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headings list	keywords list	title stringlengths 20 281	id stringlengths 20 20	toc stringlengths 57 522 ⌀	sections list	abstract list	summary list	year stringclasses 13 values
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "genetics and genomics/genomics", "genetics and genomics/gene discovery", "genetics and genomics/gene expression", "genetics and genomics/functional genomics", "plant biology", "plant biology/plant-environment interactions", "genetics and genomics/gene function", "plant biology/plant growth and develo...	Identification and Functional Analysis of Light-Responsive Unique Genes and Gene Family Members in Rice	journal.pgen.1000164	null	[ [ "Gene inactivation by the insertion of T-DNA is a common tool used for functional studies of genes in model plants such as Arabidopsis or rice .", "T-DNA insertional mutants have been generated for virtually all of the annotated genes in Arabidopsis thaliana .", "Recently , researchers working with Ar...	[ "Functional redundancy limits detailed analysis of genes in many organisms .", "Here , we report a method to efficiently overcome this obstacle by combining gene expression data with analysis of gene-indexed mutants .", "Using a rice NSF45K oligo-microarray to compare 2-week-old light- and dark-grown rice leaf ...	[ "Rice , a model monocot , is the first crop plant to have its entire genome sequenced .", "Although genome-wide transcriptome analysis tools and genome-wide , gene-indexed mutant collections have been generated for rice , the functions of only a handful of rice genes have been revealed thus far .", "Functional ...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience/behavioral neuroscience", "neuroscience/cognitive neuroscience", "neuroscience/sensory systems" ]	Influence of Dopaminergically Mediated Reward on Somatosensory Decision-Making	journal.pbio.1000164	This pharmacological fMRI study shows that during reward-based sensory decision-making, dopamine is crucially involved in reward-related modulation of human primary sensory cortex.	[ [ "A role for dopamine in Pavlovian and instrumental learning , as well as in consolidating plastic changes in corticostriatal pathways , is well established [1] , [2] .", "Although research on reward has focused on learning , there is growing interest in a possible reward-mediated modulation of perception ...	[ "Reward-related dopaminergic influences on learning and overt behaviour are well established , but any influence on sensory decision-making is largely unknown .", "We used functional magnetic resonance imaging ( fMRI ) while participants judged electric somatosensory stimuli on one hand or other , before being re...	[ "The rewards one receives during decision-making has a profound impact on learning .", "Much recent interest has focused on the role of the neurotransmitter dopamine in the basal ganglia for influencing learning and behaviour .", "Here , we ask whether reward can influence low-level sensory processing , for ins...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "schistosoma", "invertebrates", "schistosoma mansoni", "medicine and health sciences", "engineering and technology", "helminths", "light microscopy", "animals", "cell phones", "protozoans", "microscopy", "digestive system", "research and analysis methods", "schistosoma haematobium", "com...	Accuracy of Mobile Phone and Handheld Light Microscopy for the Diagnosis of Schistosomiasis and Intestinal Protozoa Infections in Côte d’Ivoire	journal.pntd.0004768	null	[ [ "Neglected tropical diseases have considerable detrimental impacts in resource-constrained settings as they can result in chronic disability and stigmatization , and have profound negative economic consequences [1 , 2] .", "Microscopy is an essential tool in the diagnosis and surveillance of many neglecte...	[ "Handheld light microscopy using compact optics and mobile phones may improve the quality of health care in resource-constrained settings by enabling access to prompt and accurate diagnosis .", "Laboratory technicians were trained to operate two handheld diagnostic devices ( Newton Nm1 microscope and a clip-on ve...	[ "Handheld light microscopes are new technologies that may be helpful in enabling better access to diagnostic testing for people living in resource-constrained settings in tropical and subtropical countries .", "Recent studies evaluating the accuracy of such devices have focused on their use by expert microscopist...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/animal genetics", "genetics and genomics/bioinformatics", "neuroscience/neurodevelopment" ]	Integrating Computational Biology and Forward Genetics in Drosophila	journal.pgen.1000351	null	[ [ "The demand by systems biology for bona fide , in vivo validated , biochemical interaction data and high quality functional annotations is much higher than the supply that geneticists are able to provide , principally because genetic approaches mainly focus on generating data on a gene-by-gene basis .", "...	[ "Genetic screens are powerful methods for the discovery of gene–phenotype associations .", "However , a systems biology approach to genetics must leverage the massive amount of “omics” data to enhance the power and speed of functional gene discovery in vivo .", "Thus far , few computational methods for gene fun...	[ "Genome sequencing and annotation , combined with large-scale molecular experiments to query gene expression and molecular interactions , collectively known as Systems Biology , have resulted in an enormous wealth in biological databases .", "Yet , it remains a daunting task to use these data to decipher the rule...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/neglected tropical diseases", "public health and epidemiology/infectious diseases", "genetics and genomics/population genetics" ]	Microsatellites Reveal a High Population Structure in Triatoma infestans from Chuquisaca, Bolivia	journal.pntd.0000202	null	[ [ "Chagas disease is a parasitic disease in which the pathogenic agent , Trypanosoma cruzi is transmitted by hematophagous insects of the sub-family Triatominae .", "Triatoma infestans is the major vector in the Andean highlands where the disease is endemic and has infected humans for over 9000 years [1] ."...	[ "For Chagas disease , the most serious infectious disease in the Americas , effective disease control depends on elimination of vectors through spraying with insecticides .", "Molecular genetic research can help vector control programs by identifying and characterizing vector populations and then developing effec...	[ "Chagas disease is a protozoan infection caused by the parasite Trypanosoma cruzi .", "Chagas is prevalent throughout Central and South America , and it remains a chief concern in Bolivia .", "A movement that began in 1991 called the Southern Cone Initiative has been successful in reducing the incidence of Chag...	2008
[ "Introduction", "Materials and Methods", "Results", "Discussion", "Conclusions" ]	[ "invertebrates", "borrelia infection", "medicine and health sciences", "pathology and laboratory medicine", "evolutionary biology", "acinetobacter infections", "pathogens", "population genetics", "microbiology", "animals", "bacterial diseases", "body lice", "population biology", "insect ve...	Head Lice of Pygmies Reveal the Presence of Relapsing Fever Borreliae in the Republic of Congo	journal.pntd.0005142	null	[ [ "The head louse , Pediculus humanus capitis , and the body louse , P . h .", "humanus , are obligatory hematophagous parasite that thrived exclusively on human blood for thousands of years [1 , 2] .", "The two lice are now usually considered members of a single species as opposed to separate species [...	[ "Head lice , Pediculus humanus capitis , occur in four divergent mitochondrial clades ( A , B , C and D ) , each having particular geographical distributions .", "Recent studies suggest that head lice , as is the case of body lice , can act as a vector for louse-borne diseases .", "Therefore , understanding the...	[ "Head lice , Pediculus capitis humanus , and body lice , Pediculus h .", "humanus , are obligatory ectoparasites that feed exclusively on human blood .", "Currently , the body louse is the only recognized vector of at least three deadly bacterial pathogens that have killed millions of peoples , namely: Ricketts...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "biotechnology", "retrotransposons", "brassica", "plant science", "model organisms", "rice", "genome analysis", "experimental organism systems", "genetic elements", "plant genomics", "molecular biology techniques", "plants", "arabidopsis thaliana", "research and analysis methods", "genom...	Sequencing the extrachromosomal circular mobilome reveals retrotransposon activity in plants	journal.pgen.1006630	null	[ [ "Transposable elements ( TEs ) are major players in the evolution of animal and plant genomes [1–3] .", "The observation of both a complex epigenetic repression of TE expression and a large compartment occupied by TE copies in most sequenced eukaryotic genomes reflects a fine-tuned interaction between TEs...	[ "Retrotransposons are mobile genetic elements abundant in plant and animal genomes .", "While efficiently silenced by the epigenetic machinery , they can be reactivated upon stress or during development .", "Their level of transcription not reflecting their transposition ability , it is thus difficult to evalua...	[ "Long time considered as « junk DNA » , the evolutive force of transposable elements ( TEs ) is now well established and TEs contribute strongly to eukaryote genome plasticity .", "However , it is difficult to fully characterize the mobile part of a genome , or active mobilome , and tracking TE activity remains c...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "homo (human)", "genetics and genomics" ]	Direct Inference of SNP Heterozygosity Rates and Resolution of LOH Detection	journal.pcbi.0030244	null	[ [ "Single nucleotide polymorphisms ( SNPs ) are common DNA sequence variations and have been widely investigated for their roles in disease causation [1] or association [2 , 3] , heterogeneous responses to drug therapies [4–6] , genetic linkage analysis [7 , 8] , and evolutionary biology [9 , 10] .", "This ...	[ "Single nucleotide polymorphisms ( SNPs ) have been increasingly utilized to investigate somatic genetic abnormalities in premalignancy and cancer .", "LOH is a common alteration observed during cancer development , and SNP assays have been used to identify LOH at specific chromosomal regions .", "The design of...	[ "More than 99% of each person's genome is identical to everyone else's .", "Many of the differences involve single base pairs , termed single nucleotide polymorphisms ( SNPs ) .", "SNPs are used as genetic markers to facilitate identification of disease-causing genes , as well as in cancer studies by aiding in ...	2007
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "epidemiology" ]	Epidemiology of Dengue Disease in the Philippines (2000–2011): A Systematic Literature Review	journal.pntd.0003027	null	[ [ "Dengue is a growing health concern in the Philippines .", "Outbreaks were reported in1926 [1] , [2] , and the first recorded epidemic in Southeast Asia occurred in Manila in 1954 [3] , [4] .", "Further epidemics occurred in 1966 , 1983 , and 1998 , with increasing reported cases of dengue disease [5]...	[ "PROSPERO CRD42012002292" ]	[ "Dengue disease is a tropical and subtropical mosquito-borne viral illness and is a major health concern in the Philippines .", "To determine the dengue disease burden in the Philippines and identify gaps and future research needs , we conducted a literature analysis and review to describe the epidemiology of den...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "phosphorylation", "mathematics", "signaling cascades", "protein structure", "sequence motif analysis", "protein structure databases", "discrete mathematics", "combinatorics", "research and analysis methods", "protein kinase signaling cascade", "sequence analysis", "bioinformatics", "protein...	Co-occurring protein phosphorylation are functionally associated	journal.pcbi.1005502	null	[ [ "In addition to gene expression and translation , post-translational modification ( PTM ) represent another level of regulation that expands the functional capacity of proteins .", "It play a crucial role in a plethora of biological processes including regulation of gene expression [1] , modulation of enz...	[ "Post-translational modifications ( PTMs ) add a further layer of complexity to the proteome and regulate a wide range of cellular protein functions .", "With the increasing number of known PTM sites , it becomes imperative to understand their functional interplays .", "In this study , we proposed a novel analy...	[ "In addition to gene expression and translation control , post-translational modifications ( PTMs ) represent another level to regulate proteins functions .", "Different PTM sites within a protein usually co-operate to fulfill their functional roles .", "Recent advances in high-throughput mass spectrometry ( MS...	2017
[ "Introduction", "Results/Discussion", "Conclusions" ]	[ "genome sequencing", "genome analysis tools", "gene ontologies", "genomics", "genome scans", "speciation", "introgression", "population genetics", "hybridization", "biology", "evolutionary biology", "gene flow", "evolutionary processes", "transcriptomes" ]	The Genomic Architecture of Population Divergence between Subspecies of the European Rabbit	journal.pgen.1003519	null	[ [ "Most research into the genetic underpinnings of speciation is based on laboratory studies of specific reproductively isolating phenotypes [1] , [2] .", "A small number of these studies have identified individual genes that confer lower fitness when in a foreign or admixed genetic background [3]–[6] .", ...	[ "The analysis of introgression of genomic regions between divergent populations provides an excellent opportunity to determine the genetic basis of reproductive isolation during the early stages of speciation .", "However , hybridization and subsequent gene flow must be relatively common in order to localize indi...	[ "A number of laboratory studies of speciation have uncovered individual genes that confer lower fitness when in a divergent genetic background .", "It is , however , unclear whether these genes were ever relevant to restricting gene flow in nature , or whether they are indirect consequences of functional divergen...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "plant anatomy", "plant growth and development", "gene regulation", "plant embryo anatomy", "regulatory proteins", "dna-binding proteins", "plant physiology", "developmental biology", "micrornas", "plant science", "transcription factors", "seedlings", "molecular biology techniques", "plant...	Coordinated regulation of Arabidopsis microRNA biogenesis and red light signaling through Dicer-like 1 and phytochrome-interacting factor 4	journal.pgen.1007247	null	[ [ "Light is one of the most important environmental factors to regulate multiple growth and developmental processes of plants , including germination , de-etiolation , phototropism , flowering , leaf and stem growth , circadian clock adjustment , stomatal opening , chloroplast relocation , and anthocyanin synth...	[ "Light and microRNAs ( miRNAs ) are key external and internal signals for plant development , respectively .", "However , the relationship between the light signaling and miRNA biogenesis pathways remains unknown .", "Here we found that miRNA processer proteins DCL1 and HYL1 interact with a basic helix-loop-hel...	[ "External light and internal miRNAs are important for plant development .", "This study revealed that the miRNA-processing enzyme DCL1 interacts with the red-light-regulated transcription factor PIF4 , which modulates the stability of DCL1 during dark-to-red-light or red-light-to-dark transitions and acts as a tr...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "parasite replication", "pathogens", "immunology", "microbiology", "parasitic diseases", "protozoan life cycles", "parasitic protozoans", "parasitology", "developmental biology", "protozoans...	Cysteine Peptidase B Regulates Leishmania mexicana Virulence through the Modulation of GP63 Expression	journal.ppat.1005658	null	[ [ "The protozoan Leishmania parasitizes macrophages and causes a spectrum of human diseases ranging from self-healing cutaneous lesions to a progressive visceral infection that can be fatal if left untreated .", "Infection is initiated when promastigote forms of the parasite are inoculated into the mammalia...	[ "Cysteine peptidases play a central role in the biology of Leishmania .", "In this work , we sought to further elucidate the mechanism ( s ) by which the cysteine peptidase CPB contributes to L . mexicana virulence and whether CPB participates in the formation of large communal parasitophorous vacuoles induced by...	[ "The parasite Leishmania mexicana expresses several cysteine peptidases of the papain family that are involved in processes such as virulence and evasion of host immune responses .", "The cysteine peptidase CPB is required for survival within macrophages and for lesion formation in susceptible mice .", "Upon th...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neurological disorders" ]	Protein Aggregation and Protein Instability Govern Familial Amyotrophic Lateral Sclerosis Patient Survival	journal.pbio.0060170	Increased protein aggregation and decreased protein stability are shown to be central to familial amyotrophic lateral sclerosis etiology.	[ [ "Amyotrophic lateral sclerosis ( ALS ) is an adult-onset neurodegenerative disease with roughly 10% of the cases being inherited or familial [1] .", "The cause of sporadic ALS ( sALS ) is unknown while familial ALS ( fALS ) is known to be caused by mutations in six different genes and six different chromo...	[ "The nature of the “toxic gain of function” that results from amyotrophic lateral sclerosis ( ALS ) - , Parkinson- , and Alzheimer-related mutations is a matter of debate .", "As a result no adequate model of any neurodegenerative disease etiology exists .", "We demonstrate that two synergistic properties , nam...	[ "Amyotrophic lateral sclerosis ( ALS ) , also known in America as Lou Gehrig's disease , is a fatal neurodegenerative disease with no effective treatment .", "Paralysis occurs as the result of the death of cells that connect the brain to various muscles , namely , the motor neurons of the brain and spinal cord ."...	2008
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "cell binding", "antimicrobials", "cell physiology", "medicine and health sciences", "pathology and laboratory medicine", "viral transmission and infection", "dose prediction methods", "pathogens", "drugs", "microbiology", "pseudomonas aeruginosa", "antibiotic resistance", "pharmaceutics", ...	Mathematical model predicts anti-adhesion–antibiotic–debridement combination therapies can clear an antibiotic resistant infection	journal.pcbi.1007211	null	[ [ "Antimicrobial resistance ( AMR ) is on the rise [1–3] and with it the need to develop and apply novel treatment strategies [4 , 5] .", "In this paper , we formulate and analyse mathematical models of combination therapies , bringing together traditional antibiotics and debridement with a new anti-adhesio...	[ "As antimicrobial resistance increases , it is crucial to develop new treatment strategies to counter the emerging threat .", "In this paper , we consider combination therapies involving conventional antibiotics and debridement , coupled with a novel anti-adhesion therapy , and their use in the treatment of antim...	[ "Since the development of the first antibiotics , bacteria have utilised and developed resistance mechanisms , helping them to avoid being eliminated and to survive within a host .", "Traditionally , the solution to this problem has been to treat with multiple antibiotics , switching to a new type when the one cu...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cellular stress responses", "molecular cell biology", "viral immune evasion", "virology", "biology", "microbiology", "pathogenesis" ]	Cytomegalovirus Downregulates IRE1 to Repress the Unfolded Protein Response	journal.ppat.1003544	null	[ [ "During viral replication large amounts of viral proteins must be synthesized , folded , and posttranslationally modified .", "Folding , maturation and multi-subunit assembly of secreted and transmembrane proteins take place in the endoplasmic reticulum ( ER ) and require an elaborate system of chaperones...	[ "During viral infection , a massive demand for viral glycoproteins can overwhelm the capacity of the protein folding and quality control machinery , leading to an accumulation of unfolded proteins in the endoplasmic reticulum ( ER ) .", "To restore ER homeostasis , cells initiate the unfolded protein response ( U...	[ "Viruses abuse the cell's protein synthesis and folding machinery to produce large amounts of viral proteins .", "This enforced synthesis overloads the cell's capacity and leads to an accumulation of unfolded proteins in the endoplasmic reticulum ( ER ) resulting in ER stress , which can compromise cell viability...	2013
[ "Introduction", "Results", "Discussion", "Conclusion", "Materials and methods" ]	[ "invertebrates", "nucleic acid synthesis", "enzymes", "annealing (genetics)", "dna-binding proteins", "enzymology", "animals", "microhomology-mediated end joining", "phosphatases", "animal models", "drosophila melanogaster", "model organisms", "polymerases", "experimental organism systems"...	Drosophila DNA polymerase theta utilizes both helicase-like and polymerase domains during microhomology-mediated end joining and interstrand crosslink repair	journal.pgen.1006813	null	[ [ "DNA double strand breaks ( DSBs ) and interstrand crosslinks ( ICLs ) compromise both strands of the DNA duplex and must be repaired to ensure cellular survival .", "While DSBs disrupt the physical integrity of DNA , ICLs tether DNA strands together through a covalent bond .", "Thus , both types of l...	[ "Double strand breaks ( DSBs ) and interstrand crosslinks ( ICLs ) are toxic DNA lesions that can be repaired through multiple pathways , some of which involve shared proteins .", "One of these proteins , DNA Polymerase θ ( Pol θ ) , coordinates a mutagenic DSB repair pathway named microhomology-mediated end join...	[ "Error-prone DNA Polymerase θ ( Pol θ ) plays a conserved role in a mutagenic DNA double-strand break repair mechanism called microhomology-mediated end joining ( MMEJ ) .", "In many organisms , it also participates in a process crucial to the removal/repair of DNA interstrand crosslinks .", "The exact mechanis...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "social sciences", "vertebrates", "neuroscience", "animals", "mammals", "primates", "mathematics", "network analysis", "computational neuroscience", "vision", "neuroimaging", "neuronal tuning", "old world monkeys", "research and analysis methods", "computer and information sciences", "...	Functional triplet motifs underlie accurate predictions of single-trial responses in populations of tuned and untuned V1 neurons	journal.pcbi.1006153	null	[ [ "In the visual system , decades of research have probed stimulus parameters that evoke responses in single neurons and these responses have been generally trial-averaged [1] .", "These response properties have revealed principles of functional organization in primary visual cortex ( V1 ) , such as orienta...	[ "Visual stimuli evoke activity in visual cortical neuronal populations .", "Neuronal activity can be selectively modulated by particular visual stimulus parameters , such as the direction of a moving bar of light , resulting in well-defined trial averaged tuning properties .", "However , given any single stimul...	[ "V1 populations have historically been characterized by single cell response properties and pairwise co-variability .", "Many cells , however , do not show obvious dependencies to a given stimulus or behavioral task , and have consequently gone unanalyzed .", "We densely record from large V1 populations to meas...	2018
[ "Introduction", "Results", "Discussion", "Material and methods" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "gene regulation", "pathogens", "endothelial cells", "microbiology", "long non-coding rnas", "epithelial cells", "viruses", "oncology", "micrornas", "dna viruses", "bioassays and physiological analysis", "herpesviruses", ...	microRNA dependent and independent deregulation of long non-coding RNAs by an oncogenic herpesvirus	journal.ppat.1006508	null	[ [ "Kaposi’s sarcoma-associated herpesvirus ( KSHV ) is an opportunistic human oncovirus , which causes Kaposi’s sarcoma ( KS ) , Primary Effusion lymphoma ( PEL ) and Multicentric Castleman’s disease ( MCD ) in immunocompromised individuals , primarily AIDS patients and organ-transplant recipients [1] .", "...	[ "Kaposi’s sarcoma ( KS ) is a highly prevalent cancer in AIDS patients , especially in sub-Saharan Africa .", "Kaposi’s sarcoma-associated herpesvirus ( KSHV ) is the etiological agent of KS and other cancers like Primary Effusion Lymphoma ( PEL ) .", "In KS and PEL , all tumors harbor latent KSHV episomes and ...	[ "KS is the most prevalent cancer associated with AIDS in sub-Saharan Africa , and is also common in males not affected by AIDS .", "KSHV manipulates human cells by targeting protein-coding genes and cell signaling .", "Here we show that KSHV alters the expression of hundreds of human lncRNAs , a broad class of ...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "multiple sclerosis", "natural antisense transcripts", "gene regulation", "neurodegenerative diseases", "immunology", "plasmid construction", "micrornas", "clinical medicine", "demyelinating disorders", "dna construction", "molecular genetics", "molecular biol...	A genetic variant associated with multiple sclerosis inversely affects the expression of CD58 and microRNA-548ac from the same gene	journal.pgen.1007961	null	[ [ "In the past 10 years , genome-wide association studies ( GWAS ) assaying hundreds of thousands of single-nucleotide polymorphisms ( SNPs ) rapidly expanded our knowledge of genetic loci contributing to complex multifactorial diseases .", "The current GWAS catalog contains already more than 89000 unique S...	[ "Genome-wide association studies have identified more than 200 genetic variants to be associated with an increased risk of developing multiple sclerosis ( MS ) .", "Still , little is known about the causal molecular mechanisms that underlie the genetic contribution to disease susceptibility .", "In this study ,...	[ "More than 200 genetic loci have been associated with an increased risk of developing multiple sclerosis ( MS ) .", "Here , we investigated the role of a single-nucleotide polymorphism ( SNP ) , which is located within the microRNA-548ac stem-loop sequence in the first intron of the CD58 gene .", "We analyzed e...	2019
[ "Introduction", "Methods", "Search for optimal vaccine serotype compositions", "Uncertainty in carriage proportions", "Proportionality assumption (A1)", "Results", "Discussion" ]	[ "algorithms", "medicine", "bacterial diseases", "infectious diseases", "computer science", "pediatric epidemiology", "mathematics", "pneumococcus", "epidemiology", "statistics", "global health", "applied mathematics", "infectious disease control" ]	Optimal Serotype Compositions for Pneumococcal Conjugate Vaccination under Serotype Replacement	journal.pcbi.1003477	null	[ [ "The bacterial pathogen Streptococcus pneumoniae ( the pneumococcus ) is a major cause of morbidity and mortality worldwide .", "Pneumococcal conjugate vaccines ( PCV ) were introduced over a decade ago and have proved highly effective in eliminating vaccine-type ( VT ) pneumococcal carriage and invasive ...	[ "Pneumococcal conjugate vaccination has proved highly effective in eliminating vaccine-type pneumococcal carriage and disease .", "However , the potential adverse effects of serotype replacement remain a major concern when implementing routine childhood pneumococcal conjugate vaccination programmes .", "Applyin...	[ "The bacterial pathogen Streptococcus pneumoniae ( pneumococcus ) is a major contributor to child mortality worldwide .", "Hence , effective pneumococcal vaccination programmes are globally among the most cost-effective public health interventions .", "Three different conjugate vaccine compositions , targeting ...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "disabilities", "economic analysis", "tropical diseases", "geographical locations", "social sciences", "health care", "north america", "neglected tropical diseases", "infectious disease control", "public and occupational health", "infectious diseases", "econom...	Economic impact of dengue in Mexico considering reported cases for 2012 to 2016	journal.pntd.0006938	null	[ [ "Dengue fever ( DF ) is a vector-borne viral infection , the incidence of which has increased and expanded geographically over the past 50 years .", "The World Health Organization estimates reported a total of 50–100 million infections per year for the period 2010 to 2013 [1] .", "According to the Glo...	[ "Given that dengue disease is growing and may progress to dengue hemorrhagic fever ( DHF ) , data on economic cost and disease burden are important .", "However , data for Mexico are limited .", "Burden of dengue fever ( DF ) and DHF in Mexico was assessed using official databases for epidemiological informatio...	[ "Dengue fever is caused by a flavivirus transmitted predominantly by the mosquito Aedes aegypti .", "Infection causes a broad spectrum of clinical signs and symptoms , from mild disease , such as dengue fever to a life threatening form known as dengue hemorrhagic fever .", "The disease is widespread in tropical...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	The lncRNA RZE1 Controls Cryptococcal Morphological Transition	journal.pgen.1005692	null	[ [ "In many human fungal pathogens , the morphological transition from yeast to hypha plays a central role in pathogenesis [1 , 2] , as demonstrated in the ascomycetes Candida albicans , Penicillium marneffei , Histoplasma capsulatum , Coccidioides immitis , and Paracoccidiodides brasiliensis [3–6] .", "Diff...	[ "In the fungal pathogen Cryptococcus neoformans , the switch from yeast to hypha is an important morphological process preceding the meiotic events during sexual development .", "Morphotype is also known to be associated with cryptococcal virulence potential .", "Previous studies identified the regulator Znf2 a...	[ "The involvement of non-protein regulators in developmental processes in higher eukaryotes is an area that has come to light more recently .", "Earlier known as the dark matter of the genome , the non-protein coding genes are now recognized for their important regulatory roles in the life of eukaryotes .", "Usi...	2015
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "neuroscience", "drosophila", "genetics and genomics" ]	Genomic and Functional Studies of Drosophila Sex Hierarchy Regulated Gene Expression in Adult Head and Nervous System Tissues	journal.pgen.0030216	null	[ [ "Genomic microarray approaches have allowed scientists to address questions that were previously intractable using molecular-genetic approaches .", "For example , in studies of Drosophila , microarrays can facilitate the identification of genes that underlie complex behaviors in the adult .", "These g...	[ "The Drosophila sex determination hierarchy controls all aspects of somatic sexual differentiation , including sex-specific differences in adult morphology and behavior .", "To gain insight into the molecular-genetic specification of reproductive behaviors and physiology , we identified genes expressed in the adu...	[ "The fruit fly Drosophila is an excellent model system to use to understand the molecular-genetic basis of male courtship behavior , as the potential for this behavior is specified by a well-understood genetic regulatory hierarchy , called the sex determination hierarchy .", "The sex hierarchy consists of a pre-m...	2007
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "global health", "epidemiology", "biology", "microbiology", "public health" ]	Shifts in Geographic Distribution and Antimicrobial Resistance during a Prolonged Typhoid Fever Outbreak — Bundibugyo and Kasese Districts, Uganda, 2009–2011	journal.pntd.0002726	null	[ [ "Salmonella enterica serovar Typhi ( Salmonella Typhi ) is the Gram-negative bacillus that causes typhoid fever , a systemic infection transmitted through food and water contaminated with human feces .", "Typhoid fever is characterized by numerous non-specific symptoms , including high fever , headache , ...	[ "Salmonella enterica serovar Typhi is transmitted by fecally contaminated food and water and causes approximately 22 million typhoid fever infections worldwide each year .", "Most cases occur in developing countries , where approximately 4% of patients develop intestinal perforation ( IP ) .", "In Kasese Distri...	[ "Typhoid fever is an acute febrile illness caused by the bacteria Salmonella Typhi and transmitted through food and water contaminated with the feces of typhoid fever patients or carriers .", "We investigated typhoid fever outbreaks in two neighboring Ugandan districts , Kasese and Bundibugyo , where typhoid feve...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "organismal evolution", "medicine and health sciences", "pathology and laboratory medicine", "evolutionary biology", "enzymes", "pathogens", "enzymology", "microbiology", "retroviruses", "epistasis", "immunodeficiency viruses", "viruses", "rna viruses", "microbial evolution", "pharmacolo...	Strong Selection Significantly Increases Epistatic Interactions in the Long-Term Evolution of a Protein	journal.pgen.1005960	null	[ [ "The interactions between the residues within a single protein ( within-protein epistasis [1] ) often determine the structure and function of the protein [2–4] .", "Understanding these epistatic interactions is important because they shape the protein fitness landscape and thus guide the evolution of a pr...	[ "Epistatic interactions between residues determine a protein’s adaptability and shape its evolutionary trajectory .", "When a protein experiences a changed environment , it is under strong selection to find a peak in the new fitness landscape .", "It has been shown that strong selection increases epistatic inte...	[ "Evolution is often viewed as a process that occurs “mutation by mutation” , suggesting that the effect of each mutation is independent of that of others .", "However , in reality the effect of a mutation often depends on the context of other mutations , a dependence known as “epistasis” .", "Even though epista...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "phosphorylation", "medicine and health sciences", "protein interactions", "chemical compounds", "nervous system", "enzymes", "immunology", "enzymology", "neuroscience", "organic compounds", "clinical medicine", "tyrosine", "immunoprecipitation", "amino acids", "hypersensitivity", "res...	Extracellular phosphorylation of a receptor tyrosine kinase controls synaptic localization of NMDA receptors and regulates pathological pain	journal.pbio.2002457	null	[ [ "Modification of protein function by phosphorylation controls many aspects of cellular function and signaling [1] .", "Interestingly , the first evidence for phosphoproteins came from the observation that the secreted milk protein , casein , contained phosphate , suggesting that phosphorylation can occur ...	[ "Extracellular phosphorylation of proteins was suggested in the late 1800s when it was demonstrated that casein contains phosphate .", "More recently , extracellular kinases that phosphorylate extracellular serine , threonine , and tyrosine residues of numerous proteins have been identified .", "However , the f...	[ "The activity of proteins can be finely and reversibly tuned by post-translational modifications .", "The attachment of phosphate groups to tyrosine residues is one of such modifications .", "While the existence of extracellular phosphoproteins has been known , the functional significance of extracellular phosp...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine" ]	The Use of a Mobile Laboratory Unit in Support of Patient Management and Epidemiological Surveillance during the 2005 Marburg Outbreak in Angola	journal.pntd.0001183	null	[ [ "Marburg virus ( MARV ) is classified as members of the family Filoviridae , genus Marburgvirus , type species Lake Victoria marburgvirus .", "A single species has been described which includes several virus strains [1] .", "Today , the geographic distribution of MARV seems to primarily involve areas ...	[ "Marburg virus ( MARV ) , a zoonotic pathogen causing severe hemorrhagic fever in man , has emerged in Angola resulting in the largest outbreak of Marburg hemorrhagic fever ( MHF ) with the highest case fatality rate to date .", "A mobile laboratory unit ( MLU ) was deployed as part of the World Health Organizati...	[ "A mobile laboratory unit ( MLU ) was deployed to Uige , Angola as part of the World Health Organization response to an outbreak of viral hemorrhagic fever caused by Marburg virus ( MARV ) .", "Utilizing mainly quantitative real-time PCR assays , this laboratory provided specific MARV diagnostics in the field .",...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Genome-Wide Negative Feedback Drives Transgenerational DNA Methylation Dynamics in Arabidopsis	journal.pgen.1005154	null	[ [ "Epigenetic variation of gene expression is mediated by chromatin marks , such as modifications of histones and DNA .", "Importantly , these marks and associated gene expression patterns can be inherited over multiple generations in both animals and plants [1 , 2] .", "Transgenerational epigenetic inh...	[ "Epigenetic variations of phenotypes , especially those associated with DNA methylation , are often inherited over multiple generations in plants .", "The active and inactive chromatin states are heritable and can be maintained or even be amplified by positive feedback in a transgenerational manner .", "However...	[ "DNA methylation is important for controlling activity of transposable elements and genes .", "An intriguing feature of DNA methylation in plants is that its pattern can be inherited over multiple generations at high fidelity in a Mendelian manner .", "However , mechanisms controlling the trans-generational DNA...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "computer science", "hematology/hemoglobinopathies", "pathology/pathophysiology", "physics/condensed matter", "physiology/cardiovascular physiology and circulation", "physics/fluids, plasmas, and electric discharges", "physiology/integrative physiology", "biotechnology/bioengineering", "mathematics/...	Statistical Dynamics of Flowing Red Blood Cells by Morphological Image Processing	journal.pcbi.1000288	null	[ [ "Red blood cells are the major component of blood and with a radius of ∼4 µm and a thickness of ∼1–2 µm are sufficiently large that the effects of thermal fluctuations are typically negligible , i . e . their equilibrium diffusivity is very small ( where f is the viscous drag coefficient for a flat disk with ...	[ "Blood is a dense suspension of soft non-Brownian cells of unique importance .", "Physiological blood flow involves complex interactions of blood cells with each other and with the environment due to the combined effects of varying cell concentration , cell morphology , cell rheology , and confinement .", "We a...	[ "Viewed from a distance , flowing blood looks like a uniform fluid , but up close the cells in the blood change their position and speed somewhat heterogeneously .", "These individual cell movements may play a role in the physiology and pathophysiology of nutrient and gas transport , clotting , and diseases where...	2009
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "cell death", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "pathogens", "immunology", "cell processes", "microbiology", "staphylococcus aureus", "pulmonology", "salmonellosis", "pneumonia", "methicillin-resistant staphylococcus aureus"...	NLRP6 negatively regulates pulmonary host defense in Gram-positive bacterial infection through modulating neutrophil recruitment and function	journal.ppat.1007308	null	[ [ "Acute pneumonia is a leading cause of childhood mortality ( <5 years of age ) accounting for the death of 920 , 136 children annually [1] , and methicillin-resistant Staphylococcus aureus ( MRSA ) has been implicated in severe life-threatening infections , including necrotizing pneumonia and sepsis [2] .", ...	[ "Gram-positive bacteria , including Staphylococcus aureus are endemic in the U . S . , which cause life-threatening necrotizing pneumonia .", "Neutrophils are known to be critical for clearance of S . aureus infection from the lungs and extrapulmonary organs .", "Therefore , we investigated whether the NLRP6 in...	[ "Gram-positive bacteria , including Staphylococcus aureus remain a major cause of acute pneumonia worldwide .", "Due to emergence of multidrug-resistant strains , alternative strategies for treatment of S . aureus pneumonia are needed .", "To this end , it may be possible to harness host defenses to eradicate t...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology/morphogenesis and cell biology", "cell biology/cell signaling", "cell biology/developmental molecular mechanisms", "developmental biology/molecular development", "molecular biology", "genetics and genomics", "cardiovascular disorders" ]	Murine Dishevelled 3 Functions in Redundant Pathways with Dishevelled 1 and 2 in Normal Cardiac Outflow Tract, Cochlea, and Neural Tube Development	journal.pgen.1000259	null	[ [ "Normal mammalian development is the result of complex signaling networks that regulate and coordinate cell behavior .", "Wnt signaling controls a broad spectrum of cell fate decisions during embryogenesis and is critical for cell to cell communication in mammalian development .", "Through the activat...	[ "Dishevelled ( Dvl ) proteins are important signaling components of both the canonical β-catenin/Wnt pathway , which controls cell proliferation and patterning , and the planar cell polarity ( PCP ) pathway , which coordinates cell polarity within a sheet of cells and also directs convergent extension cell ( CE ) m...	[ "Multi-gene families , comprising a set of very similar genes with shared nucleotide sequences , are common in mammals .", "Individual family members may be expressed in different places and perform separate functions .", "Alternatively , the genes may have redundant functions , but distinct dosage requirements...	2008
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "toxins", "pathology and laboratory medicine", "viral transmission and infection", "pathogens", "endothelial cells", "microbiology", "cadherins", "toxic agents", "toxicology", "pseudomonas aeruginosa", "epithelial cells", "enterobacteriaceae", "serratia", ...	Pseudomonas aeruginosa ExlA and Serratia marcescens ShlA trigger cadherin cleavage by promoting calcium influx and ADAM10 activation	journal.ppat.1006579	null	[ [ "Multicellular organisms have developed barriers to protect their internal body from microbial invasion .", "Mucosae constituted of single-layered epithelial cells are the favoured tissue barriers that bacteria may cross .", "Pathogenic bacteria have engineered different weapons to traverse these bord...	[ "Pore-forming toxins are potent virulence factors secreted by a large array of bacteria .", "Here , we deciphered the action of ExlA from Pseudomonas aeruginosa and ShlA from Serratia marcescens on host cell-cell junctions .", "ExlA and ShlA are two members of a unique family of pore-forming toxins secreted by ...	[ "Pore-forming toxins are the most widespread toxins delivered by pathogenic bacteria and are required for full virulence .", "Pore-forming toxins perforate membranes of host cells for intracellular delivery of bacterial factors , for bacterial escape from phagosomes or in order to kill cells .", "Loss of membra...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genomics", "genome evolution", "microbial evolution", "genetics and genomics", "biology", "evolutionary biology", "genomic evolution", "comparative genomics", "evolutionary genetics", "microbiology" ]	Sequence Conservation and Functional Constraint on Intergenic Spacers in Reduced Genomes of the Obligate Symbiont Buchnera	journal.pgen.1002252	null	[ [ "Obligate bacterial symbionts possess the smallest cellular genomes [1] .", "Due to their extreme genome reduction , they retain only small fractions of ancestral gene sets .", "Comparisons of complete genome sequences within clades have revealed that genomes of obligate symbionts are stable , with fe...	[ "Analyses of genome reduction in obligate bacterial symbionts typically focus on the removal and retention of protein-coding regions , which are subject to ongoing inactivation and deletion .", "However , these same forces operate on intergenic spacers ( IGSs ) and affect their contents , maintenance , and rates ...	[ "Endosymbiotic associations , such as that between Buchnera aphidicola and its aphid hosts , persist for millions of years and result in substantial changes to symbiont genomes .", "Most notably , symbionts exhibit reductions in genome size , the accumulation of slightly deleterious mutations , and rapid rates of...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	A Common Mechanism Underlying Food Choice and Social Decisions	journal.pcbi.1004371	null	[ [ "The most basic tenet in standard economic theory is that individuals know their preferences , and those preferences in turn determine their choices .", "In this approach , preference and choice are one and the same thing .", "However , this fundamental assumption is at odds with an extensive experime...	[ "People make numerous decisions every day including perceptual decisions such as walking through a crowd , decisions over primary rewards such as what to eat , and social decisions that require balancing own and others’ benefits .", "The unifying principles behind choices in various domains are , however , still ...	[ "One critical question that concerns all disciplines involved in the study of human decision-making is whether different types of decisions are made in different ways , or whether there exists a common decision mechanism that underlies human choices .", "If the latter , what are the properties of that mechanism ?...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "aspergillus fumigatus", "medicine and health sciences", "chemical compounds", "pathology and laboratory medicine", "aspergillus", "fungal genetics", "gene regulation", "pathogens", "regulatory proteins", "microbiology", "dna-binding proteins", "organic compounds", "fungi", "transcription ...	A Novel Zn2-Cys6 Transcription Factor AtrR Plays a Key Role in an Azole Resistance Mechanism of Aspergillus fumigatus by Co-regulating cyp51A and cdr1B Expressions	journal.ppat.1006096	null	[ [ "Aspergillosis is one of the most common infectious diseases by mold , with Aspergillus fumigatus being the most frequently causative fungus with high mortality ( more than 60% ) .", "Despite the importance of this disease , approved antifungals for treatment of aspergillosis are quite limited .", "To...	[ "Successful treatment of aspergillosis caused by Aspergillus fumigatus is threatened by an increasing incidence of drug resistance .", "This situation is further complicated by the finding that strains resistant to azoles , the major antifungal drugs for aspergillosis , have been widely disseminated across the gl...	[ "Better survival of chronically ill patients has produced an increased number of cases involving fungal infectious disease .", "This is partly due to a larger number of immunocompromised patients .", "Meanwhile , the catalogue of antifungal drugs remains quite limited and the appearance of resistant isolates is...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "invertebrates", "caenorhabditis", "animals", "collagens", "animal models", "developmental biology", "caenorhabditis elegans", "drosophila melanogaster", "model organisms", "experimental organism systems", "embryos", "drosophila", "research and analysis methods", "embryolo...	Dissection of Nidogen function in Drosophila reveals tissue-specific mechanisms of basement membrane assembly	journal.pgen.1007483	null	[ [ "Basement membranes ( BM ) are specialized thin extracellular matrices underlying all epithelia and endothelia , and surrounding many mesenchyme cells .", "This thin layer structure , which appears early in development , plays key roles in the morphogenesis , function , compartmentalization and maintenanc...	[ "Basement membranes ( BMs ) are thin sheet-like specialized extracellular matrices found at the basal surface of epithelia and endothelial tissues .", "They have been conserved across evolution and are required for proper tissue growth , organization , differentiation and maintenance .", "The major constituents...	[ "Basement membranes ( BMs ) are thin layers of specialized extracellular matrices present in every tissue of the human body .", "Its main constituents are two networks of laminin and Type IV Collagen linked by Nidogen ( Ndg ) and proteoglycans .", "They form an organized scaffold that regulates organ morphogene...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/functional genomics", "geriatrics/dementia", "biochemistry/chemical biology of the cell", "genetics and genomics/disease models", "genetics and genomics/gene function", "biochemistry/cell signaling and trafficking structures", "microbiology", "chemical biology" ]	Srf1 Is a Novel Regulator of Phospholipase D Activity and Is Essential to Buffer the Toxic Effects of C16:0 Platelet Activating Factor	journal.pgen.1001299	null	[ [ "Perturbations in glycerophosphocholine ( GPC ) metabolism are linked to the pathogenesis of Alzheimer's Disease ( AD ) with the accumulation of choline-containing lipids in AD patients associated with accelerated cognitive decline [1]–[4] .", "Soluble amyloid-β42 ( Aβ42 ) oligomers can increase hydrolysi...	[ "During Alzheimer's Disease , sustained exposure to amyloid-β42 oligomers perturbs metabolism of ether-linked glycerophospholipids defined by a saturated 16 carbon chain at the sn-1 position .", "The intraneuronal accumulation of 1-O-hexadecyl-2-acetyl-sn-glycerophosphocholine ( C16:0 PAF ) , but not its immediat...	[ "Accelerated cognitive decline in Alzheimer's patients is associated with accumulation of choline-containing lipids .", "One of these lipids , C16:0 platelet activating factor ( PAF ) , is specifically elevated in brains of Alzheimer's patients .", "As elevated exposure to C16:0 PAF ultimately leads to neuronal...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "inflammation", "immunity", "microbial pathogens", "biology", "microbiology", "host-pathogen interaction", "microbial growth and development", "bacterial pathogens" ]	GogB Is an Anti-Inflammatory Effector that Limits Tissue Damage during Salmonella Infection through Interaction with Human FBXO22 and Skp1	journal.ppat.1002773	null	[ [ "Horizontal gene transfer ( HGT ) is an important contributor to the genetic and phenotypic diversity of enteric bacteria .", "Plasmids and genetic regions called pathogenicity islands ( PAI ) can provide a fitness advantage and the ability to colonize and expand into novel host niches [1] .", "HGT ha...	[ "Bacterial pathogens often manipulate host immune pathways to establish acute and chronic infection .", "Many Gram-negative bacteria do this by secreting effector proteins through a type III secretion system that alter the host response to the pathogen .", "In this study , we determined that the phage-encoded G...	[ "Bacterial pathogens have evolved sophisticated ways to subvert the innate defenses of their host .", "One way in which pathogens do so is by blocking or dampening the inflammatory response that is triggered once a microorganism is detected by the innate immune system .", "In this way , the microorganism can li...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/mechanisms of resistance and susceptibility, including host genetics", "virology/viral replication and gene regulation", "virology" ]	A Unique Role for the Host ESCRT Proteins in Replication of Tomato bushy stunt virus	journal.ppat.1000705	null	[ [ "Plus-stranded ( + ) RNA viruses replicate in the infected cells by assembling viral replicase complexes consisting of viral- and host-coded proteins in combination with the viral RNA template .", "Although major progress has recently been made in understanding the functions of the viral replication prote...	[ "Plus-stranded RNA viruses replicate in infected cells by assembling viral replicase complexes consisting of viral- and host-coded proteins .", "Previous genome-wide screens with Tomato bushy stunt tombusvirus ( TBSV ) in a yeast model host revealed the involvement of seven ESCRT ( endosomal sorting complexes req...	[ "Plus-stranded RNA viruses , which are important pathogens of humans , animals and plants , replicate in infected cells by assembling viral replicase complexes consisting of viral- and host-coded proteins .", "In this paper , we show that a group of host factors called ESCRT proteins ( endosomal sorting complexes...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "genetics and genomics/genomics", "microbiology/medical microbiology", "infectious diseases/bacterial infections" ]	Genotyping of Human Lice Suggests Multiple Emergences of Body Lice from Local Head Louse Populations	journal.pntd.0000641	null	[ [ "Lice are extremely well-adapted ectoparasites that are usually host-specific [1] .", "Three recognized taxa of lice feed on humans: head lice ( Pediculus humanus capitis ) , body lice ( Pediculus humanus humanus ) , and pubic lice ( Pthirius pubis ) , feed on humans .", "As one of the most intimate p...	[ "Genetic analyses of human lice have shown that the current taxonomic classification of head lice ( Pediculus humanus capitis ) and body lice ( Pediculus humanus humanus ) does not reflect their phylogenetic organization .", "Three phylotypes of head lice A , B and C exist but body lice have been observed only in...	[ "While being phenotypically and physiologically different , human head and body lice are indistinguishable based on mitochondrial and nuclear genes .", "As protein-coding genes are too conserved to provide significant genetic diversity , we performed strain-typing of a large collection of human head and body lice...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "danio (zebrafish)", "vertebrates", "molecular biology" ]	Targeted Inhibition of miRNA Maturation with Morpholinos Reveals a Role for miR-375 in Pancreatic Islet Development	journal.pbio.0050203	The authors show that morpholinos can be used to knock down zebrafish miRNAs, revealing that miR-375 is important for vertebrate pancreas development.	[ [ "MicroRNAs ( miRNAs ) have a profound impact on the development of multicellular organisms .", "Animals lacking the Dicer enzyme , which is responsible for the processing of the precursor miRNA into the mature form , cannot live [1–3] .", "MiRNA mutants have been described only for Caenorhabditis eleg...	[ "Several vertebrate microRNAs ( miRNAs ) have been implicated in cellular processes such as muscle differentiation , synapse function , and insulin secretion .", "In addition , analysis of Dicer null mutants has shown that miRNAs play a role in tissue morphogenesis .", "Nonetheless , only a few loss-of-function...	[ "The striking tissue-specific expression patterns of microRNAs ( miRNAs ) suggest that they play a role in tissue development .", "These small RNA molecules ( ∼22 bases in length ) are processed from long primary transcripts ( pri-miRNA ) and regulate gene expression at the posttranscriptional level .", "There ...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "meiosis", "plant growth and development", "cell cycle and cell division", "plant cell biology", "cell processes", "brassica", "cytogenetic analysis", "developmental biology", "plant science", "model organisms", "plants", "arabidopsis thaliana", "research and analysis methods", "chromosome...	Arabidopsis thaliana WAPL Is Essential for the Prophase Removal of Cohesin during Meiosis	journal.pgen.1004497	null	[ [ "The timely establishment and dissolution of sister chromatid cohesion is essential for the proper segregation of chromosomes during cell division , as well as the repair of DNA damage and the control of transcription ( reviewed in [1]–[4] ) .", "Four proteins form the core cohesin complex: Structural Mai...	[ "Sister chromatid cohesion , which is mediated by the cohesin complex , is essential for the proper segregation of chromosomes in mitosis and meiosis .", "The establishment of stable sister chromatid cohesion occurs during DNA replication and involves acetylation of the complex by the acetyltransferase CTF7 .", ...	[ "Wapl has been shown to play an integral role in the removal of cohesin from chromosomes during mitotic prophase .", "While Wapl's role appears to be conserved between yeast , fly and animal cells , structural and possible mechanistic differences have also been identified .", "As part of a study to better under...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "carbohydrate metabolism", "cell death", "chemical compounds", "oxygen", "cell cycle and cell division", "cell processes", "carbohydrates", "glucose metabolism", "organic compounds", "glucose", "oxygen metabolism", "cellular structures and organelles", "extracellular matrix", "chemistry", ...	Inferring Growth Control Mechanisms in Growing Multi-cellular Spheroids of NSCLC Cells from Spatial-Temporal Image Data	journal.pcbi.1004412	null	[ [ "In early development , tumors grow up to 1–2mm in diameter , nourished by the nutrients and oxygen provided by the existing vasculature .", "Either 2D or 3D cell culture systems are utilized as biological models to study that phase , or aspects usually occurring in later phases of tumor growth and develo...	[ "We develop a quantitative single cell-based mathematical model for multi-cellular tumor spheroids ( MCTS ) of SK-MES-1 cells , a non-small cell lung cancer ( NSCLC ) cell line , growing under various nutrient conditions: we confront the simulations performed with this model with data on the growth kinetics and spa...	[ "We here present how to parameterize a mathematical agent-based model of growing MCTS almost completely from experimental data .", "MCTS show a similar establishment of pathophysiological gradients and concentric arrangement of heterogeneous cell populations as found in avascular tumor nodules .", "We build a p...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "inflammatory diseases", "heme", "medicine and health sciences", "parasite groups", "body fluids", "pathology and laboratory medicine", "plasmodium", "immunology", "tropical diseases", "bile", "biomarkers", "parasitic diseases", "parasitology", "apicomplexa", "signs and symptoms", "kid...	Distinct inflammatory profile underlies pathological increases in creatinine levels associated with Plasmodium vivax malaria clinical severity	journal.pntd.0006306	null	[ [ "Malaria is an infectious disease known for millennia .", "Although substantial investments have been made in the last couple of decades , with slight improvements regarding control of disease transmission in some endemic territories , the disease is still responsible for over 200 million cases annually ,...	[ "Although Plasmodium vivax infection is a frequent cause of malaria worldwide , severe presentations have been more regularly described only in recent years .", "In this setting , despite clinical descriptions of multi-organ involvement , data associating it with kidney dysfunction are relatively scarce .", "He...	[ "Severe clinical presentations of Plasmodium vivax malaria are not completely understood .", "Multi-organ involvement is described in severe vivax cases , however data associating it with kidney dysfunction are relatively scarce , in part because the clinical signs only appear late during kidney injury .", "We ...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "cell death", "medicine and health sciences", "diabetic endocrinology", "cell cycle and cell division", "cell processes", "messenger rna", "hormones", "erk signaling cascade", "insulin", "endocrinology", "biochemistry", "rna", "signal transduction", "biochemical simulations", "cell biolo...	A mechanistic pan-cancer pathway model informed by multi-omics data interprets stochastic cell fate responses to drugs and mitogens	journal.pcbi.1005985	null	[ [ "Oncogene-targeted small molecule kinase inhibitors , like imatinib for BCR-ABL [1] , have transformed chemotherapy .", "However , such precision medicine approaches are not always efficacious .", "In some cases , mutation-matched patients do not respond to the drug [2] , or alternatively , resistance...	[ "Most cancer cells harbor multiple drivers whose epistasis and interactions with expression context clouds drug and drug combination sensitivity prediction .", "We constructed a mechanistic computational model that is context-tailored by omics data to capture regulation of stochastic proliferation and death by pa...	[ "Cancer is a complex and diverse disease .", "Two people with the same cancer type often respond differently to the same treatment .", "These differences are primarily driven by the fact that two type-matched tumors can possess distinct sets of mutations and gene expression profiles , provoking differential sen...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Relationship between Distinct African Cholera Epidemics Revealed via MLVA Haplotyping of 337 Vibrio cholerae Isolates	journal.pntd.0003817	null	[ [ "Since 1817 , seven cholera pandemics have plagued humans worldwide [1] .", "During the current pandemic , the disease first appeared on the African continent when Vibrio cholerae was imported by migrants traveling to the Guinean capital of Conakry in 1970 [1] .", "Following this importation of the ba...	[ "Since cholera appeared in Africa during the 1970s , cases have been reported on the continent every year .", "In Sub-Saharan Africa , cholera outbreaks primarily cluster at certain hotspots including the African Great Lakes Region and West Africa .", "In this study , we applied MLVA ( Multi-Locus Variable Numb...	[ "Cholera is caused by the toxigenic bacterium Vibrio cholerae .", "Since cholera was imported into the West African country of Guinea in 1970 , cases have been reported on the continent every year .", "In Sub-Saharan Africa , cholera occurs in a heterogeneous manner; outbreaks primarily cluster at certain hotsp...	2015
[ "Introduction", "Result", "Discussion", "Methods" ]	[]	A Simple Model-Based Approach to Inferring and Visualizing Cancer Mutation Signatures	journal.pgen.1005657	null	[ [ "Cancer is a genomic disease .", "As we lead a life , DNA within our cells acquires random somatic mutations , mainly caused by DNA replication errors and exposures to mutagens such as chemical substances , radioactivities and inflammatory reactions .", "Although most mutations are harmless ( called “...	[ "Recent advances in sequencing technologies have enabled the production of massive amounts of data on somatic mutations from cancer genomes .", "These data have led to the detection of characteristic patterns of somatic mutations or “mutation signatures” at an unprecedented resolution , with the potential for new...	[ "Somatic ( non-inherited ) mutations are acquired throughout our lives in cells throughout our body .", "These mutations can be caused , for example , by DNA replication errors or exposure to environmental mutagens such as tobacco smoke .", "Some of these mutations can lead to cancer .", "Different cancers , ...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "biochemistry", "infectious diseases", "mycology", "medical microbiology", "immunology", "biology", "microbiology", "pathogenesis" ]	A Polysaccharide Virulence Factor from Aspergillus fumigatus Elicits Anti-inflammatory Effects through Induction of Interleukin-1 Receptor Antagonist	journal.ppat.1003936	null	[ [ "Aspergillus fumigatus is an opportunistic fungus that causes infections under specific conditions , of which secondary immunodeficiency is by far the largest risk factor for the development of invasive infections [1] .", "In order to initiate an effective host response against Aspergillus , recognition o...	[ "The galactosaminogalactan ( GAG ) is a cell wall component of Aspergillus fumigatus that has potent anti-inflammatory effects in mice .", "However , the mechanisms responsible for the anti-inflammatory property of GAG remain to be elucidated .", "In the present study we used in vitro PBMC stimulation assays to...	[ "Aspergillus fumigatus is an opportunistic pathogenic fungus that primarily causes infections in the immunocompromised host .", "It is known that Aspergillus employs various strategies to evade immune recognition by the host's immune system .", "Recently , galactosaminogalactan ( GAG ) , a new component of the ...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Bistability in a Metabolic Network Underpins the De Novo Evolution of Colony Switching in Pseudomonas fluorescens	journal.pbio.1002109	The molecular basis of an experimentally evolved colony-level phenotype switch is revealed to affect a metabolic bifurcation point where nucleotides can be used for either cell division or capsule polymer synthesis.	[ [ "Life is constantly challenged by environmental change .", "Survival requires that organisms match their phenotype to current conditions .", "In predictable environments , this occurs by phenotypic acclimation [1] .", "In unpredictable environments , where the quality of environmental information ...	[ "Phenotype switching is commonly observed in nature .", "This prevalence has allowed the elucidation of a number of underlying molecular mechanisms .", "However , little is known about how phenotypic switches arise and function in their early evolutionary stages .", "The first opportunity to provide empirical...	[ "Phenotype switching—the ability to switch rapidly between phenotypic states—is an evolutionary survival strategy commonly used by organisms in the face of unpredictable environmental conditions .", "However , little is known about how phenotype switches emerge and function in their early evolutionary stages .", ...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "animal models", "animal models of infection", "model organisms", "viral immune evasion", "immunity", "virology", "innate immunity", "viral persistence and latency", "immune defense", "biology", "microbiology", "mouse", "pathogenesis" ]	A Gammaherpesvirus Cooperates with Interferon-alpha/beta-Induced IRF2 to Halt Viral Replication, Control Reactivation, and Minimize Host Lethality	journal.ppat.1002371	null	[ [ "The gammaherpesviruses ( γHVs ) establish life-long latent infection in memory B lymphocytes .", "The human γHVs Epstein-Barr virus ( EBV ) and Kaposi's sarcoma-associated herpesvirus ( KSHV ) are the causes of infectious mononucleosis and Kaposi's sarcoma ( KS ) , respectively [1] , [2] .", "γHV lat...	[ "The gammaherpesviruses , including Epstein-Barr virus ( EBV ) and Kaposi's sarcoma-associated herpesvirus ( KSHV ) , establish latency in memory B lymphocytes and promote lymphoproliferative disease in immunocompromised individuals .", "The precise immune mechanisms that prevent gammaherpesvirus reactivation and...	[ "Herpesviruses establish life-long infection in a non-replicating state termed latency .", "During immune compromise , herpesviruses can reactivate and cause severe disease , including cancer .", "We investigated mechanisms by which interferons alpha/beta ( IFNαβ ) , a family of antiviral immune genes , inhibit...	2011
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "nonlinear dynamics", "mathematics", "theoretical biology", "viral transmission and infection", "population modeling", "virology", "immunology", "biology", "computational biology", "microbiology", "viral load", "immune response" ]	Modeling Within-Host Dynamics of Influenza Virus Infection Including Immune Responses	journal.pcbi.1002588	null	[ [ "Despite vaccines and antiviral agents , influenza A virus infection remains a major public health problem worldwide .", "Seasonal and pandemic influenza results in approximately 3 to 5 million cases of severe illness and approximately 250 , 000 to 500 , 000 deaths worldwide [1] .", "Influenza viruses...	[ "Influenza virus infection remains a public health problem worldwide .", "The mechanisms underlying viral control during an uncomplicated influenza virus infection are not fully understood .", "Here , we developed a mathematical model including both innate and adaptive immune responses to study the within-host ...	[ "Influenza , commonly referred to as the flu , is a contagious respiratory illness caused by influenza virus infections .", "Although most infected subjects with intact immune systems are able to clear the virus without developing serious flu complications , the mechanisms underlying viral control are not fully u...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Polycomb Protein SCML2 Regulates the Cell Cycle by Binding and Modulating CDK/CYCLIN/p21 Complexes	journal.pbio.1001737	A transcription-independent role is identified for the human Polycomb group protein SCML2B in regulating the cell cycle. SCML2B cooperates with p21 to inhibit CDK2/CYCE complexes during early G1, resulting in delayed entry into S phase.	[ [ "Polycomb group ( PcG ) proteins are key developmental regulators that maintain epigenetic silencing of genes [1] and determine the expression patterns of homeobox genes during embryonic development .", "In Drosophila five different PcG complexes have been described: Polycomb Repressive Complex 1 ( PRC1 )...	[ "Polycomb group ( PcG ) proteins are transcriptional repressors of genes involved in development and differentiation , and also maintain repression of key genes involved in the cell cycle , indirectly regulating cell proliferation .", "The human SCML2 gene , a mammalian homologue of the Drosophila PcG protein SCM...	[ "The processes of development and differentiation require an exquisite coordination of the gene expression program with the proliferation of the cells .", "The Polycomb group of proteins are important development regulators and most research to date has focused on their involvement in maintaining epigenetic silen...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal models", "caenorhabditis elegans", "cellular neuroscience", "animal genetics", "model organisms", "genetics", "biology", "neuroscience", "genetics and genomics" ]	The Secreted Immunoglobulin Domain Proteins ZIG-5 and ZIG-8 Cooperate with L1CAM/SAX-7 to Maintain Nervous System Integrity	journal.pgen.1002819	null	[ [ "The structural organization of an adult nervous system depends on two genetically separable processes .", "First , during development - the wiring phase - the soma and axonal/dendritic extensions of neurons need to be accurately positioned .", "This process depends on the precisely orchestrated activ...	[ "During nervous system development , neuronal cell bodies and their axodendritic projections are precisely positioned through transiently expressed patterning cues .", "We show here that two neuronally expressed , secreted immunoglobulin ( Ig ) domain-containing proteins , ZIG-5 and ZIG-8 , have no detectable rol...	[ "The structure of nervous systems is determined during embryonic development .", "After this developmental patterning phase , active maintenance mechanisms are required to uphold the structural integrity of the nervous system .", "This concept was revealed through the genetic elimination of factors in the nemat...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Genome-Wide Association Analysis of Adaptation Using Environmentally Predicted Traits	journal.pgen.1005594	null	[ [ "The genetic basis of environmental adaptation in natural and agricultural populations is a topic of growing interest and urgency .", "Conventionally , the search for adaptive genes involves testing for associations of genomic markers with either ecologically relevant traits measured in common garden expe...	[ "Current methods for studying the genetic basis of adaptation evaluate genetic associations with ecologically relevant traits or single environmental variables , under the implicit assumption that natural selection imposes correlations between phenotypes , environments and genotypes .", "In practice , observed tr...	[ "Finding genes involved in adaptation to the environment has long been of interest to evolutionary biologists and ecologists .", "Most commonly , researchers look for loci whose differences in allelic state correlate with differences in a particular trait or environmental variable such as temperature .", "The i...	2015
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "mathematics", "plasmodium", "computational biology", "evolutionary biology", "eubacteria" ]	Using Likelihood-Free Inference to Compare Evolutionary Dynamics of the Protein Networks of H. pylori and P. falciparum	journal.pcbi.0030230	null	[ [ "Genomic sequence data provides substantial evidence for the abundance of duplicated genes in all organisms surveyed: at least 40% of genes in two prokaryotes [1 , 2] and 15%–90% of genes in eukaryotes [3–5] appear to be products of gene duplication .", "This suggests that gene duplication is a key mechan...	[ "Gene duplication with subsequent interaction divergence is one of the primary driving forces in the evolution of genetic systems .", "Yet little is known about the precise mechanisms and the role of duplication divergence in the evolution of protein networks from the prokaryote and eukaryote domains .", "We de...	[ "The importance of gene duplication to biological evolution has been recognized since the 1930s .", "For more than a decade , substantial evidence has been collected from genomic sequence data in order to elucidate the importance and the mechanisms of gene duplication; however , most biological characteristics ar...	2007
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "bacteriology", "medicine and health sciences", "immune physiology", "enzyme-linked immunoassays", "pathology and laboratory medicine", "pathogens", "immunology", "microbiology", "vaccines", "bacterial diseases", "enterobacteriaceae", "infectious disease control", "antibodies", "immunologi...	Development of a glycoconjugate vaccine to prevent invasive Salmonella Typhimurium infections in sub-Saharan Africa	journal.pntd.0005493	null	[ [ "Non-typhoidal Salmonella ( NTS ) are important human pathogens worldwide where infection in healthy adults normally results in self-limiting gastroenteritis .", "They can also cause fulminant invasive disease ( e . g . , bacteremia , septicemia , meningitis ) , particularly in hosts with immunological im...	[ "Invasive infections associated with non-typhoidal Salmonella ( NTS ) serovars Enteritidis ( SE ) , Typhimurium ( STm ) and monophasic variant 1 , 4 , [5] , 12:i:- are a major health problem in infants and young children in sub-Saharan Africa , and currently , there are no approved human NTS vaccines .", "NTS O-p...	[ "In sub-Saharan Africa , invasive non-typhoidal Salmonella ( NTS ) infections with serovars Enteritidis ( SE ) and Typhimurium ( STm ) are widespread in children , where up to 30% of cases are fatal .", "There are several licensed typhoid vaccines but no NTS vaccines .", "We previously reported that conjugates ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Laminar and Dorsoventral Molecular Organization of the Medial Entorhinal Cortex Revealed by Large-scale Anatomical Analysis of Gene Expression	journal.pcbi.1004032	null	[ [ "Spatial cognition emerges from interactions between specialized neuronal populations in the hippocampal-entorhinal system [1] .", "The medial entorhinal cortex ( MEC ) is of particular importance for cognitive functions that rely on estimation of spatial position and orientation [2] .", "Neurons in e...	[ "Neural circuits in the medial entorhinal cortex ( MEC ) encode an animal’s position and orientation in space .", "Within the MEC spatial representations , including grid and directional firing fields , have a laminar and dorsoventral organization that corresponds to a similar topography of neuronal connectivity ...	[ "Higher brain functions such as spatial cognition are carried out in specialized brain areas .", "Within a specialized brain area nerve cells with different functions are organized in layers and gradients .", "It is possible that this topographical organization reflects underlying differences in molecular organ...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "nervous system", "membrane potential", "ions", "electrophysiology", "neuroscience", "simulation and modeling", "computational neuroscience", "neuronal dendrites", "physical chemistry", "research and analysis methods", "animal cells", "chemistry", "cellular ...	Effect of Ionic Diffusion on Extracellular Potentials in Neural Tissue	journal.pcbi.1005193	null	[ [ "The number of ions exchanged between neurons and the extracellular space ( ECS ) during a brief period of activity ( i . e . , due to the integration of synaptic input and generation of a few action potentials ) is typically too small to evoke significant changes in extracellular ion concentrations .", "...	[ "Recorded potentials in the extracellular space ( ECS ) of the brain is a standard measure of population activity in neural tissue .", "Computational models that simulate the relationship between the ECS potential and its underlying neurophysiological processes are commonly used in the interpretation of such meas...	[ "When electrical potentials are measured in the extracellular space ( ECS ) of the brain , they are interpreted as a signature of neural signalling .", "The relationship between the ECS potentials and the underlying neuronal processes is often studied with the aid of computer models .", "The ECS potential is ty...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "mutation", "haplotypes", "genomics", "adaptation", "genetic mutation", "genetic polymorphism", "natural selection", "genetics", "population genetics", "evolutionary selection", "biology", "comparative genomics", "evolutionary biology", "evolutionary immunology", "population biology", ...	Extreme Population Differences in the Human Zinc Transporter ZIP4 (SLC39A4) Are Explained by Positive Selection in Sub-Saharan Africa	journal.pgen.1004128	null	[ [ "Zinc homeostasis is critically important for human health .", "Similarly to iron , zinc has manifold functions in the body , such as in the immune system [1] , aging [2] , DNA repair [3] , signaling [4] and in diseases such as diabetes [5] and cancer [6] .", "On the molecular level , zinc acts as a c...	[ "Extreme differences in allele frequency between West Africans and Eurasians were observed for a leucine-to-valine substitution ( Leu372Val ) in the human intestinal zinc uptake transporter , ZIP4 , yet no further evidence was found for a selective sweep around the ZIP4 gene ( SLC39A4 ) .", "By interrogating alle...	[ "Zinc is an essential trace element with many biological functions in the body , whose concentrations are tightly regulated by different membrane transporters .", "Here we report an unusual case of positive natural selection for an amino acid replacement in the human intestinal zinc uptake transporter ZIP4 .", ...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "invertebrates", "innate immune system", "medicine and health sciences", "pathology and laboratory medicine", "caenorhabditis", "immunology", "microbiology", "animals", "animal models", "bacterial diseases", "caenorhabditis elegans", "model organisms", "pseudomonas infections", "research a...	The Evolutionarily Conserved Mediator Subunit MDT-15/MED15 Links Protective Innate Immune Responses and Xenobiotic Detoxification	journal.ppat.1004143	null	[ [ "In nature , organisms encounter environmental insults , such as chemical toxins , secreted microbial virulence factors and invasive pathogens , that threaten their ability to survive and reproduce .", "As a result , metazoans have evolved protective pathways to counter these challenges .", "For examp...	[ "Metazoans protect themselves from environmental toxins and virulent pathogens through detoxification and immune responses .", "We previously identified a small molecule xenobiotic toxin that extends survival of Caenorhabditis elegans infected with human bacterial pathogens by activating the conserved p38 MAP kin...	[ "Metazoans respond to environmental threats in part through conserved pathways that coordinate protective transcriptional responses .", "During infection with an invasive pathogen , for example , innate immune pathways regulate the secretion of antimicrobial immune effectors .", "Likewise , exposure to toxic mo...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Rapid Intrahost Evolution of Human Cytomegalovirus Is Shaped by Demography and Positive Selection	journal.pgen.1003735	null	[ [ "Human cytomegalovirus ( HCMV ) is a β-herpesvirus with seroprevalence of 30–90% in the United States [1] .", "In healthy individuals , primary HCMV infection is usually asymptomatic or causes a mild febrile illness .", "However , in the immuno-compromised or immune-naïve host , HCMV infection can lea...	[ "Populations of human cytomegalovirus ( HCMV ) , a large DNA virus , are highly polymorphic in patient samples , which may allow for rapid evolution within human hosts .", "To understand HCMV evolution , longitudinally sampled genomic populations from the urine and plasma of 5 infants with symptomatic congenital ...	[ "The large , dsDNA virus Human cytomegalovirus ( HCMV ) is the most genetically complex viral pathogen of humans .", "HCMV populations are highly variable , which may allow the virus to evolve in human hosts on short timescales .", "We tested this hypothesis by longitudinally sampling HCMV populations from the ...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "cancer genomics", "medicine and health sciences", "genetic networks", "protein interactions", "protein interaction networks", "basic cancer research", "oncology", "integrins", "pharmaceutics", "network analysis", "cellular structures and organelles", "computer and information sciences", "pr...	Identification of pathways associated with chemosensitivity through network embedding	journal.pcbi.1006864	null	[ [ "Large-scale cancer genomics projects , such as the Cancer Genome Atlas [1] , the Cancer Genome project [2] , and the Cancer Cell Line Encyclopedia project [3] , and cancer pharmacology projects , such as the Genomics of Drug Sensitivity in Cancer project [2] , have generated a large volume of genomics and ph...	[ "Basal gene expression levels have been shown to be predictive of cellular response to cytotoxic treatments .", "However , such analyses do not fully reveal complex genotype- phenotype relationships , which are partly encoded in highly interconnected molecular networks .", "Biological pathways provide a complem...	[ "Gene expression levels have been used to study the cellular response to drug treatments .", "However , analysis of gene expression without considering gene interactions cannot fully reveal complex genotype-phenotype relationships .", "Biological pathways reveal the interactions among genes , thus providing a c...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "gram negative", "microbial pathogens", "biology", "microbiology", "host-pathogen interaction", "bacterial pathogens" ]	Lipid Exchange between Borrelia burgdorferi and Host Cells	journal.ppat.1003109	null	[ [ "Borrelia burgdorferi , the causative agent of Lyme disease [1] , [2] , is unusual among prokaryotes in that in addition to phosphatidylcholine , phosphatidylglycerol [3]–[7] and many different lipoproteins [4] , [5] , [8]–[10] , it has free cholesterol and cholesterol-glycolipids in its outer membrane ( OM )...	[ "Borrelia burgdorferi , the agent of Lyme disease , has cholesterol and cholesterol-glycolipids that are essential for bacterial fitness , are antigenic , and could be important in mediating interactions with cells of the eukaryotic host .", "We show that the spirochetes can acquire cholesterol from plasma membra...	[ "Lyme disease , the most prevalent arthropod-borne disease in North America , is caused by the spirochete Borrelia burgdorferi .", "Cholesterol is a significant component of the B . burgdorferi membrane lipids , and is processed to make cholesterol-glycolipids .", "Our interest in the presence of cholesterol in...	2013
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "cell biology/microbial physiology and metabolism", "microbiology/microbial growth and development", "microbiology/cellular microbiology and pathogenesis" ]	Type 1 Fimbriae, a Colonization Factor of Uropathogenic Escherichia coli, Are Controlled by the Metabolic Sensor CRP-cAMP	journal.ppat.1000303	null	[ [ "Bacteria have the ability to rapidly adapt to changes in the environment , a feature that is important for survival and multiplication both during colonization of host organisms and in the environment .", "An efficient adaptation implies the ability to sense external parameters and to transduce the perce...	[ "Type 1 fimbriae are a crucial factor for the virulence of uropathogenic Escherichia coli during the first steps of infection by mediating adhesion to epithelial cells .", "They are also required for the consequent colonization of the tissues and for invasion of the uroepithelium .", "Here , we studied the role...	[ "Attachment of bacteria to the surface of host tissues is a crucial initial step in the establishment of bacterial infections .", "This process is mediated by adhesins , such as the type 1 fimbriae of Escherichia coli , which play a key role during urinary tract infections by mediating adhesion to the uroepitheli...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics", "biology", "evolutionary biology", "evolutionary genetics", "genetics and genomics", "gene function" ]	Functional Evolution of Mammalian Odorant Receptors	journal.pgen.1002821	null	[ [ "Odorant receptors ( ORs ) expressed at the cell-surface of olfactory sensory neurons ( OSNs ) in the main olfactory epithelium detect chemical cues in the proximate environment .", "The ability to detect these cues is crucial for survival of an individual and a species; odorants can signify favorable or ...	[ "The mammalian odorant receptor ( OR ) repertoire is an attractive model to study evolution , because ORs have been subjected to rapid evolution between species , presumably caused by changes of the olfactory system to adapt to the environment .", "However , functional assessment of ORs in related species remains...	[ "The mammalian odorant receptor repertoire has been subjected to significant gene duplication and gene loss between species , presumably to adapt to the environment of an organism .", "However , even in distantly related species , a clear orthologous relationship exists for many genes .", "While ligands have be...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "computational biology", "biophysics", "animals" ]	Pathway Switching Explains the Sharp Response Characteristic of Hypoxia Response Network	journal.pcbi.0030171	null	[ [ "Molecular oxygen is the terminal electron acceptor in the mitochondrial electron transport chain .", "Hypoxia , or oxygen deficiency , induces a number of metabolic changes with rapid and profound consequences on cell physiology .", "A hypoxia-induced shortage of energy alters gene expression , energ...	[ "Hypoxia induces the expression of genes that alter metabolism through the hypoxia-inducible factor ( HIF ) .", "A theoretical model based on differential equations of the hypoxia response network has been previously proposed in which a sharp response to changes in oxygen concentration was observed but not quanti...	[ "A complex biomolecular network utilizes different pathways to perform different functions .", "However , the interactions within the network are typically so complicated that the pathway structure is usually hidden .", "By some mathematical techniques , the pathways can be identified and possibly decoupled , w...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "complex systems", "cell motility", "mathematics", "applied mathematics", "biology", "computational biology", "microbiology", "biophysics", "microbial growth and development" ]	The Mechanistic Basis of Myxococcus xanthus Rippling Behavior and Its Physiological Role during Predation	journal.pcbi.1002715	null	[ [ "Spatial self-organization of developing cells , which results the formation of complex dynamic structures , remains one of the most intriguing phenomena in modern biology [1]–[4] .", "Analogous developmental behaviors are observed as bacterial cells form biofilms , which are populations of surface-associ...	[ "Myxococcus xanthus cells self-organize into periodic bands of traveling waves , termed ripples , during multicellular fruiting body development and predation on other bacteria .", "To investigate the mechanistic basis of rippling behavior and its physiological role during predation by this Gram-negative soil bac...	[ "Myxococcus xanthus cells collectively move on solid surfaces and reorganize their colonies in response to environmental cues .", "Under some conditions , cells exhibit an intriguing form of collective motility by self-organizing into bands of travelling alternating-density waves termed ripples .", "These waves...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "parastic protozoans", "protozoology", "biology", "microbiology", "parasitology" ]	Memantine, an Antagonist of the NMDA Glutamate Receptor, Affects Cell Proliferation, Differentiation and the Intracellular Cycle and Induces Apoptosis in Trypanosoma cruzi	journal.pntd.0002717	null	[ [ "Trypanosoma cruzi is the etiological agent of Chagas' disease , which affects approximately 10 million people living in endemic areas of Mexico and Central and South America , with 28 million people at risk of infection [1] .", "T . cruzi has a complex life cycle that alternates between a reduviid insect...	[ "Chagas' disease is caused by the protozoan parasite Trypanosoma cruzi and affects approximately 10 million people in endemic areas of Mexico and Central and South America .", "Currently available chemotherapies are limited to two compounds: Nifurtimox and Benznidazole .", "Both drugs reduce the symptoms of the...	[ "Trypanosoma cruzi is a parasite transmitted to mammal hosts by insect vectors known as kissing bugs .", "This species can result pathogenic for humans , causing Chagas' disease in the Americas .", "Its treatment relies on two drugs discovered more than 40 years ago .", "Besides their toxicity , a main drawba...	2014
[ "Introduction", "Results/Discussion", "Methods" ]	[ "genetics and genomics/bioinformatics", "computational biology/genomics" ]	Role of Duplicate Genes in Robustness against Deleterious Human Mutations	journal.pgen.1000014	null	[ [ "The ability of an organism to survive in various environmental conditions indicates robustness to external perturbations .", "On the other hand , relative insensitivity to harmful genetic mutations represents genetic robustness .", "Several large scale gene deletion studies demonstrated that organism...	[ "It is now widely recognized that robustness is an inherent property of biological systems [1] , [2] , [3] .", "The contribution of close sequence homologs to genetic robustness against null mutations has been previously demonstrated in simple organisms [4] , [5] .", "In this paper we investigate in detail the ...	[ "Genetic robustness is the ability of an organism to buffer deleterious genetic mutations .", "It has been previously demonstrated that the functional compensation by duplicates plays an important role in protection against gene deletions in model organisms .", "Close duplicates often share similar functions , ...	2008
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "biotechnology", "meiosis", "plant anatomy", "gene regulation", "cell cycle and cell division", "cell processes", "plant science", "rice", "genetically modified plants", "experimental organism systems", "sequence motif analysis", "plants", "flower anatomy", "genetic engineering", "resear...	EAT1 transcription factor, a non-cell-autonomous regulator of pollen production, activates meiotic small RNA biogenesis in rice anther tapetum	journal.pgen.1007238	null	[ [ "Small noncoding RNAs are 20–30 nucleotides ( nt ) long and associate with Argonaute family proteins to serve as guide molecules for RNA silencing in various biological processes , such as cell type specification , cell proliferation , cell death , metabolic control , transposon silencing and antiviral defens...	[ "The 24-nucleotides ( nt ) phased secondary small interfering RNA ( phasiRNA ) is a unique class of plant small RNAs abundantly expressed in monocot anthers at early meiosis .", "Previously , 44 intergenic regions were identified as the loci for longer precursor RNAs of 24-nt phasiRNAs ( 24-PHASs ) in the rice ge...	[ "Meiotic crossover formation shuffles homologous genes between parental genomes , and enables transmission of new gene sets to the offspring .", "Frequency and positions of crossovers are determined by numerous genetic and epigenetic factors , and low nucleosome-density regions are associated with crossover hot s...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "immune cells", "nk cells", "immunity", "innate immunity", "hiv", "immunology", "biology", "viral diseases" ]	Association of Activating KIR Copy Number Variation of NK Cells with Containment of SIV Replication in Rhesus Monkeys	journal.ppat.1002436	null	[ [ "Natural killer ( NK ) cells are the primary effector cells of the innate immune system , representing a first line of defense against viruses through their ability to lyse virally infected cells without prior antigen sensitization [1]–[3] .", "NK cells express a complicated set of activating and inhibito...	[ "While the contribution of CD8+ cytotoxic T lymphocytes to early containment of HIV-1 spread is well established , a role for NK cells in controlling HIV-1 replication during primary infection has been uncertain .", "The highly polymorphic family of KIR molecules expressed on NK cells can inhibit or activate thes...	[ "NK cells are effector cells of the innate immune system that contribute to protection against virus infections through their ability to lyse virus-infected cells without prior antigen sensitization .", "Their role in controlling HIV-1 replication during primary infection has been uncertain .", "NK cell activat...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "computational neuroscience", "sensory systems", "biology", "computational biology" ]	Trading Speed and Accuracy by Coding Time: A Coupled-circuit Cortical Model	journal.pcbi.1003021	null	[ [ "It is likely that the cerebral cortex evolved to provide a model of the world , serving decisions for action .", "Our actions take place in space and time and both of these dimensions are considered in the dominant hypothesis of decision making , where noisy spatial evidence is averaged over time ( see [...	[ "Our actions take place in space and time , but despite the role of time in decision theory and the growing acknowledgement that the encoding of time is crucial to behaviour , few studies have considered the interactions between neural codes for objects in space and for elapsed time during perceptual decisions .", ...	[ "Studies in neuroscience have characterized how the brain represents objects in space and how these objects are selected for detailed perceptual processing .", "The selection process entails a decision about which object is favoured by the available evidence over time .", "This period of time is typically in th...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Systems Genetics Reveals the Functional Context of PCOS Loci and Identifies Genetic and Molecular Mechanisms of Disease Heterogeneity	journal.pgen.1005455	null	[ [ "Polycystic ovary syndrome ( PCOS ) occurs in 6–10% of reproductive age women by NIH diagnostic criteria , and is characterized by hyperandrogenism and oligo- or amenorrhea [1] .", "Metabolic risk factors for type 2 diabetes and cardiovascular disease such as insulin resistance and obesity are common in w...	[ "Genome wide association studies ( GWAS ) have revealed 11 independent risk loci for polycystic ovary syndrome ( PCOS ) , a common disorder in young women characterized by androgen excess and oligomenorrhea .", "To put these risk loci and the single nucleotide polymorphisms ( SNPs ) therein into functional contex...	[ "Polycystic ovary syndrome ( PCOS ) is the most common hormonal disturbance in reproductive age women and features high levels of male sex hormones , such as testosterone , and infrequent ovulation .", "Twin studies have demonstrated that inheritance plays a significant role in PCOS , and recent genome wide assoc...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "livestock", "medicine and health sciences", "immunology", "geographical locations", "vaccines", "preventive medicine", "bacterial diseases", "infectious disease control", "vaccination and immunization", "africa", "veterinary science", "veterinary medicine", "public and occupational health",...	Modeling the environmental suitability of anthrax in Ghana and estimating populations at risk: Implications for vaccination and control	journal.pntd.0005885	null	[ [ "Anthrax is a soil-borne , zoonotic disease found on nearly every continent ( except Antarctica ) that primarily infects herbivorous animals while secondarily infecting humans through the handling or ingestion of contaminated meat or animal by-products [1 , 2] .", "The geographic distribution of the disea...	[ "Anthrax is hyper-endemic in West Africa .", "Despite the effectiveness of livestock vaccines in controlling anthrax , underreporting , logistics , and limited resources makes implementing vaccination campaigns difficult .", "To better understand the geographic limits of anthrax , elucidate environmental factor...	[ "Anthrax is a soil-borne zoonotic disease found worldwide .", "In the West African nation of Ghana , anthrax outbreaks occur annually with a high burden to livestock keepers and their animals .", "To control anthrax in both humans and animals , annual livestock vaccination is recommended in endemic regions .", ...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "tropical diseases", "database searching", "parasitic diseases", "parasitic protozoans", "electrocardiography", "mathematics", "protozoans", "statistics (mathematics)", "bioassays and physiological analysis", "neglected tropical diseases", "research and analysis...	Electrocardiographic abnormalities in Chagas disease in the general population: A systematic review and meta-analysis	journal.pntd.0006567	null	[ [ "Chagas disease ( CD ) , is caused by the protozoan Trypanosoma cruzi[1] .", "It affects individuals from more than 21 countries , being a major public health concern in Latin Americas and a potentially serious emerging threat to a number of non-endemic countries[2] .", "In Latin American countries , ...	[ "Chagas disease ( CD ) is a major public health concern in Latin America and a potentially serious emerging threat in non-endemic countries .", "Although the association between CD and cardiac abnormalities is widely reported , study design diversity , sample size and quality challenge the information , calling f...	[ "Chagas disease ( CD ) is a major public health concern in Latin America and a potentially serious emerging threat in non-endemic countries .", "Although the association between CD and cardiac abnormalities is widely reported , study design diversity , sample size and quality challenge the information , calling f...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "sequencing techniques", "gene regulation", "regulatory proteins", "dna-binding proteins", "dna transcription", "transcription factors", "sequence motif analysis", "molecular biology techniques", "epigenetics", "chromatin", "research and analysis methods", "sequence analysis", "sequence alig...	Downstream Antisense Transcription Predicts Genomic Features That Define the Specific Chromatin Environment at Mammalian Promoters	journal.pgen.1006224	null	[ [ "The promoter region is intimately tied to the transcription of genes , providing the initial site of transcriptional machinery binding and assembly .", "Comprised of DNA elements in defined spatial arrangements [1] , promoters also display key genomic features that facilitate gene regulation .", "Act...	[ "Antisense transcription is a prevalent feature at mammalian promoters .", "Previous studies have primarily focused on antisense transcription initiating upstream of genes .", "Here , we characterize promoter-proximal antisense transcription downstream of gene transcription starts sites in human breast cancer c...	[ "Gene transcription is regulated by the coordinated interaction of genetic , epigenetic and trans-acting factors .", "The chromatin environment at gene promoters , including positioned nucleosomes that may display functional histone modifications , is a key regulator of gene expression , contributing to transcrip...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "dermatology", "immunity to infections", "immunology", "microbiology", "staphylococcus aureus", "animal models", "bacterial diseases", "model organisms", "skin infections", "staphylococci", "immunologic techniques", "bacterial pathogens", "infectious diseases", "inflammation"...	Neutrophil-derived IL-1β Is Sufficient for Abscess Formation in Immunity against Staphylococcus aureus in Mice	journal.ppat.1003047	null	[ [ "Neutrophil abscess formation represents an important component of the innate immune response , which helps control the spread of an invading pathogen into deeper tissues and systemically [1] .", "At the site of infection , neutrophils primarily function through the phagocytosis of microorganisms and util...	[ "Neutrophil abscess formation is critical in innate immunity against many pathogens .", "Here , the mechanism of neutrophil abscess formation was investigated using a mouse model of Staphylococcus aureus cutaneous infection .", "Gene expression analysis and in vivo multispectral noninvasive imaging during the S...	[ "Invasive infections caused by the human pathogen Staphylococcus aureus result in more deaths annually than infections caused by any other single infectious agent in the United States .", "Although neutrophil recruitment and abscess formation is crucial for effective host defense against this pathogen , how neutr...	2012
[ "Introduction", "Results", "Discussion", "Conclusions", "Methods" ]	[ "medicine and health sciences", "chemical compounds", "diabetic endocrinology", "carbohydrates", "organic compounds", "glucose", "hormones", "physiological processes", "systems science", "mathematics", "homeostasis", "evolutionary adaptation", "insulin", "computer and information sciences"...	Dynamical compensation and structural identifiability of biological models: Analysis, implications, and reconciliation	journal.pcbi.1005878	null	[ [ "Some biological systems are capable of maintaining an approximatively constant output despite environmental fluctuations .", "It has long been accepted that negative feedback plays a central role in biological phenomena such as homeostasis .", "Feedback mechanisms are capable of rendering a system ro...	[ "The concept of dynamical compensation has been recently introduced to describe the ability of a biological system to keep its output dynamics unchanged in the face of varying parameters .", "However , the original definition of dynamical compensation amounts to lack of structural identifiability .", "This is r...	[ "A robust behaviour is a desirable feature in many biological systems .", "The study of mechanisms capable of maintaining the transient response unchanged despite environmental disturbances has recently motivated the introduction of a new concept: Dynamical Compensation ( DC ) .", "However , the original defini...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics", "molecular biology", "biology and life sciences", "microbiology" ]	The Listeria Small RNA Rli27 Regulates a Cell Wall Protein inside Eukaryotic Cells by Targeting a Long 5′-UTR Variant	journal.pgen.1004765	null	[ [ "Listeria monocytogenes is a facultative intracellular food-borne bacterium responsible for serious clinical manifestations including febrile gastroenteritis , meningitis , encephalitis and maternofetal infections in humans and livestock , with an estimated fatality rate of 20–30% of infected individuals [1]–...	[ "Listeria monocytogenes is a bacterial pathogen whose genome encodes many cell wall proteins that bind covalently to peptidoglycan .", "Some members of this protein family have a key role in virulence , and recent studies show that some of these , such as Lmo0514 , are upregulated in bacteria that colonize eukary...	[ "Listeria monocytogenes has evolved to adapt to numerous environments , including the intracellular niche of eukaryotic cells .", "Small RNAs ( sRNA ) play important regulatory roles in changing environments , and are thus predicted to modulate L . monocytogenes adaption to the intracellular lifestyle .", "This...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Temporal pattern separation in hippocampal neurons through multiplexed neural codes	journal.pcbi.1006932	null	[ [ "Understanding what computations hippocampal neurons perform and how they support episodic memory is a longstanding goal in neuroscience .", "The hippocampus is notably critical for the discrimination of memories that are similar in content [1] .", "This cognitive function has long been hypothesized t...	[ "Pattern separation is a central concept in current theories of episodic memory: this computation is thought to support our ability to avoid confusion between similar memories by transforming similar cortical input patterns of neural activity into dissimilar output patterns before their long-term storage in the hip...	[ "Pattern separation ( the process of disambiguating incoming patterns of neuronal activity ) is a central concept in all current theories of episodic memory , as it is hypothesized to support our ability to avoid confusion between similar memories .", "For the last thirty years , pattern separation has been attri...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "systems biology", "biology", "computational biology", "genetics and genomics" ]	Reversible and Noisy Progression towards a Commitment Point Enables Adaptable and Reliable Cellular Decision-Making	journal.pcbi.1002273	null	[ [ "Cellular decision-making underlies many biological processes such as multipotent differentiation , where cells commit to one of several distinct fates .", "Such cell fate choice must permit individual cells to reach a decision even in fluctuating extracellular environments [1] .", "At the same time ,...	[ "Cells must make reliable decisions under fluctuating extracellular conditions , but also be flexible enough to adapt to such changes .", "How cells reconcile these seemingly contradictory requirements through the dynamics of cellular decision-making is poorly understood .", "To study this issue we quantitative...	[ "Cells must continuously make decisions in response to changes in their environment .", "These decisions must be irreversible , to prevent cells from reverting back to unfit cellular states , but also be flexible , to allow cells to go back to their previous state upon environmental changes .", "Using single-ce...	2011
[ "Introduction", "Results", "Materials and methods" ]	[ "plant anatomy", "chemical compounds", "apoplastic space", "vascular bundles", "plant physiology", "nitrates", "xylem", "plant science", "biological transport", "cellular structures and organelles", "proteins", "endodermis", "chemistry", "leaves", "iodides", "cell membranes", "bioche...	Root zone–specific localization of AMTs determines ammonium transport pathways and nitrogen allocation to shoots	journal.pbio.2006024	null	[ [ "A major function of plant roots is the uptake and subsequent translocation of nutrients from soil to above-ground plant organs .", "To reach the shoot , nutrients need first to be transported radially across the root tissue before entering the xylem for root-to-shoot translocation .", "Once nutrients...	[ "In plants , nutrient provision of shoots depends on the uptake and transport of nutrients across the root tissue to the vascular system .", "Nutrient delivery to the vasculature is mediated via the apoplastic transport pathway ( ATP ) , which uses the free space in the cell walls and is controlled by apoplastic ...	[ "Radial transport of nutrients from the soil to the vascular system of plant roots occurs via the symplastic transport pathway ( STP ) and apoplastic transport pathway ( ATP ) .", "Nutrients move along the STP when crossing the plasma membrane of outer cells and moving to xylem through the cytoplasmic continuum f...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "death rates", "medicine and health sciences", "tropical diseases", "vector-borne diseases", "social sciences", "geographical locations", "parasitic diseases", "parasitic protozoans", "health care", "north america", "protozoans", "neglected tropical diseases", "population biology", "infect...	The economic value of identifying and treating Chagas disease patients earlier and the impact on Trypanosoma cruzi transmission	journal.pntd.0006809	null	[ [ "While previous studies have evaluated the economic value of earlier treatment of Chagas disease ( caused by the protozoan parasite Trypanosoma cruzi ) in individuals , none have considered the spread or how it may prevent the spread of Chagas disease .", "Studies have estimated the cost of treating Chaga...	[ "The World Health Organization’s 2020 Goals for Chagas disease include access to antiparasitic treatment and care of all infected/ill patients .", "Policy makers need to know the economic value of identifying and treating patients earlier .", "However , the economic value of earlier treatment to cure and preven...	[ "The World Health Organization’s 2020 Goals for Chagas disease include access to antiparasitic treatment and care of all infected/ill patients .", "Policy makers need to know the economic value of identifying and treating patients earlier and what can be invested .", "We evaluated the impact and economic outcom...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "chagas disease", "neglected tropical diseases" ]	Activity In Vivo of Anti-Trypanosoma cruzi Compounds Selected from a High Throughput Screening	journal.pntd.0001298	null	[ [ "It is estimated that around 100 million people live with the risk of infection with T . cruzi in endemic areas in Latin America , with approximately 8 million already infected .", "The considerable influx of immigrants from Latin American countries to USA , Canada and Europe has also made Chagas disease ...	[ "Novel technologies that include recombinant pathogens and rapid detection methods are contributing to the development of drugs for neglected diseases .", "Recently , the results from the first high throughput screening ( HTS ) to test compounds for activity against Trypanosoma cruzi trypomastigote infection of h...	[ "Chagas is a devastating disease affecting about 100 million people in Latin America .", "The drugs available for treatment against the causative agent , the parasite Trypanosoma cruzi , have associated toxicity and are not completely effective against the chronic form of the disease , which is the most common pr...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Neuropeptide-Driven Cross-Modal Plasticity following Sensory Loss in Caenorhabditis elegans	journal.pbio.1002348	Touch-sensing neurons in the nematode Caenorhabditis elegans secrete neuropeptides to suppress olfaction via a specific synapse in the olfactory circuit. Loss of touch releases this suppression, enhancing the sense of smell.	[ [ "Sensory loss often elicits cross-modal plasticity , either enhancing or reducing the performance of remaining unimpaired sensory modalities .", "These effects have been broadly described in humans and other mammals [1 , 2] and exemplify the remarkable plasticity and adaptability of the brain .", "Wha...	[ "Sensory loss induces cross-modal plasticity , often resulting in altered performance in remaining sensory modalities .", "Whereas much is known about the macroscopic mechanisms underlying cross-modal plasticity , only scant information exists about its cellular and molecular underpinnings .", "We found that Ca...	[ "The brain has the remarkable capacity to respond to sensory loss by boosting remaining functioning senses .", "For example , certain features of hearing are improved in blind people .", "What are the cellular and molecular mechanisms underlying this effect ?", "How is a certain sense strengthened ?", "If i...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "parasite groups", "oocysts", "chemical compounds", "respiratory infections", "ketones", "enzymology", "cryptosporidium", "parasitic diseases", "parasitic protozoans", "pyruvate", "pulmonology", "parasitology", "apicomplexa", "protozoans", "enzyme inhibi...	Novel lactate dehydrogenase inhibitors with in vivo efficacy against Cryptosporidium parvum	journal.ppat.1007953	null	[ [ "The zoonotic and anthroponotic protozoan parasite , Cryptosporidium parvum , is a major cause of diarrheal diseases in children under the age of two , resulting in significant morbidity and mortality in poor-resource areas of developing countries [1] .", "In livestock , particularly in calves , lambs and...	[ "Cryptosporidium parvum is a highly prevalent zoonotic and anthroponotic protozoan parasite that causes a diarrheal syndrome in children and neonatal livestock , culminating in growth retardation and mortalities .", "Despite the high prevalence of C . parvum , there are no fully effective and safe drugs for treat...	[ "Cryptosporidium parvum is a protozoan parasite that can cause a life-threatening gastrointestinal disease in children and in immunocompromised adults .", "The only approved drug for treatment of Cryptosporidium infections in humans is nitazoxanide , but it is not effective in immunocompromised individuals or in ...	2019
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "biochemistry", "evolutionary biology/human evolution", "microbiology/microbial evolution and genomics", "infectious diseases/helminth infections", "microbiology/parasitology", "microbiology/microbial physiology and metabolism" ]	The Heme Biosynthetic Pathway of the Obligate Wolbachia Endosymbiont of Brugia malayi as a Potential Anti-filarial Drug Target	journal.pntd.0000475	null	[ [ "Human filarial nematodes affect more than 150 million people worldwide with 1 billion people at risk in over 80 countries , and lead to some of the most debilitating tropical diseases , including elephantiasis and African river blindness [1] , [2] .", "The current anti-filarial treatments e . g . DEC , i...	[ "Filarial parasites ( e . g . , Brugia malayi , Onchocerca volvulus , and Wuchereria bancrofti ) are causative agents of lymphatic filariasis and onchocerciasis , which are among the most disabling of neglected tropical diseases .", "There is an urgent need to develop macro-filaricidal drugs , as current anti-fil...	[ "Human filarial nematodes are causative agents of elephantiasis and African river blindness , which are among the most debilitating tropical diseases .", "Currently used drugs mainly affect microfilariae ( mf ) and have less effect on adult filarial nematodes , which can live in the human host for more than a dec...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "parasite groups", "medicine and health sciences", "plasmodium", "viral transmission and infection", "enzymes", "enzymology", "microbiology", "parasitic diseases", "parasitic protozoans", "parasitology", "membrane proteins", "apicomplexa", "protozoans", "cellular structures and organelles"...	Stable Translocation Intermediates Jam Global Protein Export in Plasmodium falciparum Parasites and Link the PTEX Component EXP2 with Translocation Activity	journal.ppat.1005618	null	[ [ "Five species of Plasmodium parasites cause human malaria .", "Of these P . falciparum is responsible for the majority of the over 500’000 annually recorded malaria deaths [1] .", "The pathology of malaria is caused by the continuous propagation of the parasite within red blood cells ( RBCs ) .", ...	[ "Protein export is central for the survival and virulence of intracellular P . falciparum blood stage parasites .", "To reach the host cell , exported proteins cross the parasite plasma membrane ( PPM ) and the parasite-enclosing parasitophorous vacuole membrane ( PVM ) , a process that requires unfolding , sugge...	[ "P . falciparum parasites , the deadliest agent of human malaria , develop within erythrocytes where they are surrounded by a parasitophorous vacuolar membrane ( PVM ) .", "To ensure intracellular survival , the parasite exports a large repertoire of proteins into the host cell .", "Exported proteins require un...	2016
[ "Introduction", "Methods", "Results/Discussion" ]	[ "medicine" ]	Molecular Evolution of Zika Virus during Its Emergence in the 20th Century	journal.pntd.0002636	null	[ [ "Zika virus ( ZIKV ) is a mosquito-borne flavivirus , a member of the Spondweni serocomplex , whose natural transmission cycle involves mainly vectors from the Aedes genus ( A . furcifer , A . taylori , A . luteocephalus and A . africanus ) and monkeys [1] , while humans are occasional hosts .", "Clinical...	[ "Zika virus ( ZIKV ) is a mosquito-borne flavivirus first isolated in Uganda in 1947 .", "Although entomological and virologic surveillance have reported ZIKV enzootic activity in diverse countries of Africa and Asia , few human cases were reported until 2007 , when a Zika fever epidemic took place in Micronesia ...	[ "Zika fever is a mosquito-borne illness caused by a flavivirus .", "Human infections with Zika virus ( ZIKV ) could cause fever , malaise and cutaneous rash .", "Despite several ZIKV reports since 1947 when it was first isolated at Zika forest in Uganda , molecular evolution of ZIKV as an emerging agent remains...	2014
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "cognitive neurology", "medicine and health sciences", "ontologies", "social sciences", "neuroscience", "learning and memory", "face recognition", "perception", "data management", "cognitive neuroscience", "cognitive psychology", "cognition", "brain mapping", "memory", "vision", "neuro...	Atlases of cognition with large-scale human brain mapping	journal.pcbi.1006565	null	[ [ "A major challenge to reaching a global understanding of the functional organization of the human brain is that each neuroimaging experiment only probes a small number of cognitive processes .", "Cognitive neuroscience is faced with a profusion of findings relating specific psychological functions to brai...	[ "To map the neural substrate of mental function , cognitive neuroimaging relies on controlled psychological manipulations that engage brain systems associated with specific cognitive processes .", "In order to build comprehensive atlases of cognitive function in the brain , it must assemble maps for many differen...	[ "Cognitive neuroscience uses neuroimaging to identify brain systems engaged in specific cognitive tasks .", "However , linking unequivocally brain systems with cognitive functions is difficult: each task probes only a small number of facets of cognition , while brain systems are often engaged in many tasks .", ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "viruses", "virology", "in vitro", "immunology", "mus (mouse)" ]	Role of Dendritic Cells in Differential Susceptibility to Viral Demyelinating Disease	journal.ppat.0030124	null	[ [ "Susceptibility to immune-mediated diseases induced by microbial infections varies between individuals .", "Several genes involved in innate and adaptive immune responses are known to be associated with such differential susceptibility [1 , 2] .", "Consequently , different levels and types of immune r...	[ "Although persistent viral diseases are a global health concern , the mechanisms of differential susceptibility to such infections among individuals are unknown .", "Here , we report that differential interactions between dendritic cells ( DCs ) and virus are critical in determining resistance versus susceptibili...	[ "Many chronic viral diseases are associated with prolonged viral persistence levels , which vary from one individual to another .", "However , the mechanisms of differential susceptibility to persistent viral infections are unknown .", "Theiler murine encephalomyelitis virus ( TMEV ) induces a chronic demyelina...	2007
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "enzymes", "ears", "enzymology", "neuroscience", "phosphatases", "animal models", "outer hair cells", "otology", "inner ear", "model organisms", "experimental organism systems", "hearing disorders", "research and analysis methods", "animal cells", "prote...	Mutations in Diphosphoinositol-Pentakisphosphate Kinase PPIP5K2 are associated with hearing loss in human and mouse	journal.pgen.1007297	null	[ [ "Hearing loss ( HL ) is a heterogeneous neurosensory deficiency that occurs at all ages with varying severities , affecting 1 in 500 newborns and >360 million people worldwide [1] .", "Many forms of HL are inherited , and ~400 syndromic forms occur with linked medical comorbidities .", "Genetically co...	[ "Autosomal recessive nonsyndromic hearing loss is a genetically heterogeneous disorder .", "Here , we report a severe-to-profound sensorineural hearing loss locus , DFNB100 on chromosome 5q13 . 2-q23 . 2 .", "Exome enrichment followed by massive parallel sequencing revealed a c . 2510G>A transition variant in P...	[ "Exome sequencing coupled with homozygosity mapping was used to identify a missense variant [c . 2510G>A; p . ( Arg837His ) ] in PPIP5K2 at the DFNB100 locus that is associated with nonsyndromic , prelingual sensorineural deafness in two large consanguineous Pakistani families .", "PPIP5Ks are pivotal enzymes for...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "public health and epidemiology/epidemiology", "infectious diseases/viral infections", "public health and epidemiology/infectious diseases", "infectious diseases/tropical and travel-associated diseases", "infectious diseases/epidemiology and control of infectious diseases" ]	The Role of Imported Cases and Favorable Meteorological Conditions in the Onset of Dengue Epidemics	journal.pntd.0000775	null	[ [ "Dengue outbreaks initiated by international tourists , immigrants , and foreign workers have been reported in numerous developed areas and countries [1] , [2] , [3] .", "Nevertheless , the interplay between infected travelers , climate , vectors , and indigenous dengue incidence remains unclear [3] , [4]...	[ "Travelers who acquire dengue infection are often routes for virus transmission to other regions .", "Nevertheless , the interplay between infected travelers , climate , vectors , and indigenous dengue incidence remains unclear .", "The role of foreign-origin cases on local dengue epidemics thus has been largel...	[ "Dengue/dengue hemorrhagic fever is the world's most widely spread mosquito-borne arboviral disease and threatens more than two-thirds of the world's population .", "Cases are mainly distributed in tropical and subtropical areas in accordance with vector habitats for Aedes aegypti and Ae .", "albopictus .", "...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "evolutionary biology", "drosophila", "genetics and genomics" ]	Phenotypic Plasticity in Drosophila Pigmentation Caused by Temperature Sensitivity of a Chromatin Regulator Network	journal.pgen.0030030	null	[ [ "Phenotypic plasticity and buffering are concepts describing the phenotypic outcome of genotype-environment interactions .", "Phenotypic plasticity is the ability of a given genotype to produce different phenotypes in different environments [1] .", "It has been the subject of increasing interest as it...	[ "Phenotypic plasticity is the ability of a genotype to produce contrasting phenotypes in different environments .", "Although many examples have been described , the responsible mechanisms are poorly understood .", "In particular , it is not clear how phenotypic plasticity is related to buffering , the maintena...	[ "The phenotype of an individual is not fully controlled by its genes .", "Environmental conditions ( food , light , temperature , pathogens , etc . ) can also contribute to phenotypic variation .", "This phenomenon is called phenotypic plasticity .", "We investigate here the genetic basis of the phenotypic pl...	2007
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "dimers (chemical physics)", "crystal structure", "condensed matter physics", "dna-binding proteins", "mutation", "mutation databases", "crystallography", "basic helix-loop-helix domains", "physical chemistry", "chemical properties", "research and analysis methods", "solid state physics", "d...	Ligand-induced perturbation of the HIF-2α:ARNT dimer dynamics	journal.pcbi.1006021	null	[ [ "Hypoxia inducible factors ( HIFs ) are obligate heterodimers belonging to the basic helix−loop−helix ( bHLH ) superfamily of transcription factors that mediate the physiological responses to hypoxia .", "This extensive protein family is characterized by a 4–6 basic amino acids next to a HLH dimerization ...	[ "Hypoxia inducible factors ( HIFs ) are transcription factors belonging to the basic helix−loop−helix PER-ARNT-SIM ( bHLH-PAS ) protein family with a role in sensing oxygen levels in the cell .", "Under hypoxia , the HIF-α degradation pathway is blocked and dimerization with the aryl hydrocarbon receptor nuclear ...	[ "A low oxygen condition , called hypoxia , often occurs in tumor masses and generally correlates with worse prognosis .", "Cells in a tumor react to low oxygen levels with a metabolism modification induced by the activation of hypoxia inducible factors ( HIFs ) through dimerization with a partner protein and bind...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "fluorescence imaging", "plant anatomy", "plant cell biology", "brassica", "light microscopy", "plant science", "confocal laser microscopy", "microscopy", "confocal microscopy", "plant pathology", "plants", "research and analysis methods", "imaging techniques", "plant bacterial pathogens",...	New insight into bacterial social communication in natural host: Evidence for interplay of heterogeneous and unison quorum response	journal.pgen.1008395	null	[ [ "Pathogenic bacteria coordinate several social behaviors via production , secretion and perception of diverse diffusible cell-cell signaling molecules by a process called quorum sensing ( QS ) .", "QS synchronizes the bacteria to perform social task in unison by coordinating production of exo-products as ...	[ "Many microbes exhibit quorum sensing ( QS ) to cooperate , share and perform a social task in unison .", "Recent studies have shown the emergence of reversible phenotypic heterogeneity in the QS-responding pathogenic microbial population under laboratory conditions as a possible bet-hedging survival strategy .",...	[ "Pathogenic bacteria synchronize and coordinate the production of virulence associated function-components in a density dependent fashion via quorum sensing .", "In general , QS-response and regulation has been studied under laboratory conditions in vitro , where the QS-responding bacterial population exhibits he...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "taxonomy", "organismal evolution", "medicine and health sciences", "pathology and laboratory medicine", "viral transmission and infection", "pathogens", "microbiology", "retroviruses", "viruses", "immunodeficiency viruses", "phylogenetics", "data management", "rna viruses", "phylogenetic ...	Viral genetic variation accounts for a third of variability in HIV-1 set-point viral load in Europe	journal.pbio.2001855	null	[ [ "The outcome of infection by the human immunodeficiency virus-1 ( HIV-1 , henceforth “HIV” for simplicity ) is highly variable across individuals , with time to AIDS ranging from 2 years to more than 20 years [1–4] .", "Quantifying the fraction of this variability explained by genetic variability in the v...	[ "HIV-1 set-point viral load—the approximately stable value of viraemia in the first years of chronic infection—is a strong predictor of clinical outcome and is highly variable across infected individuals .", "To better understand HIV-1 pathogenesis and the evolution of the viral population , we must quantify the ...	[ "The severity of the outcome of infection by a pathogen depends on many distinct factors .", "These include the environment and the genetic sequences of both the host and the pathogen , among others .", "The fraction of variability in disease outcome explained by pathogen genetic factors is termed “heritability...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "rna interference", "chromosome structure and function", "gene function", "histone modification", "fungi", "model organisms", "epigenetics", "chromatin", "schizosaccharomyces", "genetic engineering", "research and analysis methods", "chromosome biology", "gene expression",...	The Proper Splicing of RNAi Factors Is Critical for Pericentric Heterochromatin Assembly in Fission Yeast	journal.pgen.1004334	null	[ [ "Eukaryotic genomic DNA associates with histone and non-histone proteins to form chromatin , which is necessary for the spatial and temporal organization of chromosomes .", "A distinction is commonly drawn between two types of chromatin: euchromatin and heterochromatin .", "Euchromatin is less condens...	[ "Heterochromatin preferentially assembles at repetitive DNA elements , playing roles in transcriptional silencing , recombination suppression , and chromosome segregation .", "The RNAi machinery is required for heterochromatin assembly in a diverse range of organisms .", "In fission yeast , RNA splicing factors...	[ "Heterochromatin formation at specific genomic regions is critical for processes as diverse as gene expression and chromosome segregation .", "The formation of silent heterochromatin at repetitive DNA elements requires processing of transcripts by the RNA interference machinery .", "Curiously , factors involved...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "developmental neuroscience", "cellular neuroscience", "synaptic plasticity", "behavioral neuroscience", "computational neuroscience", "single neuron function", "biology and life sciences", "computational biology", "neuroscience", "neuronal plasticity" ]	A New Framework for Cortico-Striatal Plasticity: Behavioural Theory Meets In Vitro Data at the Reinforcement-Action Interface	journal.pbio.1002034	A computational model yields new insights into the bewildering complexity of cortico-striatal plasticity and its rationale for supporting operant learning.	[ [ "Learning from reinforcement requires a neural interface between reinforcement signals and action representations .", "Since the tentative identification of the ventral striatum as this “limbic-motor” interface by Mogenson and colleagues [1] , separate strands of work have elaborated four key elements cen...	[ "Operant learning requires that reinforcement signals interact with action representations at a suitable neural interface .", "Much evidence suggests that this occurs when phasic dopamine , acting as a reinforcement prediction error , gates plasticity at cortico-striatal synapses , and thereby changes the future ...	[ "A key component of survival is the ability to learn which actions , in what contexts , yield useful and rewarding outcomes .", "Actions are encoded in the brain in the cortex but , as many actions are possible at any one time , there needs to be a mechanism to select which one is to be performed .", "This prob...	2015

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