 by an HIV-encoded protein , Tat , to activate proviral transcription .", "To identify novel ...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "public health and epidemiology/infectious diseases", "infectious diseases", "pediatrics and child health" ]	Ocular Sequelae of Congenital Toxoplasmosis in Brazil Compared with Europe	journal.pntd.0000277	null	[ [ "Toxoplasmic retinochoroiditis appears to be more common in Brazil than in Europe or North America and more severe .", "It is a leading cause of blindness in Brazil[1] but not in Europe or North America .", "[2] , [3] These differences are not adequately explained by high rates of postnatal or congeni...	[ "Toxoplasmic retinochoroiditis appears to be more severe in Brazil , where it is a leading cause of blindness , than in Europe , but direct comparisons are lacking .", "Evidence is accumulating that more virulent genotypes of Toxoplasma gondii predominate in South America .", "We compared prospective cohorts of...	[ "Toxoplasma gondii is found throughout the world and is the most common parasitic infection in humans .", "Infection can cause inflammatory lesions at the back of the eye , which sometimes affect vision .", "These complications appear to be more common and more severe when people acquire infection in Brazil tha...	2008
[ "Introduction", "Methods", "Results", "Conclusion" ]	[ "cell physiology", "protein interactions", "protein interaction networks", "data mining", "text mining", "artificial intelligence", "network analysis", "gene types", "information technology", "extraction techniques", "research and analysis methods", "computer and information sciences", "prot...	ProtFus: A Comprehensive Method Characterizing Protein-Protein Interactions of Fusion Proteins	journal.pcbi.1007239	null	[ [ "Fusion proteins resulting from chromosomal translocations have important roles in several types of cancer and are extensively discussed in cancer research literature .", "The current biomedical literature resources , such as PubMed , comprise more than 28 million citations , with approximately 14 , 000 c...	[ "Tailored therapy aims to cure cancer patients effectively and safely , based on the complex interactions between patients' genomic features , disease pathology and drug metabolism .", "Thus , the continual increase in scientific literature drives the need for efficient methods of data mining to improve the extra...	[ "Tailored therapy aims to cure cancer patients in a fully personal way .", "Thus , the continual increase in scientific information and , particularly , in published literature , drives the need for efficient methods of data mining to find unique personal genomic features and their connections .", "Fusion prote...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "arthropoda", "animal models", "cell death", "invertebrates", "drosophila melanogaster", "model organisms", "cell biology", "olfactory system", "biology and life sciences", "cell processes", "sensory systems", "molecular cell biology", "drosophila", "neuroscience", "animals", "insects"...	Caspase Inhibition in Select Olfactory Neurons Restores Innate Attraction Behavior in Aged Drosophila	journal.pgen.1004437	null	[ [ "Neuronal dysfunction and cell death are hallmarks of age-related neurodegenerative disorders , such as Alzheimer's disease .", "Epidemiological and biomedical studies have demonstrated that both genetic and age-related factors are crucial for the development and progression of these disorders .", "At...	[ "Sensory and cognitive performance decline with age .", "Neural dysfunction caused by nerve death in senile dementia and neurodegenerative disease has been intensively studied; however , functional changes in neural circuits during the normal aging process are not well understood .", "Caspases are key regulator...	[ "The approaching era of an “aging society” is receiving considerable attention amongst biomedical researchers in advanced nations .", "In order to understand the molecular mechanisms underlying age-related alterations of neural circuitry , we focused on caspase-3 , a cysteine protease that induces apoptotic cell ...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	The Mammalian Orthologs of Drosophila Lgd, CC2D1A and CC2D1B, Function in the Endocytic Pathway, but Their Individual Loss of Function Does Not Affect Notch Signalling	journal.pgen.1005749	null	[ [ "CC2D1A ( Coiled-coil and C2 domain-containing protein 1A ) /LGD2 and CC2D1B/LGD1 belong to the evolutionary conserved Lgd protein family that is present in the genomes of all metazoans [1] .", "Members of this family contain four tandem repeats of the DM14 domain and one C2 domain .", "The D . melano...	[ "CC2D1A and CC2D1B belong to the evolutionary conserved Lgd protein family with members in all multi-cellular animals .", "Several functions such as centrosomal cleavage , involvement in signalling pathways , immune response and synapse maturation have been described for CC2D1A .", "Moreover , the Drosophila me...	[ "The proteins of the Lgd/CC2D1 family are conserved in all multicellular animals .", "The Drosophila melanogaster ortholog Lgd is involved in the regulation of signalling receptor degradation via the endosomal pathway .", "Loss of lgd function causes ectopic ligand-independent activation of the Notch signalling...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "physics", "computational chemistry", "statistical mechanics", "chemistry", "biology", "computational biology", "biophysics", "macromolecular structure analysis" ]	Residual Structures, Conformational Fluctuations, and Electrostatic Interactions in the Synergistic Folding of Two Intrinsically Disordered Proteins	journal.pcbi.1002353	null	[ [ "It is now widely recognized that many functional proteins lack stable tertiary structures under physiological conditions [1]–[5] .", "Importantly , such intrinsically disordered proteins ( IDPs ) are highly prevalent in proteomes [6] , play crucial roles in cellular areas such as signaling and regulation...	[ "To understand the interplay of residual structures and conformational fluctuations in the interaction of intrinsically disordered proteins ( IDPs ) , we first combined implicit solvent and replica exchange sampling to calculate atomistic disordered ensembles of the nuclear co-activator binding domain ( NCBD ) of t...	[ "Intrinsically disordered proteins ( IDPs ) are now widely recognized to play fundamental roles in biology and to be frequently associated with human diseases .", "Although the potential advantages of intrinsic disorder in cellular signaling and regulation have been widely discussed , the physical basis for these...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "toxins", "classical mechanics", "pathology and laboratory medicine", "enzymes", "enzymology", "toxicology", "collagens", "toxic agents", "membrane proteins", "damage mechanics", "cellular structures and organelles", "venoms", "proteins", "proteomics", "...	Muscle Tissue Damage Induced by the Venom of Bothrops asper: Identification of Early and Late Pathological Events through Proteomic Analysis	journal.pntd.0004599	null	[ [ "The viperid snake Bothrops asper is responsible for most snakebite cases in Central America and some regions of Mexico and South America [1 , 2] .", "The local pathology induced by viperid snakes is characterized by edema , blistering , hemorrhage , lymphatic vessel damage , and necrosis of skin and musc...	[ "The time-course of the pathological effects induced by the venom of the snake Bothrops asper in muscle tissue was investigated by a combination of histology , proteomic analysis of exudates collected in the vicinity of damaged muscle , and immunodetection of extracellular matrix proteins in exudates .", "Proteom...	[ "The local pathology induced by viperid snakes is characterized by a complex of alterations as consequence of direct and indirect effects of the toxins present in the venom , as well as the host response to tissue damage , and constitutes a dynamic process of degenerative and reparative events .", "The pathogenes...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "nervous system", "pathogens", "immunology", "microbiology", "brain", "animal models", "viruses", "model organisms", "rna viruses", "signs and symptoms", "cerebellum", "research and anal...	Zika (PRVABC59) Infection Is Associated with T cell Infiltration and Neurodegeneration in CNS of Immunocompetent Neonatal C57Bl/6 Mice	journal.ppat.1006004	null	[ [ "Zika virus ( ZIKV ) is an emerging mosquito-borne pathogen that belongs to the Flavivirus genus of the Flaviviridae family , which includes globally relevant arthropod-transmitted human pathogens such as dengue ( DENV ) , yellow fever ( YFV ) , West Nile ( WNV ) , Japanese encephalitis ( JEV ) , and tick-bor...	[ "The recent spread of Zika virus ( ZIKV ) and its association with increased rates of Guillain Barre and other neurological disorders as well as congenital defects that include microcephaly has created an urgent need to develop animal models to examine the pathogenesis of the disease and explore the efficacy of pot...	[ "The recent spread of Zika virus ( ZIKV ) and its association with increased rates of neurological disorders and congenital defects created an urgent need for animal models to examine the pathogenesis of the disease and explore the efficacy of potential therapeutics and vaccines .", "We describe the first symptom...	2016
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "chemical compounds", "gene regulation", "metabolic processes", "cell processes", "carbohydrates", "organic compounds", "glucose", "acidic amino acids", "amino acids", "mitochondria", "bioenergetics", "cellular structures and organelles", "small interfering rnas", "lipids", "cell prolife...	Identifying off-target effects of etomoxir reveals that carnitine palmitoyltransferase I is essential for cancer cell proliferation independent of β-oxidation	journal.pbio.2003782	null	[ [ "During the last decade , carnitine palmitoyltransferase I ( CPT1 ) has been identified as a potential therapeutic target for a growing list of cancers that include breast cancer , prostate cancer , glioblastoma , colon cancer , gastric cancer , myeloma , and others [1–6] .", "In these cancers , CPT1 expr...	[ "It has been suggested that some cancer cells rely upon fatty acid oxidation ( FAO ) for energy .", "Here we show that when FAO was reduced approximately 90% by pharmacological inhibition of carnitine palmitoyltransferase I ( CPT1 ) with low concentrations of etomoxir , the proliferation rate of various cancer ce...	[ "Oxidation of long-chain fatty acids inside of the mitochondrial matrix provides an essential source of energy for some cells .", "Since long-chain fatty acids cannot freely pass into the mitochondrial matrix , they rely on a protein called carnitine palmitoyltransferase I ( CPT1 ) for transport .", "Prior rese...	2018
[ "Introduction", "Material and Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "markov models", "tropical diseases", "geographical locations", "parasitic diseases", "animals", "data management", "ascaris", "ascaris lumbricoides", "mathematics", "tanzania", "neglected tropical diseases", "africa", "computer and inform...	Markov Model Predicts Changes in STH Prevalence during Control Activities Even with a Reduced Amount of Baseline Information	journal.pntd.0004371	null	[ [ "Soil-transmitted helminths ( STHs ) is a group of four species of intestinal worms: Ascaris lumbricoides , Trichuris trichiura , Necator americanus and Ancylostoma duodenale .", "The latter two species are indistinguishable by microscopic examination of the eggs and are therefore frequently reported coll...	[ "Estimating the reduction in levels of infection during implementation of soil-transmitted helminth ( STH ) control programmes is important to measure their performance and to plan interventions .", "Markov modelling techniques have been used with some success to predict changes in STH prevalence following treatm...	[ "Several million children are periodically dewormed to prevent the impairments to health and the economy caused by soil-transmitted helminths in endemic communities .", "It is important that managers of STH control programmes be able to anticipate the impact of the control measures on the prevalence of the diseas...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "public health and epidemiology", "rna viruses", "virology", "viral classification", "biology", "microbiology", "evolutionary biology", "public health" ]	Ancient Ancestry of KFDV and AHFV Revealed by Complete Genome Analyses of Viruses Isolated from Ticks and Mammalian Hosts	journal.pntd.0001352	null	[ [ "Alkhurma hemorrhagic fever virus ( AHFV ) is a variant of Kyasanur Forest disease virus ( KFDV ) , and like KFDV , is a member of the mammalian tick-borne encephalitis group [family Flaviviridae , genus Flavivirus] .", "AHFV and KFDV cause similar disease syndromes in humans marked by fever , severe head...	[ "Alkhurma hemorrhagic fever virus ( AHFV ) and Kyasanur forest disease virus ( KFDV ) cause significant human disease and mortality in Saudi Arabia and India , respectively .", "Despite their distinct geographic ranges , AHFV and KFDV share a remarkably high sequence identity .", "Given its emergence decades af...	[ "Alkhurma hemorrhagic fever ( AHF ) and Kyasanur Forest disease ( KFD ) viruses both cause serious and sometimes fatal human disease in their respective ranges , Saudi Arabia and India .", "AHFV was first identified in the mid-1990s and due to its strong genetic similarity to KFDV it has since been considered the...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "parasite groups", "medicine and health sciences", "namibia", "education", "plasmodium", "angola", "sociology", "tropical diseases", "geographical locations", "social sciences", "parasitic diseases", "parasitic protozoans", "parasitology", "apicomplexa", "protozoans", "molecular biolog...	Molecular detection of P. vivax and P. ovale foci of infection in asymptomatic and symptomatic children in Northern Namibia	journal.pntd.0007290	null	[ [ "Progress in malaria elimination efforts have intensified across the Southern African Development Community ( SADC ) with the aim of elimination by 2030 for most countries [1] , [2] , [3] , [4] .", "This means a knowledge of current levels of transmission as part of the malariogenic potential is required ...	[ "Knowledge of the foci of Plasmodium species infections is critical for a country with an elimination agenda .", "Namibia is targeting malaria elimination by 2020 .", "To support decision making regarding targeted intervention , we examined for the first time , the foci of Plasmodium species infections and regi...	[ "Namibia is a member of the SADC elimination 8 ( E8 ) group with a target to eliminate malaria by 2020 .", "This target stems from years of aggressive interventional strategies that has led to significant reductions in morbidity and mortality .", "The focus of this strategy is mainly on Plasmodium falciparum as...	2019
[ "Introduction", "Methods", "Results and Discussion" ]	[]	The Trigger Factor Chaperone Encapsulates and Stabilizes Partial Folds of Substrate Proteins	journal.pcbi.1004444	null	[ [ "While many proteins can successfully fold independently and spontaneously in vitro [1] , folding within the cell is facilitated by molecular chaperones [2 , 3] .", "Trigger factor ( TF ) is a general ATP-independent chaperone [4 , 5] found in bacteria ( e . g . , E . coli ) [6] and chloroplasts [7 , 8] ....	[ "How chaperones interact with protein chains to assist in their folding is a central open question in biology .", "Obtaining atomistic insight is challenging in particular , given the transient nature of the chaperone-substrate complexes and the large system sizes .", "Recent single-molecule experiments have sh...	[ "Trigger Factor ( TF ) is an ATP-independent chaperone protein that assists in folding and prevents misfolding .", "Up to now , it is a general unsolved question how chaperones assist in the folding of protein chains .", "Experimental methods that can probe at the length and timescales of inter-residue interact...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "organismal evolution", "viral vaccines", "medicine and health sciences", "influenza", "immunology", "cell-mediated immunity", "microbiology", "vaccines", "preventive medicine", "microbial evolution", "vaccination and immunization", "public and occupational health", "infectious diseases", ...	Universal or Specific? A Modeling-Based Comparison of Broad-Spectrum Influenza Vaccines against Conventional, Strain-Matched Vaccines	journal.pcbi.1005204	null	[ [ "Seasonal and pandemic influenza pose major public health challenges [1 , 2] Vaccines against seasonal influenza aim to raise antibodies against the hemagglutinin ( HA ) and neuraminidase ( NA ) surface proteins of circulating strains [3] .", "While these targets offer the best correlates for immune prote...	[ "Despite the availability of vaccines , influenza remains a major public health challenge .", "A key reason is the virus capacity for immune escape: ongoing evolution allows the continual circulation of seasonal influenza , while novel influenza viruses invade the human population to cause a pandemic every few de...	[ "Influenza vaccines used today offer good protection , but have limitations: they have to be updated regularly , to remain effective in the face of ongoing virus evolution , and they cannot be used in advance of an influenza pandemic .", "In this study we considered how such ‘conventional’ vaccines might compare ...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "reverse transcriptase-polymerase chain reaction", "medicine and health sciences", "immune cells", "molecular probe techniques", "granulomas", "gene regulation", "immunology", "immunoblotting", "notch signaling", "molecular biology techniques", "research and analysis methods", ...	MUSASHI-Mediated Expression of JMJD3, a H3K27me3 Demethylase, Is Involved in Foamy Macrophage Generation during Mycobacterial Infection	journal.ppat.1005814	null	[ [ "Macrophages recruit to the site/s of mycobacterial infection and differentiate to several cell types including the lipid droplet loaded foamy macrophages ( FMs ) [1] .", "The characteristic lipid body ( LB ) generation in the FMs provides a suitable survival niche for the mycobacteria in the granuloma [2...	[ "Foamy macrophages ( FM ) s harbor lipid bodies that not only assist mycobacterial persistence within the granulomas but also are sites for intracellular signaling and inflammatory mediators which are essential for mycobacterial pathogenesis .", "However , molecular mechanisms that regulate intracellular lipid ac...	[ "Foamy macrophages ( FMs ) not only provide a suitable survival niche for the mycobacteria in the granuloma but also are reservoirs for several inflammatory mediators that regulate mycobacterial pathogenesis .", "Hence , understanding the mechanisms that regulate infection-induced FM generation assumes importance...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Blimp1/Prdm1 Functions in Opposition to Irf1 to Maintain Neonatal Tolerance during Postnatal Intestinal Maturation	journal.pgen.1005375	null	[ [ "The zinc finger transcriptional repressor Blimp1 originally cloned as a negative regulator of beta-interferon gene expression [1] is known to control cell fate decisions in the developing embryo and adult organism [2] .", "Blimp1 acting as a master regulator of plasma cell differentiation directly repres...	[ "The neonatal intestine is a very complex and dynamic organ that must rapidly adapt and remodel in response to a barrage of environmental stimuli during the first few postnatal weeks .", "Recent studies demonstrate that the zinc finger transcriptional repressor Blimp1/Prdm1 plays an essential role governing postn...	[ "The transcriptional repressor Blimp1/Prdm1 plays a pivotal role in the metabolic switch that occurs in the small intestine during the suckling to weaning transition .", "Notably , expression profiling of perinatal Blimp1-deficient small intestine revealed premature activation of metabolic genes normally restrict...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "ophthalmology", "genetics and genomics/complex traits", "ophthalmology/retinal disorders" ]	A Genome-Wide Association Analysis Identified a Novel Susceptible Locus for Pathological Myopia at 11q24.1	journal.pgen.1000660	null	[ [ "Myopia is a refractive error ( http://en . wikipedia . org/wiki/Refractive_error ) of the eye in which parallel rays of light focus in a plane anterior to the retina resulting in blurred vision .", "Myopia is one of the most common ocular disorders worldwide , and is in much higher prevalence in Asians t...	[ "Myopia is one of the most common ocular disorders worldwide .", "Pathological myopia , also called high myopia , comprises 1% to 5% of the general population and is one of the leading causes of legal blindness in developed countries .", "To identify genetic determinants associated with pathological myopia in J...	[ "Myopia is one of the most common ocular disorders with elongation of axis of the eyeball .", "Pathological myopia or high myopia , a subset of myopia which is characterized with excessive axial elongation and degenerative changes of the eye , is a leading cause of visual impairment .", "Since genetic factors p...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "microbial mutation", "retrovirology and hiv immunopathogenesis", "immunology", "microbiology", "host-pathogen interaction", "immunodeficiency viruses", "animal models of infection", "infectious diseases", "virulence factors and mechanisms", "viral immune evasion", "hiv", "biolog...	HIV Restriction by APOBEC3 in Humanized Mice	journal.ppat.1003242	null	[ [ "Innate immune restriction factors embody specialized barriers to zoonotic transmission of viruses .", "Substantial consideration has been given to their potential use for therapeutic benefit [1] , [2] .", "The apolipoprotein B mRNA editing enzyme catalytic polypeptide 3 ( APOBEC3 ) family of cytidine...	[ "Innate immune restriction factors represent important specialized barriers to zoonotic transmission of viruses .", "Significant consideration has been given to their possible use for therapeutic benefit .", "The apolipoprotein B mRNA editing enzyme catalytic polypeptide 3 ( APOBEC3 ) family of cytidine deamina...	[ "The APOBEC3 family of proteins is a potent cellular defense mechanism capable of restricting a broad range of viruses including HIV .", "HIV requires a critical accessory protein , Vif , which targets APOBEC3 for degradation thereby shielding its genome from lethal mutagenesis .", "Previous in vitro studies ha...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "physics", "biology and life sciences", "physical sciences", "biophysics", "biophysical simulations" ]	Investigating the Structure and Dynamics of the PIK3CA Wild-Type and H1047R Oncogenic Mutant	journal.pcbi.1003895	null	[ [ "The PI3Kα protein is involved in cellular processes vital for cancer progression , such as cell growth , proliferation , motility , survival , and metabolism [1] .", "As a result , deregulation of PI3Kα signaling is one of the most frequent events leading to cancer [2] .", "PI3Kα uses ATP to phosphor...	[ "The PIK3CA gene is one of the most frequently mutated oncogenes in human cancers .", "It encodes p110α , the catalytic subunit of phosphatidylinositol 3-kinase alpha ( PI3Kα ) , which activates signaling cascades leading to cell proliferation , survival , and cell growth .", "The most frequent mutation in PIK3...	[ "The PI3Kα protein is involved in cellular processes such as cell growth , division , and formation of new blood vessels ( angiogenesis ) that aid cancer cell survival .", "In certain types of cancer cells , PI3Kα is found to be altered compared to healthy cells .", "These PI3Kα alterations , called mutations ,...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "lysosomes", "molecular probe techniques", "brain", "notch signaling", "membrane proteins", "molecular biology techniques", "immunologic techniques", "cellular structures and organelles", "research and analysis methods", "specimen preparation and treatment", "st...	Rer1-mediated quality control system is required for neural stem cell maintenance during cerebral cortex development	journal.pgen.1007647	null	[ [ "Newly synthesized proteins are primarily assessed by the ER quality control system for correct folding , modification , and complex formation .", "Nevertheless , some immature or misfolded proteins escape from the ER to post-ER compartments .", "However , they are recognized by several retrieval rece...	[ "Rer1 is a retrieval receptor for endoplasmic reticulum ( ER ) retention of various ER membrane proteins and unassembled or immature components of membrane protein complexes .", "However , its physiological functions during mammalian development remain unclear .", "This study aimed to investigate the role of Re...	[ "We showed that Rer1 functions as an early-Golgi quality control pathway that maintains γ-secretase activity by maintaining sufficient cell surface expression of γ-secretase complex during cerebral cortex development , thereby modulating Notch signaling ." ]	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "dermatology", "genetics", "biology", "human genetics", "genetics of disease" ]	BMS1 Is Mutated in Aplasia Cutis Congenita	journal.pgen.1003573	null	[ [ "Aplasia cutis congenita ( ACC [MIM 107600] ) manifests at birth as a localized skin defect that usually heals with a hypertrophic scar .", "Most commonly the scalp skin is affected and results in localized alopecia at the site of the defect , but sometimes the defect can extend into deeper structures inv...	[ "Aplasia cutis congenita ( ACC ) manifests with localized skin defects at birth of unknown cause , mostly affecting the scalp vertex .", "Here , genome-wide linkage analysis and exome sequencing was used to identify the causative mutation in autosomal dominant ACC .", "A heterozygous Arg-to-His missense mutatio...	[ "Elucidating the pathomechanisms in congenital diseases of the skin provides the opportunity to learn what cellular processes are important during embryonic development of the skin structures .", "Aplasia cutis congenita ( ACC ) manifests with localized skin defects , most commonly affecting the scalp skin .", ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology/cell growth and division", "cell biology", "computer science/systems and control theory", "cell biology/cell adhesion", "cell biology/cytoskeleton" ]	A Polarised Population of Dynamic Microtubules Mediates Homeostatic Length Control in Animal Cells	journal.pbio.1000542	An analysis of cells grown on micro-patterned lines, and of cells during zebrafish development, identifies a population of microtubules that align along the long axis of cells to mediate homeostatic length control.	[ [ "The physical properties of a system depend to a large extent upon its scale .", "Therefore , it is not surprising to find that many biological structures are maintained within relatively tightly constrained size limits [1] , [2] .", "In some cases , the dimensions of macromolecular assemblies are enf...	[ "Because physical form and function are intimately linked , mechanisms that maintain cell shape and size within strict limits are likely to be important for a wide variety of biological processes .", "However , while intrinsic controls have been found to contribute to the relatively well-defined shape of bacteria...	[ "Because many physical processes change with scale , size control is a fundamental problem for living systems .", "While in some instances the size of a structure is directly determined by the dimensions of its individual constituents , many biological structures are dynamic , self-organising assemblies of relati...	2010
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases/protozoal infections", "infectious diseases/neglected tropical diseases", "infectious diseases/antimicrobials and drug resistance" ]	Tamoxifen Is Effective in the Treatment of Leishmania amazonensis Infections in Mice	journal.pntd.0000249	null	[ [ "Protozoan parasites of Leishmania genus are the etiological agents of leishmaniasis , a disease distributed worldwide with a broad spectrum of clinical manifestations according to the causative species and immunological status of the host .", "Leishmaniasis current therapy is mainly based on the systemic...	[ "Chemotherapy is still a critical issue in the management of leishmaniasis .", "Until recently , pentavalent antimonials , amphotericin B or pentamidine compounded the classical arsenal of treatment .", "All these drugs are toxic and have to be administered by the parenteral route .", "Tamoxifen has been used...	[ "Leishmaniasis is an antropozoonotic disease with a wide range of clinical manifestations .", "In humans , signs of disease vary from skin and mucosal ulcers to enlargement of internal organs such as the liver and spleen .", "The unicellular parasite Leishmania amazonensis is able to infect humans and cause loc...	2008
[ "Introduction", "Results and Discussion", "Methods" ]	[ "stereochemistry", "molecular dynamics", "molecular conformation", "chemistry", "physical sciences", "computational chemistry" ]	A New Model for Pore Formation by Cholesterol-Dependent Cytolysins	journal.pcbi.1003791	null	[ [ "Cholesterol dependent cytolysins ( CDCs ) represent a major branch of the CDC/membrane attack complex/perforin-like ( MACPF ) protein superfamily .", "Originally identified as virulence factors produced by Gram positive pathogens , CDC toxins have recently been identified in Gram negative bacteria such a...	[ "Cholesterol Dependent Cytolysins ( CDCs ) are important bacterial virulence factors that form large ( 200–300 Å ) membrane embedded pores in target cells .", "Currently , insights from X-ray crystallography , biophysical and single particle cryo-Electron Microscopy ( cryo-EM ) experiments suggest that soluble mo...	[ "Pore formation is central to the ability of cholesterol dependent cytolysins ( CDCs ) to act as important bacterial virulence factors .", "Secreted by numerous pathogens the toxins assemble into a circular ring and then perforate the target membrane to form the largest self-assembling proteinaceous pores known ....	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "microbiology", "molecular biology", "genetics and genomics" ]	Interlocking Transcriptional Feedback Loops Control White-Opaque Switching in Candida albicans	journal.pbio.0050256	Analysis of mutations inCandida albicans indicates that the four genes in a circuit controlling white-opaque switching form a network of positive feedback loops, with the master regulatorWOR1 occupying a central position.	[ [ "Transcriptional circuits are central to the regulation of many biological processes .", "Often the logic of the circuit , rather than the nature of its components , makes up its most critical feature .", "In this paper we describe an interlocking network of positive feedback loops that underlies whit...	[ "The human pathogen Candida albicans can assume either of two distinct cell types , designated “white” and “opaque . ”", "Each cell type is maintained for many generations; switching between them is rare and stochastic , and occurs without any known changes in the nucleotide sequence of the genome .", "The two ...	[ "The opportunistic fungal pathogen Candida albicans can switch between two heritable states—the “white” and “opaque” states .", "These two cell types differ in many characteristics , including cell structure , mating competence , and virulence .", "Recent studies of the molecular mechanism of regulating the whi...	2007
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "applied mathematics", "ocular anatomy", "neuroscience", "simulation and modeling", "algorithms", "probability distribution", "mathematics", "ganglion cells", "computational neuroscience", "thermodynamics", "coding mechanisms", "research and analysis methods",...	Signatures of criticality arise from random subsampling in simple population models	journal.pcbi.1005718	null	[ [ "Recent advances in neural recording technology [1 , 2] and computational tools for describing neural population activity [3] make it possible to empirically examine the statistics of large neural populations and search for principles underlying their collective dynamics [4] .", "One hypothesis that has e...	[ "The rise of large-scale recordings of neuronal activity has fueled the hope to gain new insights into the collective activity of neural ensembles .", "How can one link the statistics of neural population activity to underlying principles and theories ?", "One attempt to interpret such data builds upon analogie...	[ "Understanding how populations of neurons collectively encode sensory information is one of the central goals of computational neuroscience .", "In physics , systems are often characterized by identifying and describing critical points ( e . g . the transition between two states of matter ) .", "The success of ...	2017
[ "Introduction", "Methods", "Results and discussion" ]	[ "cell physiology", "protein metabolism", "chemical compounds", "aliphatic amino acids", "enzymes", "enzymology", "carbohydrates", "cell metabolism", "organic compounds", "glucose", "threonine", "fungi", "model organisms", "experimental organism systems", "amino acids", "saccharomyces",...	Population FBA predicts metabolic phenotypes in yeast	journal.pcbi.1005728	null	[ [ "A cell’s phenotype—its set of distinguishing observable traits—can be as much an emergent property of the cell’s environment and gene expression state as it is a result of the cell’s genotype .", "While some observables , like an organism’s response to Gram staining , can be immutable and tied to specifi...	[ "Using protein counts sampled from single cell proteomics distributions to constrain fluxes through a genome-scale model of metabolism , Population flux balance analysis ( Population FBA ) successfully described metabolic heterogeneity in a population of independent Escherichia coli cells growing in a defined mediu...	[ "No two living cells are exactly the same .", "Even cells from a clonal population with identical genomes living in the same environment will express proteins in different numbers simply due to the random nature of the chemistry involved in gene expression .", "The consequences of this stochastic gene expressio...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "bacteriology", "infographics", "biofilms", "population dynamics", "cell cycle and cell division", "cell processes", "microbiology", "probability distribution", "mathematics", "population biology", "skewness", "computer and information sciences", "probability theory", "population metrics",...	The effect of spatial randomness on the average fixation time of mutants	journal.pcbi.1005864	null	[ [ "Fixation is the replacement of an initially heterogeneous population with the offspring of just one individual .", "The probability of fixation and the average time that is required for a mutant to take over the population are two fundamental quantities in ecology and evolution .", "Both fixation pro...	[ "The mean conditional fixation time of a mutant is an important measure of stochastic population dynamics , widely studied in ecology and evolution .", "Here , we investigate the effect of spatial randomness on the mean conditional fixation time of mutants in a constant population of cells , N . Specifically , we...	[ "We study the influence of randomness on evolutionary dynamics , assuming that a newly arising mutant may experience a different set of environments compared to the wild type .", "We calculate the mean conditional fixation time of the mutant under different assumptions on spatial interactions , and show that rand...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "innate immune system", "medicine and health sciences", "aspergillus fumigatus", "immune cells", "immune physiology", "pathology and laboratory medicine", "cytokines", "aspergillus", "pathogens", "immunology", "microbiology", "pulmonology", "animal models", "developmental ...	Central Role of IL-23 and IL-17 Producing Eosinophils as Immunomodulatory Effector Cells in Acute Pulmonary Aspergillosis and Allergic Asthma	journal.ppat.1006175	null	[ [ "Aspergillus fumigatus is an opportunistic mold that produces conidia that are both small ( 2 . 5–3 μm in diameter ) and readily airborne [1] .", "These characteristics make A . fumigatus conidia easily dispersible , while also promoting access to the alveolar spaces in the human airway [2] .", "It is...	[ "Aspergillus fumigatus causes invasive pulmonary disease in immunocompromised hosts and allergic asthma in atopic individuals .", "We studied the contribution of lung eosinophils to these fungal diseases .", "By in vivo intracellular cytokine staining and confocal microscopy , we observed that eosinophils act a...	[ "The opportunistic fungus , Aspergillus fumigatus , causes a spectrum of diseases ranging from invasive aspergillosis in the severely immunosuppressed to allergic asthma in atopic individuals .", "Here we explored the contribution of eosinophils , a type of white blood cell , to host defenses and pathogenesis in ...	2017
[ "Introduction", "Methodology", "Results", "Discussion", "Conclusion" ]	[ "medicine and health sciences", "vector-borne diseases", "tropical diseases", "vertebrates", "geographical locations", "sand flies", "parasitic diseases", "dogs", "animals", "mammals", "mathematics", "neglected tropical diseases", "infectious disease control", "insect vectors", "statisti...	Risk analysis and prediction of visceral leishmaniasis dispersion in São Paulo State, Brazil	journal.pntd.0005353	null	[ [ "Visceral leishmaniasis ( VL ) , also known as kala-azar , is characterized by irregular bouts of fever , weight loss , enlargement of the spleen and liver , and anemia [1] .", "It is an important disease that occurs around the world [2] , and Brazil is one of six countries that concentrates 90% of new hu...	[ "Visceral leishmaniasis ( VL ) is an important neglected disease caused by a protozoan parasite , and represents a serious public health problem in many parts of the world .", "It is zoonotic in Europe and Latin America , where infected dogs constitute the main domestic reservoir for the parasite and play a key r...	[ "Visceral leishmaniasis [VL] is an important but neglected tropical disease that occurs worldwide .", "In areas where the disease is zoonotic , it is considered a serious public and animal health problem .", "In Brazil , despite the existing prevention and control programs , the disease is spreading , and in Sã...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "systems biology", "biochemistry", "genetic networks", "genomics", "functional genomics", "protein interactions", "proteins", "genome analysis", "genetics", "biology and life sciences", "proteomics", "computational biology" ]	Comparative Analysis of Human Tissue Interactomes Reveals Factors Leading to Tissue-Specific Manifestation of Hereditary Diseases	journal.pcbi.1003632	null	[ [ "Hereditary diseases arise due to germline aberrations that are present across the human body .", "Enormous progress has been made over the years in mapping the genetic causes for a large variety of hereditary diseases .", "To date , causal germline aberrations for over 1 , 500 hereditary diseases can...	[ "An open question in human genetics is what underlies the tissue-specific manifestation of hereditary diseases , which are caused by genomic aberrations that are present in cells across the human body .", "Here we analyzed this phenomenon for over 300 hereditary diseases by using comparative network analysis .", ...	[ "An open question in human genetics is what underlies the tissue-specific manifestation of hereditary diseases , which are caused by genomic aberrations that are present in cells across the entire human body .", "In order to answer this question , we created an extensive resource of protein expression and interac...	2014
[ "Introduction", "Methods", "Results and discussion" ]	[ "taxonomy", "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "microbiology", "vertebrates", "animals", "salmonellosis", "bacterial diseases", "reptile genomics", "phylogenetics", "data management", "enterobacteriaceae", "reptiles", "pharmacology", "bact...	The diversity, evolution and ecology of Salmonella in venomous snakes	journal.pntd.0007169	null	[ [ "Salmonella is a clinically relevant bacterial pathogen that poses a significant burden upon public health worldwide [1–4] .", "Two groups of Salmonella serovars have clinical relevance with distinct host-specificity and disease manifestations .", "Typhoidal Salmonella is restricted to human hosts and...	[ "Reptile-associated Salmonella bacteria are a major , but often neglected cause of both gastrointestinal and bloodstream infection in humans globally .", "The diversity of Salmonella enterica has not yet been determined in venomous snakes , however other ectothermic animals have been reported to carry a broad ran...	[ "Salmonella enterica is a remarkable bacterial species that causes Neglected Tropical Diseases globally .", "The burden of disease is greatest in some of the most poverty-afflicted regions of Africa , where salmonellosis frequently causes bloodstream infection with fatal consequences .", "The bacteria have the ...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "phosphorylation", "invertebrates", "medicine and health sciences", "parasite groups", "body fluids", "plasmodium", "parasitic diseases", "animals", "parasitic protozoans", "parasitology", "cell signaling", "c-jun n-terminal kinase signaling cascade", "apicomplexa", "protozoans", "insect...	Inhibition of JNK signaling in the Asian malaria vector Anopheles stephensi extends mosquito longevity and improves resistance to Plasmodium falciparum infection	journal.ppat.1007418	null	[ [ "The etiologic agents of malaria are protozoan parasites in the genus Plasmodium and are responsible for 216 million new cases and 445 , 000 deaths worldwide in 2016 [1] .", "Artemisinin-based combination therapies ( ACTs ) have been adopted as first-line treatments of uncomplicated and severe Plasmodium ...	[ "Malaria is a global health concern caused by infection with Plasmodium parasites .", "With rising insecticide and drug resistance , there is a critical need to develop novel control strategies , including strategies to block parasite sporogony in key mosquito vector species .", "MAPK signaling pathways regulat...	[ "Malaria is a global health concern caused by infection with Plasmodium parasites .", "With rising insecticide and drug resistance , there is a critical need to develop novel control strategies .", "One strategy is to develop a Plasmodium-resistant mosquito through the manipulation of key signaling pathways and...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "invertebrates", "fluorescence imaging", "medicine and health sciences", "neurochemistry", "caenorhabditis", "nervous system", "immunology", "electrophysiology", "neuroscience", "animals", "motor neurons", "animal models", "caenorhabditis elegans", "model organisms", "clinical medicine",...	The C-terminal of CASY-1/Calsyntenin regulates GABAergic synaptic transmission at the Caenorhabditis elegans neuromuscular junction	journal.pgen.1007263	null	[ [ "A remarkable feature of the nervous system is the specific connections between neurons , which allows for orchestrated neural networks and circuitry of the brain .", "Many cell adhesion molecules ( CAMs ) are concentrated at synaptic sites in neuronal axons and dendrites , serving as dynamic regulators o...	[ "The C . elegans ortholog of mammalian calsyntenins , CASY-1 , is an evolutionarily conserved type-I transmembrane protein that is highly enriched in the nervous system .", "Mammalian calsyntenins are strongly expressed at inhibitory synapses , but their role in synapse development and function is still elusive ....	[ "GABA acts as a major inhibitory neurotransmitter in both vertebrate and invertebrate nervous systems .", "Despite the potential deregulation of GABA signaling in several neurological disorders , our understanding of the genetic factors that regulate GABAergic synaptic transmission has just started to evolve .", ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience", "physiology" ]	From Rapid Place Learning to Behavioral Performance: A Key Role for the Intermediate Hippocampus	journal.pbio.1000089	The translation of hippocampal rapid place learning into successful search behavior requires the intermediate region of the hippocampus, which integrates accurate visuo-spatial processing with behavioral control.	[ [ "A classical distinction in animal learning theory is that between “learning” and “performance” [1 , 2] .", "The processes involved in encoding and storing new information are conceptually distinct from those involved in translating that information into useful behavior .", "The recent preoccupation w...	[ "Rapid place encoding by hippocampal neurons , as reflected by place-related firing , has been intensely studied , whereas the substrates that translate hippocampal place codes into behavior have received little attention .", "A key point relevant to this translation is that hippocampal organization is characteri...	[ "The ability to remember locations in space is dependent on an area of the brain called the hippocampus .", "A much-studied property of neurons in the hippocampus is that they rapidly come to represent or code for specific places—i . e . , the hippocampus “learns” places—as animals or humans move through an envir...	2009
[ "Introduction", "Materials and Methods", "QM/MM methods", "Results", "Discussion" ]	[]	Protein Topology Determines Cysteine Oxidation Fate: The Case of Sulfenyl Amide Formation among Protein Families	journal.pcbi.1004051	null	[ [ "Cysteine residues are involved in a plethora of roles in proteins , particularly in the context of cellular signaling , substrate and metal binding , protein–protein interactions and enzymatic activity .", "[1–4] However , most reactive cysteine residues are also quite sensitive to oxidative modification...	[ "Cysteine residues have a rich chemistry and play a critical role in the catalytic activity of a plethora of enzymes .", "However , cysteines are susceptible to oxidation by Reactive Oxygen and Nitrogen Species , leading to a loss of their catalytic function .", "Therefore , cysteine oxidation is emerging as a ...	[ "Cysteine oxidation is emerging as a relevant regulatory mechanism of enzymatic function in the cell .", "Many proteins are protected from over oxidation by reactive oxygen species by the formation of a cyclic sulfenyl amide .", "Understanding how cyclic sulfenyl amide is formed and its dependence on protein st...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "gene regulation", "carcinomas", "cancers and neoplasms", "oncology", "regulator genes", "head and neck tumors", "gene types", "head and neck squamous cell carcinoma", "small interfering rnas", "genomic signal processing", "gene expression", "head and neck can...	Molecular dissection of the oncogenic role of ETS1 in the mesenchymal subtypes of head and neck squamous cell carcinoma	journal.pgen.1008250	null	[ [ "Head and neck squamous cell carcinoma ( HNSCC ) is the sixth most common cancer world-wide , with an annual incidence of roughly 600 , 000 cases; 50 , 000 cases are diagnosed annually in the United States alone[1 , 2] .", "HNSCC carries a 5-year mortality rate of nearly 50% , making it a leading cause of...	[ "Head and Neck Squamous Cell Carcinoma ( HNSCC ) is a heterogeneous disease of significant mortality and with limited treatment options .", "Recent genomic analysis of HNSCC tumors has identified several distinct molecular classes , of which the mesenchymal subtype is associated with Epithelial to Mesenchymal Tra...	[ "The expression of the transcriptional regulator , E26 transformation-specific 1 ( ETS1 ) , is elevated in many epithelial cancers and portends aggressive tumor behavior and poor survival .", "Within these carcinomas , ETS1 function has been shown to be associated with a wide range of cellular responses that incl...	2019
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	CD4+CD25hiFOXP3+ Regulatory T Cells and Cytokine Responses in Human Schistosomiasis before and after Treatment with Praziquantel	journal.pntd.0003995	null	[ [ "The immune system has evolved several regulatory mechanisms to maintain immune homeostasis , prevent autoimmunity and restrain inflammation [1–3] .", "Many pathogens have developed mechanisms to manipulate the regulatory network of the host to their advantage , thereby generating conditions that ensure t...	[ "Chronic schistosomiasis is associated with T cell hypo-responsiveness and immunoregulatory mechanisms , including induction of regulatory T cells ( Tregs ) .", "However , little is known about Treg functional capacity during human Schistosoma haematobium infection .", "CD4+CD25hiFOXP3+ cells were characterized...	[ "Schistosomiasis , a parasitic worm infection , affects over 240 million people worldwide , especially children in sub-Saharan Africa .", "It is associated with immune hypo-responsiveness which results in an inability of the immune system to eliminate parasites .", "Animal models suggest that helminths induce r...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "neuropsychiatric disorders", "medicine and health sciences", "anxiety disorders", "natural antisense transcripts", "gene regulation", "vertebrates", "social sciences", "mice", "animals", "mammals", "micrornas", "genome analysis", "mitochondria", "bioenergetics", "cellul...	Multi-omics analysis identifies mitochondrial pathways associated with anxiety-related behavior	journal.pgen.1008358	null	[ [ "Chronic stress is a significant risk factor for human anxiety disorders [1] , yet not all individuals exposed to stress develop a clinically relevant anxiety symptomatology .", "The underlying reasons for these differences are not yet fully understood but involve an interaction of complex genetic and env...	[ "Stressful life events are major environmental risk factors for anxiety disorders , although not all individuals exposed to stress develop clinical anxiety .", "The molecular mechanisms underlying the influence of environmental effects on anxiety are largely unknown .", "To identify biological pathways mediatin...	[ "Genetic and environmental factors contribute to the etiology of psychiatric diseases but the underlying mechanisms are poorly understood .", "Chronic psychosocial stress is a well-known risk factor for anxiety disorders .", "To identify biological pathways involved in psychosocial stress-induced anxiety and re...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "systems biology", "regulatory networks", "biology", "computational biology" ]	Important miRs of Pathways in Different Tumor Types	journal.pcbi.1002883	null	[ [ "MicroRNAs ( miRs ) are small non-coding RNAs that interact with their gene target coding mRNAs .", "Such small RNAs putatively inhibit translation by direct and imperfect binding to the 3′- and 5′-untranslated regions ( UTR ) [1] and exert expression control with other regulatory elements such as transcr...	[ "We computationally determined miRs that are significantly connected to molecular pathways by utilizing gene expression profiles in different cancer types such as glioblastomas , ovarian and breast cancers .", "Specifically , we assumed that the knowledge of physical interactions between miRs and genes indicated ...	[ "We assume that a network of physical interactions between miRs and genes allows us to determine miRs that influence the expression of whole pathways in different tumor types .", "Specifically , we represented each pathway by an enrichment score and an array of miRs counting the number of genes in the pathway a g...	2013
[ "Introduction", "Results", "Discussion" ]	[ "action potentials", "medicine and health sciences", "neural networks", "nervous system", "population dynamics", "membrane potential", "electrophysiology", "neuroscience", "network analysis", "computational neuroscience", "population biology", "mood disorders", "computer and information scie...	Modeling driver cells in developing neuronal networks	journal.pcbi.1006551	null	[ [ "Coordinated neuronal activity is critical for a proper development and later supports sensory processing , learning and cognition in the mature brain .", "Coordinated activity represents also an important biomarker of pathological brain states such as epilepsy [1] .", "It is therefore essential to un...	[ "Spontaneous emergence of synchronized population activity is a characteristic feature of developing brain circuits .", "Recent experiments in the developing neo-cortex showed the existence of driver cells able to impact the synchronization dynamics when single-handedly stimulated .", "We have developed a spiki...	[ "There is timely interest on the impact of peculiar neurons ( driver cells ) and of small neuronal sub-networks ( cliques ) on operational brain dynamics .", "We first provide experimental data concerning the effect of stimulated driver cells on the bursting activity observable in the developing entorhinal cortex...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/neglected tropical diseases", "public health and epidemiology/epidemiology", "public health and epidemiology/infectious diseases", "infectious diseases/protozoal infections", "infectious diseases/epidemiology and control of infectious diseases" ]	Visceral Leishmaniasis Relapse in Southern Sudan (1999–2007): A Retrospective Study of Risk Factors and Trends	journal.pntd.0000705	null	[ [ "Visceral leishmaniasis ( VL , kala-azar ) is a systemic parasitic disease caused by the Leishmania donovani species complex .", "VL manifests with irregular bouts of fever , substantial weight loss , hepatosplenomegaly , pancytopenia , and susceptibility to opportunistic infection [1] .", "VL is typi...	[ "Risk factors associated with L . donovani visceral leishmaniasis ( VL; kala azar ) relapse are poorly characterized .", "We investigated patient characteristics and drug regimens associated with VL relapse using data from Médecins Sans Frontières - Holland ( MSF ) treatment centres in Southern Sudan .", "We us...	[ "Visceral leishmaniasis ( kala-azar ) caused by Leishmania donovani is spread from person to person by Phlebotomus sandflies .", "Major epidemics of visceral leishmaniasis have occurred in Southern Sudan during the 20th century .", "The worst of these killed 100 , 000 people in the western Upper Nile area of So...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "medicine and health sciences", "chromosome structure and function", "microbiology", "chromosome mapping", "dna replication", "bacterial genetics", "forms of dna", "dna", "molecular biology techniques", "microbial genetics", "microbial genomics", "research and analysis method...	The MaoP/maoS Site-Specific System Organizes the Ori Region of the E. coli Chromosome into a Macrodomain	journal.pgen.1006309	null	[ [ "The size of genomes with respect to cellular dimensions imposes the need for extensive chromosome condensation that is compatible with the genome replication and the expression of genetic information .", "The bacterial chromosome is organized at multiple levels from the genome content ( including the dis...	[ "The Ori region of bacterial genomes is segregated early in the replication cycle of bacterial chromosomes .", "Consequently , Ori region positioning plays a pivotal role in chromosome dynamics .", "The Ori region of the E . coli chromosome is organized as a macrodomain with specific properties concerning DNA m...	[ "The Ori region from bacterial chromosomes plays a pivotal role in chromosome organization and segregation as it is replicated and segregated early in cell division cycle and its positioning impacts the cellular organization of the chromosome in the cell .", "The E . coli chromosome is divided into four macrodoma...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Co-Circulation of Toscana Virus and Punique Virus in Northern Tunisia: A Microneutralisation-Based Seroprevalence Study	journal.pntd.0002429	null	[ [ "The risk of human infection with sand fly-transmitted viruses has been shown to cover extended geographic areas ( southern Europe , Africa , Middle-East , central and western Asia ) because of the presence of the sand fly vectors [1] .", "In countries bordering the Mediterranean basin , phlebotomine sand...	[ "In northern Tunisia , the co-circulation of two related sand fly-borne phleboviruses , Toscana virus ( TOSV ) and Punique virus ( PUNV ) was previously demonstrated .", "In contrast to TOSV , a prominent human pathogen , there is no data supporting that PUNV is capable to infect and cause disease to humans .", ...	[ "In northern Tunisia , two different pheboviruses are known to circulate in sand fly population , Toscana virus ( TOSV ) and Punique virus ( PUNV ) .", "In contrast to TOSV , a prominent human pathogen , there is no data supporting that PUNV is capable to infect humans and to cause a disease .", "We studied the...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "bacteriology", "immune cells", "immunology", "microbiology", "vaccines", "infectious disease immunology", "immunologic adjuvants", "vaccination and immunization", "bacterial genes", "immunomodulation", "animal cells", "molecular biology", "immune system", "immunopathology", "prophylaxis...	HSP70 Domain II of Mycobacterium tuberculosis Modulates Immune Response and Protective Potential of F1 and LcrV Antigens of Yersinia pestis in a Mouse Model	journal.pntd.0003322	null	[ [ "Plague caused by Y . pestis ( a Gram negative bacterium ) is a zoonotic infectious disease that has profoundly affected the course of history [1] , [2] and troubles human populations , leading to millions of deaths .", "According to the World Health Organization ( WHO ) , plague has been classified as a ...	[ "No ideal vaccine exists to control plague , a deadly dangerous disease caused by Yersinia pestis .", "In this context , we cloned , expressed and purified recombinant F1 , LcrV antigens of Y . pestis and heat shock protein70 ( HSP70 ) domain II of M . tuberculosis in E . coli .", "To evaluate the protective po...	[ "Efforts are in progress by various scientific groups towards the development of plague vaccines .", "However , lack of better understanding about the Y . pestis infection mechanisms and pathogenesis prevents the development of an effective vaccine .", "In our effort to develop a more efficacious plague vaccine...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "virology", "hiv", "biology", "microbiology", "viral diseases" ]	Stromal Down-Regulation of Macrophage CD4/CCR5 Expression and NF-κB Activation Mediates HIV-1 Non-Permissiveness in Intestinal Macrophages	journal.ppat.1002060	null	[ [ "Macrophages play crucial roles in the establishment , pathogenesis and latency of human immunodeficiency virus-1 ( HIV-1 ) infection [1] , [2] , [3] through their ability to support viral replication [4] , [5] , transmit virus [6] and act as a viral reservoir [6] , [7] , [8] , [9] .", "In this connection...	[ "Tissue macrophages are derived exclusively from blood monocytes , which as monocyte-derived macrophages support HIV-1 replication .", "However , among human tissue macrophages only intestinal macrophages are non-permissive to HIV-1 , suggesting that the unique microenvironment in human intestinal mucosa renders ...	[ "Human intestinal macrophages , unlike lymphoid tissue macrophages , brain microglia and genital ( vaginal ) macrophages , are profoundly incapable of supporting productive HIV-1 infection .", "Intriguingly , all macrophages are derived exclusively from blood monocytes , which are HIV-1 permissive after different...	2011
[ "Introduction", "Discussion", "Acknowledgments" ]	[ "computational biology/systems biology" ]	The Presence of VEGF Receptors on the Luminal Surface of Endothelial Cells Affects VEGF Distribution and VEGF Signaling	journal.pcbi.1000622	null	[ [ "Physiologic angiogenesis , the growth of new capillaries from pre-existing blood vessels , occurs in wound healing , pregnancy , exercise , and embryonic development .", "Diseases such as cancer and age-related macular degeneration are angiogenesis-dependent [1] .", "The growth of new capillaries fro...	[ "Vascular endothelial growth factor ( VEGF ) is a potent cytokine that binds to specific receptors on the endothelial cells lining blood vessels .", "The signaling cascade triggered eventually leads to the formation of new capillaries , a process called angiogenesis .", "Distributions of VEGF receptors and VEGF...	[ "Angiogenesis is the growth of new blood vessels from pre-existing vasculature that occurs in physiological ( e . g . , exercise ) and pathological contexts ( e . g . , cancer ) .", "This process is often triggered by a signaling cascade that occurs upon ligand-receptor binding between vascular endothelial growth...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics and genomics/disease models", "genetics and genomics/genetics of disease", "genetics and genomics/complex traits" ]	Quantifying the Underestimation of Relative Risks from Genome-Wide Association Studies	journal.pgen.1001337	null	[ [ "Genome-wide association studies ( GWAS ) have been extremely successful across many diseases in identifying loci harbouring genetic variants that affect disease susceptibility .", "Virtually all associated variants identified from GWAS to date have relatively small effects: each additional copy of the ri...	[ "Genome-wide association studies ( GWAS ) have identified hundreds of associated loci across many common diseases .", "Most risk variants identified by GWAS will merely be tags for as-yet-unknown causal variants .", "It is therefore possible that identification of the causal variant , by fine mapping , will ide...	[ "Genome-wide association studies ( GWAS ) exploit the correlation in genetic diversity along chromosomes in order to detect effects on disease risk without having to type causal loci directly .", "The inevitable downside of this approach is that , when the correlation between the marker and the causal variant is ...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "death rates", "invertebrates", "medicine and health sciences", "pathology and laboratory medicine", "infectious disease epidemiology", "demography", "pathogens", "immunology", "vector-borne diseases", "culicoides", "microbiology", "animals", "reoviruses", "bluetongue virus", "viruses", ...	The Interaction between Vector Life History and Short Vector Life in Vector-Borne Disease Transmission and Control	journal.pcbi.1004837	null	[ [ "The language of probabilities and chance entered mathematical epidemiology , then dubbed pathometry , almost from its foundations [1] .", "However , the common use , and huge success , of deterministic models for disease dynamics ( ODEs ) have made certain probabilistic assumptions very popular in the li...	[ "Epidemiological modelling has a vital role to play in policy planning and prediction for the control of vectors , and hence the subsequent control of vector-borne diseases .", "To decide between competing policies requires models that can generate accurate predictions , which in turn requires accurate knowledge ...	[ "The basic reproductive ratio ( R0 ) is a crucial measure of transmission intensity , lying at the interface between mathematical modelling and policy decision making .", "If control measures can induce a situation where R0 ≤ 1 for a sustained period of time then the pathogen must be eradicated .", "For disease...	2016
[ "Introduction", "Results", "Discussion", "Material and Methods" ]	[ "systems biology", "biochemistry", "biology", "genomics", "molecular cell biology", "genetics and genomics" ]	The Circadian Clock Coordinates Ribosome Biogenesis	journal.pbio.1001455	The authors identify a new role of the circadian clock in coordinating mRNA translation during ribosome biogenesis, a key process for cell metabolism.	[ [ "Circadian rhythms in behavior and physiology reflect the adaptation of organisms exposed to daily light-dark cycles .", "As a consequence , most aspects of metabolism and behaviour are under the control of these rhythms [1] .", "At a molecular level , in all the studied species , the rhythmic express...	[ "Biological rhythms play a fundamental role in the physiology and behavior of most living organisms .", "Rhythmic circadian expression of clock-controlled genes is orchestrated by a molecular clock that relies on interconnected negative feedback loops of transcription regulators .", "Here we show that the circa...	[ "Most living organisms on earth present biological rhythms that play a fundamental role in the coordination of their physiology and behavior .", "The discovery of the molecular circadian clock gives important insight into the mechanisms involved in the generation of these rhythms .", "Indeed , this molecular cl...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	The Interaction of Deworming, Improved Sanitation, and Household Flooring with Soil-Transmitted Helminth Infection in Rural Bangladesh	journal.pntd.0004256	null	[ [ "The World Health Organization recommends mass drug administration of albendazole or mebendazole to school-aged children to control soil-transmitted helminths in endemic countries; in addition , they recommend improved sanitation and hygiene to ensure long-term sustainability of deworming efforts [1] .", ...	[ "The combination of deworming and improved sanitation or hygiene may result in greater reductions in soil-transmitted helminth ( STH ) infection than any single intervention on its own .", "We measured STH prevalence in rural Bangladesh and assessed potential interactions among deworming , hygienic latrines , and...	[ "Soil-transmitted helminth infections remain prevalent in many low-resource areas of the world .", "The World Health Organization recommends that schoolchildren in countries where these infections remain common receive deworming medication two times a year .", "However , previous research has shown that people ...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "flow cytometry", "medicine and health sciences", "immune cells", "immune physiology", "pathology and laboratory medicine", "pathogens", "immunology", "microbiology", "cloning", "retroviruses", "viruses", "rna viruses", "cytotoxic t cells", "molecular biology techniques", ...	CADM1/TSLC1 Identifies HTLV-1-Infected Cells and Determines Their Susceptibility to CTL-Mediated Lysis	journal.ppat.1005560	null	[ [ "Human T-lymphotropic virus 1 ( HTLV-1 ) is a retrovirus that predominantly infects CD4+ T cells .", "An estimated 10–20 million people are infected , with regions of high prevalence including Japan , Africa , the Caribbean and South America .", "The viral burden ( proviral load , PVL ) is strongly co...	[ "Human T cell lymphotropic virus-1 ( HTLV-1 ) primarily infects CD4+ T cells , causing inflammatory disorders or a T cell malignancy in 5% to 10% of carriers .", "The cytotoxic T lymphocyte ( CTL ) response is a key factor that controls the viral load and thus the risk of disease .", "The ability to detect the ...	[ "Human T cell lymphotropic virus-1 ( HTLV-1 ) infects white blood cells ( CD4+ T cells ) for the lifetime of the host .", "The immune response limits viral spread , and people with a weak immune response have a high risk of developing an aggressive blood cancer , or a condition involving irreversible spinal cord ...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Cross-Species Array Comparative Genomic Hybridization Identifies Novel Oncogenic Events in Zebrafish and Human Embryonal Rhabdomyosarcoma	journal.pgen.1003727	null	[ [ "Rhabdomyosaroma ( RMS ) is the most common soft tissue sarcoma of childhood [1] and falls into two major histopathologic subtypes in children - embryonal and alveolar .", "Embryonal rhabdomyosaroma ( ERMS ) accounts for approximately 60% of childhood cases and is frequently associated with RAS pathway ac...	[ "Human cancer genomes are highly complex , making it challenging to identify specific drivers of cancer growth , progression , and tumor maintenance .", "To bypass this obstacle , we have applied array comparative genomic hybridization ( array CGH ) to zebrafish embryonal rhabdomyosaroma ( ERMS ) and utilized cro...	[ "Cancer is a complex genetic disease that is often associated with regional gains and losses of genomic DNA segments .", "These changes result in aberrant gene expression and drive continued tumor growth .", "Because amplified and deleted DNA segments tend to span large regions of chromosomes , it has been chal...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology and life sciences", "computational biology" ]	Novel Inhibitors Induce Large Conformational Changes of GAB1 Pleckstrin Homology Domain and Kill Breast Cancer Cells	journal.pcbi.1004021	null	[ [ "Overexpression of Grb2-associated binding protein 1 ( GAB1 ) has been observed in several human cancers , such as breast and lung cancers [1]–[4] .", "This protein is a substrate of several growth factors and interleukin receptors , and it is involved in the integration of different signal transductions ...	[ "The Grb2-associated binding protein 1 ( GAB1 ) integrates signals from different signaling pathways and is over-expressed in many cancers , therefore representing a new therapeutic target .", "In the present study , we aim to target the pleckstrin homology ( PH ) domain of GAB1 for cancer treatment .", "Using ...	[ "In this paper , we described the identification and evaluation of a set of first-in-class potent inhibitors targeting a new cancer target , Grb2-associated binder-1 ( GAB1 ) , which integrates signals from different signaling pathways , and is frequently over-expressed in cancer cells .", "To achieve our goals ,...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "adaptive immunity", "immunity", "biology", "microbiology", "bacterial pathogens" ]	A LigA Three-Domain Region Protects Hamsters from Lethal Infection by Leptospira interrogans	journal.pntd.0001422	null	[ [ "Pathogenic Leptospira species are globally distributed spirochetes that cause 350 , 000–500 , 000 severe human infections annually with an incidence of >10 cases per 100 , 000 population in humid , subtropical regions of the world and a mortality rate of 10% [1] , [2] , [3] .", "These figures are likely ...	[ "The leptospiral LigA protein consists of 13 bacterial immunoglobulin-like ( Big ) domains and is the only purified recombinant subunit vaccine that has been demonstrated to protect against lethal challenge by a clinical isolate of Leptospira interrogans in the hamster model of leptospirosis .", "We determined th...	[ "Leptospirosis is the most widespread bacterial infection transmitted to humans from host animals that harbor the bacteria in their kidneys .", "Human infections caused by the bacterium , Leptospira interrogans , frequently result in a life-threatening illness characterized by jaundice and kidney failure .", "V...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "invertebrates", "fluorescence imaging", "engineering and technology", "caenorhabditis", "neuroscience", "animals", "animal models", "caenorhabditis elegans", "human factors engineering", "model organisms", "neuroimaging", "research and analysis methods", "computer and information sciences",...	Accurate Automatic Detection of Densely Distributed Cell Nuclei in 3D Space	journal.pcbi.1004970	null	[ [ "The animal brain is the most complex information processing system in living organisms .", "To elucidate how real nervous systems perform computations is one of the fundamental goals of neuroscience and systems biology .", "The wiring information for neural circuits and visualization of their activit...	[ "To measure the activity of neurons using whole-brain activity imaging , precise detection of each neuron or its nucleus is required .", "In the head region of the nematode C . elegans , the neuronal cell bodies are distributed densely in three-dimensional ( 3D ) space .", "However , no existing computational m...	[ "To reach the ultimate goal of neuroscience to understanding how each neuron functions in the brain , whole-brain activity imaging techniques with single-cell resolution have been intensively developed .", "There are many neurons in the whole-brain images and manual detection of the neurons is very time-consuming...	2016
[ "Introduction", "Results/Discussion", "Methods" ]	[ "cellular stress responses", "genetic mutation", "chromosome biology", "gene expression", "genetics", "biology", "molecular cell biology", "chromatin", "histone modification" ]	Nucleosome Acidic Patch Promotes RNF168- and RING1B/BMI1-Dependent H2AX and H2A Ubiquitination and DNA Damage Signaling	journal.pgen.1004178	null	[ [ "Eukaryotic DNA is bound by histone proteins and organized into chromatin , the true in vivo substrate of transcription , replication and DNA repair , processes that are important in preserving genome integrity .", "Chromatin structure and function are highly regulated by histone post-translational modifi...	[ "Histone ubiquitinations are critical for the activation of the DNA damage response ( DDR ) .", "In particular , RNF168 and RING1B/BMI1 function in the DDR by ubiquitinating H2A/H2AX on Lys-13/15 and Lys-118/119 , respectively .", "However , it remains to be defined how the ubiquitin pathway engages chromatin t...	[ "Post-translational modifications of histones play important roles in regulating both the structure and function of chromatin .", "As all DNA based processes , including transcription , DNA replication and DNA repair , occur within the context of chromatin , the actual in vivo substrate of these reactions is chro...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "death rates", "medicine and health sciences", "tracheostomy", "pathology and laboratory medicine", "immunology", "surgical and invasive medical procedures", "health care", "preventive medicine", "bacterial diseases", "sepsis", "signs and symptoms", "population biology", "vaccination and imm...	Pre-post effects of a tetanus care protocol implementation in a sub-Saharan African intensive care unit	journal.pntd.0006667	null	[ [ "Despite being a vaccine-preventable disease , tetanus is frequently encountered in sub-Saharan Africa [2 , 3] .", "The incidence of non-neonatal tetanus cases has fallen since the initiation of the vaccination programme but the number of cases remains high , with 4 , 604 non-neonatal cases reported in 20...	[ "Tetanus is a vaccine-preventable , neglected disease that is life threatening if acquired and occurs most frequently in regions where vaccination coverage is incomplete .", "Challenges in vaccination coverage contribute to the occurrence of non-neonatal tetanus in sub-Saharan countries , with high case fatality ...	[ "Tetanus is a disease characterized by violent , repetitive muscular spasms that are frequently lethal .", "It rarely occurs in high-income countries due to a highly effective vaccine coupled with a strong immunisation system .", "Tanzania is a large low-income country in East Africa .", "Its size and rapidly...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "bioinformatics", "epidemiology", "database and informatics methods", "biology and life sciences", "computational biology", "disease informatics", "research and analysis methods" ]	A Novel Model to Combine Clinical and Pathway-Based Transcriptomic Information for the Prognosis Prediction of Breast Cancer	journal.pcbi.1003851	null	[ [ "Breast cancer is the second ( after skin cancer ) most frequently diagnosed cancer in women , and ranks second ( after lung cancer ) in the deaths of women in year 2013 [1] .", "Most clinical studies categorize breast cancer into four molecular subtypes: Luminal A , Luminal B , Triple Negative/Basal like...	[ "Breast cancer is the most common malignancy in women worldwide .", "With the increasing awareness of heterogeneity in breast cancers , better prediction of breast cancer prognosis is much needed for more personalized treatment and disease management .", "Towards this goal , we have developed a novel computatio...	[ "With the increasing awareness of heterogeneity in breast cancers , better prediction of breast cancer prognosis is much needed early on for more personalized treatment and management .", "Towards this goal we propose in this study a novel pathway-based prognosis prediction model , which emphasizes on individuali...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "pineal gland", "vertebrates", "animals", "biomechanics", "biological locomotion", "hormones", "circadian oscillators", "animal models", "osteichthyes", "developmental biology", "model organisms", "chronobiology", "research and analysis methods", "fishes",...	Genetically Blocking the Zebrafish Pineal Clock Affects Circadian Behavior	journal.pgen.1006445	null	[ [ "Numerous aspects of animal behavior and physiology vary dramatically during the course of the day-night cycle as an adaptation to recurring environmental fluctuations [1] .", "These variations are driven by an endogenous timing mechanism , the circadian clock , which is adjusted by external signals such ...	[ "The master circadian clock in fish has been considered to reside in the pineal gland .", "This dogma is challenged , however , by the finding that most zebrafish tissues contain molecular clocks that are directly reset by light .", "To further examine the role of the pineal gland oscillator in the zebrafish ci...	[ "Most physiological and behavioral processes exhibit daily rhythms which are driven by an internal timing mechanism known as the circadian clock .", "Circadian systems are thought to be organized in a hierarchical manner , with a central pacemaker in the brain regulating peripheral clocks throughout the body .", ...	2016
[ "Introduction", "Models", "Results", "Discussion" ]	[ "physics", "cell signaling", "biochemistry", "cell motility", "signal transduction", "cell biology", "membrane receptor signaling", "proteins", "biophysics theory", "transmembrane receptors", "biology and life sciences", "physical sciences", "computational biology", "molecular cell biology...	The Role of Membrane-Mediated Interactions in the Assembly and Architecture of Chemoreceptor Lattices	journal.pcbi.1003932	null	[ [ "The chemotaxis signal transduction pathway [1] allows bacteria to respond to minute relative changes in chemical concentration over several orders of magnitude in ambient chemical concentration [2] , and ranks among the most studied signaling pathways in biology .", "The extreme sensitivity of the chemot...	[ "In vivo fluorescence microscopy and electron cryo-tomography have revealed that chemoreceptors self-assemble into extended honeycomb lattices of chemoreceptor trimers with a well-defined relative orientation of trimers .", "The signaling response of the observed chemoreceptor lattices is remarkable for its extre...	[ "The chemotaxis system allows bacteria to respond to minute changes in chemical concentration , and serves as a paradigm for biological signal processing and the self-assembly of large protein lattices in living cells .", "The sensitivity of the chemotaxis system relies crucially on cooperative interactions among...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases", "biology and life sciences", "parasitology", "medicine and health sciences" ]	Leishmania donovani Infection Enhances Lateral Mobility of Macrophage Membrane Protein Which Is Reversed by Liposomal Cholesterol	journal.pntd.0003367	null	[ [ "The protozoa parasite , Leishmania donovani , ( LD ) replicates within the macrophage of the mammalian host [1] .", "The parasite during their intracellular life cycle causes wide variety of defects in cellular physiology like decrease in membrane cholesterol [2] with concomitant increase in membrane flu...	[ "The protozoan parasite Leishmania donovani ( LD ) reduces cellular cholesterol of the host possibly for its own benefit .", "Cholesterol is mostly present in the specialized compartment of the plasma membrane .", "The relation between mobility of membrane proteins and cholesterol depletion from membrane contin...	[ "The protozoan parasites , Leishmania donovani , replicate within the macrophages of the mammalian hosts .", "During its intracellular lifecycle , the parasite induces a wide variety of defects in the membrane homeostasis .", "Membrane bound receptor molecules are important for interacting with external stimuli...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Drosophila Fatty Acid Taste Signals through the PLC Pathway in Sugar-Sensing Neurons	journal.pgen.1003710	null	[ [ "The gustatory system is critical for interpreting the nutritional value and potential toxicity of food compounds prior to ingestion .", "Nutritionally relevant food components are detected through specialized taste receptors expressed in sensory neurons that are broadly tuned to specific taste modalities...	[ "Taste is the primary sensory system for detecting food quality and palatability .", "Drosophila detects five distinct taste modalities that include sweet , bitter , salt , water , and the taste of carbonation .", "Of these , sweet-sensing neurons appear to have utility for the detection of nutritionally rich f...	[ "The gustatory system is largely responsible for interpreting the nutritional value and potential toxicity of food compounds prior to ingestion .", "The receptors and neural circuits mediating the detection of sweet and bitter compounds have been identified in fruit fly , but neural mechanisms underlying detectio...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/virion structure, assembly, and egress", "cell biology", "virology" ]	Kaposi's Sarcoma-Associated Herpesvirus ORF45 Interacts with Kinesin-2 Transporting Viral Capsid-Tegument Complexes along Microtubules	journal.ppat.1000332	null	[ [ "Kaposi's sarcoma–associated herpesvirus ( KSHV ) , also known as the human herpesvirus 8 ( HHV-8 ) , is a human DNA tumor virus [1] .", "KSHV is etiologically associated with the endothelial neoplasm Kaposi's sarcoma ( KS ) and with certain lymphoproliferative disorders like primary effusion lymphoma ( P...	[ "Open reading frame ( ORF ) 45 of Kaposi's sarcoma-associated herpesvirus ( KSHV ) is a tegument protein .", "A genetic analysis with a null mutant suggested a possible role for this protein in the events leading to viral egress .", "In this study , ORF45 was found to interact with KIF3A , a kinesin-2 motor pro...	[ "Kaposi's sarcoma–associated herpesvirus ( KSHV ) is a tumor virus associated with Kaposi's sarcoma ( KS ) and a spectrum of other lymphomas .", "These tumor cells are usually latently infected with this virus .", "The inactive virus in cells can get reactivated , whereupon there is viral DNA replication and vi...	2009

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