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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" ]	[]	Rac1 Regulates Endometrial Secretory Function to Control Placental Development	journal.pgen.1005458	null	[ [ "Shortly after fertilization , the uterus transitions to a receptive state that allows embryo attachment and invasion , and this process must be synchronized with embryonic development in order to ensure maximal reproductive success [1–5] .", "To enable this synchronization , an intricate maternal-fetal d...	[ "During placenta development , a succession of complex molecular and cellular interactions between the maternal endometrium and the developing embryo ensures reproductive success .", "The precise mechanisms regulating this maternal-fetal crosstalk remain unknown .", "Our study revealed that the expression of Ra...	[ "During early pregnancy , a succession of molecular interactions between the uterus and the developing embryo ensures reproductive success .", "Although it is conceivable that signaling cues originating in the uterus impact on the developing embryo at the time of placenta establishment , the precise mechanisms re...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "biotechnology", "traumatic injury", "medicine and health sciences", "engineering and technology", "biomimetics", "simulation and modeling", "physiological processes", "histology", "mathematics", "statistics (mathematics)", "cartilage", "bone fracture", "research and analysis methods", "bi...	Simulation enabled search for explanatory mechanisms of the fracture healing process	journal.pcbi.1005980	null	[ [ "Annually , there are approximately 15 million fractures in the United States , and a significant portion ( 10–15% ) fail to heal properly [1] .", "Both numbers and costs are predicted to increase as the population ages and as the number of osteoporosis-related fractures increases [2] .", "Therefore ,...	[ "A significant portion of bone fractures fail to heal properly , increasing healthcare costs .", "Advances in fracture management have slowed because translation barriers have limited generation of mechanism-based explanations for the healing process .", "When uncertainties are numerous , analogical modeling ca...	[ "Translation barriers have limited the generation of mechanism-based explanations of fracture healing processes .", "Those barriers help explain why , to date , biological therapeutics have had only a minor impact on fracture management .", "Alternative approaches are needed , and we present one that is intende...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "schistosoma", "invertebrates", "medicine and health sciences", "body fluids", "pathology and laboratory medicine", "helminths", "antiviral therapy", "pathogens", "immunology", "tropical diseases", "microbiology", "parasitic diseases", "animals", "retroviruses", "viruses", "immunodefic...	Effect of schistosomiasis on the outcome of patients infected with HIV-1 starting antiretroviral therapy in rural Tanzania	journal.pntd.0006844	null	[ [ "The geographic distributions of HIV/AIDS and schistosomiasis largely overlap in sub-Saharan Africa , where Schistosoma prevalence reaches up to 30% in HIV cohorts [1–4] .", "In settings of coinfection , Schistosoma and HIV mutually interfere on several levels , which may impact the course of the associat...	[ "It has been hypothesized that schistosomiasis negatively influences immune reconstitution in people living with HIV starting antiretroviral therapy ( ART ) .", "In this study , we investigated the effect of schistosomiasis on the course of HIV infection in patients starting ART in a rural part of Tanzania .", ...	[ "Infections with HIV and blood flukes ( Schistosoma ) both exert chronic modulatory effects on the host’s immune system .", "Coinfections , meaning the host is simultaneously infected with both pathogens , are common in sub-Saharan Africa .", "In this situation the induced immune modulation of one pathogen may ...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Placental Syncytium Forms a Biophysical Barrier against Pathogen Invasion	journal.ppat.1003821	null	[ [ "Intrauterine infection is associated with pregnancy complications such as preterm labor [1] , which affects 10% of all live births [2] .", "All of the hematogenous placental microbes have at least partially intracellular life cycles [3] .", "Among these is L . monocytogenes , a facultative intracellu...	[ "Fetal syncytiotrophoblasts form a unique fused multinuclear surface that is bathed in maternal blood , and constitutes the main interface between fetus and mother .", "Syncytiotrophoblasts are exposed to pathogens circulating in maternal blood , and appear to have unique resistance mechanisms against microbial i...	[ "Infection of the placenta can lead to pregnancy complications as well as fetal and maternal disease and death .", "We developed a novel system to study placental infections using murine fetal placental progenitor cells and the bacterial pathogen Listeria monocytogenes .", "In the mature placenta fetal progenit...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "enzymes", "immunology", "enzymology", "dna-binding proteins", "dna damage", "mutation", "dna", "white blood cells", "animal cells", "proteins", "t cells", "biochemistry", "antibody-producing cells", "point mutation", "...	ATP-dependent helicase activity is dispensable for the physiological functions of Recql4	journal.pgen.1008266	null	[ [ "Rothmund-Thomson syndrome ( RTS ) ( OMIM #268400 ) is a rare autosomal recessive disorder characterized by skin rash ( poikiloderma ) , skeletal dysplasia , small stature , sparse or absent hair , gastrointestinal complications , and high predisposition to specific malignancies such as osteosarcoma ( OS ) an...	[ "Rothmund-Thomson syndrome ( RTS ) is a rare autosomal recessive disorder characterized by skin rash ( poikiloderma ) , skeletal dysplasia , small stature , juvenile cataracts , sparse or absent hair , and predisposition to specific malignancies such as osteosarcoma and hematological neoplasms .", "RTS is caused ...	[ "DNA helicases unwind double-stranded nucleic acids using energy from ATP to access genetic information during cell replication .", "In humans , several families of helicases have been described and one of particular importance is the RecQ family , where mutations in three of five members cause human disease .", ...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell motility", "medicine and health sciences", "actin filaments", "cell processes", "respiratory system", "kidneys", "cellular structures and organelles", "cytoskeleton", "dynamic actin filaments", "contractile proteins", "polymer chemistry", "actins", "actin polymerization", "proteins",...	Fragility of foot process morphology in kidney podocytes arises from chaotic spatial propagation of cytoskeletal instability	journal.pcbi.1005433	null	[ [ "Podocytes , visceral epithelial cells of the kidney glomerulus , enable the selectivity of the glomerular filtration barrier through their specialized morphology .", "The cytoskeleton of each highly differentiated podocyte is composed of F-actin , microtubules , and intermediate filaments .", "All th...	[ "Kidney podocytes’ function depends on fingerlike projections ( foot processes ) that interdigitate with those from neighboring cells to form the glomerular filtration barrier .", "The integrity of the barrier depends on spatial control of dynamics of actin cytoskeleton in the foot processes .", "We determined ...	[ "Podocytes are specialized kidney cells with intricate geometries .", "Regulation of cell morphology and cell-cell interactions is crucial for podocyte function within the delicate glomerular filtration unit .", "While the cellular cytoskeleton is dynamic , it must be tightly regulated so that the cell shape an...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "dna transcription", "rna transport", "rna processing", "gene expression", "genetics", "gene regulation", "molecular genetics", "gene splicing", "biology", "evolutionary biology", "cell differentiation", "evolutionary developmental biology", "gene function" ]	The RNA Export Factor, Nxt1, Is Required for Tissue Specific Transcriptional Regulation	journal.pgen.1003526	null	[ [ "Export of mRNAs from the nucleus is a fundamental aspect of gene expression regulation .", "This involves RNA processing and packaging followed by translocation via nuclear pores ( reviewed in [1] , [2] ) .", "During transcription , nascent RNA associates with hnRNPs and a succession of export factor...	[ "The highly conserved , Nxf/Nxt ( TAP/p15 ) RNA nuclear export pathway is important for export of most mRNAs from the nucleus , by interacting with mRNAs and promoting their passage through nuclear pores .", "Nxt1 is essential for viability; using a partial loss of function allele , we reveal a role for this gene...	[ "In multicellular organisms , differentiated cells have a cell-type specific profile of gene expression .", "Sperm production is particularly specialised , and as a result over 5% of all genes are expressed exclusively in the sperm precursor cells , termed primary spermatocytes .", "Expression of these genes de...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "circuit models", "neurophysiology", "synapses", "biophysic al simulations", "computational neuroscience", "physiology", "biology", "anatomy and physiology", "neurological system", "neuroscience", "computational biology" ]	A Tale of Two Stories: Astrocyte Regulation of Synaptic Depression and Facilitation	journal.pcbi.1002293	null	[ [ "Activity-dependent modification of synaptic transmission critically moulds the properties of synaptic information transfer with important implications for computation performed by neuronal circuitry [1]–[4] .", "Multiple mechanisms could coexist in the same synapse , regulating the strength or the effica...	[ "Short-term presynaptic plasticity designates variations of the amplitude of synaptic information transfer whereby the amount of neurotransmitter released upon presynaptic stimulation changes over seconds as a function of the neuronal firing activity .", "While a consensus has emerged that the resulting decrease ...	[ "Synaptic plasticity is the capacity of a preexisting connection between two neurons to change in strength as a function of neuronal activity .", "Because it admittedly underlies learning and memory , the elucidation of its constituting mechanisms is of crucial importance in many aspects of normal and pathologica...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Coronary Artery Disease Associated Transcription Factor TCF21 Regulates Smooth Muscle Precursor Cells That Contribute to the Fibrous Cap	journal.pgen.1005155	null	[ [ "Atherosclerotic coronary heart disease ( CAD ) continues to be the dominant medical problem in the Western world and is growing in minority groups in this country and in developing populations [1–4] .", "Despite extensive investigation of epidemiological and cellular features of the disease , there are s...	[ "Recent genome wide association studies have identified a number of genes that contribute to the risk for coronary heart disease .", "One such gene , TCF21 , encodes a basic-helix-loop-helix transcription factor believed to serve a critical role in the development of epicardial progenitor cells that give rise to ...	[ "Coronary artery disease ( CAD ) is responsible for the majority of deaths in the Western world , and is due in part to environmental and metabolic factors .", "However , half of the risk for developing heart disease is genetically predetermined .", "Genome-wide association studies in human populations have ide...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "parasite groups", "centrosomes", "parasitic cell cycles", "toxoplasma gondii", "cell cycle and cell division", "cell processes", "parasitic protozoans", "parasitology", "mitosis", "developmental biology", "apicomplexa", "tachyzoites", "protozoans", "toxoplasma", "cellular structures and...	Checkpoints of apicomplexan cell division identified in Toxoplasma gondii	journal.ppat.1006483	null	[ [ "Obligate intracellular parasites of the phylum Apicomplexa are responsible for many important diseases in humans and animals , including malaria , toxoplasmosis and cryptosporidiosis .", "Severity of the disease is tightly linked to parasite burden , and currently , the most successful therapies block pa...	[ "The unusual cell cycles of Apicomplexa parasites are remarkably flexible with the ability to complete cytokinesis and karyokinesis coordinately or postpone cytokinesis for several rounds of chromosome replication , and are well recognized .", "Despite this surprising biology , the molecular machinery required to...	[ "Apicomplexan parasites are unicellular eukaryotes that replicate in unusual ways different from their multicellular hosts .", "From a single infection , different apicomplexans can produce as few as two or up to many hundreds of progeny .", "How these flexible division cycles are regulated is poorly understood...	2017
[ "Introduction", "Results and Discussion", "Material and Methods" ]	[]	Silencing of DNase Colicin E8 Gene Expression by a Complex Nucleoprotein Assembly Ensures Timely Colicin Induction	journal.pgen.1005354	null	[ [ "Colicins are high-molecular-weight toxic proteins that are produced by and specifically target Escherichia coli and its close relatives [1] .", "These narrow-spectrum antibiotics kill by either targeting the DNA , RNA or cell membranes of susceptible cells .", "Cytoplasmic colicins are released upon ...	[ "Colicins are plasmid-encoded narrow spectrum antibiotics that are synthesized by strains of Escherichia coli and govern intraspecies competition .", "In a previous report , we demonstrated that the global transcriptional factor IscR , co dependently with the master regulator of the DNA damage response , LexA , d...	[ "Colicins are considered model proteins for studying bacterial toxins .", "These narrow spectrum antibiotics can kill by a variety of mechanisms , e . g . by forming pores in the membranes of susceptible cells or by degrading their nucleic acids .", "Colicin genes are plasmid-encoded and repressed by the master...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "cloning", "physiological processes", "age groups", "adults", "homeostasis", "stem cells", "molecular biology techniques", "cardia", "digestive system", "research and analysis methods", "animal cells", "biological tissue", "molecular biology", "jak-stat si...	Regulation of Stem Cell Proliferation and Cell Fate Specification by Wingless/Wnt Signaling Gradients Enriched at Adult Intestinal Compartment Boundaries	journal.pgen.1005822	null	[ [ "The evolutionarily conserved Wnt/β-catenin signal transduction pathway regulates cell proliferation and tissue patterning in metazoans , and deregulation of this pathway is associated with numerous human diseases [1 , 2] .", "In the absence of Wnt/Wg exposure , the key transcriptional activator β-catenin...	[ "Intestinal stem cell ( ISC ) self-renewal and proliferation are directed by Wnt/β-catenin signaling in mammals , whereas aberrant Wnt pathway activation in ISCs triggers the development of human colorectal carcinoma .", "Herein , we have utilized the Drosophila midgut , a powerful model for ISC regulation , to e...	[ "The highly conserved Wingless/Wnt signal transduction pathway directs many cellular processes in metazoans and its deregulation underlies numerous human congenital diseases and cancers .", "Most notably , more than 80% of colon cancers arise from aberrant activation of the Wnt pathway .", "A better understandi...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Systematic Structural Analyses of Attachment Organelle in Mycoplasma pneumoniae	journal.ppat.1005299	null	[ [ "Mycoplasmas are parasitic and occasionally commensal bacteria that lack a peptidoglycan layer and have small genomes [1] .", "Mycoplasma pneumoniae is a causative pathogen of human bronchitis and walking pneumonia .", "Outbreaks of mycoplasma pneumonia occur frequently in many parts of the world , an...	[ "Mycoplasma pneumoniae , a human pathogenic bacterium , glides on host cell surfaces by a unique and unknown mechanism .", "It forms an attachment organelle at a cell pole as a membrane protrusion composed of surface and internal structures , with a highly organized architecture .", "In the present study , we s...	[ "Human mycoplasma pneumonia , an epidemic of which occurred around the world a few years ago , is caused by a pathogenic bacterium , Mycoplasma pneumoniae .", "This tiny bacterium , about 2 μm long , infects humans by gliding on the surface of the trachea through binding to sialylated oligosaccharides , which are...	2015
[ "Introduction", "Results/Discussion", "Methods" ]	[ "evolutionary biology", "biochemistry/molecular evolution", "diabetes and endocrinology/reproductive endocrinology" ]	Protein Evolution by Molecular Tinkering: Diversification of the Nuclear Receptor Superfamily from a Ligand-Dependent Ancestor	journal.pbio.1000497	Phylogenetic reconstruction of the structure and function of the ancestor of the nuclear receptor protein family reveals how functional diversity evolves by subtle tinkering with an ancestral template.	[ [ "By sequencing genomes of taxa occupying key positions in the metazoan tree of life , it has become possible to infer when important animal gene families originated and proliferated [1]–[3] .", "Sequence data alone , however , cannot yield insight into the functions and structures of ancient proteins or t...	[ "Understanding how protein structures and functions have diversified is a central goal in molecular evolution .", "Surveys of very divergent proteins from model organisms , however , are often insufficient to determine the features of ancestral proteins and to reveal the evolutionary events that yielded extant di...	[ "Many protein families are so diverse that it is hard to determine their ancestral functions and to understand how their derived functions evolved .", "The existence of so many different functions within protein families often creates the impression that complex , novel functions must have evolved repeatedly and ...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Regulation of Protein Quality Control by UBE4B and LSD1 through p53-Mediated Transcription	journal.pbio.1002114	A new protein quality control regulatory pathway is identified in which a ubiquitin ligase and a lysine-specific demethylase act together on the transcription factor p53 to control protein degradation systems.	[ [ "Living organisms endure environmental stress and metabolic errors that inflict damage on macromolecules , including DNA and protein , which are either repaired or removed by quality control programs in the cell .", "Toxicity resulting from protein misfolding and aggregation , known as proteotoxicity , un...	[ "Protein quality control is essential for clearing misfolded and aggregated proteins from the cell , and its failure is associated with many neurodegenerative disorders .", "Here , we identify two genes , ufd-2 and spr-5 , that when inactivated , synergistically and robustly suppress neurotoxicity associated with...	[ "To function properly , proteins must assume their correct three-dimensional shapes .", "There are numerous mechanisms within the cell , collectively referred to as protein quality control ( PQC ) , that verify proper folding .", "If abnormal folding is detected , PQC can either help the protein to refold or ta...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biochemistry/molecular evolution", "evolutionary biology/microbial evolution and genomics", "microbiology/microbial evolution and genomics", "biochemistry/chemical biology of the cell", "evolutionary biology/animal behavior", "computational biology/evolutionary modeling", "biochemistry/cell signaling a...	Evolution of Taxis Responses in Virtual Bacteria: Non-Adaptive Dynamics	journal.pcbi.1000084	null	[ [ "Bacterial responses to external stimuli and the pathways with which they are mediated are model systems for studying the molecular basis of behaviour .", "Much of the research in this field has focused on chemotaxis , the ability of bacteria to swim up a gradient of a chemical attractant , as performed i...	[ "Bacteria are able to sense and respond to a variety of external stimuli , with responses that vary from stimuli to stimuli and from species to species .", "The best-understood is chemotaxis in the model organism Escherichia coli , where the dynamics and the structure of the underlying pathway are well characteri...	[ "Here , we study how signalling networks mediating chemotaxis could have evolved .", "We simulated the evolution of virtual bacteria , which can explore their environment by alternating between swimming and tumbling .", "The tumbling frequency is dictated by the output of a signalling network that senses extrac...	2008
[ "Introduction", "Material and Methods", "Results", "Discussion" ]	[]	Pentoxifylline Reverses Chronic Experimental Chagasic Cardiomyopathy in Association with Repositioning of Abnormal CD8+ T-Cell Response	journal.pntd.0003659	null	[ [ "Chagas disease ( CD ) , a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi , affects 6 to 8 million people in Latin America [1] .", "The cardiac form , the most frequent clinical manifestation of CD , is characterized by fibrosis with remodeling of the myocardium and vasculat...	[ "Chronic chagasic cardiomyopathy ( CCC ) , the main clinical sign of Chagas disease , is associated with systemic CD8+ T-cell abnormalities and CD8-enriched myocarditis occurring in an inflammatory milieu .", "Pentoxifylline ( PTX ) , a phosphodiesterase inhibitor , has immunoregulatory and cardioprotective prope...	[ "Chronic chagasic cardiomyopathy ( CCC ) is the main clinical manifestation of Chagas disease ( CD ) , a neglected illness caused by the protozoan parasite Trypanosoma cruzi .", "More than hundred years after its discovery , CD continues to be a public health problem and millions of chronically infected people wa...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "hematologic cancers and related disorders", "medicine", "leukemias", "hematopoiesis", "immune cells", "acute lymphoblastic leukemia", "t cells", "immunology", "biology", "hematology" ]	The Nuclear Effector of Wnt-Signaling, Tcf1, Functions as a T-Cell–Specific Tumor Suppressor for Development of Lymphomas	journal.pbio.1001430	Tcf1 is known to function as a transcriptional activator of Wnt-induced proliferation during T cell development in the thymus. Evidence for an additional contrasting role for Tcf1 as a T-cell specific tumor suppressor gene is now presented.	[ [ "Cancers often develop as consequence of deregulated expression of key factors that operate during normal development .", "Deregulation of the Wnt signaling pathway has been implicated in many types of malignancies , especially in solid tumors ( reviewed in [1]–[3] ) .", "Mutations in different compon...	[ "The HMG-box factor Tcf1 is required during T-cell development in the thymus and mediates the nuclear response to Wnt signals .", "Tcf1−/− mice have previously been characterized and show developmental blocks at the CD4−CD8− double negative ( DN ) to CD4+CD8+ double positive transition .", "Due to the blocks in...	[ "Cancers often develop as a consequence of deregulated expression of key factors that operate during normal development .", "T-cell factor 1 ( Tcf1 ) has an established role in the nuclear response to Wnt signaling during normal T-cell development in the thymus .", "Here we show in mice that the absence of Tcf1...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "viral latency", "infectious diseases", "immunity", "virology", "innate immunity", "immunology", "cytomegalovirus infection", "biology", "microbiology", "viral diseases", "viral replication" ]	Reversible Silencing of Cytomegalovirus Genomes by Type I Interferon Governs Virus Latency	journal.ppat.1003962	null	[ [ "Herpesviruses are characterized by their ability to establish a lifelong latent infection in their natural host and reactivate upon immunosuppression .", "Cytomegaloviruses ( CMV ) are paradigmatic β-herpesviruses , characterized by strict species specificity , but highly prevalent in numerous mammalian ...	[ "Herpesviruses establish a lifelong latent infection posing the risk for virus reactivation and disease .", "In cytomegalovirus infection , expression of the major immediate early ( IE ) genes is a critical checkpoint , driving the lytic replication cycle upon primary infection or reactivation from latency .", ...	[ "Cytomegalovirus ( CMV ) is a widespread herpesvirus that establishes a détente with the host immune system .", "Therefore , the CMV reactivates from latency in immunocompromised hosts , resulting in life-threatening disease of the vulnerable patients .", "However , the exact mechanism by which the immune syste...	2014
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "enzyme-linked immunoassays", "immune physiology", "crimean-congo hemorrhagic fever", "purification techniques", "immunology", "tropical diseases", "parasitic diseases", "health care", "nucleoproteins", "neglected tropical diseases", "antibodies", "immunologic...	Sensitive and specific detection of Crimean-Congo Hemorrhagic Fever Virus (CCHFV)—Specific IgM and IgG antibodies in human sera using recombinant CCHFV nucleoprotein as antigen in μ-capture and IgG immune complex (IC) ELISA tests	journal.pntd.0006366	null	[ [ "Being endemic in a variety of countries in Asia , Africa , the Middle East and Southeastern Europe [1] , the Crimean-Congo Hemorrhagic Fever Virus ( CCHFV , family: Nairoviridae , genus: Orthonairovirus; [2] ) is the geographically most widespread tick-borne pathogen [3 , 4] .", "An infection with this z...	[ "As the most widespread tick-borne arbovirus causing infections in numerous countries in Asia , Africa and Europe , Crimean-Congo Hemorrhagic Fever Virus ( CCHFV , family Nairoviridae ) was included in the WHO priority list of emerging pathogens needing urgent Research & Development attention .", "To ensure prepa...	[ "Being endemic in several countries in Asia , Africa , the Middle East and Southeastern Europe , the Crimean-Congo Hemorrhagic Fever Virus ( CCHFV ) is the geographically most widespread tick-borne arbovirus .", "As evidenced by the recent occurrence of an autochthonous CCHFV infection in Spain , it possesses als...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	The SPF27 Homologue Num1 Connects Splicing and Kinesin 1-Dependent Cytoplasmic Trafficking in Ustilago maydis	journal.pgen.1004046	null	[ [ "The basidiomycete Ustilago maydis is the causal agent of the smut disease on corn ( Zea mays ) .", "During its life cycle , U . maydis displays yeast-like , haploid cells that divide by budding , and dikaryotic cells that grow as filamentous hyphae .", "The filamentous stage is initiated by fusion of...	[ "The conserved NineTeen protein complex ( NTC ) is an integral subunit of the spliceosome and required for intron removal during pre-mRNA splicing .", "The complex associates with the spliceosome and participates in the regulation of conformational changes of core spliceosomal components , stabilizing RNA-RNA- as...	[ "In eukaryotic cells , nascent mRNA is processed by splicing to remove introns and to join the exon sequences .", "The processed mRNA is then transported out of the nucleus and employed by ribosomes to synthesize proteins .", "Splicing is achieved by the spliceosome and associated protein complexes , among them...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biotechnology", "plant anatomy", "electrophoretic mobility shift assay", "gene regulation", "regulatory proteins", "rna extraction", "dna-binding proteins", "plant physiology", "cereal crops", "plant science", "rice", "model organisms", "genetically modified plants", "transcription factor...	A Genetic Screen Identifies a Requirement for Cysteine-Rich–Receptor-Like Kinases in Rice NH1 (OsNPR1)-Mediated Immunity	journal.pgen.1006049	null	[ [ "Despite the lack of circulating immune cells , plants share similarities with animals in their defense responses against pathogens; they both use innate immune systems to counter attacks .", "For example , plants and animals utilize membrane-localized receptors that detect conserved molecular patterns de...	[ "Systemic acquired resistance , mediated by the Arabidopsis NPR1 gene and the rice NH1 gene , confers broad-spectrum immunity to diverse pathogens .", "NPR1 and NH1 interact with TGA transcription factors to activate downstream defense genes .", "Despite the importance of this defense response , the signaling c...	[ "To survive , plants and animals must resist microbial infection .", "Plants employ an immune response called systemic acquired resistance that confers long-lasting resistance to a broad-spectrum of pathogens .", "Researchers have previously identified two key proteins ( NPR1/NH1 and TGA ) that control this imm...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Abnormal Activation of BMP Signaling Causes Myopathy in Fbn2 Null Mice	journal.pgen.1005340	null	[ [ "The fibrillins are large structural macromolecules that are important constituents of all connective tissues .", "Fibrillins form microfibrils [1–3] , and they target growth factors to the extracellular space [4–6] .", "In humans , there are 3 fibrillin genes , whereas in mouse , the gene for fibrill...	[ "Fibrillins are large extracellular macromolecules that polymerize to form the backbone structure of connective tissue microfibrils .", "Mutations in the gene for fibrillin-1 cause the Marfan syndrome , while mutations in the gene for fibrillin-2 cause Congenital Contractural Arachnodactyly .", "Both are autoso...	[ "New strategies for treating congenital muscular dystrophies are needed .", "Current treatments are limited and aim to prolong ambulation and survival .", "Since most of the genes responsible for congenital muscular dystrophies are still unknown , elucidation of these genes may provide new insights that can lea...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell walls", "chemical compounds", "cellulose", "plant growth and development", "plant cell biology", "brassica", "marker genes", "organic compounds", "plant cell walls", "developmental biology", "plant science", "model organisms", "experimental organism systems", "seedlings", "molecula...	The Arabidopsis leucine-rich repeat receptor kinase MIK2/LRR-KISS connects cell wall integrity sensing, root growth and response to abiotic and biotic stresses	journal.pgen.1006832	null	[ [ "Plant cells are surrounded by a thick cell wall that is composed primarily of complex carbohydrates [1] .", "The cell wall plays a pivotal role in plants , as it provides the mechanical strength that allows the plant to resist both external and internal ( turgor ) pressure , protects the cell from biotic...	[ "Plants actively perceive and respond to perturbations in their cell walls which arise during growth , biotic and abiotic stresses .", "However , few components involved in plant cell wall integrity sensing have been described to date .", "Using a reverse-genetic approach , we identified the Arabidopsis thalian...	[ "Plants are constantly exposed to external stresses of biotic and abiotic nature , as well as internal stresses , resulting from growth and mechanical tension .", "Feedback information about the integrity of the cell wall can enable the plant to perceive such stresses , and respond adequately .", "Plants are kn...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "chagas disease", "neglected tropical diseases", "immunology", "biology", "immunomodulation" ]	The Interaction of Classical Complement Component C1 with Parasite and Host Calreticulin Mediates Trypanosoma cruzi Infection of Human Placenta	journal.pntd.0002376	null	[ [ "Trypanosoma cruzi is the protozoan that causes Chagas' disease [1] , an acute and chronic illness affecting 9 million people in Latin America [2] and causing 50 , 000 deaths per year [3]–[5] .", "Increasing numbers of infected people have been detected in North America , Europe , Australia , and Japan ."...	[ "9 million people are infected with Trypanosoma cruzi in Latin America , plus more than 300 , 000 in the United States , Canada , Europe , Australia , and Japan .", "Approximately 30% of infected individuals develop circulatory or digestive pathology .", "While in underdeveloped countries transmission is mainly...	[ "The Trypanosoma cruzi protozoan infects 9 million people in Latin America and increasing numbers in North America , Europe , Australia , and Japan .", "It is an important neglected parasitic disease in the Americas with no safe treatment available .", "One third of those infected develops incapacitating pathol...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "acoustics", "linguistics", "neural networks", "engineering and technology", "signal processing", "social sciences", "neuroscience", "neuronal tuning", "computer and information sciences", "animal cells", "speech", "physics", "cellular neuroscience", "speech signal processing", "cell bio...	A Gestalt inference model for auditory scene segregation	journal.pcbi.1006711	null	[ [ "We live in busy environments , and our surrounds continuously flood our sensory system with complex information that needs to be analyzed in order to make sense of the world around us .", "This process , labeled scene analysis , is common across all sensory modalities including vision , audition and olfa...	[ "Our current understanding of how the brain segregates auditory scenes into meaningful objects is in line with a Gestaltism framework .", "These Gestalt principles suggest a theory of how different attributes of the soundscape are extracted then bound together into separate groups that reflect different objects o...	[ "In every day life , our brain is able to effortlessly make sense of the cacophony of sounds that constantly enter our ears and organize them into meaningful sound objects .", "In this work , we use an architecture based on stochastic neural networks to ‘learn’ from natural sounds which cues are crucial to the pr...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "plant anatomy", "plant growth and development", "plant embryo anatomy", "brassica", "developmental biology", "plant science", "model organisms", "seedlings", "cell nucleus", "embryos", "plants", "cellular structures and organelles", "nucleolus", "cotyledons (botany)", "research and anal...	Dual Role of a SAS10/C1D Family Protein in Ribosomal RNA Gene Expression and Processing Is Essential for Reproduction in Arabidopsis thaliana	journal.pgen.1006408	null	[ [ "The biogenesis of mature 5 . 8S , 18S , and 25S ribosomal RNAs ( rRNAs ) requires transcription of 45S rRNA genes ( rDNA ) and processing of 45S precursor rRNAs ( pre-rRNAs ) in the nucleolus [1] .", "The nucleolus is not enclosed by a membrane; its formation is driven by the active transcription of rDNA...	[ "In eukaryotic cells , ribosomal RNAs ( rRNAs ) are transcribed , processed , and assembled with ribosomal proteins in the nucleolus .", "Regulatory mechanisms of rRNA gene ( rDNA ) transcription and processing remain elusive in plants , especially their connection to nucleolar organization .", "We performed an...	[ "The rRNA regulatory network underlying the structure and function of the plant nucleolus is largely unknown .", "We identified a previously uncharacterized SAS10/C1D family protein THAL as a novel component important for both rRNA gene expression and processing , which further impacts nucleolar structure .", "...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "dengue virus", "medicine and health sciences", "pathology and laboratory medicine", "togaviruses", "pathogens", "neighborhoods", "vector-borne diseases", "microbiology", "social sciences", "human mobility", "alphaviruses", "viruses", "chikungunya virus", "rna viruses", "infectious disea...	Contrasting the value of targeted versus area-wide mosquito control scenarios to limit arbovirus transmission with human mobility patterns based on different tropical urban population centers	journal.pntd.0007479	null	[ [ "Infectious diseases continue to place a considerable burden on global human health and will likely continue to do so for the foreseeable future .", "Despite successes such as the eradication of smallpox and reductions in the prevalence of falciparum malaria , there are also many examples of pathogens wit...	[ "Vector control is still our primary intervention for both prevention and mitigation of epidemics of many vector-borne diseases .", "Efficiently targeting control measures is important since control can involve substantial economic costs .", "Targeting is not always straightforward , as transmission of vector-b...	[ "Control and prevention of Aedes-transmitted viruses , such as dengue , chikungunya , or Zika relies heavily on vector control approaches .", "Given the effort and cost involved in implementation of vector control , targeting of control measures is highly desirable .", "However , it is unclear to what extent th...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "biotechnology", "medicine and health sciences", "classical mechanics", "laryngology", "catheters", "tropical diseases", "tonicity", "parasitic diseases", "parasitic protozoans", "osmotic pressure", "hypertonic", "dysphagia", "organisms", "protozoans", "neglected tropical diseases", "p...	High Resolution Esophageal Manometry in Patients with Chagas Disease: A Cross-Sectional Evaluation	journal.pntd.0004416	null	[ [ "Chagas disease ( CD ) is caused by the hemoflagellate protozoan , Trypanosoma cruzi .", "CD is endemic in Latin America .", "However migratory flows have spread the disease all over the world; the non-endemic countries with more cases are The United States of America and Spain . [1]", "Its preval...	[ "Gastrointestinal involvement affects 30–40% of the patients with chronic Chagas disease .", "Esophageal symptoms appear once the structural damage is established .", "Little is known about the usefulness of high resolution manometry to early identification of esophageal involvement .", "We performed a cross-...	[ "Chagas disease is a parasitic disease mainly transmitted to humans by blood-sucking insects .", "The disease was endemic in Latin America , but it is now a global disease due to migratory movements .", "The disease can affect the heart and the digestive system ( mainly esophagus and colon ) .", "Classically ...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal models", "rna", "model organisms", "nucleic acids", "mouse", "genetics", "molecular genetics", "dna", "biology", "dna repair", "molecular cell biology", "rna synthesis", "genetics of disease", "gene function" ]	Disruption of TTDA Results in Complete Nucleotide Excision Repair Deficiency and Embryonic Lethality	journal.pgen.1003431	null	[ [ "DNA-damaging agents are a constant challenge to DNA integrity .", "A network of DNA-repair systems collectively removes most lesions and safeguards the stability of the genome [1] .", "Nucleotide excision repair ( NER ) is one such DNA-repair mechanism capable of removing a wide variety of structural...	[ "The ten-subunit transcription factor IIH ( TFIIH ) plays a crucial role in transcription and nucleotide excision repair ( NER ) .", "Inactivating mutations in the smallest 8-kDa TFB5/TTDA subunit cause the neurodevelopmental progeroid repair syndrome trichothiodystrophy A ( TTD-A ) .", "Previous studies have s...	[ "DNA is under constant attack of various environmental and cellular produced DNA damaging agents .", "DNA damage hampers normal cell function; however , different DNA repair mechanisms protect our genetic information .", "Nucleotide Excision Repair is one of the most versatile repair processes , as it removes a...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "systemic lupus erythematosus", "medicine", "rheumatology", "immunity", "genetic association studies", "innate immunity", "genetics", "immunology", "biology", "human genetics", "genetics of disease", "genetics and genomics" ]	MicroRNA-3148 Modulates Allelic Expression of Toll-Like Receptor 7 Variant Associated with Systemic Lupus Erythematosus	journal.pgen.1003336	null	[ [ "Systemic lupus erythematosus ( SLE [OMIM 152700] ) is a complex and heterogeneous autoimmune disease with a strong genetic component that is modified by environmental exposures .", "Although the detailed etiopathogenesis of SLE remains unknown , excessive innate immune activation involving toll-like rece...	[ "We previously reported that the G allele of rs3853839 at 3′untranslated region ( UTR ) of Toll-like receptor 7 ( TLR7 ) was associated with elevated transcript expression and increased risk for systemic lupus erythematosus ( SLE ) in 9 , 274 Eastern Asians [P = 6 . 5×10−10 , odds ratio ( OR ) ( 95%CI ) = 1 . 27 ( ...	[ "Systemic lupus erythematosus ( SLE ) is a debilitating autoimmune disease contributed to by excessive innate immune activation involving toll-like receptors ( TLRs , particularly TLR7/8/9 ) and type I interferon ( IFN ) signaling pathways .", "TLR7 responds against RNA–containing nuclear antigens and activates I...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Spatial Structure, Transmission Modes and the Evolution of Viral Exploitation Strategies	journal.ppat.1004810	null	[ [ "When individuals compete for a common resource natural selection often favours more aggressive exploitation strategies .", "This may lead to resource exhaustion and , consequently , to population extinction , a process known as the 'tragedy of the commons'[1] .", "Because pathogens compete for a comm...	[ "Spatial structure and local migration are predicted to promote the evolution of less aggressive host exploitation strategies in horizontally transmitted pathogens .", "Here we explore the effect of spatial structure on the evolution of pathogens that can use both horizontal and vertical routes of transmission ."...	[ "Why do some viruses use latent infection strategies and in which environments can such prudent host exploitation strategies evolve ?", "Theory of mathematical epidemiology and social evolution predicts that prudent pathogens can evolve when they cluster in space and share the mutual benefits of prudent exploitat...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine" ]	Differential Activation of Diverse Glutathione Transferases of Clonorchis sinensis in Response to the Host Bile and Oxidative Stressors	journal.pntd.0002211	null	[ [ "Clonorchis sinensis is a trematode parasite that resides in the hepatobiliary tract of mammals including humans .", "Its enzootic infection is highly prevalent in several Asian countries including China , Vietnam , Japan and Korea .", "Approximately 35 million people are infected and 600 million peop...	[ "Clonorchis sinensis causes chronic cumulative infections in the human hepatobiliary tract and is intimately associated with cholangiocarcinoma .", "Approximately 35 million people are infected and 600 million people are at risk of infections worldwide .", "C . sinensis excretory-secretory products ( ESP ) cons...	[ "Clonorchis sinensis is a trematode parasite that infects the hepatobiliary ducts of the mammals including humans .", "Approximately 35 million people are infected and 600 million people are at risk of infections .", "Epidemiological studies have convincingly demonstrated relationships between clonorchiasis and...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "antimicrobials", "cell physiology", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "chemical compounds", "pathogens", "drugs", "immunology", "microbiology", "cell metabolism", "organic compounds", "bacterial diseases", "antibiotics", ...	Methylfolate Trap Promotes Bacterial Thymineless Death by Sulfa Drugs	journal.ppat.1005949	null	[ [ "Sulfonamides , or SULFA drugs , were the first chemical substances systematically used to treat and prevent bacterial infections [1 , 2] , but the use of these drugs gradually declined because of the emergence of resistant organisms [3] .", "To increase SULFAs’ potency and prevent further resistance , tr...	[ "The methylfolate trap , a metabolic blockage associated with anemia , neural tube defects , Alzheimer’s dementia , cardiovascular diseases , and cancer , was discovered in the 1960s , linking the metabolism of folate , vitamin B12 , methionine and homocysteine .", "However , the existence or physiological signif...	[ "Sulfonamides were the first agents to successfully treat bacterial infections , but their use later declined due to the emergence of resistant organisms .", "Restoration of these drugs may be achieved through inactivation of molecular mechanisms responsible for resistance .", "A chemo-genomic screen first iden...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics", "biology", "genomics", "molecular cell biology", "genetics and genomics" ]	Complex Chromosomal Rearrangements Mediated by Break-Induced Replication Involve Structure-Selective Endonucleases	journal.pgen.1002979	null	[ [ "The maintenance of genome integrity is crucial to prevent cell death in all organisms .", "Chromosomal rearrangements such as reciprocal translocations , deletions , inversions and duplications threaten genomic stability and must be avoided to prevent cancer development and genomic disorders [1] .", ...	[ "DNA double-strand break ( DSB ) repair occurring in repeated DNA sequences often leads to the generation of chromosomal rearrangements .", "Homologous recombination normally ensures a faithful repair of DSBs through a mechanism that transfers the genetic information of an intact donor template to the broken mole...	[ "Genome rearrangements consisting of non-reciprocal translocations ( NRTs ) seem to play an important role in carcinogenesis in humans .", "They are likely caused by intracellular mechanisms that are normally committed to repair breaks occurring in the DNA molecule .", "Failure of faithful repair of DNA double-...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "algorithms", "systems biology", "computer science", "genomics", "biology", "computational biology", "comparative genomics", "metabolic networks", "genetics and genomics" ]	NIBBS-Search for Fast and Accurate Prediction of Phenotype-Biased Metabolic Systems	journal.pcbi.1002490	null	[ [ "Certain industrial processes , such as the production of hydrogen and ethanol , benefit from using prokaryotic or eukaryotic organisms to produce , reduce , and convert important chemical compounds [1] , [2] .", "Bioengineers search for ways to modify phenotypic traits , or phenotypes , of these organism...	[ "Understanding of genotype-phenotype associations is important not only for furthering our knowledge on internal cellular processes , but also essential for providing the foundation necessary for genetic engineering of microorganisms for industrial use ( e . g . , production of bioenergy or biofuels ) .", "Howeve...	[ "Genetic engineers often seek to modify the physical traits of microorganisms used in industrial processes in order to improve the efficiency of the overall process .", "The genes targeted for modification in these cases are typically identified by searching for genes whose presence in an organism is correlated w...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Imputation-Based Population Genetics Analysis of Plasmodium falciparum Malaria Parasites	journal.pgen.1005131	null	[ [ "Malaria is a major global health burden , with drug resistance in Plasmodium falciparum a major impediment to disease containment and eradication .", "A deeper understanding of the biology of this parasite and the epidemiology of the disease it causes is needed to inform public health responses , includi...	[ "Whole-genome sequencing technologies are being increasingly applied to Plasmodium falciparum clinical isolates to identify genetic determinants of malaria pathogenesis .", "However , genome-wide discovery methods , such as haplotype scans for signatures of natural selection , are hindered by missing genotypes in...	[ "Characterizing genetic diversity and function in Plasmodium falciparum , including identifying determinants of emerging drug resistance , is crucial to informing public health strategies to contain and eliminate this malaria parasite .", "The lack of a robust framework to handle missing P . falciparum genotypes ...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "ecology/global change ecology", "ecology/community ecology and biodiversity", "ecology", "ecology/marine and freshwater ecology" ]	Warming and Resource Availability Shift Food Web Structure and Metabolism	journal.pbio.1000178	Experimental warming of a marine food web suggests that ocean warming can lead to greater consumer abundance but reduced overall biomass, providing a potentially species-independent response to environmental warming.	[ [ "The ocean is a dynamic part of the global climate system .", "The temperature of the sea surface , where almost 50% of the world's primary productivity occurs [1] , varies regionally as the result of changing surface air temperatures , currents , and upwelling of deeper water .", "Though links betwee...	[ "Climate change disrupts ecological systems in many ways .", "Many documented responses depend on species' life histories , contributing to the view that climate change effects are important but difficult to characterize generally .", "However , systematic variation in metabolic effects of temperature across tr...	[ "Humans rely on marine ecosystems for economic and nutritional sustenance—including about 16% of animal protein consumed by humans—making it especially important for natural scientists , economists , conservationists and long-term policy planners to understand how climate change is likely to affect oceanic food web...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "bacteriology", "medicine", "dermatology", "infectious diseases", "buruli ulcer", "emerging infectious diseases", "medical microbiology", "neglected tropical diseases", "biology", "microbiology" ]	Secondary Bacterial Infections of Buruli Ulcer Lesions Before and After Chemotherapy with Streptomycin and Rifampicin	journal.pntd.0002191	null	[ [ "Buruli ulcer ( BU ) caused by Mycobacterium ulcerans is a necrotizing skin disease that affects mainly impoverished communities in Western and Central Africa .", "It is the third most common mycobacterial disease of humans after tuberculosis and leprosy .", "BU lesions are characterized by extensive ...	[ "Buruli ulcer ( BU ) , caused by Mycobacterium ulcerans is a chronic necrotizing skin disease .", "It usually starts with a subcutaneous nodule or plaque containing large clusters of extracellular acid-fast bacilli .", "Surrounding tissue is destroyed by the cytotoxic macrolide toxin mycolactone produced by mic...	[ "Buruli ulcer ( BU ) can lead to large ulcerative lesions due to extensive skin loss caused by the necrotizing effect of the main virulence factor mycolactone .", "For a long time the general perception was that BU lesions are not infected by other bacteria because of a postulated antimicrobial effect of the macr...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "flow cytometry", "hiv infections", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "pathogens", "immunology", "microbiology", "cell differentiation", "retroviruses", "viruses", "immunodeficiency viruses", "bone marrow cells", "developm...	CD4 is expressed on a heterogeneous subset of hematopoietic progenitors, which persistently harbor CXCR4 and CCR5-tropic HIV proviral genomes in vivo	journal.ppat.1006509	null	[ [ "Long term combination anti-retroviral therapy ( cART ) blocks viral spread in vivo but is not curative , as plasma virus rebounds after cART interruption .", "Sequence analysis of residual circulating and rebounding virus in HIV+ patients indicates that virions likely come from the activation of latent p...	[ "Latent HIV infection of long-lived cells is a barrier to viral clearance .", "Hematopoietic stem and progenitor cells are a heterogeneous population of cells , some of which are long-lived .", "CXCR4-tropic HIVs infect a broad range of HSPC subtypes , including hematopoietic stem cells , which are multi-potent...	[ "People who are effectively treated with antiretroviral medication harbor persistent forms of HIV that are integrated into the cellular genome .", "While HIV is cytopathic to most cells , transcriptionally silent , latent forms do not express toxic HIV gene products and can survive in the host for years .", "Wh...	2017
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "genetics and genomics/microbial evolution and genomics", "evolutionary biology/microbial evolution and genomics", "genetics and genomics/gene discovery", "microbiology/microbial evolution and genomics", "genetics and genomics/genome projects", "infectious diseases/respiratory infections", "infectious d...	Genomic Evidence for the Evolution of Streptococcus equi: Host Restriction, Increased Virulence, and Genetic Exchange with Human Pathogens	journal.ppat.1000346	null	[ [ "Streptococcus equi subspecies equi ( S . equi ) is the causative agent of equine strangles , characterized by abscessation of the lymph nodes of the head and neck .", "Rupture of abscesses formed in retropharyngeal lymph nodes into the guttural pouches leads to a proportion of horses becoming persistentl...	[ "The continued evolution of bacterial pathogens has major implications for both human and animal disease , but the exchange of genetic material between host-restricted pathogens is rarely considered .", "Streptococcus equi subspecies equi ( S . equi ) is a host-restricted pathogen of horses that has evolved from ...	[ "Streptococci colonize a diverse range of animals and tissues , and this association is normally harmless .", "Occasionally some strains of streptococci have an increased ability to cause disease that is often associated with a reduction in the ability to colonize and the acquisition of new genes , which enable t...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "systems biology", "biochemistry", "developmental biology", "model organisms", "genetics", "biology", "computational biology", "microbiology", "biophysics", "genetics and genomics" ]	Spo0A∼P Imposes a Temporal Gate for the Bimodal Expression of Competence in Bacillus subtilis	journal.pgen.1002586	null	[ [ "Stochastic gene expression during development has received much attention in both bacterial and eukaryotic systems [1] , [2] , [3] .", "The developmental choices exhibited by the model bacterium Bacillus subtilis have emerged as favorite subjects for the analysis of stochastic decisions [4] , [5] , [6] ,...	[ "ComK transcriptionally controls competence for the uptake of transforming DNA in Bacillus subtilis .", "Only 10%–20% of the cells in a clonal population are randomly selected for competence .", "Because ComK activates its own promoter , cells exceeding a threshold amount of ComK trigger a positive feedback loo...	[ "Populations of bacterial cells sometimes bifurcate into subpopulations with different patterns of gene expression .", "The soil bacterium B . subtilis becomes “competent” for the uptake of environmental DNA , thus acquiring new genetic information .", "About 15% of the cells are chosen for expression of the co...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "ecology and environmental sciences", "water resources", "geographical locations", "social sciences", "australia", "animals", "ddt", "insect vectors", "zoology", "law and legal sciences", "conservation biology", "infectious diseases", "agr...	The elimination of the dengue vector, Aedes aegypti, from Brisbane, Australia: The role of surveillance, larval habitat removal and policy	journal.pntd.0005848	null	[ [ "Dengue fever is the 21st Century’s most important mosquito-borne viral illness , exerting a huge economic and health burden in the tropics and sub-tropics [1] .", "The incidence of dengue has increased 30 fold over the past five decades and the disease is now estimated to affect up to 390 million people ...	[ "Aedes aegypti ( L . ) ( Diptera: Culicidae ) is a highly invasive mosquito whose global distribution has fluctuated dramatically over the last 100 years .", "In Australia the distribution of Ae .", "aegypti once spanned the eastern seaboard , for 3 , 000 km north to south .", "However , during the 1900s this...	[ "We examined the historical role that water storage practices and the enforcement of anti-mosquito regulations played in the elimination of Aedes aegypti from Brisbane , a major urban centre in Australia .", "We examined changes in regulations pertaining to mosquitoes , collected government records documenting su...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience/behavioral neuroscience", "neuroscience/animal cognition", "neuroscience/sensory systems" ]	Plant Classification from Bat-Like Echolocation Signals	journal.pcbi.1000032	null	[ [ "When orienting in space and searching for food , microchiropteran bats continuously emit echolocation signals .", "The returning echoes are analyzed in the auditory system to perform the basic echolocation tasks of detection , localization and classification [1] .", "Classification of vegetation prob...	[ "Classification of plants according to their echoes is an elementary component of bat behavior that plays an important role in spatial orientation and food acquisition .", "Vegetation echoes are , however , highly complex stochastic signals: from an acoustical point of view , a plant can be thought of as a three-...	[ "Bats are able to classify plants using echolocation .", "They emit ultrasonic signals and can recognize the plant according to the echo returning from it .", "This ability assists them in many of their daily activities , like finding food sources associated with certain plants or using landmarks for navigation...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/bacterial infections", "cell biology/cytoskeleton", "microbiology/cellular microbiology and pathogenesis", "cell biology/cell signaling" ]	Deciphering Interplay between Salmonella Invasion Effectors	journal.ppat.1000037	null	[ [ "Many bacterial pathogens employ type III secretion systems ( T3SSs ) to deliver virulence effector proteins directly into eukaryotic host cells [1] .", "An essential early T3SS-dependent step in Salmonella pathogenesis is bacterial invasion of non-phagocytic intestinal epithelial cells , an event that ca...	[ "Bacterial pathogens have evolved a specialized type III secretion system ( T3SS ) to translocate virulence effector proteins directly into eukaryotic target cells .", "Salmonellae deploy effectors that trigger localized actin reorganization to force their own entry into non-phagocytic host cells .", "Six effec...	[ "Critical to the onset of Salmonella infection is the ability of bacteria to force their own entry ( ‘invade’ ) into intestinal cells of their mammalian host from where they replicate , spread and cause damage .", "To achieve this invasion , Salmonella deliver a cocktail of proteins directly into host target cell...	2008
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Modeling the Slow CD4+ T Cell Decline in HIV-Infected Individuals	journal.pcbi.1004665	null	[ [ "HIV-1 progression to the AIDS stage within untreated patients usually takes many years .", "As HIV-1 infection progresses , the CD4+ T cell population declines slowly and the infected individual becomes progressively more susceptible to certain opportunistic infections and neoplasms .", "These are pa...	[ "The progressive loss of CD4+ T cell population is the hallmark of HIV-1 infection but the mechanism underlying the slow T cell decline remains unclear .", "Some recent studies suggested that pyroptosis , a form of programmed cell death triggered during abortive HIV infection , is associated with the release of i...	[ "The CD4+ T cell population within HIV-infected individuals declines slowly as disease progresses .", "When CD4+ cells drop to below 200 cells/ul , the infection is usually considered to enter the late stage , i . e . , acquired immune deficiency syndrome ( AIDS ) .", "CD4+ T cell depletion can take many years ...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology/aging" ]	A Mitochondrial Superoxide Signal Triggers Increased Longevity in Caenorhabditis elegans	journal.pbio.1000556	The study of long-lived C. elegans mutants suggests that mitochondrial oxidants can actually help reduce aging by acting as stress signals, rather than acting solely as toxic molecules.	[ [ "Mitochondrial function has been linked to the aging process in a number of ways [1] .", "In particular , mitochondria are crucial in energy metabolism and as such have been implicated in the aging process by one of the very first theories of aging [2] , the rate-of-living theory of aging [3] , which sugg...	[ "The nuo-6 and isp-1 genes of C . elegans encode , respectively , subunits of complex I and III of the mitochondrial respiratory chain .", "Partial loss-of-function mutations in these genes decrease electron transport and greatly increase the longevity of C . elegans by a mechanism that is distinct from that indu...	[ "An unequivocal demonstration that mitochondria are important for lifespan comes from studies with the nematode Caenorhabditis elegans .", "Mutations in mitochondrial proteins such as ISP-1 and NUO-6 , which function directly in mitochondrial electron transport , lead to a dramatic increase in the lifespan of thi...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Viral and Cellular Proteins Containing FGDF Motifs Bind G3BP to Block Stress Granule Formation	journal.ppat.1004659	null	[ [ "The Ras-GAP SH3 domain–binding proteins ( G3BP ) are multifunctional RNA-binding proteins , present in two forms , G3BP-1 and G3BP-2 ( here collectively referred to as G3BP ) .", "They have a well-described importance in mediating the formation of RNA stress granules ( SG ) , both in cells exposed to env...	[ "The Ras-GAP SH3 domain–binding proteins ( G3BP ) are essential regulators of the formation of stress granules ( SG ) , cytosolic aggregates of proteins and RNA that are induced upon cellular stress , such as virus infection .", "Many viruses , including Semliki Forest virus ( SFV ) , block SG induction by target...	[ "Stress granules ( SGs ) are dynamic aggregates of proteins and translationally silenced mRNA that are formed in cells upon various stress conditions , such as virus infection .", "SGs are thought to be antiviral , and many viruses have hence evolved countermeasures to prevent their formation , often targeting th...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "biology", "evolutionary biology" ]	FGF Signaling Regulates the Number of Posterior Taste Papillae by Controlling Progenitor Field Size	journal.pgen.1002098	null	[ [ "Taste sensory capability is mediated by aggregates of receptor cells , called taste buds , which reside within the oral and pharyngeal cavities .", "The majority of taste buds in mammals reside on the tongue in epithelial-mesenchymal specializations termed gustatory papillae .", "In the rodent tongue...	[ "The sense of taste is fundamental to our ability to ingest nutritious substances and to detect and avoid potentially toxic ones .", "Sensory taste buds are housed in papillae that develop from epithelial placodes .", "Three distinct types of gustatory papillae reside on the rodent tongue: small fungiform papil...	[ "The sense of taste is important for an animal's ability to survive and thrive , because it enables discrimination between nutritious substances and toxins .", "Taste buds are housed largely on the tongue in structures called papillae; of the three types of gustatory papillae , the circumvallate papilla ( CVP ) i...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "nuclear staining", "fibroblasts", "mutation", "developmental biology", "connective tissue cells", "nonsense mutation", "embryos", "kidneys", "cellular structures and organelles", "research and analysis methods", "missense mutation", "specimen preparation and ...	Novel NEK8 Mutations Cause Severe Syndromic Renal Cystic Dysplasia through YAP Dysregulation	journal.pgen.1005894	null	[ [ "Ciliopathies are a group of autosomal recessive disorders caused by a dysfunction of the primary cilium .", "These conditions are multisystemic disorders , affecting left-right symmetry ( situs inversus ) and various organs such as retina ( retinitis pigmentosa , Senior-Løken syndrome ) , brain ( cerebel...	[ "Ciliopathies are a group of genetic multi-systemic disorders related to dysfunction of the primary cilium , a sensory organelle present at the cell surface that regulates key signaling pathways during development and tissue homeostasis .", "In order to identify novel genes whose mutations would cause severe deve...	[ "Genes mutated in ciliopathies encode proteins with various localizations and functions at the primary cilium .", "Here we report novel NEK8 mutations in patients with renal cystic hypodysplasia and associated ciliopathy defects .", "NEK8 belongs to a protein complex defining the Inversin compartment of the cil...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "infectious diseases/bacterial infections", "infectious diseases/fungal infections", "immunology/immunity to infections" ]	Th1-Th17 Cells Mediate Protective Adaptive Immunity against Staphylococcus aureus and Candida albicans Infection in Mice	journal.ppat.1000703	null	[ [ "Staphylococcus aureus and Candida spp .", "are the second and third leading causes of bloodstream infections in hospitalized patients [1] .", "These organisms jointly cause at least 150 , 000 clinical bloodstream infections resulting billions of dollars of health-care expenditures and ∼40 , 000 death...	[ "We sought to define protective mechanisms of immunity to Staphylococcus aureus and Candida albicans bloodstream infections in mice immunized with the recombinant N-terminus of Als3p ( rAls3p-N ) vaccine plus aluminum hydroxide ( Al ( OH3 ) adjuvant , or adjuvant controls .", "Deficiency of IFN-γ but not IL-17A e...	[ "The bacterium Staphylococcus aureus and the fungus Candida are the second and third leading cause of bloodstream infections in hospitalized patients .", "A vaccine to prevent such infections would be of enormous public health benefit .", "The leading hypothesis to explain why vaccines have not been successfull...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	African Program for Onchocerciasis Control 1995–2010: Impact of Annual Ivermectin Mass Treatment on Off-Target Infectious Diseases	journal.pntd.0004051	null	[ [ "The African Program for Onchocerciasis Control ( APOC ) is an international program aimed at controlling the disease burden of human onchocerciasis ( river blindness ) in sub-Saharan Africa ( SSA ) , and elimination of infection where possible , using mass drug treatment ( MDA ) [1 , 2] .", "Since its la...	[ "Since its initiation in 1995 , the African Program for Onchocerciasis Control ( APOC ) has had a substantial impact on the prevalence and burden of onchocerciasis through annual ivermectin mass treatment .", "Ivermectin is a broad-spectrum anti-parasitic agent that also has an impact on other co-endemic parasiti...	[ "Onchocerciasis , or river blindness , is an infectious disease caused by the worm Onchocerca volvulus , which is transmitted between humans through the bites of blackflies and causes deforming skin disease , itch , and vision loss .", "The African Programme for Onchocerciasis Control ( APOC ) aims to control mor...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Trypanosoma cruzi TcSMUG L-surface Mucins Promote Development and Infectivity in the Triatomine Vector Rhodnius prolixus	journal.pntd.0002552	null	[ [ "Described by its discoverer , Carlos Chagas [1] , [2] , as “one of the most injurious tropical illnesses , specially to children in contaminated areas , either in determining a chronic sickly condition in which people become unable to perform vital activities or as an important factor of human degeneration ,...	[ "TcSMUG L products were recently identified as novel mucin-type glycoconjugates restricted to the surface of insect-dwelling epimastigote forms of Trypanosoma cruzi , the etiological agent of Chagas disease .", "The remarkable conservation of their predicted mature N-terminal region , which is exposed to the extr...	[ "Chagas disease , the major tropical human disease in much of Latin America , affects approximately 11 million people .", "There are 300 , 000 new cases of Chagas disease and approximately 21 , 000 deaths , annually .", "Triatomine vectors , including Rhodnius prolixus , are able to transmit the protozoan Trypa...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "physicians", "medical doctors", "economic analysis", "municipal government", "tropical diseases", "geographical locations", "social sciences", "political science", "health care", "research design", "health care providers", "neglected tropical diseases", "go...	Societal impact of dengue outbreaks: Stakeholder perceptions and related implications. A qualitative study in Brazil, 2015	journal.pntd.0005366	null	[ [ "Since the beginning of the 21st century , dengue fever has been a significant vector-borne arboviral disease , occurring mainly in tropical and sub-tropical countries where more than 3 . 9 billion people are at risk of infection in 128 countries [1–4] .", "With an estimated 400 million annual dengue inci...	[ "The growing burden of dengue in many countries worldwide and the difficulty of preventing outbreaks have increased the urgency to identify alternative public health management strategies and effective approaches to control and prevent dengue outbreaks .", "The objectives of this study were to understand the impa...	[ "Since the beginning of the 21st century , dengue fever has been a significant vector-borne arboviral disease; actually more than 3 . 9 billion people are at risk of infection in 128 countries .", "Dengue has become an increasing public health concern in Latin America , especially in Brazil , which has the highes...	2017
[ "Introduction", "Results and discussion", "Materials and methods" ]	[ "chemical neutralization", "medicine and health sciences", "immune physiology", "pathology and laboratory medicine", "pathogens", "immunology", "microbiology", "retroviruses", "viruses", "immunodeficiency viruses", "mathematics", "rna viruses", "forecasting", "statistics (mathematics)", ...	Prediction of HIV-1 sensitivity to broadly neutralizing antibodies shows a trend towards resistance over time	journal.pcbi.1005789	null	[ [ "With around 36 . 7 million people living with HIV in 2015 and an incidence rate of around 2 . 1 million each year [1] , infections with HIV continue to be a major global health issue .", "However , despite more than three decades of research , there is neither a vaccine against nor a cure available for i...	[ "Treatment with broadly neutralizing antibodies ( bNAbs ) has proven effective against HIV-1 infections in humanized mice , non-human primates , and humans .", "Due to the high mutation rate of HIV-1 , resistance testing of the patient’s viral strains to the bNAbs is still inevitable .", "So far , bNAb resistan...	[ "Several sequence-based approaches exist to predict the epitope of broadly neutralizing antibodies ( bNAbs ) against HIV based on the correlation between variation in the viral sequence and neutralization response to the antibody .", "Though the potential epitope sites can be used to predict the neutralization re...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases" ]	Herpesvirus Telomerase RNA (vTR) with a Mutated Template Sequence Abrogates Herpesvirus-Induced Lymphomagenesis	journal.ppat.1002333	null	[ [ "Telomerase is a multi-component ribonucleoprotein complex that governs the maintenance of telomeres , protein-associated hexameric sequence repeats at the end of linear chromosomes , and ensures chromosomal integrity and cellular survival [1] , [2] .", "The telomerase complex consists of two core compone...	[ "Telomerase reverse transcriptase ( TERT ) and telomerase RNA ( TR ) represent the enzymatically active components of telomerase .", "In the complex , TR provides the template for the addition of telomeric repeats to telomeres , a protective structure at the end of linear chromosomes .", "Human TR with a mutati...	[ "Telomerase facilitates telomere maintenance and consists of two major components: the catalytic subunit telomerase reverse transcriptase ( TERT ) and telomerase RNA ( TR ) that provides the template for the addition of telomeric repeats to telomere ends .", "Expression of TRs with a mutation in the template sequ...	2011
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "parasite groups", "medicine and health sciences", "plasmodium", "population genetics", "geographical locations", "tropical diseases", "cloning", "parasitic diseases", "parasitology", "apicomplexa", "molecular biology techniques", "population biology", "genotyping", "research and analysis ...	Complexity of Infection and Genetic Diversity in Cambodian Plasmodium vivax	journal.pntd.0004526	null	[ [ "Plasmodium vivax is the most widely distributed human malaria parasite , threatening almost 40% of the world population [1] .", "It is the major cause of malaria outside of Africa , with up to 390 million clinical infections each year , and is responsible for long-term chronic illness that has dramatic c...	[ "Plasmodium vivax is the most widely distributed human malaria parasite with 2 . 9 billion people living in endemic areas .", "Despite intensive malaria control efforts , the proportion of cases attributed to P . vivax is increasing in many countries .", "Genetic analyses of the parasite population and its dyna...	[ "Plasmodium vivax is responsible for most malaria cases outside Africa but remains poorly understood .", "Here we describe a high-throughput assay that enables genotyping more than 100 SNPs in 96 samples simultaneously .", "We applied this assay to characterize P . vivax genetic diversity in ~500 individual inf...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "luciferase", "enzymes", "dna-binding proteins", "microbiology", "negative-sense rna viruses", "enzymology", "viruses", "developmental biology", "polymerases", "rna viruses", "sequence motif analysis", "research and analysis methods", "sequence analysis", "sequence alignment", "bioinform...	Characterization of the catalytic center of the Ebola virus L polymerase	journal.pntd.0005996	null	[ [ "Ebola virus ( EBOV ) is a member of the genus Ebolavirus in the family of Filoviridae , and the causative agent of a severe hemorrhagic fever called Ebola virus disease ( EVD ) with case fatality rates of up to 90% [1] .", "While outbreaks are usually of comparatively small scale , the recent EVD epidemi...	[ "Ebola virus ( EBOV ) causes a severe hemorrhagic fever in humans and non-human primates .", "While no licensed therapeutics are available , recently there has been tremendous progress in developing antivirals .", "Targeting the ribonucleoprotein complex ( RNP ) proteins , which facilitate genome replication an...	[ "Ebola viruses cause severe hemorrhagic fevers , and were responsible for the devastating Ebola virus disease epidemic in West Africa from 2013 to 2016 .", "While a number of experimental therapeutics against these viruses target the viral polymerase , there are still significant gaps in our knowledge regarding t...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "computer science", "molecular cell biology", "computer modeling", "stem cells", "cell biology", "embryonic stem cells", "cellular types", "biology", "computational biology", "stem cell lines", "cell differentiation" ]	Spatial Pattern Dynamics of 3D Stem Cell Loss of Pluripotency via Rules-Based Computational Modeling	journal.pcbi.1002952	null	[ [ "Pluripotent embryonic stem cells ( ESCs ) have the unique ability to differentiate into cells of the three germ lineages that form all of the tissues and organs of a mature organism .", "Differentiation of pluripotent ESCs can be induced in vitro via a variety of existing approaches to emulate aspects of...	[ "Pluripotent embryonic stem cells ( ESCs ) have the unique ability to differentiate into cells from all germ lineages , making them a potentially robust cell source for regenerative medicine therapies , but difficulties in predicting and controlling ESC differentiation currently limit the development of therapies a...	[ "Pluripotent embryonic stem cells can differentiate into all cell types making up the adult body; however , this process occurs in a complex three dimensional environment with many different parameters present that are capable of influencing cell fate decisions .", "A model that can accurately predict the strengt...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "protein interactions", "drugs and devices", "pharmacodynamics", "genetics and genomics", "pharmacology", "biology", "proteomics", "drug discovery", "biochemistry", "drug research and development", "genetics", "genomics", "drug interactions", "gene networks", "computational...	Systematic Prediction of Pharmacodynamic Drug-Drug Interactions through Protein-Protein-Interaction Network	journal.pcbi.1002998	null	[ [ "Drug-drug interaction ( DDI ) is a significant cause of adverse drug reactions ( ADRs ) , especially in patient populations on multiple medications .", "A recent study indicated that medications were commonly used together in older adults , with nearly 1 in 25 individuals potentially at risk of a major D...	[ "Identifying drug-drug interactions ( DDIs ) is a major challenge in drug development .", "Previous attempts have established formal approaches for pharmacokinetic ( PK ) DDIs , but there is not a feasible solution for pharmacodynamic ( PD ) DDIs because the endpoint is often a serious adverse event rather than a...	[ "Drug-drug interaction ( DDI ) is an important problem in clinical practice .", "In this study , we developed a novel algorithm for systematically predicting pharmacodynamic ( PD ) DDIs through protein-protein-interaction ( PPI ) networks .", "We calculated a score to predict potential PD DDIs by integrating th...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "hiv infections", "urinary system procedures", "medicine and health sciences", "organ transplantation", "european union", "tropical diseases", "geographical locations", "parasitic diseases", "surgical and invasive medical procedures", "developmental biology", "renal transplantation", "neglecte...	Management of severe strongyloidiasis attended at reference centers in Spain	journal.pntd.0006272	null	[ [ "Strongyloidiasis is an infection caused by Strongyloides stercoralis .", "Other Strongyloides spp .", "include S . fuelleborni , which infects some non-human primates and may cause self-limited disease in humans .", "S . stercoralis is widely distributed , affecting up to 370 million people world...	[ "Strongyloides stercoralis is a globally distributed nematode that causes diverse clinical symptoms in humans .", "Spain , once considered an endemic country , has experienced a recent increase in imported cases .", "The introduction of serology helps diagnosis and is currently replacing microbiological techniq...	[ "Strongyloides stercoralis is a globally distributed worm .", "It has a free living cycle in wet moist soils , and an autoinfecting cycle affecting humans in their lungs , bowels and skin .", "Strongyloidiasis is the name of the infection caused by S . stercoralis and it can vary from an indolent state , with n...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "neuroscience/theoretical neuroscience", "biophysics/theory and simulation", "developmental biology/morphogenesis and cell biology", "computational biology/computational neuroscience" ]	One Rule to Grow Them All: A General Theory of Neuronal Branching and Its Practical Application	journal.pcbi.1000877	null	[ [ "Neuronal circuits are composed of a large variety of branched structures – axons and dendrites – forming a highly entangled web , reminiscent of a stochastic fractal [1] .", "Despite this apparent chaos , more than a century ago Ramón y Cajal was able to extract order from this neuroanatomical complexity...	[ "Understanding the principles governing axonal and dendritic branching is essential for unravelling the functionality of single neurons and the way in which they connect .", "Nevertheless , no formalism has yet been described which can capture the general features of neuronal branching .", "Here we propose such...	[ "More than a century has passed since Ramón y Cajal presented a set of fundamental biological laws of neuronal branching .", "He described how the shape of the core elements of the neural circuitry – axons and dendrites – are constrained by physical parameters such as space , cytoplasmic volume , and conduction t...	2010
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "genetic networks", "neural networks", "gene regulation", "protein interaction networks", "cancers and neoplasms", "brain", "neuroscience", "oncology", "neurological tumors", "network analysis", "computer and information sciences", "basal ganglia", "gene exp...	A composite network of conserved and tissue specific gene interactions reveals possible genetic interactions in glioma	journal.pcbi.1005739	null	[ [ "How can genomic information that is the same in each cell of an individual be translated into a variety of cell and tissue types ?", "It is clear that gene-regulatory mechanisms must play a leading role in differentiation processes .", "Transcription factors ( TF ) belong to the class of proteins tha...	[ "Differential co-expression network analyses have recently become an important step in the investigation of cellular differentiation and dysfunctional gene-regulation in cell and tissue disease-states .", "The resulting networks have been analyzed to identify and understand pathways associated with disorders , or...	[ "With the ever increasing availability of large sets of gene expression data , much effort has been directed towards studying shared expression patterns between different genes .", "We have developed a general method for studying the variation of gene co-expression between two different conditions , which allows ...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "sequencing techniques", "taxonomy", "vero cells", "medicine and health sciences", "reproductive system", "pathology and laboratory medicine", "pathogens", "biological cultures", "microbiology", "viruses", "amino acid sequence analysis", "phylogenetics", "data management", "rna viruses", ...	Increased growth ability and pathogenicity of American- and Pacific-subtype Zika virus (ZIKV) strains compared with a Southeast Asian-subtype ZIKV strain	journal.pntd.0007387	null	[ [ "Zika virus ( ZIKV; genus: Flavivirus; family: Flaviviridae ) was first isolated from a sentinel rhesus monkey in the Zika forest of Uganda in 1947 [1] .", "ZIKV infection in humans was first identified in Uganda and the United Republic of Tanzania in 1952 , and human ZIKV infections ( ZIKV disease , ZVD ...	[ "We investigated the growth properties and virulence in mice of three Zika virus ( ZIKV ) strains of Asian/American lineage , PRVABC59 , ZIKV/Hu/Chiba/S36/2016 ( ChibaS36 ) , and ZIKV/Hu/NIID123/2016 ( NIID123 ) , belonging to the three distinct subtypes of this lineage .", "The American-subtype strain , PRVABC59...	[ "Zika virus ( ZIKV ) is classified into two lineages , African and Asian/American .", "Phylogenetic analyses have revealed that Asian/American-lineage ZIKV strains can be divided into three distinct subtypes , the American , Pacific , and Southeast Asian subtypes , presenting several amino acid differences .", ...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biomacromolecule-ligand interactions", "immunopathology", "biochemistry", "protein chemistry", "immune cells", "mathematics", "cell biology", "animal cells", "clinical immunology", "antigen processing and recognition", "antigen-presenting cells", "biology and life sciences", "cellular types...	A New Tool to Quantify Receptor Recruitment to Cell Contact Sites during Host-Pathogen Interaction	journal.pcbi.1003639	null	[ [ "C . albicans is a commensal of the human oropharyngeal cavity , gastrointestinal tract and female lower reproductive tract .", "It is also a significant opportunistic pathogen [1] .", "Infection by Candida species causes illnesses ranging from superficial mucosal infections that markedly diminish qua...	[ "To understand the process of innate immune fungal recognition , we developed computational tools for the rigorous quantification and comparison of receptor recruitment and distribution at cell-cell contact sites .", "We used these tools to quantify pattern recognition receptor spatiotemporal distributions in con...	[ "Specialized cell-cell contacts are a common theme in cell biology .", "These structures increase sensitivity and specificity of cellular activation and information flow in contexts ranging from activation of immune responses to transmission of nerve action potentials .", "Candida species fungal pathogens are r...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "escherichia coli", "medicine", "bacterial diseases", "infectious diseases" ]	Quinolone Resistance in Absence of Selective Pressure: The Experience of a Very Remote Community in the Amazon Forest	journal.pntd.0001790	null	[ [ "Quinolones are broad-spectrum antimicrobial agents with rapid bactericidal activity , overall low toxicity , and the possibility of being administered either orally or parenterally .", "Thanks to these features , quinolones are drugs of choice for the treatment of several community- and hospital-acquired...	[ "Quinolones are potent broad-spectrum bactericidal agents increasingly employed also in resource-limited countries .", "Resistance to quinolones is an increasing problem , known to be strongly associated with quinolone exposure .", "We report on the emergence of quinolone resistance in a very remote community i...	[ "Quinolones are broad-spectrum antibiotics which bind to type II topoisomerases ( DNA gyrase and topoisomerase IV ) and inhibit DNA re-ligation after enzyme cut , exerting a rapid bactericidal activity .", "They are widely used for the treatment of several community- and hospital-acquired infections and have beco...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "lysosomes", "medicine and health sciences", "caenorhabditis", "enzymes", "endoplasmic reticulum", "cell processes", "enzymology", "cell disruption", "animals", "animal models", "physiological processes", "caenorhabditis elegans", "model organisms", "homeostasis", "exp...	Age- and stress-associated C. elegans granulins impair lysosomal function and induce a compensatory HLH-30/TFEB transcriptional response	journal.pgen.1008295	null	[ [ "Aging and stress are thought to enhance neurodegenerative disease risk through the accumulation of misfolded and aggregated proteins [1–3] .", "The lysosome is the key degradative organelle within the cell [4] , and therefore plays a pivotal role in the maintenance of protein homeostasis .", "It cont...	[ "The progressive failure of protein homeostasis is a hallmark of aging and a common feature in neurodegenerative disease .", "As the enzymes executing the final stages of autophagy , lysosomal proteases are key contributors to the maintenance of protein homeostasis with age .", "We previously reported that expr...	[ "Progressive decline in maintenance of protein homeostasis clearly contributes to the development of neurodegenerative disorders , yet the molecular basis of this decline is poorly understood .", "Here , we take advantage of molecular genetic techniques available in the model organism C . elegans to investigate t...	2019
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "blood cells", "invertebrates", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "natural antisense transcripts", "gene regulation", "immunology", "animals", "developmental biology", "micrornas", "signs and symptoms", "stomach", "anisakis", "neutrophil...	Interplay between proinflammatory cytokines, miRNA, and tissue lesions in Anisakis-infected Sprague-Dawley rats	journal.pntd.0007397	null	[ [ "Foodborne parasitic diseases have received increasing attention in recent decades .", "Some are considered emerging public health issues , due to changes in various factors influencing the propagation of parasites that cause them [1] .", "This is especially valid for several helminthiases , which hav...	[ "Anisakiasis is an emerging public health problem , caused by Anisakis spp .", "nematode larvae .", "Anisakiasis presents as variable and unspecific gastrointestinal and/or allergic clinical symptoms , which accounts for the high rate of misdiagnosed cases .", "The aim of this study was to characterize the ea...	[ "Anisakiasis is a zoonotic disease ( infection transmitted between animals and humans ) contracted by consumption of raw or undercooked seafood contaminated with Anisakis spp .", "nematode larvae .", "Anisakiasis usually presents with variable and unspecific gastrointestinal and/or allergic symptoms , which acc...	2019
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetic networks", "enzymes", "gene regulation", "messenger rna", "enzymology", "optimization", "systems science", "mathematics", "network analysis", "hypoxia", "genome analysis", "bacteria", "computer and information sciences", "genomics", "proteins", "gene expression", "actinobact...	Non-monotonic Response to Monotonic Stimulus: Regulation of Glyoxylate Shunt Gene-Expression Dynamics in Mycobacterium tuberculosis	journal.pcbi.1004741	null	[ [ "Uncovering how regulatory networks shape the dynamical properties of cellular responses to external stimuli is one of the ultimate goals of system biology .", "Despite our successes in mapping and modeling gene regulatory networks for a wide variety of model systems , only a handful of generalizable rule...	[ "Understanding how dynamical responses of biological networks are constrained by underlying network topology is one of the fundamental goals of systems biology .", "Here we employ monotone systems theory to formulate a theorem stating necessary conditions for non-monotonic time-response of a biochemical network t...	[ "Over the last several years mathematical modeling has become widely used to understand how biochemical systems respond to perturbations .", "In particular , dynamics of the response , i . e . the precise nature of how the responses changes with time , has become the focus of multiple studies .", "However , to ...	2016
[ "Introduction", "Results and discussion", "Methods" ]	[ "animal types", "ecology and environmental sciences", "animal genetics", "domestic animals", "chickens", "vertebrates", "social sciences", "animals", "animal behavior", "deserts", "bird genetics", "zoology", "ecological metrics", "birds", "ecosystems", "behavior", "gamefowl", "fowl...	Genetics of adaptation in modern chicken	journal.pgen.1007989	null	[ [ "The modern chicken ( Gallus gallus domesticus ) was domesticated from the red jungle fowl ( RJF ) [1] , but with some contributions from at least one other closely related species , the grey jungle fowl [2] .", "Domestic chicken segregate into several hundreds of distinct breeds distributed across the wo...	[ "We carried out whole genome resequencing of 127 chicken including red jungle fowl and multiple populations of commercial broilers and layers to perform a systematic screening of adaptive changes in modern chicken ( Gallus gallus domesticus ) .", "We uncovered >21 million high quality SNPs of which 34% are newly ...	[ "Domestic chickens ( Gallus gallus domesticus ) provide a critical resource for animal proteins for human nutrition worldwide .", "Chickens were primarily domesticated from the red jungle fowl ( Gallus gallus gallus ) , a bird that still runs wild in most of Southeast Asia .", "Human driven selection during dom...	2019
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "molecular biology", "cell biology/developmental molecular mechanisms", "cell biology/gene expression", "genetics and genomics/functional genomics" ]	Phenotypic Screen of Early-Developing Larvae of the Blood Fluke, Schistosoma mansoni, using RNA Interference	journal.pntd.0000502	null	[ [ "Digenetic trematodes ( parasitic flatworms ) of the genus Schistosoma infect more than 200 million people in over 70 developing countries [1] , with an additional 770 million people worldwide at risk of becoming infected [2] .", "As causative agents of chronic , often severe morbidity and responsibility ...	[ "RNA interference ( RNAi ) represents the only method currently available for manipulating gene-specific expression in Schistosoma spp .", ", although application of this technology as a functional genomic profiling tool has yet to be explored .", "In the present study 32 genes , including antioxidants , transc...	[ "RNA interference ( RNAi ) represents the only method currently available for manipulating gene-specific expression in human blood flukes , Schistosoma spp .", ", although its application as a functional genomics tool in early intramolluscan larval stages has been limited to single gene analyses .", "Accelerati...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	A Gene Gravity Model for the Evolution of Cancer Genomes: A Study of 3,000 Cancer Genomes across 9 Cancer Types	journal.pcbi.1004497	null	[ [ "Cancer development and progression are mediated by the accumulation of genomic alterations , including point mutations , insertions and deletions , gene fusions , amplifications , and chromosomal rearrangements [1 , 2] .", "The majority of the somatic mutations found in tumor cells are ‘passenger’ rather...	[ "Cancer development and progression result from somatic evolution by an accumulation of genomic alterations .", "The effects of those alterations on the fitness of somatic cells lead to evolutionary adaptations such as increased cell proliferation , angiogenesis , and altered anticancer drug responses .", "Howe...	[ "Cancer genome instabilities , such as chromosomal instability and microsatellite instability , have been recognized as a hallmark of cancer for several decades .", "However , distinguishing cancer functional somatic mutations from massive passenger mutations and non-genetic events is a major challenge in cancer ...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/gene expression", "genetics and genomics/complex traits", "genetics and genomics/genetics of disease", "diabetes and endocrinology/bone and mineral metabolism", "genetics and genomics/bioinformatics" ]	An Integration of Genome-Wide Association Study and Gene Expression Profiling to Prioritize the Discovery of Novel Susceptibility Loci for Osteoporosis-Related Traits	journal.pgen.1000977	null	[ [ "The feasibility of carrying out genome-wide association studies ( GWAS ) has led to the rapid progression of the field of complex-disease genetics over the past few years .", "Although the GWAS approach has been successful in identifying novel candidate genes leading to new discovery of pathways that are...	[ "Osteoporosis is a complex disorder and commonly leads to fractures in elderly persons .", "Genome-wide association studies ( GWAS ) have become an unbiased approach to identify variations in the genome that potentially affect health .", "However , the genetic variants identified so far only explain a small pro...	[ "BMD and hip geometry are two major predictors of osteoporotic fractures , the most severe consequence of osteoporosis in elderly persons .", "We performed sex-specific genome-wide association studies ( GWAS ) for BMD at the lumbar spine and femor neck skeletal sites as well as hip geometric indices ( NSA , NL , ...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/chromosome biology", "genetics and genomics/genetics of disease", "genetics and genomics/epigenetics", "genetics and genomics", "genetics and genomics/medical genetics" ]	Altered DNA Methylation in Leukocytes with Trisomy 21	journal.pgen.1001212	null	[ [ "It is now 5 decades since Down syndrome ( DS ) was first shown to result from trisomy 21 [1] , [2] , and some progress has been made toward understanding the genes that contribute to the complex array of DS phenotypes – mostly by studying the effects of the trisomy on transcriptional profiles in humans and m...	[ "The primary abnormality in Down syndrome ( DS ) , trisomy 21 , is well known; but how this chromosomal gain produces the complex DS phenotype , including immune system defects , is not well understood .", "We profiled DNA methylation in total peripheral blood leukocytes ( PBL ) and T-lymphocytes from adults with...	[ "Down syndrome ( DS; trisomy 21 ) is caused by the gain of a single extra chromosome 21 .", "However , the mechanisms by which this extra chromosome produces the medical abnormalities seen in DS , including not only mental retardation but also susceptibility to autoimmune diseases and recurrent infections , are s...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "sexually transmitted diseases", "medical microbiology", "virology", "microbial pathogens", "hiv", "retrovirology and hiv immunopathogenesis", "biology", "microbiology", "host-pathogen interaction", "viral diseases" ]	Allosteric Modulation of the HIV-1 gp120-gp41 Association Site by Adjacent gp120 Variable Region 1 (V1) N-Glycans Linked to Neutralization Sensitivity	journal.ppat.1003218	null	[ [ "The HIV-1 envelope glycoprotein ( Env ) complex comprises a trimer of gp120 subunits in non-covalent association with a trimer of transmembrane gp41 subunits and mediates viral attachment , membrane fusion and viral entry ( for review see [1] , [2] ) .", "Within gp120 , 5 conserved regions ( C1–C5 ) alte...	[ "The HIV-1 gp120-gp41 complex , which mediates viral fusion and cellular entry , undergoes rapid evolution within its external glycan shield to enable escape from neutralizing antibody ( NAb ) .", "Understanding how conserved protein determinants retain functionality in the context of such evolution is important ...	[ "The envelope glycoprotein gp120-gp41 complex of HIV-1 mediates receptor attachment and virus-cell membrane fusion , leading to cellular entry .", "A shield of asparagine-linked oligosaccharides occludes the gp120-gp41 protein surface and evolution of this glycan shield provides a means for evading circulating ne...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "gene regulation", "regulatory proteins", "dna-binding proteins", "nephrons", "transcription factors", "sequence motif analysis", "mammalian genomics", "kidneys", "research and analysis methods", "sequence analysis", "transcriptional control", "bioinformatics"...	Transcriptional regulatory control of mammalian nephron progenitors revealed by multi-factor cistromic analysis and genetic studies	journal.pgen.1007181	null	[ [ "The mammalian metanephric kidney maintains fluid homeostasis .", "The number of individuals afflicted with kidney disease is on the rise , and reduced nephron number has been associated with disease outcome [1] .", "In the mouse , genetic studies have demonstrated that nephrons are generated from a S...	[ "Nephron progenitor number determines nephron endowment; a reduced nephron count is linked to the onset of kidney disease .", "Several transcriptional regulators including Six2 , Wt1 , Osr1 , Sall1 , Eya1 , Pax2 , and Hox11 paralogues are required for specification and/or maintenance of nephron progenitors .", ...	[ "Nephrons , the filtering units of the kidney , derive from nephron progenitors .", "Deficiencies in nephron number increases the risk of kidney disease .", "An understanding of the regulatory programs governing progenitor actions has important translational potential .", "Several transcription factors regula...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/neglected tropical diseases", "public health and epidemiology" ]	Neglected Diseases in the News: A Content Analysis of Recent International Media Coverage Focussing on Leishmaniasis and Trypanosomiasis	journal.pntd.0000234	null	[ [ "Roughly one in six people globally , mostly the very poor , suffer from one or more NTDs .", "[1] These diseases may not directly result in high mortality rates , yet cause much morbidity , suffering and poverty .", "[2] Despite this , NTDs are a low priority for the pharmaceutical industry , lacking...	[ "Although the pharmaceutical industry's “neglect” of neglected tropical diseases ( NTDs ) has been investigated , no study evaluating media coverage of NTDs has been published .", "Poor media coverage exacerbates the neglect .", "This study aimed to investigate , describe , and analyse international media cover...	[ "In recent years , there has been a flurry of activity to reverse the neglect that has characterised NTDs , mostly focussed on drug development .", "The drug gap may be explained by market failure , yet other forces also conspire to cause the neglect of NTDs .", "One problem is the low visibility of these disea...	2008
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "taxonomy", "medicine and health sciences", "enzyme-linked immunoassays", "immune physiology", "pathology and laboratory medicine", "china", "immunology", "geographical locations", "vertebrates", "animals", "mammals", "invertebrate genomics", "phylogenetics", "data management", "phylogen...	Seroprevalence, cross antigenicity and circulation sphere of bat-borne hantaviruses revealed by serological and antigenic analyses	journal.ppat.1007545	null	[ [ "Hantaviruses ( HVs ) , members of the genus Orthohantavirus within the family Hantaviridae in the order Bunyavirales , are responsible for two major life-threatening diseases in humans: hemorrhagic fever with renal syndrome ( HFRS ) in Eurasia and hantavirus cardiopulmonary syndrome ( HCPS ) in the Americas ...	[ "Bats are newly identified reservoirs of hantaviruses ( HVs ) among which very divergent HVs have been discovered in recent years .", "However , their significance for public health remains unclear since their seroprevalence as well as antigenic relationship with human-infecting HVs have not been investigated .",...	[ "Some HVs are life-threatening pathogens predominantly carried and transmitted by rodents .", "In recent years bat-borne HVs have been identified in a broad range of bat species .", "To understand their significance to public health the present study conducted extensive investigations on genetic diversity , ser...	2019
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Permethrin-Treated Clothing as Protection against the Dengue Vector, Aedes aegypti: Extent and Duration of Protection	journal.pntd.0004109	null	[ [ "Dengue is the “most important mosquito-borne viral disease” [1] with over 3 . 5 billion people at risk of infection [2] , 50–100 million new infections and 20 , 000 deaths annually [1] .", "Most control strategies target the main urban vector , Aedes aegypti [3] , but despite multiple control programmes ...	[ "Dengue transmission by the mosquito vector , Aedes aegypti , occurs indoors and outdoors during the day .", "Personal protection of individuals , particularly when outside , is challenging .", "Here we assess the efficacy and durability of different types of insecticide-treated clothing on laboratory-reared Ae...	[ "Personal protection technologies could be a key tool in the fight against arthropod borne diseases .", "Insecticide treated clothing may have a significant effect on reducing mosquito borne disease by reducing biting rates and local vector populations .", "Currently there are four main treatment techniques; ab...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Antagonistic Coevolution Drives Whack-a-Mole Sensitivity in Gene Regulatory Networks	journal.pcbi.1004432	null	[ [ "Robustness , defined as tolerance to perturbations such as mutations and environmental fluctuations , is pervasive in biological systems [1 , 2] .", "Early computational models of evolution aimed at understanding the relationship between gene-network evolution and behavior ( gene expression dynamics ) [3...	[ "Robustness , defined as tolerance to perturbations such as mutations and environmental fluctuations , is pervasive in biological systems .", "However , robustness often coexists with its counterpart , evolvability—the ability of perturbations to generate new phenotypes .", "Previous models of gene regulatory n...	[ "Robustness , defined as tolerance to perturbations such as mutations and environmental fluctuations , is pervasive in biology .", "Previous models of gene regulatory networks have shown that robustness can evolve when the phenotype is under evolutionary pressure to remain constant ( stabilizing selection ) .", ...	2015
[ "Introduction", "Methods", "Results and Discussion" ]	[ "invertebrates", "dengue virus", "medicine and health sciences", "pathology and laboratory medicine", "gene regulation", "pathogens", "microbiology", "animals", "long non-coding rnas", "invertebrate genomics", "viruses", "micrornas", "rna viruses", "insect vectors", "aedes aegypti", "m...	Identification of Aedes aegypti Long Intergenic Non-coding RNAs and Their Association with Wolbachia and Dengue Virus Infection	journal.pntd.0005069	null	[ [ "Dengue and Zika viruses are related mosquito-borne viruses that have a common primary vector , Aedes aegypti and infect millions of people worldwide [1 , 2] .", "Recent outbreaks of Dengue and Zika in South America pose a serious risk for other tropical regions in the world as Ae .", "aegypti is one ...	[ "Long intergenic non-coding RNAs ( lincRNAs ) are appearing as an important class of regulatory RNAs with a variety of biological functions .", "The aim of this study was to identify the lincRNA profile in the dengue vector Aedes aegypti and evaluate their potential role in host-pathogen interaction .", "The ma...	[ "Aedes aegypti is a major vector of several viruses such as dengue and Zika viruses .", "Understanding the intricate interaction of viruses with mosquito vectors and the factors involved in virus replication are essential for developing effective arbovirus control strategies .", "In this study , we report a com...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "hiv", "leishmaniasis", "hiv clinical manifestations", "neglected tropical diseases", "viral diseases", "hiv opportunistic infections" ]	Predictors of Visceral Leishmaniasis Relapse in HIV-Infected Patients: A Systematic Review	journal.pntd.0001153	null	[ [ "Visceral leishmaniasis ( VL ) and human immunodeficiency virus ( HIV ) co-infection has emerged as a serious disease pattern [1] , [2] .", "HIV infection increases the risk of developing VL by 100 to 2 , 320 times in endemic areas [3] , [4] and , on the other hand , VL promotes the clinical progression o...	[ "Visceral leishmaniasis ( VL ) is a common complication in AIDS patients living in Leishmania-endemic areas .", "Although antiretroviral therapy has changed the clinical course of HIV infection and its associated illnesses , the prevention of VL relapses remains a challenge for the care of HIV and Leishmania co-i...	[ "Visceral leishmaniasis ( VL ) is the most serious form of an insect-transmitted parasitic disease prevalent in 70 countries .", "The disease is caused by species of the L . donovani complex found in different geographical regions .", "These parasites have substantially different clinical , drug susceptibility ...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	SubClonal Hierarchy Inference from Somatic Mutations: Automatic Reconstruction of Cancer Evolutionary Trees from Multi-region Next Generation Sequencing	journal.pcbi.1004416	null	[ [ "The clonal evolution hypothesis in cancer states that cancer genomes are shaped by numerous rounds of cellular diversification , selection and clonal expansion [1 , 2] .", "Recent methods to characterize tumor clonal evolution can be divided into two broad classes—sample tree reconstruction and subclone ...	[ "Recent improvements in next-generation sequencing of tumor samples and the ability to identify somatic mutations at low allelic fractions have opened the way for new approaches to model the evolution of individual cancers .", "The power and utility of these models is increased when tumor samples from multiple si...	[ "Cancer is a genetic disease , driven by DNA mutations .", "Each tumor is composed of millions of cells with differing genetic profiles that compete with each other for resources in a process similar to Darwinian evolution .", "We describe a computational framework to model tumor evolution on the cellular level...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "haplotypes", "genomics", "genetic polymorphism", "genetic association studies", "genetic screens", "genetics", "population genetics", "genetic toxicology", "biology", "human genetics", "genetic testing", "genomic medicine", "toxicology", "mitochondrial diseases" ]	Associations of Mitochondrial Haplogroups B4 and E with Biliary Atresia and Differential Susceptibility to Hydrophobic Bile Acid	journal.pgen.1003696	null	[ [ "Biliary atresia ( BA ) is characterized by progressive inflammatory cholangiopathy in infancy .", "The pathogenesis of BA may involve free radical products derived from mitochondria , resulting in significantly increased superoxide dismutase activity [1] .", "In the early stage of BA , augmented oxid...	[ "Mitochondrial dysfunction has been implicated in the pathogenesis of biliary atresia ( BA ) .", "This study aimed to determine whether a specific mitochondrial DNA haplogroup is implicated in the pathogenesis and prognosis of BA .", "We determined 40 mitochondrial single nucleotide polymorphisms in 15 major mi...	[ "Mitochondrial dysfunction has been implicated in the pathogenesis of biliary atresia ( BA ) .", "We determined 40 mitochondrial single nucleotide polymorphisms in different mitochondrial haplogroups in BA patients and controls .", "The prevalence of haplogroup B4 and E was significantly lower and higher respec...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	The Shelterin TIN2 Subunit Mediates Recruitment of Telomerase to Telomeres	journal.pgen.1005410	null	[ [ "The multi-subunit shelterin complexes bind along mammalian telomeres , shielding the natural chromosome ends from engaging the DNA damage signaling and repair machinery [1] .", "Among the shelterin components , TRF1 and TRF2 bind directly to duplex telomeric repeats [2] , while POT1 binds to the single-s...	[ "Dyskeratosis Congenita ( DC ) is a heritable multi-system disorder caused by abnormally short telomeres .", "Clinically diagnosed by the mucocutaneous symptoms , DC patients are at high risk for bone marrow failure , pulmonary fibrosis , and multiple types of cancers .", "We have recapitulated the most common ...	[ "The shelterin complex protects telomeres from being processed by the DNA damage repair machinery , and also regulates telomerase access and activity at telomeres .", "The only shelterin subunit known to promote telomerase function is TPP1 , which mediates telomerase recruitment to telomeres and stimulates telome...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics and genomics/complex traits", "evolutionary biology/animal genetics", "genetics and genomics/gene discovery", "evolutionary biology/bioinformatics" ]	How To Perform Meaningful Estimates of Genetic Effects	journal.pgen.1000062	null	[ [ "There is an increasing interest in Quantitative Genetics and Evolutionary Biology to identify genetic effects , and more particularly gene interactions , on a genome-wide scale and to understand its role in the genetic architecture of complex traits [1] , [2] .", "Genome scans for quantitative trait loci...	[ "Although the genotype-phenotype map plays a central role both in Quantitative and Evolutionary Genetics , the formalization of a completely general and satisfactory model of genetic effects , particularly accounting for epistasis , remains a theoretical challenge .", "Here , we use a two-locus genetic system in ...	[ "The rediscovery of Mendel's laws of inheritance of genetic factors gave rise to the research field of Genetics at the very beginning of the last century .", "The idea of traits being determined by the effects of inherited genes is thus the conceptual core of Genetics .", "After more than one century , however ...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Tertiary siRNAs Mediate Paramutation in C. elegans	journal.pgen.1005078	null	[ [ "Transgenerational epigenetic inheritance is the transmission of information from parent to offspring via the gametes by means other than the primary sequence of DNA [1] .", "A number of recent examples have highlighted the possibility for epigenetic inheritance of acquired traits in animals .", "This...	[ "In the nematode Caenorhabditis elegans , different small RNA-dependent gene silencing mechanisms act in the germline to initiate transgenerational gene silencing .", "Piwi-interacting RNAs ( piRNAs ) can initiate transposon and gene silencing by acting upstream of endogenous short interfering RNAs ( siRNAs ) , w...	[ "Transgenerational epigenetic gene silencing has been shown to be important for organisms to react directly to their environment without the need to acquire genetic mutations .", "The inheritance of acquired traits via the gametes can prove advantageous in fast reproducing organisms .", "In Caenorhabditis elega...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "medicine and health sciences", "parasite groups", "plasmodium", "tropical diseases", "vertebrates", "parasitic diseases", "parasitic protozoans", "animals", "parasitology", "xenopus", "animal models", "apicomplexa", "model organisms", "amphibians", "protozoans", "red ...	The Malaria Parasite's Lactate Transporter PfFNT Is the Target of Antiplasmodial Compounds Identified in Whole Cell Phenotypic Screens	journal.ppat.1006180	null	[ [ "The most virulent malaria parasite , Plasmodium falciparum , was responsible for the majority of the 214 million malaria cases and 438 , 000 malaria-attributable deaths estimated to have occurred in 2015 [1] .", "The parasite has developed resistance to most of the drugs deployed against it [2] , and it ...	[ "In this study the ‘Malaria Box’ chemical library comprising 400 compounds with antiplasmodial activity was screened for compounds that perturb the internal pH of the malaria parasite , Plasmodium falciparum .", "Fifteen compounds induced an acidification of the parasite cytosol .", "Two of these did so by inhi...	[ "The emergence and spread of Plasmodium falciparum strains resistant to leading antimalarial drugs has intensified the need to discover and develop drugs that kill the parasite via new mechanisms .", "Here we screened compounds that are known to inhibit P . falciparum growth for their effects on the pH inside the...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Extreme Recombination Frequencies Shape Genome Variation and Evolution in the Honeybee, Apis mellifera	journal.pgen.1005189	null	[ [ "In most sexual eukaryotes , average recombination rates do not greatly exceed one crossover per chromosome arm , which is commonly a minimum requirement for correct meiosis [1] .", "However , the honeybee , Apis mellifera , has extremely high recombination rates , averaging 19–37 cM/Mb [2–4] , which corr...	[ "Meiotic recombination is a fundamental cellular process , with important consequences for evolution and genome integrity .", "However , we know little about how recombination rates vary across the genomes of most species and the molecular and evolutionary determinants of this variation .", "The honeybee , Apis...	[ "Evolution results from changes in allele frequencies in populations .", "The main forces that cause such changes are natural selection and random genetic drift .", "However , an additional process , GC-biased gene conversion ( gBGC ) , associated with meiotic recombination , affects the probability that allele...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/bacterial infections", "infectious diseases/nosocomial and healthcare-associated infections", "infectious diseases/antimicrobials and drug resistance", "infectious diseases/epidemiology and control of infectious diseases" ]	Patient Referral Patterns and the Spread of Hospital-Acquired Infections through National Health Care Networks	journal.pcbi.1000715	null	[ [ "Pathogens that typically cause hospital-acquired infections have an opportunistic nature .", "These organisms are usually part of the normal bacterial flora of humans and only cause disease when reaching body sites that are normally free from bacterial colonization e . g . when anatomical barriers are br...	[ "Rates of hospital-acquired infections , such as methicillin-resistant Staphylococcus aureus ( MRSA ) , are increasingly used as quality indicators for hospital hygiene .", "Alternatively , these rates may vary between hospitals , because hospitals differ in admission and referral of potentially colonized patient...	[ "The prevalence of hospital acquired infections is widely believed to reflect the quality of health care in individual hospitals , and is therefore often used as a benchmark .", "Intuitively , the idea is that infections spread more easily in hospitals with a poor quality of health care .", "This assumes that t...	2010
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "biotechnology", "bacteriology", "medicine", "biochemistry", "infectious diseases", "bacterial diseases", "biology", "microbiology", "bacterial pathogens" ]	Identification and in vitro Analysis of the GatD/MurT Enzyme-Complex Catalyzing Lipid II Amidation in Staphylococcus aureus	journal.ppat.1002509	null	[ [ "In gram-positive bacteria a thick multilayered peptidoglycan ( PG ) constitutes the major component of the cell wall and is essential for survival , maintenance of cell shape and counterbalance of turgor pressure [1] .", "The heteropolymer consists of alternating disaccharide units composed of N-acetyl-g...	[ "The peptidoglycan of Staphylococcus aureus is characterized by a high degree of crosslinking and almost completely lacks free carboxyl groups , due to amidation of the D-glutamic acid in the stem peptide .", "Amidation of peptidoglycan has been proposed to play a decisive role in polymerization of cell wall buil...	[ "The bacterial peptidoglycan is a hetero-polymer , consisting of sugars and amino acids , that forms a stress-bearing sacculus around bacterial cells and provides cell shape .", "The cell envelope and its components represent a central interface for interactions with the environment and are therefore subject to s...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "interdigitating cells", "classical immunology", "langerhans cells", "dermatology", "dendritic cells", "medicine and health sciences", "skin infections", "immune cells", "lymphocyte activation", "cell biology", "animal cells", "antigen-presenting cells", "biology and life sciences", "cellu...	Selective Susceptibility of Human Skin Antigen Presenting Cells to Productive Dengue Virus Infection	journal.ppat.1004548	null	[ [ "Aedes mosquitoes are the primary vectors for the transmission of dengue virus ( DENV ) .", "While probing for blood microvessels from which to feed , the mosquito releases virus-containing saliva into the dermal layer of the skin .", "Studies using mosquitoes infected with the closely-related West Ni...	[ "Dengue is a growing global concern with 390 million people infected each year .", "Dengue virus ( DENV ) is transmitted by mosquitoes , thus host cells in the skin are the first point of contact with the virus .", "Human skin contains several populations of antigen-presenting cells which could drive the immune...	[ "Dengue virus ( DENV ) is transmitted by mosquitoes with skin as point of entry for the virus .", "Here , we investigated DENV infection in primary human skin cells and their initial immune response .", "Using skin from normal human donors for infection with DENV in vitro we identified antigen-presenting cells ...	2014
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "blood cells", "medicine and health sciences", "thymectomy", "immune cells", "cell cycle and cell division", "immunology", "cell processes", "homeostatic mechanisms", "surgical and invasive medical procedures", "physiological processes", "homeostasis", "cytotoxic t cells", "endocrine system ...	Age is not just a number: Naive T cells increase their ability to persist in the circulation over time	journal.pbio.2003949	null	[ [ "Naive T cells accumulate in the periphery rapidly from birth , but their numbers decline gradually from puberty onwards in both mice and humans due to the slow involution of thymus and associated decline in the export of new cells [1 , 2] .", "Despite substantial knowledge of the qualitative nature of th...	[ "The processes regulating peripheral naive T-cell numbers and clonal diversity remain poorly understood .", "Conceptually , homeostatic mechanisms must fall into the broad categories of neutral ( simple random birth–death models ) , competition ( regulation of cell numbers through quorum-sensing , perhaps via lim...	[ "The body maintains large populations of naive T cells , a type of white blood cell that is able to respond specifically to pathogens .", "This arsenal is essential for our capacity to fight novel infections throughout our lifespan , and their numbers remain quite stable despite a gradual decline in the productio...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "model organisms", "cell biology", "genetics", "biology and life sciences", "molecular cell biology", "research and analysis methods" ]	LIN-42, the Caenorhabditis elegans PERIOD homolog, Negatively Regulates MicroRNA Transcription	journal.pgen.1004486	null	[ [ "MicroRNAs ( miRNAs ) are non-coding RNA molecules that post-transcriptionally regulate gene expression [1] .", "The maturation of miRNAs is a stepwise process that begins with the RNA polymerase II-dependent transcription of long capped and polyadenylated primary miRNAs ( pri-miRNAs ) [2] , [3] .", "...	[ "During C . elegans development , microRNAs ( miRNAs ) function as molecular switches that define temporal gene expression and cell lineage patterns in a dosage-dependent manner .", "It is critical , therefore , that the expression of miRNAs be tightly regulated so that target mRNA expression is properly controll...	[ "MicroRNAs play pervasive roles in controlling gene expression throughout animal development .", "Given that individual microRNAs are predicted to regulate hundreds of mRNAs and that most mRNA transcripts are microRNA targets , it is essential that the expression levels of microRNAs be tightly regulated .", "Wi...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "optogenetics", "nociception", "immunology", "social sciences", "neuroscience", "motor neurons", "clinical medicine", "nociceptors", "brain mapping", "nerve fibers", "bioassays and physiological analysis", "hypersensitivity", "research and analysis methods",...	BMP signaling downstream of the Highwire E3 ligase sensitizes nociceptors	journal.pgen.1007464	null	[ [ "In spite of its clear medical importance , the molecular mechanisms of pain signaling remain poorly understood .", "Pain pathways in large part depend on sensory input from specialized sensory neurons called nociceptors [1] .", "Since the activation of nociceptors leads to pain sensation and the sens...	[ "A comprehensive understanding of the molecular machinery important for nociception is essential to improving the treatment of pain .", "Here , we show that the BMP signaling pathway regulates nociception downstream of the E3 ubiquitin ligase highwire ( hiw ) .", "hiw loss of function in nociceptors caused anta...	[ "Although pain is a universally experienced sensation that has a significant impact on human lives and society , the molecular mechanisms of pain remain poorly understood .", "Elucidating these mechanisms is particularly important to gaining insight into the clinical development of currently incurable chronic pai...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Whole Genome, Whole Population Sequencing Reveals That Loss of Signaling Networks Is the Major Adaptive Strategy in a Constant Environment	journal.pgen.1003972	null	[ [ "Adaptive evolution optimizes the fitness of organisms for their environment through the accumulation of beneficial mutations by natural selection [1] .", "While we understand much about the mechanisms by which natural selection operates , less is known about the beneficial mutation rate [2] , and the gen...	[ "Molecular signaling networks are ubiquitous across life and likely evolved to allow organisms to sense and respond to environmental change in dynamic environments .", "Few examples exist regarding the dispensability of signaling networks , and it remains unclear whether they are an essential feature of a highly ...	[ "When a population of organisms is faced with a selective pressure , such as a limiting nutrient , mutations that arise randomly may confer a fitness benefit on the individual carrying that mutation .", "If that individual reproduces before it is lost from the population , the frequency of that mutation may incre...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genomics", "genetics", "biology", "computational biology", "genetics and genomics" ]	Mixed Effects Modeling of Proliferation Rates in Cell-Based Models: Consequence for Pharmacogenomics and Cancer	journal.pgen.1002525	null	[ [ "The International HapMap project [1] , [2] has made available a vast amount of genetic variation data from a large number of individuals with diverse ethnic background .", "A recent population based whole-genome sequencing initiative ( 1000 Genomes Project [3] ) sought to expand on this effort by providi...	[ "The International HapMap project has made publicly available extensive genotypic data on a number of lymphoblastoid cell lines ( LCLs ) .", "Building on this resource , many research groups have generated a large amount of phenotypic data on these cell lines to facilitate genetic studies of disease risk or drug ...	[ "Cell-based models provide a convenient system to conduct studies that would be impossible to apply to human subjects , but the phenotypes measured on these models can be marred with biological noise .", "We propose a method ( MEM ) to address this issue by statistically combining data from various sources , and ...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunodeficiency viruses", "biochemistry", "dna modification", "nucleic acids", "virology", "enzymes", "dna", "biology", "enzyme kinetics", "microbiology", "viral replication", "viral nucleic acid" ]	Different Mutagenic Potential of HIV-1 Restriction Factors APOBEC3G and APOBEC3F Is Determined by Distinct Single-Stranded DNA Scanning Mechanisms	journal.ppat.1004024	null	[ [ "APOBEC3F ( A3F ) and APOBEC3G ( A3G ) are members of a family of seven single-stranded ( ss ) DNA cytosine deaminases ( A3A , A3B , A3C , A3D , A3F , A3G , and A3H ) [1] and play a role in restriction of the retrovirus HIV-1 ( referred to as HIV ) [2] .", "Research has been highly focused on primarily A3...	[ "The APOBEC3 deoxycytidine deaminase family functions as host restriction factors that can block replication of Vif ( virus infectivity factor ) deficient HIV-1 virions to differing degrees by deaminating cytosines to uracils in single-stranded ( − ) HIV-1 DNA .", "Upon replication of the ( − ) DNA to ( + ) DNA ,...	[ "Human cells possess a family of seven DNA-modification enzymes , termed APOBEC3 , that function as part of our innate immune system .", "The enzymes modify cytosine in DNA which induces mutations .", "There are particular enzymes , APOBEC3D , APOBEC3F , APOBEC3G and APOBEC3H , that appear to be most relevant t...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "viral transmission and infection", "brain", "social sciences", "vertebrates", "mice", "neuroscience", "animals", "mammals", "learning and memory", "microbiology", "viral vectors", "animal behavior", "cognition", "memory", "zoology", "mood disorders", ...	Neuropsin Inactivation Has Protective Effects against Depressive-Like Behaviours and Memory Impairment Induced by Chronic Stress	journal.pgen.1006356	null	[ [ "Stress , especially chronic stress , can lead to disorders such as depression and consequently result in significant morbidity and reduced quality of life [1] .", "Despite considerable research , the mechanisms underlying stress-related illnesses are unclear .", "Neuropsin ( NP , also named Klk8 ) is...	[ "Mounting evidence suggests the interaction between stress and genetics contribute to the development of depressive symptoms .", "Currently , the molecular mechanisms mediating this process are poorly understood , hindering the development of new clinical interventions .", "Here , we investigate the interaction...	[ "Depression is a medical condition that results in significant morbidity , mortality and reduced quality of life .", "Understanding the molecular mechanism in which stress leads to depression is essential for the discovery of new clinical interventions .", "Currently , despite considerable research , the mechan...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Computational Protein Design Quantifies Structural Constraints on Amino Acid Covariation	journal.pcbi.1003313	null	[ [ "Evolutionary selective pressures on protein structure and function have shaped the sequences of today's naturally occurring proteins [1]–[3] .", "As a result of these pressures , sequences of natural proteins are close to optimal for their structures [4] .", "Natural protein sequences therefore provi...	[ "Amino acid covariation , where the identities of amino acids at different sequence positions are correlated , is a hallmark of naturally occurring proteins .", "This covariation can arise from multiple factors , including selective pressures for maintaining protein structure , requirements imposed by a specific ...	[ "Proteins generally fold into specific three-dimensional structures to perform their cellular functions , and the presence of misfolded proteins is often deleterious for cellular and organismal fitness .", "For these reasons , maintenance of protein structure is thought to be one of the major fitness pressures ac...	2013

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