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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" ]	[ "innate immune system", "medicine and health sciences", "immune physiology", "cytokines", "pathology and laboratory medicine", "viral transmission and infection", "pathogens", "immunology", "rna extraction", "microbiology", "pseudomonas aeruginosa", "physiological processes", "developmental ...	A Novel Mechanism of Host-Pathogen Interaction through sRNA in Bacterial Outer Membrane Vesicles	journal.ppat.1005672	null	[ [ "Pseudomonas aeruginosa is a gram-negative , opportunistic pathogen that primarily infects immunocompromised hosts including cancer and AIDS patients , burn victims , patients on ventilators and individuals with chronic obstructive pulmonary disease and cystic fibrosis .", "According to the Centers for Di...	[ "Bacterial outer membrane vesicle ( OMV ) -mediated delivery of proteins to host cells is an important mechanism of host-pathogen communication .", "Emerging evidence suggests that OMVs contain differentially packaged short RNAs ( sRNAs ) with the potential to target host mRNA function and/or stability .", "In ...	[ "Pseudomonas aeruginosa is a gram-negative , opportunistic pathogen that accounts for about 10% of all hospital-acquired infections in the US and primarily infects immunocompromised hosts , including patients with chronic obstructive pulmonary disease and cystic fibrosis .", "Gram-negative bacteria like P . aerug...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "fish", "engineering and technology", "lens disorders", "ocular anatomy", "messenger rna", "vertebrates", "animals", "cell differentiation", "animal models", "osteichthyes", "developmental biology", "model organisms", "experimental organism systems", "opti...	The RNA-binding protein Celf1 post-transcriptionally regulates p27Kip1 and Dnase2b to control fiber cell nuclear degradation in lens development	journal.pgen.1007278	null	[ [ "Interaction of RNA-binding proteins ( RBPs ) with target mRNA is necessary for every aspect of its control , including its processing , export , localization , stability , and translation into protein [1] .", "These events are collectively defined as post-transcriptional control of gene expression and ar...	[ "Opacification of the ocular lens , termed cataract , is a common cause of blindness .", "To become transparent , lens fiber cells undergo degradation of their organelles , including their nuclei , presenting a fundamental question: does signaling/transcription sufficiently explain differentiation of cells progre...	[ "Besides associated with aging , the eye disease cataract can occur early in life because of defects in lens development .", "Lens fiber cells degrade their nuclei to achieve lens transparency , which poses a fundamental question: how is differentiation regulated in a cell progressing toward compromised transcrip...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases", "medicine and health sciences", "virology", "biology and life sciences", "microbiology", "viral diseases" ]	Evidence of Experimental Vertical Transmission of Emerging Novel ECSA Genotype of Chikungunya Virus in Aedes aegypti	journal.pntd.0002990	null	[ [ "Chikungunya virus ( CHIKV ) ( genus Alphavirus , family Togaviridae ) is a mosquito-borne pathogen , native to Africa that is transmitted between non human primates , mainly by forest dwelling Aedes species .", "The virus is also widespread as an urban infection throughout the old world tropics and subtr...	[ "Chikungunya virus ( CHIKV ) has emerged as one of the most important arboviruses of public health significance in the past decade .", "The virus is mainly maintained through human-mosquito-human cycle .", "Other routes of transmission and the mechanism of maintenance of the virus in nature are not clearly know...	[ "Although vertical transmission of arboviruses has been recognized for nearly a century , rates of transmission in laboratory experiments are low and their significance in terms of survival of virus during periods of low transmission appears debatable .", "Recently , major urban outbreaks of chikungunya have been...	2014
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "legs", "ixodes", "chemical compounds", "pathology and laboratory medicine", "pathogens", "microbiology", "limbs (anatomy)", "animals", "organic compounds", "rickettsia", "ticks", "alcohols", "bacteria", "bacterial pathogens", "researc...	Molecular and MALDI-TOF identification of ticks and tick-associated bacteria in Mali	journal.pntd.0005762	null	[ [ "Ticks are bloodsucking arthropods that parasitize most of the vertebrates in the world and occasionally bite humans [1] .", "About 900 tick species have been identified and classified worldwide [2] .", "In Africa , the number of tick species indexed is 223 , including 180 hard and 43 soft ticks [2] ....	[ "Ticks are considered the second vector of human and animal diseases after mosquitoes .", "Therefore , identification of ticks and associated pathogens is an important step in the management of these vectors .", "In recent years , Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry ( MA...	[ "Ticks are among the most important vectors and reservoirs of several animal and human pathogens such as viruses , bacteria and protozoa .", "However , very few studies have been done on ticks in Mali .", "At present , little information is available about tick species infesting livestock or human tick-borne di...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "mathematics", "applied mathematics", "biology", "microbiology" ]	Wolbachia Symbiont Infections Induce Strong Cytoplasmic Incompatibility in the Tsetse Fly Glossina morsitans	journal.ppat.1002415	null	[ [ "Tsetse flies are the sole vector of Human African Trypanosomiasis ( HAT ) , also known as sleeping sickness , caused by the protozoan Trypanosoma brucei spp .", "in sub-Saharan Africa .", "Recent figures released by the World Health Organization ( WHO ) indicate that the devastating HAT epidemics , w...	[ "Tsetse flies are vectors of the protozoan parasite African trypanosomes , which cause sleeping sickness disease in humans and nagana in livestock .", "Although there are no effective vaccines and efficacious drugs against this parasite , vector reduction methods have been successful in curbing the disease , espe...	[ "Infections with the parasitic bacterium Wolbachia are widespread in insects and cause a number of reproductive modifications , including cytoplasmic incompatibility ( CI ) .", "There is growing interest in Wolbachia , as CI may be able to drive desired phenotypes such as disease resistance traits , into natural ...	2011
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "neuroscience/cognitive neuroscience", "neuroscience/theoretical neuroscience", "computational biology/transcriptional regulation", "computational biology/computational neuroscience", "computational biology/metabolic networks", "mathematics/statistics", "computational biology/systems biology" ]	Comparing Families of Dynamic Causal Models	journal.pcbi.1000709	null	[ [ "Mathematical models of scientific data can be formally compared using Bayesian model evidence [1]–[3] , an approach that is now widely used in statistics [4] , signal processing [5] , machine learning [6] , natural language processing [7] , and neuroimaging [8]–[10] .", "An emerging area of application i...	[ "Mathematical models of scientific data can be formally compared using Bayesian model evidence .", "Previous applications in the biological sciences have mainly focussed on model selection in which one first selects the model with the highest evidence and then makes inferences based on the parameters of that mode...	[ "Bayesian model comparison provides a formal method for evaluating different computational models in the biological sciences .", "Emerging application domains include dynamical models of neuronal and biochemical networks based on differential equations .", "Much previous work in this area has focussed on select...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neurological disorders/cognitive neurology and dementia", "genetics and genomics/functional genomics", "genetics and genomics/disease models", "genetics and genomics/genetics of disease", "neurological disorders/neuropsychiatric disorders", "neurological disorders/developmental and pediatric neurology", ...	Forging Links between Human Mental Retardation–Associated CNVs and Mouse Gene Knockout Models	journal.pgen.1000531	null	[ [ "Mental retardation ( MR ) is defined as an overall intelligence quotient lower than 70 , and is associated with functional deficits in adaptive behaviour , such as daily-living skills , social skills and communication .", "This disorder affects 1%–3% of the population and results from extraordinarily het...	[ "Rare copy number variants ( CNVs ) are frequently associated with common neurological disorders such as mental retardation ( MR; learning disability ) , autism , and schizophrenia .", "CNV screening in clinical practice is limited because pathological CNVs cannot be distinguished routinely from benign CNVs , and...	[ "Mental retardation ( MR; also known as learning disability ) affects 1%–3% of people and is often associated with the presence of genomic copy number variations ( CNVs ) such as deletions and duplications .", "Most of these CNVs are rare and they often involve tens , sometimes hundreds , of genes .", "Pinpoint...	2009
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "medicine and health sciences", "fish", "immune cells", "body fluids", "immune physiology", "immunology", "vertebrates", "parasitic diseases", "animals", "olfactory organs", "osteichthyes", "respiratory system", "antibodies", "immune system proteins", "white blood cells"...	Mucosal immunoglobulins protect the olfactory organ of teleost fish against parasitic infection	journal.ppat.1007251	null	[ [ "Olfaction is a vital sense for all animals [1] .", "To receive an olfactory signal , terrestrial vertebrates inhale gases containing volatile chemical substances , while aquatic vertebrates like teleost fish actively draw water containing dissolved chemicals into the olfactory organs [2] .", "Simulta...	[ "The olfactory organ of vertebrates receives chemical cues present in the air or water and , at the same time , they are exposed to invading pathogens .", "Nasal-associated lymphoid tissue ( NALT ) , which serves as a mucosal inductive site for humoral immune responses against antigen stimulation in mammals , is ...	[ "The olfactory organ is a vitally important chemosensory organ in vertebrates but it is also continuously stimulated by pathogenic microorganisms in the external environment .", "In mammals and birds , nasopharynx-associated lymphoid tissue ( NALT ) is considered one of the first lines of immune defense against i...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "veterinary diseases", "zoonotic diseases", "veterinary science", "prion diseases" ]	In Situ Photodegradation of Incorporated Polyanion Does Not Alter Prion Infectivity	journal.ppat.1002001	null	[ [ "Infectious prion diseases such as Creutzfeldt Jakob disease ( CJD ) and other related human disorders , chronic wasting disease ( CWD ) , bovine spongiform encephalopathy ( BSE ) , and scrapie are associated with the conversion of a host-encoded glycoprotein ( PrPC ) into a misfolded conformer , PrPSc [3] ."...	[ "Single-stranded polyanions ≥40 bases in length facilitate the formation of hamster scrapie prions in vitro , and polyanions co-localize with PrPSc aggregates in vivo [1] , [2] .", "To test the hypothesis that intact polyanionic molecules might serve as a structural backbone essential for maintaining the infectio...	[ "Prions are unorthodox infectious agents whose composition remains undetermined .", "Previous experiments have shown that long , negatively charged polymers such as nucleic acid and carbohydrate molecules promote the formation of purified prions in test tube chemical reactions .", "Various classes of negatively...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood serum", "medicine and health sciences", "body fluids", "pathology and laboratory medicine", "enzymes", "cell cycle and cell division", "pathogens", "cell processes", "bacillus", "enzymology", "microbiology", "gene regulation", "membrane proteins", "dna damage", "prokaryotic models...	Discovery of a dual protease mechanism that promotes DNA damage checkpoint recovery	journal.pgen.1007512	null	[ [ "The DNA damage response ( DDR , SOS response in bacteria ) is an important pathway for maintaining genome integrity in all domains of life .", "Misregulation of the DDR in humans can result in various disease conditions [1 , 2] , and in bacteria the SOS response has been found to be important for surviva...	[ "The DNA damage response is a signaling pathway found throughout biology .", "In many bacteria the DNA damage checkpoint is enforced by inducing expression of a small , membrane bound inhibitor that delays cell division providing time to repair damaged chromosomes .", "How cells promote checkpoint recovery afte...	[ "Prokaryotes and eukaryotes coordinate cell division to genome integrity using DNA damage checkpoints .", "Many bacteria express a small , membrane binding protein to slow cell division when obstacles to DNA replication are encountered .", "Cell division inhibitors of this class have been identified in several ...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "social epidemiology", "bacterial diseases", "infectious diseases", "public and occupational health", "plant science", "medicine and health sciences", "primary care", "infectious disease epidemiology", "epidemiology", "plant pathology", "biology and life sciences", "population biology", "tro...	Effect of the Brazilian Conditional Cash Transfer and Primary Health Care Programs on the New Case Detection Rate of Leprosy	journal.pntd.0003357	null	[ [ "According to WHO “leprosy is a chronic infectious disease caused by Mycobacterium leprae” .", "It can lead to physical disability , social stigma and suffering .", "Although significant improvements have been achieved in disease control , leprosy remains a public health problem in many countries with...	[ "Social determinants can affect the transmission of leprosy and its progression to disease .", "Not much is known about the effectiveness of welfare and primary health care policies on the reduction of leprosy occurrence .", "The aim of this study is to evaluate the impact of the Brazilian cash transfer ( Bolsa...	[ "Leprosy is considered a poverty related disease .", "Not much is known about the effectiveness of welfare and primary health care policies on reduction of leprosy occurrence .", "We conducted a study to evaluate the impact of the Brazilian conditional cash transfer ( Bolsa Família Program ) and the Primary Hea...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Modeling of the Human Alveolar Rhabdomyosarcoma Pax3-Foxo1 Chromosome Translocation in Mouse Myoblasts Using CRISPR-Cas9 Nuclease	journal.pgen.1004951	null	[ [ "Rhabdomyosarcoma ( RMS ) is the third most common soft-tissue sarcoma in children with an annual incidence of five new cases per million .", "It accounts for 5–8% of all pediatric cancer .", "RMS belongs to the family of small round blue cell tumors of childhood and exhibits histological features of ...	[ "Many recurrent chromosome translocations in cancer result in the generation of fusion genes that are directly implicated in the tumorigenic process .", "Precise modeling of the effects of cancer fusion genes in mice has been inaccurate , as constructs of fusion genes often completely or partially lack the correc...	[ "Many cancers carry recurrent chromosome translocations , which often result in the formation of fusion genes that are directly involved in the tumorigenic process .", "Alveolar rhabdomyosarcoma , a muscle tumor in children , is typified by a translocation that fuses the PAX3 gene on chromosome 2 to the FOXO1 gen...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/virulence factors and mechanisms", "infectious diseases", "immunology/immune response", "immunology/innate immunity", "virology", "infectious diseases/viral infections", "virology/mechanisms of resistance and susceptibility, including host genetics", "immunology", "virology/immune evasion"...	Respiratory Syncytial Virus Interferon Antagonist NS1 Protein Suppresses and Skews the Human T Lymphocyte Response	journal.ppat.1001336	null	[ [ "Following the identification of the NS1 protein of influenza A virus as a type I interferon ( IFN-I ) -antagonist more than a decade ago [1] , such proteins have been identified for many viruses .", "Their effects on the innate immune system include interference with IFN-I induction , IFN-I-activated sig...	[ "We recently demonstrated that the respiratory syncytial virus ( RSV ) NS1 protein , an antagonist of host type I interferon ( IFN-I ) production and signaling , has a suppressive effect on the maturation of human dendritic cells ( DC ) that was only partly dependent on released IFN-I .", "Here we investigated wh...	[ "Respiratory syncytial virus ( RSV ) is a leading cause of pediatric lower respiratory tract disease .", "RSV has two IFN-I antagonist proteins , NS1 and NS2 .", "In this study , we infected primary human dendritic cells with recombinant RSV from which the NS1 and/or the NS2 genes were deleted , and evaluated e...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "molecular cell biology", "proteins", "biology", "microbiology", "bacterial pathogens", "toxicology" ]	Calcium Influx Rescues Adenylate Cyclase-Hemolysin from Rapid Cell Membrane Removal and Enables Phagocyte Permeabilization by Toxin Pores	journal.ppat.1002580	null	[ [ "By instantaneously disrupting bactericidal functions of host phagocytes , the adenylate cyclase toxin-hemolysin ( CyaA , ACT , or AC-Hly ) plays a major role in virulence of pathogenic Bordetellae [1] .", "The toxin rapidly paralyzes phagocytes [1] , [2] by translocating across their cytoplasmic membrane...	[ "Bordetella adenylate cyclase toxin-hemolysin ( CyaA ) penetrates the cytoplasmic membrane of phagocytes and employs two distinct conformers to exert its multiple activities .", "One conformer forms cation-selective pores that permeabilize phagocyte membrane for efflux of cytosolic potassium .", "The other conf...	[ "The adenylate cyclase toxin ( CyaA ) of pathogenic Bordetellae eliminates the first line of host innate immune defense by inhibiting the oxidative burst and complement-mediated opsonophagocytic killing of bacteria .", "The toxin penetrates myeloid phagocytes , such as neutrophil , macrophage or dendritic cells ,...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "computational biology/protein structure prediction", "computational biology/macromolecular structure analysis", "computational biology/protein homology detection", "computational biology" ]	Defining an Essence of Structure Determining Residue Contacts in Proteins	journal.pcbi.1000584	null	[ [ "The native structure of a protein is held intact by the complex and cooperative interplay of residue interactions .", "While a network of amino acid contacts is well defined given a native structure , it remains an open question if all the contacts are equivalent in terms of their contribution to the str...	[ "The network of native non-covalent residue contacts determines the three-dimensional structure of a protein .", "However , not all contacts are of equal structural significance , and little knowledge exists about a minimal , yet sufficient , subset required to define the global features of a protein .", "Chara...	[ "A protein structure can be visualized as a network of non-covalent contacts existing between amino acids .", "But not all such contacts are important structural determinants of a protein .", "We have attempted to identify a subset of amino acid contacts that are essential for reconstructing protein structures ...	2009
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "action potentials", "neural networks", "neurodegenerative diseases", "membrane potential", "signaling networks", "electrophysiology", "neuroscience", "surgical and invasive medical procedures", "synaptic plasticity", "functional electrical stimulation", "networ...	How stimulation frequency and intensity impact on the long-lasting effects of coordinated reset stimulation	journal.pcbi.1006113	null	[ [ "Synchronization of oscillations is a generic mechanism in animate and inanimate systems [1–6] .", "In fact , oscillators of qualitatively different type may share fundamental synchronization mechanisms [1–6] .", "Synchronization processes may occur within as well as between different systems of the h...	[ "Several brain diseases are characterized by abnormally strong neuronal synchrony .", "Coordinated Reset ( CR ) stimulation was computationally designed to specifically counteract abnormal neuronal synchronization processes by desynchronization .", "In the presence of spike-timing-dependent plasticity ( STDP ) ...	[ "Abnormally strong neuronal synchronization is found in a number of brain disorders .", "To specifically counteract abnormal neuronal synchrony and , hence , related symptoms , Coordinated Reset ( CR ) stimulation was developed .", "CR stimulation employs basic plasticity and dynamic self-organization principle...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics and genomics/complex traits", "microbiology/microbial growth and development", "genetics and genomics/gene function" ]	[SWI+], the Prion Formed by the Chromatin Remodeling Factor Swi1, Is Highly Sensitive to Alterations in Hsp70 Chaperone System Activity	journal.pgen.1001309	null	[ [ "Yeast prions are non-Mendelian genetic elements , most of which are amyloid aggregates formed by single proteins [1]–[8] .", "These aggregates , often referred to as seeds or propagons , whose number varies depending on the prion , serve as templates for the conversion of newly synthesized protein to the...	[ "The yeast prion [SWI+] , formed of heritable amyloid aggregates of the Swi1 protein , results in a partial loss of function of the SWI/SNF chromatin-remodeling complex , required for the regulation of a diverse set of genes .", "Our genetic analysis revealed that [SWI+] propagation is highly dependent upon the a...	[ "Yeast prions are heritable genetic elements , formed spontaneously by aggregation of a single protein .", "Prions can thus generate diverse phenotypes in a dominant , non-Mendelian fashion , without a corresponding change in chromosomal gene structure .", "Since the phenotypes caused by the presence of a prion...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	A Pan-Cancer Catalogue of Cancer Driver Protein Interaction Interfaces	journal.pcbi.1004518	null	[ [ "Cancer patients are extremely heterogeneous in their response to treatments and disease outcomes .", "The first step towards the understanding of this variability was the identification of the multitude of genes that cause cancer , the so-called cancer driver genes[1] .", "In that sense , the complet...	[ "Despite their importance in maintaining the integrity of all cellular pathways , the role of mutations on protein-protein interaction ( PPI ) interfaces as cancer drivers has not been systematically studied .", "Here we analyzed the mutation patterns of the PPI interfaces from 10 , 028 proteins in a pan-cancer c...	[ "Until now , most efforts in cancer genomics have focused on identifying genes and pathways driving tumor development .", "Although this has been unquestionably a success , as evidenced by the fact that we now have an extensive catalogue of cancer driver genes and pathways , there is still a poor understanding of...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "ecology and environmental sciences", "surface water", "rivers", "engineering and technology", "tropical diseases", "geographical locations", "parasitic diseases", "animals", "cameras", "peru", "developmental biology", "aquatic environments"...	High-accuracy detection of malaria vector larval habitats using drone-based multispectral imagery	journal.pntd.0007105	null	[ [ "The most widespread strategies to combat malaria rely on the distribution of long-lasting insecticide-treated nets ( LLINs ) [1] and the application of indoor residual spray ( IRS ) [2] that target endophagic and endophilic mosquito vectors .", "The decline in their efficiency is associated mainly with:"...	[ "Interest in larval source management ( LSM ) as an adjunct intervention to control and eliminate malaria transmission has recently increased mainly because long-lasting insecticidal nets ( LLINs ) and indoor residual spray ( IRS ) are ineffective against exophagic and exophilic mosquitoes .", "In Amazonian Peru ...	[ "The most efficient malaria vector in the Latin American region is Nyssorhynchus darlingi ( formerly Anopheles darlingi ) .", "In Amazonian Peru , where malaria is endemic , Ny .", "darlingi feeds both indoors and outdoors ( endophagy , exophagy ) , depending on the local environment , and rests outdoors ( exop...	2019
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[ "sequencing techniques", "genome sequencing", "organismal evolution", "genome complexity", "genomics", "genome evolution", "molecular biology", "animal evolution", "genetics", "biology and life sciences", "comparative genomics", "molecular biology techniques", "computational biology", "evo...	The First Myriapod Genome Sequence Reveals Conservative Arthropod Gene Content and Genome Organisation in the Centipede Strigamia maritima	journal.pbio.1002005	null	[ [ "Myriapods are today represented by two major lineages—the herbivorous millipedes ( Diplopoda ) and the carnivorous centipedes ( Chilopoda ) , together with two minor clades , the Symphyla , which look superficially like small white centipedes , and the minute Pauropoda [8] .", "All are characterised by a...	[ "Myriapods ( e . g . , centipedes and millipedes ) display a simple homonomous body plan relative to other arthropods .", "All members of the class are terrestrial , but they attained terrestriality independently of insects .", "Myriapoda is the only arthropod class not represented by a sequenced genome .", "...	[ "Arthropods are the most abundant animals on earth .", "Among them , insects clearly dominate on land , whereas crustaceans hold the title for the most diverse invertebrates in the oceans .", "Much is known about the biology of these groups , not least because of genomic studies of the fruit fly Drosophila , th...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "vaccines", "bacterial diseases", "infectious diseases", "medicine and health sciences", "cholera", "cholera vaccines", "population modeling", "neglected tropical diseases", "immunology", "biology and life sciences", "infectious disease modeling", "computational biology", "tropical diseases"...	Comparative Effectiveness of Different Strategies of Oral Cholera Vaccination in Bangladesh: A Modeling Study	journal.pntd.0003343	null	[ [ "Vibrio cholerae , the bacterium responsible for clinical cholera , has long been associated with the Bay of Bengal where it exists as an autochthonous member of the estuarine ecosystem [1] , [2] .", "This area of south Asia has been the origin for six of the seven cholera pandemics , and the burden of di...	[ "Killed , oral cholera vaccines have proven safe and effective , and several large-scale mass cholera vaccination efforts have demonstrated the feasibility of widespread deployment .", "This study uses a mathematical model of cholera transmission in Bangladesh to examine the effectiveness of potential vaccination...	[ "Bangladesh has a high burden of cholera and may become the first country to use cholera vaccine on a large scale .", "Mass cholera vaccination may be hard to justify to international funding agencies because of the modest efficacy of existing vaccines and their limited duration of protection .", "However , mas...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Sensory Neurons Arouse C. elegans Locomotion via Both Glutamate and Neuropeptide Release	journal.pgen.1005359	null	[ [ "Animals undergo periods of behavioral quiescence and arousal in response to changes in their environment and metabolic state .", "Arousal is defined as a state of heightened responsiveness to external stimuli coupled with increased motor activity whereas quiescence is associated with diminished responsiv...	[ "C . elegans undergoes periods of behavioral quiescence during larval molts ( termed lethargus ) and as adults .", "Little is known about the circuit mechanisms that establish these quiescent states .", "Lethargus and adult locomotion quiescence is dramatically reduced in mutants lacking the neuropeptide recept...	[ "Animals switch between periods of behavioral arousal and quiescence in response to environmental , developmental , and circadian cues .", "Little is known about the circuit mechanisms that produce these behavioral states .", "During larval molts , C . elegans exhibits a sleep-like state ( termed lethargus ) th...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "biotechnology", "medicine", "infectious diseases", "african trypanosomiasis", "parasitology", "neglected tropical diseases", "biology", "microbiology", "drug discovery" ]	A Static-Cidal Assay for Trypanosoma brucei to Aid Hit Prioritisation for Progression into Drug Discovery Programmes	journal.pntd.0001932	null	[ [ "Human African Trypanosomiasis ( HAT ) or sleeping sickness is an endemic disease of sub-Saharan Africa .", "It is caused by two subspecies of Trypanosoma brucei , T . b .", "rhodesiense and T . b .", "gambiense , the latter of which is responsible for 95% of all cases of HAT [1] .", "Progress...	[ "Human African Trypanosomiasis is a vector-borne disease of sub-Saharan Africa that causes significant morbidity and mortality .", "Current therapies have many drawbacks , and there is an urgent need for new , better medicines .", "Ideally such new treatments should be fast-acting cidal agents that cure the dis...	[ "Trypanosoma brucei is a protozoan parasite causing African sleeping sickness .", "Current treatments for this disease have significant limitations , underlining the need for better and safer drugs .", "To identify new chemical starting points for drug development , large compound collections are screened again...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/genomics", "genetics and genomics/epigenetics" ]	The Status of Dosage Compensation in the Multiple X Chromosomes of the Platypus	journal.pgen.1000140	null	[ [ "Monotremes are unique mammals that exhibit a mix of reptilian and mammalian features , as they lay eggs , yet have fur and produce milk for their young .", "Represented only by the fabled platypus and four species of echidna , they are distantly related to humans and other eutherian ( ‘placental’ ) mamma...	[ "Dosage compensation has been thought to be a ubiquitous property of sex chromosomes that are represented differently in males and females .", "The expression of most X-borne genes is equalized between XX females and XY males in therian mammals ( marsupials and “placentals” ) by inactivating one X chromosome in f...	[ "Dosage compensation equalizes the expression of genes found on sex chromosomes so that they are equally expressed in females and males .", "In placental and marsupial mammals , this is accomplished by silencing one of the two X chromosomes in female cells .", "In birds , dosage compensation seems not to be str...	2008
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "computer science", "computer modeling", "mathematics", "neurological disorders", "statistics", "neurology", "statistical methods", "neuroimaging" ]	Generative Embedding for Model-Based Classification of fMRI Data	journal.pcbi.1002079	null	[ [ "Despite their increasing popularity , two challenges critically limit the practical applicability of current classification methods for functional neuroimaging data .", "First , classifying subjects directly in voxel space is often a prohibitively difficult task .", "This is because functional neuroi...	[ "Decoding models , such as those underlying multivariate classification algorithms , have been increasingly used to infer cognitive or clinical brain states from measures of brain activity obtained by functional magnetic resonance imaging ( fMRI ) .", "The practicality of current classifiers , however , is restri...	[ "Neurological and psychiatric spectrum disorders are typically defined in terms of particular symptom sets , despite increasing evidence that the same symptom may be caused by very different pathologies .", "Pathophysiological classification and effective treatment of such disorders will increasingly require a me...	2011
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "chemical biology/protein chemistry and proteomics", "biochemistry/protein folding", "biochemistry/protein chemistry", "biotechnology/protein chemistry and proteomics" ]	Sequestration of the Aβ Peptide Prevents Toxicity and Promotes Degradation In Vivo	journal.pbio.1000334	An engineered protein prevents aggregation of the Aβ peptide and facilitates clearance of Aβ from the brain in a fruit fly model of Alzheimer's disease.	[ [ "Of the neurodegenerative disorders that have been linked to protein misfolding and aggregation [1] , Alzheimer's disease ( AD ) is the most common [2] , [3] .", "Transgenic animal models have shown that aggregation of the Alzheimer β-peptide ( Aβ ) causes memory impairment [4] , [5] and cognitive deficit...	[ "Protein aggregation , arising from the failure of the cell to regulate the synthesis or degradation of aggregation-prone proteins , underlies many neurodegenerative disorders .", "However , the balance between the synthesis , clearance , and assembly of misfolded proteins into neurotoxic aggregates remains poorl...	[ "Alzheimer's disease is thought to be a result of neuronal damage caused by toxic aggregated forms of the Aβ peptide in the brain .", "There is no cure and existing treatments are ineffective in reversing or preventing disease progression .", "Here we describe a novel strategy that makes use of an engineered “A...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Evidence of Selection against Complex Mitotic-Origin Aneuploidy during Preimplantation Development	journal.pgen.1005601	null	[ [ "Human reproduction is inefficient , with pregnancy loss estimated to occur in approximately 70% of all conceptions [1] .", "The majority of pregnancy losses take place before 12 weeks of gestation [2] and are mostly explained by whole-chromosome abnormalities [3 , 4] as well as structural aberrations [5]...	[ "Whole-chromosome imbalances affect over half of early human embryos and are the leading cause of pregnancy loss .", "While these errors frequently arise in oocyte meiosis , many such whole-chromosome abnormalities affecting cleavage-stage embryos are the result of chromosome missegregation occurring during the i...	[ "By day 3 of development , more than half of human embryos contain at least one cell that deviates from the typical 46-chromosome complement .", "These whole-chromosome abnormalities include polyploidies , which affect the entire chromosome set , as well as aneuploidies , which involve gains and losses of particu...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "schistosoma", "invertebrates", "livestock", "medicine and health sciences", "helminths", "china", "statistics", "metaanalysis", "tropical diseases", "geographical locations", "parasitic diseases", "animals", "gastropods", "mathematics", "neglected tropical diseases", "snails", "rese...	A meta-analysis of infection rates of Schistosoma japonicum in sentinel mice associated with infectious waters in mainland China over last 40 years	journal.pntd.0007475	null	[ [ "Schistosomiasis , caused by blood flukes of the genus Schistosoma ( phylum Platyhelminthes; class Trematoda ) , is a zoonotic parasitic disease and is one of the 18 neglected tropical disease listed by the World Health Organization [1 , 2] .", "Currently , an estimated 240 million people are infected wit...	[ "Schistosomiasis japonica is a zoonotic parasitic disease .", "After nearly 70 years of control efforts in China , Schistosomiasis transmission has been reduced to a much lower level .", "The absence or near absence of infections in humans or livestock , based on traditional fecal and serological tests , has ma...	[ "With the continued activities of the prevention and control programme in China , the prevalence and intensity of Schistosoma japonicum infection have been reduced to low levels .", "This makes it impossible to detect any infections in humans or livestock using the traditional approach of fecal and serological te...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/gene expression", "evolutionary biology/genomics", "evolutionary biology/evolutionary and comparative genetics" ]	Transcriptional Rewiring of the Sex Determining dmrt1 Gene Duplicate by Transposable Elements	journal.pgen.1000844	null	[ [ "Control and coordination of eukaryotic gene expression rely on transcriptional and posttranscriptional regulatory networks .", "From an evolutionary point of view innovations and changes in given functional linkages of regulatory networks have to occur at the DNA level by alteration of the cis-regulatory...	[ "Control and coordination of eukaryotic gene expression rely on transcriptional and posttranscriptional regulatory networks .", "Evolutionary innovations and adaptations often require rapid changes of such networks .", "It has long been hypothesized that transposable elements ( TE ) might contribute to the rewi...	[ "Evolutionary innovations and adaptations often require rapid changes in gene regulation .", "Transposable elements constitute the most dynamic part of eukaryotic genomes .", "Insertions of transposable elements can influence the expression of surrounding genes by donating new regulatory elements .", "A longs...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "systems biology", "synthetic biology", "biology", "computational biology", "molecular biology", "genetics and genomics" ]	Modular Design of Artificial Tissue Homeostasis: Robust Control through Synthetic Cellular Heterogeneity	journal.pcbi.1002579	null	[ [ "As potential solutions for this problem , we propose several increasingly robust variants of a synthetic gene network that are designed to maintain a steady level of -cells despite normal cell death and constant destruction of the -cells by the immune system .", "The synthetic gene networks continuously ...	[ "Synthetic biology efforts have largely focused on small engineered gene networks , yet understanding how to integrate multiple synthetic modules and interface them with endogenous pathways remains a challenge .", "Here we present the design , system integration , and analysis of several large scale synthetic gen...	[ "Over the last decade several relatively small synthetic gene networks have been successfully implemented and characterized , including oscillators , toggle switches , and intercellular communication systems .", "However , the ability to engineer large-scale synthetic gene networks for controlling multicellular s...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	An Adapting Auditory-motor Feedback Loop Can Contribute to Generating Vocal Repetition	journal.pcbi.1004471	null	[ [ "Many complex behaviors—human speech , playing a piano , or birdsong—consist of a set of discrete actions that can be flexibly organized into variable sequences [1–3] .", "A feature of many variably sequenced behaviors is the occurrence of repetitive sub-sequences of the same action .", "Examples incl...	[ "Consecutive repetition of actions is common in behavioral sequences .", "Although integration of sensory feedback with internal motor programs is important for sequence generation , if and how feedback contributes to repetitive actions is poorly understood .", "Here we study how auditory feedback contributes t...	[ "Repetitions are common in animal vocalizations .", "Songs of many songbirds contain syllables that repeat a variable number of times , with non-Markovian distributions of repeat counts .", "The neural mechanism underlying such syllable repetitions is unknown .", "In this work , we show that auditory feedback...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "circuit models", "neural networks", "computational neuroscience", "biology and life sciences", "computational biology", "neuroscience", "learning and memory" ]	A Signature of Attractor Dynamics in the CA3 Region of the Hippocampus	journal.pcbi.1003641	null	[ [ "Theoretical work has shown how networks with excitatory recurrent connections can function as an associative memory [1]–[4] .", "Specifically , Hebbian plasticity at the synapses of recurrent connections leads to the association of the elements of a memory .", "Information stored in this way can be r...	[ "The notion of attractor networks is the leading hypothesis for how associative memories are stored and recalled .", "A defining anatomical feature of such networks is excitatory recurrent connections .", "These “attract” the firing pattern of the network to a stored pattern , even when the external input is in...	[ "A type of neural network called an “attractor network” is thought to underlie memory associations .", "Importantly , when such a network is presented with part of a memory , the network activity is attracted to the complete memory .", "However , it has been difficult to obtain clear experimental evidence for s...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "genome-wide association studies", "medicine and health sciences", "statistics", "immunology", "variant genotypes", "alleles", "genetic mapping", "multivariate analysis", "clinical medicine", "linkage disequilibrium", "mathematics", "genome analysis", "molecular genetics", "research and an...	Genome-wide association study in Turkish and Iranian populations identify rare familial Mediterranean fever gene (MEFV) polymorphisms associated with ankylosing spondylitis	journal.pgen.1008038	null	[ [ "Ankylosing spondylitis ( AS ) is a common form of arthritis affecting primarily the spine and pelvic sacroiliac joints .", "Twin studies indicate that the disease is highly heritable , with over 90% of the risk of developing the condition being genetically determined [1 , 2] .", "To date 114 loci hav...	[ "Ankylosing spondylitis ( AS ) is a highly heritable immune-mediated arthritis common in Turkish and Iranian populations .", "Familial Mediterranean Fever ( FMF ) is an autosomal recessive autoinflammatory disease most common in people of Mediterranean origin .", "MEFV , an FMF-associated gene , is also a candi...	[ "Ankylosing spondylitis ( AS ) is a highly heritable immune-mediated arthritis .", "To identify new genetic associations with AS , we performed genome-wide association studies in Turkish and Iranian AS patients and controls .", "We identified a novel rare coding MEFV variant associated with AS .", "Rare polym...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "velocity", "invertebrates", "somatosensory system", "medicine and health sciences", "classical mechanics", "engineering and technology", "caenorhabditis", "nociception", "lasers", "social sciences", "random variables", "neuroscience", "animals", "covariance", "animal models", "caenorh...	Stereotypical Escape Behavior in Caenorhabditis elegans Allows Quantification of Effective Heat Stimulus Level	journal.pcbi.1005262	null	[ [ "A grand goal in understanding sensory systems is to predict the behavioral response of an organism to specific sensory stimuli; or , conversely , to infer the sensory stimuli from measurements of the behavioral response .", "Such a goal requires careful experimental design , precise control of the sensor...	[ "A goal of many sensorimotor studies is to quantify the stimulus-behavioral response relation for specific organisms and specific sensory stimuli .", "This is especially important to do in the context of painful stimuli since most animals in these studies cannot easily communicate to us their perceived levels of ...	[ "A doctor assesses pain by asking her patient to “rate your pain on the scale of 1 to 10 . ”", "She may then prescribe some drugs and later ask the question again to see if they worked .", "New drugs are often developed using animal models , but we cannot ask an animal , especially a small invertebrate animal ,...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "cell death", "molecular neuroscience", "neuroscience", "membrane receptor signaling", "signaling pathways", "signaling in cellular processes", "endocrinology", "diabetes and endocrinology", "biology", "neuroendocrinology", "molecular biology", "signal transduction", "cell biol...	Neurosteroid Dehydroepiandrosterone Interacts with Nerve Growth Factor (NGF) Receptors, Preventing Neuronal Apoptosis	journal.pbio.1001051	null	[ [ "Dehydroepiandrosterone ( DHEA ) is a steroid , produced in adrenals , in neurons and in glia [1] .", "The physiological role of brain DHEA appears to be local , i . e . paracrine , while that produced from adrenals , which represents the almost exclusive source of circulating DHEA , is systemic .", "...	[ "The neurosteroid dehydroepiandrosterone ( DHEA ) , produced by neurons and glia , affects multiple processes in the brain , including neuronal survival and neurogenesis during development and in aging .", "We provide evidence that DHEA interacts with pro-survival TrkA and pro-death p75NTR membrane receptors of n...	[ "Dehydroepiandrosterone ( DHEA ) and its sulphate ester are the most abundant steroid hormones in humans , and DHEA was described as the first neurosteroid produced in the brain .", "DHEA is known to participate in multiple events in the brain , including neuronal survival and neurogenesis .", "However , to dat...	2011
[ "Introduction", "Results", "Discussion", "Methods", "Supporting Information" ]	[ "evolutionary biology", "genetics and genomics", "mammals", "computational biology" ]	Adaptive Evolution of Conserved Noncoding Elements in Mammals	journal.pgen.0030147	null	[ [ "Phenotypic evolution proceeds both by changes in protein coding sequences and by changes in gene expression that determine when , where , and how much genes are expressed [1–3] .", "Although recent genome-wide studies have begun the process of identifying genes that show signals of adaptive evolution in ...	[ "Conserved noncoding elements ( CNCs ) are an abundant feature of vertebrate genomes .", "Some CNCs have been shown to act as cis-regulatory modules , but the function of most CNCs remains unclear .", "To study the evolution of CNCs , we have developed a statistical method called the “shared rates test” to iden...	[ "Conservation of DNA sequences across evolutionary history is a highly informative signal for identifying regions with important biological functions .", "In particular , conserved noncoding regions have been shown to be good candidates for containing regulatory elements that have roles in gene regulation .", "...	2007
[ "Introduction", "Materials and Methods", "Results/Discussion" ]	[ "microbiology/environmental microbiology", "biochemistry/biocatalysis", "physiology/sensory systems", "physiology/genomics", "cell biology/cell growth and division", "microbiology/microbial evolution and genomics", "molecular biology", "molecular biology/bioinformatics", "microbiology/microbial phys...	Genetic and Computational Identification of a Conserved Bacterial Metabolic Module	journal.pgen.1000310	null	[ [ "Inositol , or cyclohexanehexol , is one of the most abundant carbohydrates in freshwater and terrestrial ecosystems [1] .", "Phosphorylated and lipidated derivatives of inositol serve as important signaling molecules in eukaryotic cells and are critical components of cellular membranes .", "Among pro...	[ "We have experimentally and computationally defined a set of genes that form a conserved metabolic module in the α-proteobacterium Caulobacter crescentus and used this module to illustrate a schema for the propagation of pathway-level annotation across bacterial genera .", "Applying comprehensive forward and reve...	[ "More than 1 , 000 microbial genomes have been sequenced to date , containing millions of predicted genes .", "While the broad functional category of many of these individual genes can be reliably predicted using sequence homology , sequence information alone is often insufficient to assign a gene a specific cell...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology/neuronal and glial cell biology", "biochemistry", "cell biology", "genetics and genomics/disease models", "genetics and genomics/genetics of disease", "genetics and genomics/gene function", "genetics and genomics" ]	An ALS-Linked Mutant SOD1 Produces a Locomotor Defect Associated with Aggregation and Synaptic Dysfunction When Expressed in Neurons of Caenorhabditis elegans	journal.pgen.1000350	null	[ [ "A number of neurodegenerative diseases have been associated with protein misfolding and aggregation , with a specific protein in each case observed to aggregate in a particular population of neurons .", "For example , in the case of amyotrophic lateral sclerosis ( Lou Gehrig's Disease ) , a dominantly in...	[ "The nature of toxic effects exerted on neurons by misfolded proteins , occurring in a number of neurodegenerative diseases , is poorly understood .", "One approach to this problem is to measure effects when such proteins are expressed in heterologous neurons .", "We report on effects of an ALS-associated , mis...	[ "A new animal model of the human neurodegenerative disease amyotrophic lateral sclerosis ( ALS; Lou Gehrig's Disease ) is presented .", "Two percent of ALS cases result from heritable mutations affecting the abundant enzyme superoxide dismutase ( SOD1 ) .", "Such mutations have been indicated to impair the fold...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "computational biology/evolutionary modeling", "evolutionary biology" ]	Natural Selection Fails to Optimize Mutation Rates for Long-Term Adaptation on Rugged Fitness Landscapes	journal.pcbi.1000187	null	[ [ "Mutation is the ultimate source of genetic variation , and thus the rate at which spontaneous mutations appear is a fundamental evolutionary parameter .", "The mechanisms of DNA replication and repair are themselves genetically encoded and variable [1]–[5] , making mutation rates potential targets of evo...	[ "The rate of mutation is central to evolution .", "Mutations are required for adaptation , yet most mutations with phenotypic effects are deleterious .", "As a consequence , the mutation rate that maximizes adaptation will be some intermediate value .", "Here , we used digital organisms to investigate the abi...	[ "Natural selection is shortsighted and therefore does not necessarily drive populations toward improved long-term performance .", "Some traits may evolve because they provide immediate gains , even though they are less successful in the long run than some alternatives .", "Here , we use digital organisms to ana...	2008
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "genome-wide association studies", "medicine and health sciences", "genetic networks", "skeletal muscles", "brain", "physiological processes", "developmental biology", "organism development", "network analysis", "genome analysis", "musculoskeletal system", "computer and information sciences", ...	Cross-species functional modules link proteostasis to human normal aging	journal.pcbi.1007162	null	[ [ "Aging is a process that affects most living organisms and results in a progressive decline in life function and a gain in vulnerability to death [1] .", "In humans , aging is the main risk factor in a wide spectrum of diseases .", "The recent increase in human healthspan , also called ‘normal’ , ‘dis...	[ "The evolutionarily conserved nature of the few well-known anti-aging interventions that affect lifespan , such as caloric restriction , suggests that aging-related research in model organisms is directly relevant to human aging .", "Since human lifespan is a complex trait , a systems-level approach will contribu...	[ "Aging leads to changes in the activity of genes , but these changes are much more subtle than those between health and disease .", "This makes finding the genes involved in aging difficult .", "We have combined two ways to improve information on the involvement of genes in aging .", "First , important gene a...	2019
[ "Introduction", "Methods", "Results", "Discussion", "Conclusions" ]	[ "children", "medicine and health sciences", "body fluids", "education", "sociology", "tropical diseases", "geographical locations", "social sciences", "parasitic diseases", "parasitic protozoans", "north america", "age groups", "protozoans", "neglected tropical diseases", "infectious dis...	Partnering for impact: Integrated transmission assessment surveys for lymphatic filariasis, soil transmitted helminths and malaria in Haiti	journal.pntd.0005387	null	[ [ "Globally , lymphatic filariasis ( LF ) , soil transmitted helminths ( STH ) and malaria are frequently co-endemic , presenting opportunities for integration of programs targeting their control and elimination .", "The WHO Global Program to Eliminate LF ( GPELF ) was launched in 2000 with a commitment to ...	[ "Since 2001 , Haiti’s National Program for the Elimination of Lymphatic Filariasis ( NPELF ) has worked to reduce the transmission of lymphatic filariasis ( LF ) through annual mass drug administration ( MDA ) with diethylcarbamazine and albendazole .", "The NPELF reached full national coverage with MDA for LF in...	[ "Lymphatic filariasis and malaria are mosquito-borne parasitic infections that are endemic in Haiti .", "Soil-transmitted helminths are also present in Haiti , infecting large numbers of people every year .", "Since 2001 , Haiti’s National Program for the Elimination of Lymphatic Filariasis ( NPELF ) has worked...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Re-assess Vector Indices Threshold as an Early Warning Tool for Predicting Dengue Epidemic in a Dengue Non-endemic Country	journal.pntd.0004043	null	[ [ "Dengue viruses ( DENV ) are the most widespread arthropod-borne viruses affecting humans .", "A recent study estimates that annually 390 million DENV infections occur worldwide with 500 , 000 severe cases and 25 , 000 deaths , mostly affecting children[1] .", "Infection with DENV can result in a rang...	[ "Despite dengue dynamics being driven by complex interactions between human hosts , mosquito vectors and viruses that are influenced by climate factors , an operational model that will enable health authorities to anticipate the outbreak risk in a dengue non-endemic area has not been developed .", "The objectives...	[ "With the continuously high levels of worldwide dengue transmission , predicting dengue outbreaks in advance of their occurrence or identifying specific locations where outbreak risks are highest is of critical importance .", "However , only few studies have been conducted in dengue non-endemic countries to evalu...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Binding of Multiple Rap1 Proteins Stimulates Chromosome Breakage Induction during DNA Replication	journal.pgen.1005283	null	[ [ "Telomeres are specialized nucleoprotein complexes at the ends of linear eukaryotic chromosomes .", "The DNA component of telomeres typically comprises a double-stranded DNA ( dsDNA ) region of a tandem repeat and a 3’ protruding single-stranded DNA ( ssDNA ) region of the G-rich strand [1 , 2] .", "B...	[ "Telomeres , the ends of linear eukaryotic chromosomes , have a specialized chromatin structure that provides a stable chromosomal terminus .", "In budding yeast Rap1 protein binds to telomeric TG repeat and negatively regulates telomere length .", "Here we show that binding of multiple Rap1 proteins stimulates...	[ "Telomere length is maintained primarily through equilibrium between telomerase-mediated lengthening and the loss of telomeric sequence through the end-replication problem .", "In budding yeast Rap1 protein binds to telomeric TG repeat and negatively regulates telomerase recruitment in a dosage-dependent manner ....	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	The Role of TcdB and TccC Subunits in Secretion of the Photorhabdus Tcd Toxin Complex	journal.ppat.1003644	null	[ [ "Photorhabdus are Enterobacteriaceae which live in an obligate mutualistic association with entomopathogenic nematodes ( Heterorhabditis ) , which invade and kill insects in the soil [1] .", "Upon invasion of the insect's open blood system the nematode regurgitates Photorhabdus bacteria which release a pl...	[ "The Toxin Complex ( TC ) is a large multi-subunit toxin encoded by a range of bacterial pathogens .", "The best-characterized examples are from the insect pathogens Photorhabdus , Xenorhabdus and Yersinia .", "They consist of three large protein subunits , designated A , B and C that assemble in a 5∶1∶1 stoich...	[ "The Toxin Complex ( TC ) is a large multimeric protein complex first identified in the insect pathogens Photorhabdus and Xenorhabdus .", "TC isolates from these pathogens exhibit oral toxicity to a diverse range of insects .", "As such there is significant interest in developing them as candidates for crop pro...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Nebula/DSCR1 Upregulation Delays Neurodegeneration and Protects against APP-Induced Axonal Transport Defects by Restoring Calcineurin and GSK-3β Signaling	journal.pgen.1003792	null	[ [ "Virtually all Down syndrome ( DS ) adults develop progressive neurodegeneration as seen in Alzheimer's disease ( AD ) , and overexpression of the amyloid precursor protein ( APP ) , a gene located on chromosome 21 , is thought to contribute to AD in DS [1]–[3] .", "Consistently , duplication of a normal ...	[ "Post-mortem brains from Down syndrome ( DS ) and Alzheimer's disease ( AD ) patients show an upregulation of the Down syndrome critical region 1 protein ( DSCR1 ) , but its contribution to AD is not known .", "To gain insights into the role of DSCR1 in AD , we explored the functional interaction between DSCR1 an...	[ "Alzheimer's disease ( AD ) is a debilitating neurodegenerative disease characterized by gradual neuronal cell loss and memory decline .", "Importantly , Down syndrome ( DS ) individuals over 40 years of age almost always develop neuropathological features of AD , although most do not develop dementia until at le...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "plant science", "cell biology", "gene expression", "plant cell biology", "genetics", "biology and life sciences", "plant genetics", "molecular cell biology", "plant physiology", "genetic engineering", "gene function" ]	Intron Retention in the 5′UTR of the Novel ZIF2 Transporter Enhances Translation to Promote Zinc Tolerance in Arabidopsis	journal.pgen.1004375	null	[ [ "The transition metal zinc ( Zn ) is a micronutrient essential for optimal plant growth and development , serving as a catalytic co-factor or structural motif in numerous proteins required for basic cellular processes .", "However , its propensity to inactivate other crucial proteins also renders Zn a pot...	[ "Root vacuolar sequestration is one of the best-conserved plant strategies to cope with heavy metal toxicity .", "Here we report that zinc ( Zn ) tolerance in Arabidopsis requires the action of a novel Major Facilitator Superfamily ( MFS ) transporter .", "We show that ZIF2 ( Zinc-Induced Facilitator 2 ) locali...	[ "Alternative splicing , which generates multiple messenger RNAs ( mRNAs ) from the same gene , is a key posttranscriptional regulatory mechanism in higher eukaryotes whose functional relevance in plants remains poorly understood .", "The sequestration of metal ions inside the vacuole of root cells is an important...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "death rates", "invertebrates", "medicine and health sciences", "ecology and environmental sciences", "body fluids", "pathology and laboratory medicine", "pathogens", "microbiology", "vertebrates", "diet", "animals", "viruses", "nutrition", "rna viruses", "population biology", "insect ...	Evaluation of a novel West Nile virus transmission control strategy that targets Culex tarsalis with endectocide-containing blood meals	journal.pntd.0007210	null	[ [ "West Nile virus ( WNV ) is an arthropod-borne flavivirus , and the leading cause of domestically acquired arboviral disease in the United States [1 , 2] , resulting in significant disease and death every year in humans , domesticated animals , and wildlife .", "From 1999–2017 , >48 , 000 cases of human W...	[ "Control of arbovirus transmission remains focused on vector control through application of insecticides directly to the environment .", "However , these insecticide applications are often reactive interventions that can be poorly-targeted , inadequate for localized control during outbreaks , and opposed due to e...	[ "West Nile virus ( WNV ) is a mosquito-borne virus that causes significant disease and death every year in humans , domesticated animals , and wildlife .", "Control of WNV transmission is focused on controlling the mosquito vector through applications of insecticides directly to the environment .", "In this stu...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "pathogens", "plasmids", "immunology", "microbiology", "plasmid construction", "bacterial diseases", "antibiotic resistance", "enterobacteriaceae", "genetic elements", "forms of dna", "dna...	Expression of a novel class of bacterial Ig-like proteins is required for IncHI plasmid conjugation	journal.pgen.1008399	null	[ [ "Infectious diseases , despite the availability of antibiotics , remain an important public health issue , representing the second leading cause of death worldwide [1] .", "Antimicrobial resistance ( AMR ) is in several instances underlying the evolution of fatal bacterial infections .", "The gradual ...	[ "Antimicrobial resistance ( AMR ) is currently one of the most important challenges to the treatment of bacterial infections .", "A critical issue to combat AMR is to restrict its spread .", "In several instances , bacterial plasmids are involved in the global spread of AMR .", "Plasmids belonging to the inco...	[ "Dissemination of antimicrobial resistance ( AMR ) among different bacterial populations occurs due to mainly the presence of plasmids that encode AMR determinants .", "IncHI plasmids are one of the groups of bacterial plasmids that confer AMR to several enterobacteria .", "Recently , resistance to one of the l...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "velocity", "invertebrates", "classical mechanics", "social sciences", "neuroscience", "animals", "animal models", "perception", "drosophila melanogaster", "model organisms", "cognitive psychology", "experimental organism systems", "vision", "drosophila", "research and analysis methods",...	Multi-stability with ambiguous visual stimuli in Drosophila orientation behavior	journal.pbio.2003113	null	[ [ "Sensory stimuli serve an animal to organize its behavior .", "They may have a meaning or relevance .", "A stimulus may elicit a certain behavior , but often stimuli are ambiguous .", "A dark patch in the visual surround of an animal may be a potential hiding place or a predator .", "If the fi...	[ "It is widely accepted for humans and higher animals that vision is an active process in which the organism interprets the stimulus .", "To find out whether this also holds for lower animals , we designed an ambiguous motion stimulus , which serves as something like a multi-stable perception paradigm in Drosophil...	[ "Vision is considered an active process in humans and higher animals in which the stimulus is interpreted by the subject and can be perceived in different ways if it is ambiguous .", "We aimed to find out whether this also holds for lower animals , such as the fruit fly Drosophila melanogaster .", "To provide a...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "cell death", "innate immune system", "medicine and health sciences", "rna interference", "immune physiology", "cytokines", "gene regulation", "immunology", "cell processes", "animals", "animal models", "developmental biology", "regulator genes", "drosophila melanogaster...	Hippo, TGF-β, and Src-MAPK pathways regulate transcription of the upd3 cytokine in Drosophila enterocytes upon bacterial infection	journal.pgen.1007091	null	[ [ "The digestive tract is uniquely challenged by its high degree of exposure to the external environment .", "The transit of nutrients through the gastrointestinal ( GI ) tract is accompanied by frequent introduction of biotic and abiotic stresses .", "In particular , digestive tissue is constantly expo...	[ "Cytokine signaling is responsible for coordinating conserved epithelial regeneration and immune responses in the digestive tract .", "In the Drosophila midgut , Upd3 is a major cytokine , which is induced in enterocytes ( EC ) and enteroblasts ( EB ) upon oral infection , and initiates intestinal stem cell ( ISC...	[ "Tissue regeneration is a fundamental process that maintains the integrity of the intestinal epithelium when faced with chemical or microbial stresses .", "In both healthy and diseased conditions , pro-regenerative cytokines function as central coordinators of gut renewal , linking inflammation to stem cell activ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "homo (human)", "genetics and genomics" ]	Large-Scale Population Study of Human Cell Lines Indicates that Dosage Compensation Is Virtually Complete	journal.pgen.0040009	null	[ [ "Dosage compensation is a regulatory process that alters gene expression along entire X chromosomes resulting in equivalent levels of X-linked gene products in males and females .", "Dosage compensation has evolved independently several times and is achieved in various ways .", "In Drosophila melanoga...	[ "X chromosome inactivation in female mammals results in dosage compensation of X-linked gene products between the sexes .", "In humans there is evidence that a substantial proportion of genes escape from silencing .", "We have carried out a large-scale analysis of gene expression in lymphoblastoid cell lines fr...	[ "The males and females of many species are distinguished by their inheritance of different sets of sex chromosomes .", "This creates a significant imbalance in gene number between the sexes .", "Dosage compensation is the correction for this imbalance and is achieved by regulating gene activity across entire se...	2008
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Intradermal Immunization of Leishmania donovani Centrin Knock-Out Parasites in Combination with Salivary Protein LJM19 from Sand Fly Vector Induces a Durable Protective Immune Response in Hamsters	journal.pntd.0004322	null	[ [ "Leishmaniasis is a disease with a wide spectrum of clinical manifestations caused by different species of protozoa belonging to the Leishmania genus that are transmitted by sand fly vectors [1] .", "The disease causes high morbidity and significant mortality throughout the world , where 350 million peopl...	[ "Visceral leishmaniasis ( VL ) is a neglected tropical disease and is fatal if untreated .", "There is no vaccine available against leishmaniasis .", "The majority of patients with cutaneous leishmaniasis ( CL ) or VL develop a long-term protective immunity after cure from infection , which indicates that devel...	[ "Leishmaniasis is a disease with a wide spectrum of clinical manifestations caused by different species of protozoa belonging to the Leishmania genus that are transmitted by sand fly vectors .", "Visceral infections of Leishmania cause significant mortality and morbidity and development of a vaccine to prevent le...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biotechnology", "bioengineering", "biomedical engineering", "engineering" ]	The Effect of Sustained Compression on Oxygen Metabolic Transport in the Intervertebral Disc Decreases with Degenerative Changes	journal.pcbi.1002112	null	[ [ "Degenerative changes of the intervertebral discs ( IVDs ) occur either in a pathological manner or as a consequence of aging , and seriously compromise the tissue capability to sustain the stressful loads transmitted throughout the spine [1] , [2] .", "The IVD is the largest avascular tissue in our body ...	[ "Intervertebral disc metabolic transport is essential to the functional spine and provides the cells with the nutrients necessary to tissue maintenance .", "Disc degenerative changes alter the tissue mechanics , but interactions between mechanical loading and disc transport are still an open issue .", "A porome...	[ "Low back pain is a very common pathology in industrialized countries , often due to bad posture .", "It is also highly related to intervertebral disc aging .", "Aging of the disc is a normal process characterized by series of changes in its structure and function .", "The events that convert normal aging int...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Relatedness, Conflict, and the Evolution of Eusociality	journal.pbio.1002098	Mathematical modelling shows that the evolution of sterile castes requires genetic relatedness but also involves conflicts between kin; these results contradict recent claims but agree with inclusive fitness theory.	[ [ "The eusocial insects have occupied an important place in biology because of their extraordinary levels of cooperation [1–4] .", "In ants , termites , some bees , some wasps , and a few other taxa , certain individuals , called workers , give up their own reproduction in order to help others reproduce .",...	[ "The evolution of sterile worker castes in eusocial insects was a major problem in evolutionary theory until Hamilton developed a method called inclusive fitness .", "He used it to show that sterile castes could evolve via kin selection , in which a gene for altruistic sterility is favored when the altruism suffi...	[ "The evolution of sterile worker castes in social insects has fascinated biologists ever since Darwin; how can selection favor a trait that decreases reproductive fitness ?", "W . D . Hamilton solved this dilemma in the 1960s with a theory showing that reproductive altruism could evolve if it increased the worker...	2015
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "populus", "oryza", "plant biology", "arabidopsis", "computational biology" ]	Intragenomic Matching Reveals a Huge Potential for miRNA-Mediated Regulation in Plants	journal.pcbi.0030238	null	[ [ "Small RNAs are now accepted as major players in the control of eukaryotic gene expression .", "Most well known are microRNAs ( miRNAs ) and small interfering RNAs ( siRNAs ) , both of which are derived from the processing of dsRNA molecules by members of the Drosha/Dicer family of endonucleases .", "...	[ "microRNAs ( miRNAs ) are important post-transcriptional regulators , but the extent of this regulation is uncertain , both with regard to the number of miRNA genes and their targets .", "Using an algorithm based on intragenomic matching of potential miRNAs and their targets coupled with support vector machine cl...	[ "microRNAs ( miRNAs ) are small RNA molecules that regulate gene expression by complementary basepairing to mRNAs .", "In plants , this base-pairing is almost perfect along the whole length of miRNAs .", "This long stretch of complementarity makes it relatively easy to make computational predictions of the targ...	2007
[ "Introduction", "Materials and Methods", "Results/Discussion" ]	[ "computational biology/systems biology", "computational biology" ]	Predicting and Validating Protein Interactions Using Network Structure	journal.pcbi.1000118	null	[ [ "For understanding the complex activities within an organism , a complete and error-free network of protein interactions which occur in the organism would be a significant step forward .", "Experimentally , protein interactions can be detected by a number of techniques , and the data is publicly available...	[ "Protein interactions play a vital part in the function of a cell .", "As experimental techniques for detection and validation of protein interactions are time consuming , there is a need for computational methods for this task .", "Protein interactions appear to form a network with a relatively high degree of ...	[ "For understanding the complex activities within an organism , a complete and error-free network of protein interactions which occur in the organism would be a significant step forward .", "The large amount of experimentally derived data now available has provided us with a chance to study the complicated behavio...	2008
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "animal types", "demography", "domestic animals", "population genetics", "wolves", "vertebrates", "pets and companion animals", "dogs", "mammals", "animals", "mammalian genomics", "population biology", "zoology", "animal genomics", "people and places", "natural selection", "evolution...	Demographically-Based Evaluation of Genomic Regions under Selection in Domestic Dogs	journal.pgen.1005851	null	[ [ "Identifying regions of the genome that have undergone recent positive selection is central to understanding the causes of evolutionary diversification .", "Nevertheless , developing efficient and statistically robust methods for distinguishing genomic regions under selection from the neutral background e...	[ "Controlling for background demographic effects is important for accurately identifying loci that have recently undergone positive selection .", "To date , the effects of demography have not yet been explicitly considered when identifying loci under selection during dog domestication .", "To investigate positiv...	[ "Identification of the genomic regions under selection during dog domestication is extremely challenging because the demographic fluctuations associated with domestication can produce signals in polymorphism data that mimic those imposed by selective sweeps .", "We perform the first analysis of selection on the d...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "developmental biology", "homo (human)", "computational biology", "evolutionary biology", "molecular biology", "genetics and genomics" ]	The Molecular Anatomy of Spontaneous Germline Mutations in Human Testes	journal.pbio.0050224	The frequency of Apert syndrome mutations is 100-1,000 times higher than expected from average mutation rates, and it is due to positive selection in the testis increasing the frequency of germ cells carrying the defect.	[ [ "Current methods to measure directly the frequency at which human germline nucleotide substitutions arise each generation include the analysis of sporadic cases of human autosomal dominant or sex-linked diseases [1 , 2] and DNA analysis of sperm [3–5] .", "Studies of the fibroblast growth factor receptor ...	[ "The frequency of the most common sporadic Apert syndrome mutation ( C755G ) in the human fibroblast growth factor receptor 2 gene ( FGFR2 ) is 100–1 , 000 times higher than expected from average nucleotide substitution rates based on evolutionary studies and the incidence of human genetic diseases .", "To determ...	[ "Some human disease mutations occur 100–1 , 000 times more frequently than would be predicted from genome wide studies of mutation in different species .", "In Apert syndrome , for example , two-thirds of all new causal mutations occur at only one base in the affected gene .", "This unusually high frequency sug...	2007
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "animal types", "livestock", "medicine and health sciences", "zoonotic pathogens", "animal pathogens", "pathology and laboratory medicine", "ruminants", "pathogens", "domestic animals", "vertebrates", "animals", "mammals", "diarrhea", "signs and symptoms", "gastroenterology and hepatolog...	Animal-related factors associated with moderate-to-severe diarrhea in children younger than five years in western Kenya: A matched case-control study	journal.pntd.0005795	null	[ [ "Diarrheal disease remains among the leading causes of global mortality in children younger than 5 years [1 , 2] .", "Although the mortality rate due to diarrheal disease in this age group in Africa has decreased by nearly 4% per year since 2000 , it remains unacceptably high: it is estimated that 12% of ...	[ "Diarrheal disease remains among the leading causes of global mortality in children younger than 5 years .", "Exposure to domestic animals may be a risk factor for diarrheal disease .", "The objectives of this study were to identify animal-related exposures associated with cases of moderate-to-severe diarrhea (...	[ "Diarrheal disease is one of the leading causes of death worldwide in children younger than 5 years .", "Exposure to animals in homes may be a risk factor for diarrhea in children .", "To test this , we studied a subset of children in the Global Enteric Multicenter Study ( GEMS ) in rural western Kenya , whose ...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "death rates", "antimicrobials", "medicine and health sciences", "ecology and environmental sciences", "population dynamics", "drugs", "population genetics", "cell processes", "microbiology", "cell cycle and cell division", "antibiotics", "pharmacology", "population biology", "ecological m...	Death and population dynamics affect mutation rate estimates and evolvability under stress in bacteria	journal.pbio.2005056	null	[ [ "One of the most puzzling and controversial microbial evolution experiments of the 20th century may be the one performed by Cairns and colleagues [1 , 2] in which lac− cells are plated on lactose as the sole carbon source and therefore cannot grow .", "Revertants toward the lac+ genotype continuously appe...	[ "The stress-induced mutagenesis hypothesis postulates that in response to stress , bacteria increase their genome-wide mutation rate , in turn increasing the chances that a descendant is able to better withstand the stress .", "This has implications for antibiotic treatment: exposure to subinhibitory doses of ant...	[ "The effect of environmental stress on bacterial mutagenesis has been a paradigm-shift discovery .", "Recent developments include evidence that various antibiotics increase mutation rates in bacteria when used at subinhibitory concentrations .", "It is therefore suggested that such treatments promote resistance...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "innate immune system", "medicine and health sciences", "immune physiology", "cytokines", "pathology and laboratory medicine", "pathogens", "immunology", "microbiology", "orthomyxoviruses", "epithelial cells", "viruses", "bone marrow cells", "developmental biology", "h5n1", "rna viruses"...	Internal genes of a highly pathogenic H5N1 influenza virus determine high viral replication in myeloid cells and severe outcome of infection in mice	journal.ppat.1006821	null	[ [ "The outcome of infection with an influenza virus can vary widely from asymptomatic infection to death .", "Although infection outcomes can be influenced by host factors such as age , prior immunity , genetic susceptibility and comorbidities [1–4] , differences in the virus itself undoubtedly contribute t...	[ "The highly pathogenic avian influenza ( HPAI ) H5N1 influenza virus has been a public health concern for more than a decade because of its frequent zoonoses and the high case fatality rate associated with human infections .", "Severe disease following H5N1 influenza infection is often associated with dysregulate...	[ "Some avian influenza viruses , including highly pathogenic H5N1 virus , cause severe disease in humans and in experimental animal models associated with excessive cytokine production .", "We aimed to understand the virological mechanism behind the cytokine storm , and particularly the contribution of internal ge...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "public health and epidemiology", "epidemiology", "global health", "ophthalmology", "neglected tropical diseases", "public health" ]	Azithromycin Mass Treatment for Trachoma Control: Risk Factors for Non-Participation of Children in Two Treatment Rounds	journal.pntd.0001576	null	[ [ "Trachoma is a leading cause of preventable blindness [1] .", "Nearly 41 million individuals across the globe are estimated to suffer from active trachoma [2] .", "Of these , the majority are children from impoverished regions [3] , [4] .", "Virtually all trachoma burden is either concentrated in ...	[ "Persistent non-participation of children in mass drug administration ( MDAs ) for trachoma may reduce program impact .", "Risk factors that identify families where participation is a problem or program characteristics that foster non-participation are poorly understood .", "We examined risk factors for househo...	[ "The World Health Organization advocates at least three mass drug administrations ( MDAs ) with antibiotics when the prevalence of follicular trachoma ( TF ) is greater than 10% in children under age ten .", "Full child participation is necessary for maximizing the impact of trachoma control programs .", "The p...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal models of infection", "infectious diseases", "veterinary diseases", "medicine and health sciences", "emerging infectious diseases", "pathology and laboratory medicine", "host-pathogen interactions", "veterinary virology", "virology", "emerging viral diseases", "biology and life sciences"...	A Human Lung Xenograft Mouse Model of Nipah Virus Infection	journal.ppat.1004063	null	[ [ "Nipah virus ( NiV ) is a member of the genus Henipavirus ( family Paramyxoviridae ) that causes severe and often lethal respiratory illness and encephalitis in humans resulting in case fatality rates of up to 92% [1] .", "The first human cases of NiV infection were identified during an outbreak of severe...	[ "Nipah virus ( NiV ) is a member of the genus Henipavirus ( family Paramyxoviridae ) that causes severe and often lethal respiratory illness and encephalitis in humans with high mortality rates ( up to 92% ) .", "NiV can cause Acute Lung Injury ( ALI ) in humans , and human-to-human transmission has been observed...	[ "Nipah virus ( NiV ) is a highly pathogenic zoonotic virus that causes fatal disease in humans and a variety of other mammalian hosts including pigs .", "Given the lack of effective therapeutics and vaccines , this virus is considered a public health and agricultural concern , and listed as category C priority pa...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "death rates", "classical mechanics", "chemical compounds", "fluid mechanics", "demography", "microbiology", "carbohydrates", "geometry", "organic compounds", "glucose", "mathematical models", "developmental biology", "mathematics", "statistics (mathematics)", "population biology", "mi...	Growth of bacteria in 3-d colonies	journal.pcbi.1005679	null	[ [ "In 1942 , Jacques Monod developed a mathematical model of bacterial growth in a liquid culture , where the bacterial cells and nutrient molecules were homogeneously distributed [1 , 2] .", "A simple ordinary differential equation was accurate enough to account for the exponential growth of bacteria and t...	[ "The dynamics of growth of bacterial populations has been extensively studied for planktonic cells in well-agitated liquid culture , in which all cells have equal access to nutrients .", "In the real world , bacteria are more likely to live in physically structured habitats as colonies , within which individual c...	[ "The vast majority of theoretical and experimental studies assume that bacteria exist as planktonic cells in well-mixed liquid cultures , all with equal access to nutrients , wastes , toxins , antibiotics , bacterial viruses , and each other .", "However , in the real world , bacteria are more often found in phys...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal models", "medicine", "developmental biology", "model organisms", "molecular development", "genetics", "biology", "human genetics", "morphogenesis", "genetics and genomics", "clinical genetics" ]	Loss of Tgif Function Causes Holoprosencephaly by Disrupting the Shh Signaling Pathway	journal.pgen.1002524	null	[ [ "Holoprosencephaly ( HPE ) is a prevalent human disorder affecting forebrain and craniofacial development , with an incidence of up to 1∶250 during embryogenesis , and a high frequency of intrauterine lethality [1] , [2] .", "Recent estimates of the frequency of HPE live births are as high as 1 . 3 per 10...	[ "Holoprosencephaly ( HPE ) is a severe human genetic disease affecting craniofacial development , with an incidence of up to 1/250 human conceptions and 1 . 3 per 10 , 000 live births .", "Mutations in the Sonic Hedgehog ( SHH ) gene result in HPE in humans and mice , and the Shh pathway is targeted by other muta...	[ "Holoprosencephaly ( HPE ) is a devastating genetic disease affecting human brain development .", "HPE affects more than 1/8 , 000 live births and up to 1/250 conceptions .", "Several genetic loci are associated with HPE , and the mutated genes have been identified at some .", "We have analyzed the role of th...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "systems biology", "spectrometric identification of proteins", "biochemistry", "mathematics", "protein interactions", "protein abundance", "statistics", "regulatory networks", "biology", "computational biology", "signaling networks", "proteomics", "biostatistics" ]	Recovering Protein-Protein and Domain-Domain Interactions from Aggregation of IP-MS Proteomics of Coregulator Complexes	journal.pcbi.1002319	null	[ [ "CoRegs are members of multi-protein complexes transiently assembled for regulation of gene expression [1] .", "Assembly of these complexes is affected by ligands that bind to nuclear receptors ( NRs ) , such as steroids , retinoids , and glucocorticoids [2]–[5] .", "CoRegs complexes exist in many com...	[ "Coregulator proteins ( CoRegs ) are part of multi-protein complexes that transiently assemble with transcription factors and chromatin modifiers to regulate gene expression .", "In this study we analyzed data from 3 , 290 immuno-precipitations ( IP ) followed by mass spectrometry ( MS ) applied to human cell lin...	[ "In response to various extracellular stimuli , protein complexes are transiently assembled within the nucleus of cells to regulate gene transcription in a context dependent manner .", "Here we analyzed data from 3 , 290 proteomics experiments that used as bait different member proteins from regulatory complexes ...	2011
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "blood cells", "inflammatory diseases", "cell death", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "immunology", "cell processes", "signs and symptoms", "neutrophils", "white blood cells", "inflammation", "animal cells", "immune response", "diagnos...	Identifying important parameters in the inflammatory process with a mathematical model of immune cell influx and macrophage polarization	journal.pcbi.1007172	null	[ [ "Macrophages play an essential role in both the progression and the resolution of inflammation .", "These contradictory roles may be explained by the idea of a spectrum of macrophage phenotypes , ranging from the inflammatory M1 phenotype to the anti-inflammatory M2 phenotype at either extreme , with dive...	[ "In an inflammatory setting , macrophages can be polarized to an inflammatory M1 phenotype or to an anti-inflammatory M2 phenotype , as well as existing on a spectrum between these two extremes .", "Dysfunction of this phenotypic switch can result in a population imbalance that leads to chronic wounds or disease ...	[ "Using experimental data and mathematical analysis , we develop a model for the inflammatory response that includes macrophage polarization between M1 and M2 phenotypes .", "Dysfunction of this phenotypic switch can disrupt the timely influx and egress of immune cells during the healing process and lead to chroni...	2019
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "computational biology/systems biology", "physics/interdisciplinary physics", "computational biology/transcriptional regulation" ]	Reliability of Transcriptional Cycles and the Yeast Cell-Cycle Oscillator	journal.pcbi.1000842	null	[ [ "Cells have to operate reliably under internal and external noise in order to survive .", "Their robustness is partially a result of various signal-processing sub-networks called “motifs , ” embedded in the transcriptional network of the cell that controls gene expression [1]–[5] .", "Such motifs are ...	[ "A recently published transcriptional oscillator associated with the yeast cell cycle provides clues and raises questions about the mechanisms underlying autonomous cyclic processes in cells .", "Unlike other biological and synthetic oscillatory networks in the literature , this one does not seem to rely on a con...	[ "Technologies such as gene arrays enable acquisition of large amounts of data on gene expression variations , which reveal the structures of gene regulatory networks that govern the metabolic and developmental machinery in the cell .", "We study a model of an oscillatory gene regulatory network that has been rece...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "blood cells", "phosphorylation", "innate immune system", "medicine and health sciences", "immune cells", "body fluids", "immune physiology", "cytokines", "immunology", "tropical diseases", "cloning", "bacterial diseases", "developmental biology", "molecular development", "molecular biol...	Aberrant plasma IL-7 and soluble IL-7 receptor levels indicate impaired T-cell response to IL-7 in human tuberculosis	journal.ppat.1006425	null	[ [ "T cells are crucial for protection against Mycobacterium ( M . ) tuberculosis infection but biomarkers that characterise T-cell failure and progression towards tuberculosis disease are not available [1] .", "CD4+ T cells are key to anti-mycobacterial immune protection [2] and CD4+ T-cell deficiency , e ....	[ "T-cell proliferation and generation of protective memory during chronic infections depend on Interleukin-7 ( IL-7 ) availability and receptivity .", "Regulation of IL-7 receptor ( IL-7R ) expression and signalling are key for IL-7-modulated T-cell functions .", "Aberrant expression of soluble ( s ) and membran...	[ "IL-7 is important for the development and homeostasis of T cells and promotes antigen-specific T-cell responses .", "Aberrant expression of plasma IL-7 and soluble IL-7R are found in autoimmune diseases and chronic viral infections .", "In AIDS patients—especially those who fail to reconstitute T-cell numbers ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Genome-Wide Detection of Fitness Genes in Uropathogenic Escherichia coli during Systemic Infection	journal.ppat.1003788	null	[ [ "Uropathogenic Escherichia coli ( UPEC ) , one of the most common bacterial pathogens infecting humans , is the primary etiological agent of urinary tract infections ( UTI ) in otherwise healthy individuals [1] .", "UPEC is a subset of extraintestinal pathogenic E . coli ( ExPEC ) , which causes a broad s...	[ "Uropathogenic Escherichia coli ( UPEC ) is a leading etiological agent of bacteremia in humans .", "Virulence mechanisms of UPEC in the context of urinary tract infections have been subjected to extensive research .", "However , understanding of the fitness mechanisms used by UPEC during bacteremia and systemi...	[ "Uropathogenic E . coli is a major cause of bacterial bloodstream infections in humans .", "Dissemination of E . coli into the bloodstream during urinary tract infections may lead to potentially fatal complications .", "This pathogen is becoming increasingly resistant to currently used antibiotics .", "To dev...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology and life sciences" ]	OsHUS1 Facilitates Accurate Meiotic Recombination in Rice	journal.pgen.1004405	null	[ [ "Meiosis is a highly dynamic process in which chromosomes undergo dramatic structural changes and movements [1] , [2] .", "During the course of meiosis , intimate interactions develop between homologous chromosomes .", "Among these interactions , homologous recombination ( HR ) and pairing are the cor...	[ "Meiotic recombination normally takes place between allelic sequences on homologs .", "This process can also occur between non-allelic homologous sequences .", "Such ectopic interaction events can lead to chromosome rearrangements and are normally avoided .", "However , much remains unknown about how these ec...	[ "Meiosis is a special type of cell division that generates gametes for sexual reproduction .", "During meiosis , recombination not only occurs between allelic sequences on homologs , but also between non-allelic homologous sequences at dispersed loci .", "Such ectopic recombination is the main cause of chromoso...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	The CD8-Derived Chemokine XCL1/Lymphotactin Is a Conformation-Dependent, Broad-Spectrum Inhibitor of HIV-1	journal.ppat.1003852	null	[ [ "The replication of HIV-1 is regulated in vivo by a complex network of cytokines and chemokines expressed by immune and inflammatory cells .", "Key players in the mechanisms of HIV-1 control are CD8+ T cells , which , in addition to their cytolytic activity , secrete soluble factors that suppress HIV-1 in...	[ "CD8+ T cells play a key role in the in vivo control of HIV-1 replication via their cytolytic activity as well as their ability to secrete non-lytic soluble suppressive factors .", "Although the chemokines that naturally bind CCR5 ( CCL3/MIP-1α , CCL4/MIP- 1β , CCL5/RANTES ) are major components of the CD8-derive...	[ "Although HIV , the causative agent of AIDS , establishes a lifelong infection that cannot be eradicated even with effective treatment , the host immune system has the ability to contain its replication for many years in which the disease remains asymptomatic .", "Key players in HIV control are CD8+ T cells , spe...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "death rates", "invertebrates", "medicine and health sciences", "chemical compounds", "malathion", "animals", "organic compounds", "developmental biology", "organophosphates", "ddt", "mutation", "population biology", "insect vectors", "agrochemicals", "infectious diseases", "life cycle...	Fast emerging insecticide resistance in Aedes albopictus in Guangzhou, China: Alarm to the dengue epidemic	journal.pntd.0007665	null	[ [ "Dengue is one of the most rapidly spreading mosquito-borne diseases in the world .", "Currently , 3 . 9 billion people in 128 countries or regions are at risk of dengue fever [1–3] .", "Guangzhou , the largest city in southern China and the capital of Guangdong Province , has become the epicenter of ...	[ "Dengue is one of the most serious mosquito-borne infectious diseases in the world .", "Aedes albopictus is the most invasive mosquito and one of the primary vectors of dengue .", "Vector control using insecticides is the only viable strategy to prevent dengue virus transmission .", "In Guangzhou , after the ...	[ "Guangzhou is the most epidemic area of dengue in China .", "Massive insecticides have been used to control the vector mosquito Ae .", "albopictus , as no specific vaccines are available for dengue .", "Regular monitoring of insecticide susceptibility is essential for insecticide resistance management .", "...	2019
[ "Introduction", "Results/Discussion", "Methods" ]	[ "genetics and genomics/genomics", "genetics and genomics/functional genomics", "genetics and genomics/genetics of disease", "genetics and genomics/gene function", "computational biology/genomics" ]	Functional Genomics Complements Quantitative Genetics in Identifying Disease-Gene Associations	journal.pcbi.1000991	null	[ [ "Understanding the genetic bases of human disease has been an overarching goal of biology since the foundation of genetics as a scientific discipline .", "Efforts in quantitative genetics have utilized new laboratory technology to quickly genotype and phenotype large populations in order to determine whic...	[ "An ultimate goal of genetic research is to understand the connection between genotype and phenotype in order to improve the diagnosis and treatment of diseases .", "The quantitative genetics field has developed a suite of statistical methods to associate genetic loci with diseases and phenotypes , including quan...	[ "Many recent efforts to understand the genetic origins of complex diseases utilize statistical approaches to analyze phenotypic traits measured in genetically well-characterized populations .", "While these quantitative genetics methods are powerful , their success is limited by sampling biases and other confound...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics and genomics/animal genetics", "developmental biology", "developmental biology/morphogenesis and cell biology", "genetics and genomics/gene expression", "genetics and genomics/gene function", "developmental biology/organogenesis", "developmental biology/developmental molecular mechanisms" ]	Kidney Development in the Absence of Gdnf and Spry1 Requires Fgf10	journal.pgen.1000809	null	[ [ "Signaling by the secreted protein GDNF through the RET receptor tyrosine kinase ( RTK ) and the GFRα1 co-receptor plays a central role in the initiating event of kidney development , the outgrowth of the ureteric bud ( UB ) from the Wolffian duct ( WD ) into the metanephric mesenchyme ( MM ) .", "They ar...	[ "GDNF signaling through the Ret receptor tyrosine kinase ( RTK ) is required for ureteric bud ( UB ) branching morphogenesis during kidney development in mice and humans .", "Furthermore , many other mutant genes that cause renal agenesis exert their effects via the GDNF/RET pathway .", "Therefore , RET signali...	[ "Kidney development requires the secreted protein GDNF , which signals via its cellular receptor RET to promote growth and branching of the ureteric bud , the progenitor of the collecting duct system .", "The transcription factors ETV4 and ETV5 regulate gene expression in response to GDNF .", "We report that de...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cellular stress responses", "mechanisms of signal transduction", "gene regulation", "rna stability", "gene function", "crosstalk", "biological transport", "molecular genetics", "stress signaling cascade", "gene expression", "biology", "molecular biology", "systems biology", "biochemistry"...	The Yeast Rab GTPase Ypt1 Modulates Unfolded Protein Response Dynamics by Regulating the Stability of HAC1 RNA	journal.pgen.1002862	null	[ [ "In eukaryotes , folding and assembly of most membrane-bound and secreted proteins takes place in the endoplasmic reticulum ( ER ) .", "When proper folding of proteins in the ER is disrupted , cells turn on a protective mechanism known as the unfolded protein response ( UPR ) .", "In a cascade conserv...	[ "The unfolded protein response ( UPR ) is a conserved mechanism that mitigates accumulation of unfolded proteins in the ER .", "The yeast UPR is subject to intricate post-transcriptional regulation , involving recruitment of the RNA encoding the Hac1 transcription factor to the ER and its unconventional splicing ...	[ "The unfolded protein response ( UPR ) , which allows eukaryotic cells to cope with stresses that impair their ability to properly fold and assemble their membrane and secreted proteins , is implicated in many human diseases such as diabetes , neurodegeneration , and cancer .", "In yeast , the HAC1 gene encodes a...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "medicine and health sciences", "caenorhabditis", "nervous system", "cell processes", "electrophysiology", "neurites", "neuroscience", "animals", "animal models", "caenorhabditis elegans", "signal inhibition", "model organisms", "experimental organism systems", "cellular...	A Wnt-planar polarity pathway instructs neurite branching by restricting F-actin assembly through endosomal signaling	journal.pgen.1006720	null	[ [ "Branching of the axon or dendrite expands the connectivity of neural circuits and is critical for the functions of the nervous system .", "Transcription factors have been shown to specify the morphology of neuronal branch arbors as part of cell fate determination [1] .", "In addition , diffusible , s...	[ "Spatial arrangement of neurite branching is instructed by both attractive and repulsive cues .", "Here we show that in C . elegans , the Wnt family of secreted glycoproteins specify neurite branching sites in the PLM mechanosensory neurons .", "Wnts function through MIG-1/Frizzled and the planar cell polarity ...	[ "Extrinsic cues instruct neurite branching patterns through cytoskeletal remodeling at precise locations .", "We show that the Wnt glycoproteins signal through the Frizzled receptor and the Planar Cell Polarity ( PCP ) protein VANG-1 to instruct neurite branching in the nematode C . elegans , by restricting F-act...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "immunology", "cell-mediated immunity", "diet", "physiological processes", "bacterial diseases", "infectious disease immunology", "clinical medicine", "nutrition", "homeostasis", "digestive system", "infectious diseases", "wh...	HIC1 links retinoic acid signalling to group 3 innate lymphoid cell-dependent regulation of intestinal immunity and homeostasis	journal.ppat.1006869	null	[ [ "The intestinal immune system is held in a tightly regulated balance between immune activation in response to potential pathogens and the maintenance of tolerance to innocuous antigens , such as food and commensal flora .", "Disruption of this balance can lead to the development of serious inflammatory di...	[ "The intestinal immune system must be able to respond to a wide variety of infectious organisms while maintaining tolerance to non-pathogenic microbes and food antigens .", "The Vitamin A metabolite all-trans-retinoic acid ( atRA ) has been implicated in the regulation of this balance , partially by regulating in...	[ "Innate lymphoid cells ( ILCs ) are emerging as important regulators of immune responses at barrier sites such as the intestine .", "However , the molecular mechanisms that control this are not well described .", "In the intestine , the Vitamin A metabolite all-trans-retinoic acid ( atRA ) has been shown to be ...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genome sequencing", "genome expression analysis", "genome databases", "emerging infectious diseases", "microbial pathogens", "comparative genomics", "biology", "genomics", "microbiology", "host-pathogen interaction", "parasitology", "pathogenesis" ]	Distinctive Expansion of Potential Virulence Genes in the Genome of the Oomycete Fish Pathogen Saprolegnia parasitica	journal.pgen.1003272	null	[ [ "Saprolegnia species are watermolds or oomycetes that are endemic to probably all fresh water ecosystems .", "These understudied pathogens can cause destructive diseases of amphibians , crustaceans , fish and insects in aquaculture and in natural environments worldwide [1] , [2] .", "With the rise of ...	[ "Oomycetes in the class Saprolegniomycetidae of the Eukaryotic kingdom Stramenopila have evolved as severe pathogens of amphibians , crustaceans , fish and insects , resulting in major losses in aquaculture and damage to aquatic ecosystems .", "We have sequenced the 63 Mb genome of the fresh water fish pathogen ,...	[ "Fish are an increasingly important source of animal protein globally , with aquaculture production rising dramatically over the past decade .", "Saprolegnia is a fungal-like oomycete and one of the most destructive fish pathogens , causing millions of dollars in losses to the aquaculture industry annually .", ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "cell cycle and cell division", "cell processes", "ocular anatomy", "social sciences", "vertebrates", "neuroscience", "animals", "alleles", "cell differentiation", "animal models", "osteichthyes", "mitosis", "developmental biology", "model organisms", "e...	Genetic Dissection of Dual Roles for the Transcription Factor six7 in Photoreceptor Development and Patterning in Zebrafish	journal.pgen.1005968	null	[ [ "Sensory systems provide a critical link for an animal to its ever changing and complex environment .", "Retinal photoreceptors are the highly specialized neurons that transduce light into the chemical and electrical signals of the nervous system .", "Representatives from nearly all classes of extant ...	[ "The visual system of a particular species is highly adapted to convey detailed ecological and behavioral information essential for survival .", "The consequences of structural mutations of opsins upon spectral sensitivity and environmental adaptation have been studied in great detail , but lacking is knowledge o...	[ "Vision begins when an image is focused on the neural retina where rod and cone photoreceptors convert light into the electrical signals of the brain .", "The 4 cone subtypes in retinas of the majority of fishes , lizards and birds , provide rich color vision .", "In contrast , retinas of most mammals are bette...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/comparative genomics", "genetics and genomics/gene expression", "infectious diseases/neglected tropical diseases", "biochemistry/chemical biology of the cell", "cell biology/membranes and sorting", "infectious diseases/helminth infections", "hematology/anemias", "nutrition/malnu...	Genome-Wide Analysis Reveals Novel Genes Essential for Heme Homeostasis in Caenorhabditis elegans	journal.pgen.1001044	null	[ [ "From a nutritional perspective , heme is a readily bioavailable source of iron for human consumption [1] , [2] .", "From a cellular perspective , heme is an iron-containing porphyrin which serves as a prosthetic group in diverse biological processes ranging from gas-sensing to microRNA processing [3] .",...	[ "Heme is a cofactor in proteins that function in almost all sub-cellular compartments and in many diverse biological processes .", "Heme is produced by a conserved biosynthetic pathway that is highly regulated to prevent the accumulation of heme—a cytotoxic , hydrophobic tetrapyrrole .", "Caenorhabditis elegans...	[ "Heme is an iron-containing cofactor for proteins involved in many critical cellular processes .", "However , free heme is toxic to cells , suggesting that heme synthesis , acquisition , and transport is highly regulated .", "Efforts to understand heme trafficking in multicellular organisms have failed primaril...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics", "biochemistry", "biology and life sciences", "chronobiology" ]	Phosphorylation of a Central Clock Transcription Factor Is Required for Thermal but Not Photic Entrainment	journal.pgen.1004545	null	[ [ "A large variety of life forms manifest circadian ( ≅24 hr ) rhythms in behavior and physiology that are driven by endogenous cellular clocks or pacemakers [1] , [2] .", "Perhaps the most biologically relevant property of circadian clocks is that they can be synchronized ( entrained ) to local time by ext...	[ "Transcriptional/translational feedback loops drive daily cycles of expression in clock genes and clock-controlled genes , which ultimately underlie many of the overt circadian rhythms manifested by organisms .", "Moreover , phosphorylation of clock proteins plays crucial roles in the temporal regulation of clock...	[ "Circadian clocks are synchronized to local time by daily cycles in light-dark and temperature .", "Although light is generally thought to be the most dominant entraining cue in nature , daily cycles in temperature are sufficient to synchronize clocks in a large range of organisms .", "In Drosophila , dCLOCK is...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "schistosoma", "invertebrates", "schistosoma mansoni", "medicine and health sciences", "immune physiology", "helminths", "immunology", "animals", "antibodies", "extraction techniques", "research and analysis methods", "immune system proteins", "protein extraction", "proteins", "recombina...	Schistosoma mansoni Infection of Mice, Rats and Humans Elicits a Strong Antibody Response to a Limited Number of Reduction-Sensitive Epitopes on Five Major Tegumental Membrane Proteins	journal.pntd.0005306	null	[ [ "Schistosomiasis is a disease affecting more than 200 million individuals living mostly in underdeveloped tropical and subtropical regions ( http://www . who . int/mediacentre/factsheets/fs115/en/ ) .", "The disease is caused by infection with schistosome blood flukes which can survive , if untreated , fo...	[ "Schistosomiasis is a major disease of the developing world for which no vaccine has been successfully commercialized .", "While numerous Schistosoma mansoni worm antigens have been identified that elicit antibody responses during natural infections , little is known as to the identities of the schistosome antige...	[ "Schistosomiasis is caused by blood flukes residing in the veins of infected individuals and afflicts millions of people in the developing world .", "The schistosome worms can remain healthy in the bloodstream for more than 10 years , implying an extraordinary ability to evade host immune damage .", "Scientists...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "tropical diseases", "geographical locations", "census", "surgical and invasive medical procedures", "bacterial diseases", "research design", "eye diseases", "sexually transmitted diseases", "global health", "neglected tropical diseases", "eyes", "africa", "...	Cross-Sectional Surveys of the Prevalence of Follicular Trachoma and Trichiasis in The Gambia: Has Elimination Been Reached?	journal.pntd.0004906	null	[ [ "Trachoma , caused by the obligate intracellular bacterium Chlamydia trachomatis , is believed to be endemic in at least fifty countries , primarily in Africa and Asia [1] .", "The disease is characterized by repeated episodes of follicular conjunctivitis in childhood , resulting in progressive scarring o...	[ "The Gambia’s National Eye Health Programme has made a concerted effort to reduce the prevalence of trachoma .", "The present study had two objectives .", "The first was to conduct surveillance following mass drug administrations to determine whether The Gambia has reached the World Health Organization’s ( WHO ...	[ "Trachoma , the world’s leading infectious cause of blindness , is caused by ocular infection with the bacterium Chlamydia trachomatis .", "The Gambia , situated in West Africa , has implemented all facets of the World Health Organization-recommended SAFE strategy for trachoma control including surgery to correct...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biomacromolecule-ligand interactions", "enzymes", "macromolecular assemblies", "viral enzymes", "microbiology", "viral preintegration complex", "proteins", "biology", "viral replication complex", "viral replication", "biophysics", "biochemistry", "virology", "computational biology", "ma...	The Interdomain Linker of AAV-2 Rep68 Is an Integral Part of Its Oligomerization Domain: Role of a Conserved SF3 Helicase Residue in Oligomerization	journal.ppat.1002764	null	[ [ "The four adeno-associated virus ( AAV ) Rep proteins are generated from a single open reading frame by the transcriptional use of two different promoters ( p5 and p19 ) and subsequent alternative splicing mechanisms [1] , [2] , [3] .", "These reactions produce proteins that share three functional domains...	[ "The four Rep proteins of adeno-associated virus ( AAV ) orchestrate all aspects of its viral life cycle , including transcription regulation , DNA replication , virus assembly , and site-specific integration of the viral genome into the human chromosome 19 .", "All Rep proteins share a central SF3 superfamily he...	[ "Viruses have to optimize the limited size of their genomes in order to generate the proteins required for infection and replication .", "Several mechanisms are used to accomplish this including the use of multiple promoters and alternative splicing .", "These processes generate gene products with diverse funct...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "immune physiology", "leptospira", "pathology and laboratory medicine", "acute phase proteins", "pathogens", "immunology", "tropical diseases", "microbiology", "bacterial diseases", "neglected tropical diseases", "bioassays and physiological analysis", "antibo...	Distinct antibody responses of patients with mild and severe leptospirosis determined by whole proteome microarray analysis	journal.pntd.0005349	null	[ [ "Leptospirosis causes over one million cases and nearly 60 , 000 deaths annually , with the greatest disease burden in urban slums in tropical and subtropical countries [1–3] .", "Ten pathogenic Leptospira species , over 200 serovars , and a large number of mammalian reservoirs , including rats , have fac...	[ "Leptospirosis is an important zoonotic disease worldwide .", "Humans usually present a mild non-specific febrile illness , but a proportion of them develop more severe outcomes , such as multi-organ failure , lung hemorrhage and death .", "Such complications are thought to depend on several factors , including...	[ "Leptospirosis is zoonotic disease of global importance , with over a million cases and nearly 60 , 000 deaths annually .", "Symptomatic disease presentation ranges from a mild febrile disease with non-specific symptoms to severe forms , characterized by multi-organ failure , lung hemorrhage , and death .", "Fa...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell death", "invertebrates", "cellular stress responses", "cell cycle and cell division", "cell processes", "dna-binding proteins", "chromatids", "departures from diploidy", "animals", "animal models", "developmental biology", "drosophila melanogaster", "model organisms", "experimental o...	Induced aneuploidy in neural stem cells triggers a delayed stress response and impairs adult life span in flies	journal.pbio.3000016	A novel genetic tool for inducing chromosomal imbalance in fruit flies in an acute and time-controlled manner reveals that the brain is the most sensitive tissue when it comes to coping with abnormal karyotypes during development.	[ [ "Aneuploidy , a state of chromosome imbalance , was observed over a century ago .", "Since then , numerous studies have shown that aneuploidy is largely detrimental both at cellular and organism level .", "In multicellular organisms , chromosome gain or loss results in lethality or developmental defec...	[ "Studying aneuploidy during organism development has strong limitations because chronic mitotic perturbations used to generate aneuploidy usually result in lethality .", "We developed a genetic tool to induce aneuploidy in an acute and time-controlled manner during Drosophila development .", "This is achieved b...	[ "Aneuploidy—the presence of an abnormal number of chromosomes in a cell—is a hallmark of cancer and developmental disorders .", "However , it is notoriously difficult to study in a living organism .", "We have thus developed a new genetic tool that allows for the inducible generation of aneuploidy in the fruit ...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases", "genetics and genomics" ]	Regulatory Hotspots in the Malaria Parasite Genome Dictate Transcriptional Variation	journal.pbio.0060238	Heritable levels of transcriptional variation, predominantly regulated by genomic copy number variants via trans mechanisms, are surprisingly abundant in drug-resistant malaria parasites.	[ [ "Plasmodium falciparum is an apicomplexan parasite that causes the most severe and lethal form of human malaria .", "Parasites isolated from patients across the globe exhibit a wide range of phenotypic variation , including drug responses , growth rates , and a variety of virulence factors .", "Until ...	[ "The determinants of transcriptional regulation in malaria parasites remain elusive .", "The presence of a well-characterized gene expression cascade shared by different Plasmodium falciparum strains could imply that transcriptional regulation and its natural variation do not contribute significantly to the evolu...	[ "Development of the malaria parasite , Plasmodium falciparum , in the blood is driven by a number of different genes expressed at different times and at different levels .", "Exactly what influences such transcriptional changes remains elusive , particularly in regard to important phenotypes like drug resistance ...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "systems biology", "medicine", "mental health", "genetics", "biology", "genomics", "neuroscience", "genetics and genomics" ]	Networks of Neuronal Genes Affected by Common and Rare Variants in Autism Spectrum Disorders	journal.pgen.1002556	null	[ [ "Autism is the most severe end of a group of neurodevelopmental disorders referred to as autism spectrum disorders ( ASDs ) .", "ASD is a heterogeneous genetic syndrome characterized by social deficits , language impairments and repetitive behaviors .", "Although it is known that ASD has a genetic bas...	[ "Autism spectrum disorders ( ASD ) are neurodevelopmental disorders with phenotypic and genetic heterogeneity .", "Recent studies have reported rare and de novo mutations in ASD , but the allelic architecture of ASD remains unclear .", "To assess the role of common and rare variations in ASD , we constructed a ...	[ "Autism spectrum disorders ( ASD ) are neurodevelopmental syndromes with a strong genetic basis , but are influenced by many different genes .", "Recent studies have identified multiple genetic risk factors , including rare mutations and genetic variations common in the population .", "To identify possible conn...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell division", "dna replication", "nucleic acids", "cell biology", "genetics", "dna", "biology", "molecular cell biology", "dna repair", "molecular biology", "genetics and genomics" ]	Coordinated Degradation of Replisome Components Ensures Genome Stability upon Replication Stress in the Absence of the Replication Fork Protection Complex	journal.pgen.1003213	null	[ [ "Initiation of DNA replication is directed by the formation of the pre-replication complex ( pre-RC ) at the origin of replication [1] .", "The pre-RC includes a number of essential replication proteins such as origin recognition complex ( ORC ) , Cdc6 , Cdt1 , and the mini-chromosome maintenance ( MCM ) ...	[ "The stabilization of the replisome complex is essential in order to achieve highly processive DNA replication and preserve genomic integrity .", "Conversely , it would also be advantageous for the cell to abrogate replisome functions to prevent inappropriate replication when fork progression is adversely perturb...	[ "Replication stress interferes with the normal progression of the replication fork .", "Under these conditions , cells activate the replication checkpoint to coordinate DNA repair with cell cycle arrest .", "The current understanding is that , in response to replication block , this checkpoint stabilizes replic...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "togaviruses", "chikungunya infection", "pathogens", "geographical locations", "microbiology", "tropical diseases", "alphaviruses", "viruses", "age groups", "chikungunya virus", "rna viruses", "neglected tropical diseases...	Evidence of previous but not current transmission of chikungunya virus in southern and central Vietnam: Results from a systematic review and a seroprevalence study in four locations	journal.pntd.0006246	null	[ [ "Chikungunya virus ( CHIKV ) belongs to alphavirus of the family Togaviridae .", "The name chikungunya is derived from the East African language Makonde from the root verb kungunyala which means “that which bends up” , describing the stooped posture in CHIKV cases caused by swelling , stiff joints , and m...	[ "Arbovirus infections are a serious concern in tropical countries due to their high levels of transmission and morbidity .", "With the outbreaks of chikungunya ( CHIKV ) in surrounding regions in recent years and the fact that the environment in Vietnam is suitable for the vectors of CHIKV , the possibility of tr...	[ "In recent years , the reemergence of chikungunya has gained global attention and threatened to become a global outbreak .", "Although the epidemiology of chikungunya is known globally , the viral activity in Vietnam has not been thoroughly investigated .", "In this paper , we used information from a systematic...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "cancer genomics", "medicine and health sciences", "breast tumors", "reproductive system", "cancers and neoplasms", "basic cancer research", "human genomics", "oncology", "chromosome mapping", "molecular biology techniques", "epigenetics", "chromatin", "research and analysis methods", "gen...	Analysis of the relationship between coexpression domains and chromatin 3D organization	journal.pcbi.1005708	null	[ [ "Genome-wide expression studies have shown that gene order is not random in eukaryotes , and that genes with similar expression patterns are often linked ( reviewed in [1 , 2] ) .", "For instance , early work in yeast showed that neighboring pairs of genes ( adjacent and nonadjacent-but-nearby ) have corr...	[ "Gene order is not random in eukaryotic chromosomes , and co-regulated genes tend to be clustered .", "The mechanisms that determine co-regulation of large regions of the genome and its connection with chromatin three-dimensional ( 3D ) organization are still unclear however .", "Here we have adapted a recently...	[ "Prokaryotic operons normally comprise functionally related genes whose expression is coordinated .", "Even though operons do not exist in most eukaryotes , results from the last fifteen years indicate that gene order is nonetheless not random in eukaryotes , and that coexpressed genes tend to be grouped in the g...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "mineral metabolism and the kidney", "epilepsy", "medicine and health sciences", "neurology", "developmental and pediatric neurology", "nephrology" ]	CNNM2 Mutations Cause Impaired Brain Development and Seizures in Patients with Hypomagnesemia	journal.pgen.1004267	null	[ [ "Brain defects including seizures , migraine , depression and intellectual disability are frequently associated with hypomagnesemia [1] .", "Indeed , low Mg2+ concentrations may cause epileptiform activity during development [2] .", "Specifically , the Mg2+ channel transient receptor potential melasta...	[ "Intellectual disability and seizures are frequently associated with hypomagnesemia and have an important genetic component .", "However , to find the genetic origin of intellectual disability and seizures often remains challenging because of considerable genetic heterogeneity and clinical variability .", "In t...	[ "Mental retardation affects 1–3% of the population and has a strong genetic etiology .", "Consequently , early identification of the genetic causes of mental retardation is of significant importance in the diagnosis of the disease , as predictor of the progress of the disease and for the determination of treatmen...	2014
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "organismal evolution", "plant growth and development", "plant cell biology", "marine biology", "developmental biology", "plant science", "plant morphology", "molecular cell biology", "organism development", "morphogenesis", "cellular structures and organelles", "pattern formation", "phycolo...	An Intracellular Transcriptomic Atlas of the Giant Coenocyte Caulerpa taxifolia	journal.pgen.1004900	null	[ [ "Convergent morphologies have arisen multiple times in plants ( Viridiplantae ) .", "Diverse cellular architectures underlie these moprhologies , with varying relationships between the number of nuclei per cell and the number of cells within an organism .", "Within the Chlorophyta , Acetabularia posse...	[ "Convergent morphologies have arisen in plants multiple times .", "In non-vascular and vascular land plants , convergent morphology in the form of roots , stems , and leaves arose .", "The morphology of some green algae includes an anchoring holdfast , stipe , and leaf-like fronds .", "Such morphology occurs ...	[ "Plants include both the green algae and land plants .", "Multiple times , root , stem , and leaf-like structures arose independently in plant lineages .", "In some instances , such as the siphonous algae , these structures arose in the absence of multicellularity .", "It has been argued by some that the morp...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "sequencing techniques", "rheumatology", "medicine and health sciences", "senescence", "forkhead box", "green fluorescent protein", "physiological processes", "developmental biology", "luminescent proteins", "organism development", "stem cells", "molecular biology techniques", "rna sequencin...	Up-regulation of FOXD1 by YAP alleviates senescence and osteoarthritis	journal.pbio.3000201	The Hippo signalling effector YAP and the transcription factor FOXD1 play a role in alleviating cellular senescence and osteoarthritis, identifying the YAP-FOXD1 axis as a potential therapeutic target for aging-associated disorders.	[ [ "Mesenchymal stem cells ( MSCs ) are widely distributed in adult tissues and have the capacities of self-renewal and differentiation into multiple cell lineages , such as chondrocytes , osteoblasts , and adipocytes [1] .", "MSCs are involved in tissue repair and homeostatic maintenance [2 , 3] .", "Ov...	[ "Cellular senescence is a driver of various aging-associated disorders , including osteoarthritis .", "Here , we identified a critical role for Yes-associated protein ( YAP ) , a major effector of Hippo signaling , in maintaining a younger state of human mesenchymal stem cells ( hMSCs ) and ameliorating osteoarth...	[ "Stem cell aging contributes to aging-associated degenerative diseases .", "Studies aiming to characterize the mechanisms of stem cell aging are critical for obtaining a comprehensive understanding of the aging process and developing novel strategies to treat aging-related diseases .", "As a prevalent aging-ass...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/disease models", "genetics and genomics/cancer genetics" ]	Combined Analysis of Murine and Human Microarrays and ChIP Analysis Reveals Genes Associated with the Ability of MYC To Maintain Tumorigenesis	journal.pgen.1000090	null	[ [ "Overexpression of MYC is one of the most frequent events in human tumorigenesis [1] .", "MYC overexpression is thought to induce tumorigenesis by causing inappropriate gene expression resulting in autonomous cellular growth , proliferation , and the inhibition of cellular differentiation [2] , [3] .", ...	[ "The MYC oncogene has been implicated in the regulation of up to thousands of genes involved in many cellular programs including proliferation , growth , differentiation , self-renewal , and apoptosis .", "MYC is thought to induce cancer through an exaggerated effect on these physiologic programs .", "Which of ...	[ "The targeted inactivation of oncogenes may be a specific and effective treatment of cancer .", "However , how oncogene inactivation leads to tumor regression is not clear .", "Previously , we have shown that even the brief inactivation of the MYC oncogene can result in the sustained regression of at least some...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "plant biology/plant growth and development", "plant biology/plant genetics and gene expression", "plant biology/plant biochemistry and physiology" ]	SHINE Transcription Factors Act Redundantly to Pattern the Archetypal Surface of Arabidopsis Flower Organs	journal.pgen.1001388	null	[ [ "In contrast to other plant cell layers , the epidermis develops a unique cell wall that not merely constitutes of cellulose , hemicelluloses , pectins , and proteins but also of a cuticular matrix , which is largely composed of cutin embedded and overlaid with waxes [1] .", "Cutin , an insoluble cuticula...	[ "Floral organs display tremendous variation in their exterior that is essential for organogenesis and the interaction with the environment .", "This diversity in surface characteristics is largely dependent on the composition and structure of their coating cuticular layer .", "To date , mechanisms of flower org...	[ "The cuticular layer that covers all aerial parts of plants plays a vital role not only in the interaction with environment but also in plant development and growth .", "Despite the recent significant achievements in the identification of structural genes involved in cuticle biosynthesis and secretion , little is...	2011
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "immunity", "immunology", "biology", "immune response" ]	Potentiating Effects of MPL on DSPC Bearing Cationic Liposomes Promote Recombinant GP63 Vaccine Efficacy: High Immunogenicity and Protection	journal.pntd.0001429	null	[ [ "Leishmaniasis represents infections caused by obligate heterogenous kinetoplastid protozoan parasites , Leishmania , transmitted by the bite of infected female sand fly Phlebotomus .", "It afflicts hundreds of thousands of people in tropical and subtropical areas every year , is currently endemic in 88 c...	[ "Vaccines that activate strong specific Th1-predominant immune responses are critically needed for many intracellular pathogens , including Leishmania .", "The requirement for sustained and efficient vaccination against leishmaniasis is to formulate the best combination of immunopotentiating adjuvant with the sta...	[ "Visceral leishmaniasis ( VL ) , a vector-transmitted disease caused by Leishmania donovani , is potentially fatal if left untreated .", "Vaccination against VL has received limited attention compared with cutaneous leishmaniasis , although the need for an effective vaccine is pressing for the control of the dise...	2011
[ "Introduction", "Results and discussion", "Materials and methods" ]	[ "medicine and health sciences", "toxins", "pathology and laboratory medicine", "nucleases", "deoxyribonucleases", "enzymes", "pathogens", "dna-binding proteins", "enzymology", "microbiology", "toxic agents", "toxicology", "pseudomonas aeruginosa", "genome analysis", "sequence motif analy...	Diversity and distribution of nuclease bacteriocins in bacterial genomes revealed using Hidden Markov Models	journal.pcbi.1005652	null	[ [ "Bacteriocins were the first of the interbacterial competition systems to be discovered [1] .", "They take the form of antimicrobial peptides or proteins released to the environment that have activity against closely related organisms .", "Experimental and theoretical work has suggested that bacterioc...	[ "Bacteria exploit an arsenal of antimicrobial peptides and proteins to compete with each other .", "Three main competition systems have been described: type six secretion systems ( T6SS ) ; contact dependent inhibition ( CDI ) ; and bacteriocins .", "Unlike T6SS and CDI systems , bacteriocins do not require con...	[ "Bacteria deploy a variety of antimicrobials to kill competing bacteria .", "Nuclease bacteriocins are a miscellaneous group of protein toxins that target closely related species , cleaving nucleic acids in the cytoplasm .", "It has proved difficult to establish how widespread bacteriocins are in bacterial popu...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "plant growth and development", "gene regulation", "regulatory proteins", "brassica", "dna-binding proteins", "hormones", "developmental biology", "plant science", "model organisms", "plant hormones", "experimental organism systems", "transcription factors", "seedlings", "embryos", "plan...	PRC2 Represses Hormone-Induced Somatic Embryogenesis in Vegetative Tissue of Arabidopsis thaliana	journal.pgen.1006562	null	[ [ "Plant cells have long been recognized for their capacity to become pluripotent and to enter various differentiation pathways in response to chemical or mechanical stimuli .", "This is exemplified by ectopic organ formation and entire plant regeneration from vegetative tissue in response to plant hormone ...	[ "Many plant cells can be reprogrammed into a pluripotent state that allows ectopic organ development .", "Inducing totipotent states to stimulate somatic embryo ( SE ) development is , however , challenging due to insufficient understanding of molecular barriers that prevent somatic cell dedifferentiation .", "...	[ "Somatic embryogenesis provides the strongest support for plant cell totipotency but reprogramming of non-reproductive tissue is problematic or even impossible in many plant species .", "Here we show that the activity of Polycomb Repressive Complex 2 ( PRC2 ) constitutes a major barrier to hormone-mediated establ...	2017

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