bluuebunny/crossref_metadata_2025_split huggingface dataset:
The depletion of MARVELD1 leads to placenta accreta via integrin β4-dependent trophoblast cell invasion
Authors: Chen Yue , Zhang Hui , Han Fang , Yue Lei , Qiao Chunxiao , Zhang Yao , Dou Peng , Liu Weizhe , Li Yu 
Published: February 2017

AstractThe mammalian placenta is a remarkable organ. It serves as the interface between the mother and the fetus. Proper invasion of trophoblast cells into the maternal decidua is required for a successful pregnancy. Previous studies have found that the adhesion molecule integrin β4 plays important roles during trophoblast cell invasion. Here, we found that the overall birth rate of the MARVELD1 knockout mouse is much lower than that of the wild-type mouse (P<0.001). In E18.5 MARVELD1 knockout mice, we observed an over-invasion of trophoblast cells, and indeed, the pregnant mice had a partial placenta accreta phenotype. The HTR8/SVneo cell line was used as an in vitro model to elucidate the underlying mechanisms of MARVELD1-mediated trophoblast invasion. We detected a diminished expression of integrin β4 upon the downregulation of MARVELD1 and enhanced migration and invasive abilities of trophoblast cells both in vivo and in vitro. The integrin β4 rescue assay also supported the results. In conclusion, this study found that MARVELD1 mediated the invasion of trophoblast cells via regulating the expression of integrin β4.
Metabolic Network Analysis and Metatranscriptomics Reveals Auxotrophies and Nutrient Sources of the Cosmopolitan Freshwater Microbial Lineage aci
Authors: Hamilton Joshua J. , Garcia Sarahi L. , Brown Brittany S. , Oyserman Ben O. , Moya-Flores Francisco , Bertilsson Stefan , Malmstrom Rex R. , Forest Katrina T. , McMahon Katherine D. 
Published: February 2017

AbstractAn explosion in the number of available genome sequences obtained through metagenomics and single-cell genomics has enabled a new view of the diversity of microbial life, yet we know surprisingly little about how microbes interact with each other or their environment. In fact, the majority of microbial species remain uncultivated, while our perception of their ecological niches is based on reconstruction of their metabolic potential. In this work, we demonstrate how the “seed set framework”, which computes the set of compounds that an organism must acquire from its environment (1), enables computational analysis of metabolic reconstructions, while providing new insights into a microbe’s metabolic capabilities, such as nutrient use and auxotrophies. We apply this framework to members of the ubiquitous freshwater Actinobacterial lineage acI, confirming and extending previous experimental and genomic observations implying that acI bacteria are heterotrophs reliant on peptides and saccharides. We also present the first metatranscriptomic study of the acI lineage, revealing high expression of transport proteins and the light-harvesting protein actinorhodopsin. Putative transport proteins complement predictions of nutrients and essential metabolites while providing additional support to the hypothesis that members of the acI are photoheterotrophs.ImportanceThe metabolic activity of uncultivated microorganisms contributes to numerous ecosystem processes, ranging from nutrient cycling in the environment to influencing human health and disease. Advances in sequencing technology have enabled the assembly of genomes for these microorganisms, but our ability to generate reference genomes far outstrips our ability to analyze them. Common approaches to analyzing microbial metabolism require reconstructing the entirety of an organism’s metabolic pathways, or performing targeted searches for genes involved in a specific process. This paper presents a third approach, in which draft metabolic reconstructions are used to identify compounds through which an organism may interact with its environment. These compounds can then guide more intensive metabolic reconstruction efforts, and also provide new hypotheses about the specific contributions microbes make to ecosystem-scale metabolic processes.
CpG methylation accounts for genome-wide C>T mutation variation and cancer driver formation across cancer types
Authors: Poulos Rebecca C. , Olivier Jake , Wong Jason W. H. 
Published: February 2017

AbstractCytosine methylation (5mC) is vital for cellular function, and yet 5mC sites are also commonly mutated in the genome. In this study, we analyse the genomes of over 900 cancer samples, together with tissue type-specific methylation and replication timing data. We describe a strong mutation-methylation association in colorectal cancers with microsatellite instability (MSI) or withPolymerase epsilon (POLE)exonuclease domain mutation. We describe a potential role for mismatch repair in the correction of mismatches resulting from deamination of 5mC, and propose a mutator phenotype to exist inPOLE-mutant cancers specifically at 5mC sites. We also associatePOLE-mutant hotspot coding mutations inAPCandTP53with CpG methylation. Analysing mutations across additional cancer types, we identify nucleotide excision repair- and AID/APOBEC-induced processes to underlie differential mutation-methylation associations in certain cancer subtypes. This study reveals differential associations vital for accurately mapping regional variation in mutation density and pinpointing driver mutations in cancer.
Re-evaluating inheritance in genome evolution: widespread transfer of LINEs between species
Authors: Ivancevic Atma M. , Daniel Kortschak R. , Bertozzi Terry , Adelson David L. 
Published: February 2017

Transposable elements (TEs) are mobile DNA sequences, colloquially known as ‘jumping genes’ because of their ability to replicate to new genomic locations. Given a vector of transfer (e.g. tick or virus), TEs can jump further: between organisms or species in a process known as horizontal transfer (HT). Here we propose that LINE-1 (L1) and Bovine-B (BovB), the two most abundant TE families in mammals, were initially introduced as foreign DNA via ancient HT events. Using a 503-genome dataset, we identify multiple ancient L1 HT events in eukaryotes and provide evidence that L1s infiltrated the mammalian lineage after the monotreme-therian split. We also extend the BovB paradigm by increasing the number of estimated transfer events compared to previous studies, finding new potential blood-sucking parasite vectors and occurrences in new lineages (e.g. bats, frog). Given that these TEs make up nearly half of the genome sequence in today’s mammals, our results provide the first evidence that HT can have drastic and long-term effects on the new host genomes. This revolutionizes our perception of genome evolution to consider external factors, such as the natural introduction of foreign DNA. With the advancement of genome sequencing technologies and bioinformatics tools, we anticipate our study to be the first of many large-scale phylogenomic analyses exploring the role of HT in genome evolution.Significance statementLINE-1 (L1) elements occupy about half of most mammalian genomes (1), and they are believed to be strictly vertically inherited (2). Mutagenic L1 insertions are thought to account for approximately 1 of every 1000 random, disease-causing insertions in humans (4-7). Our research indicates that the very presence of L1s in humans, and other therian mammals, is due to an ancient transfer event – which has drastic implications for our perception of genome evolution. Usinga machinaanalyses over 503 genomes, we trace the origins of L1 and BovB retrotransposons across the tree of life, and provide evidence of their long-term impact on eukaryotic evolution.
A nanobody-based toolset to investigate the role of protein localization and dispersal inDrosophila
Authors: Harmansa Stefan , Alborelli Ilaria , Caussinus Emmanuel , Affolter Markus 
Published: February 2017

AbstractInvestigating the role of protein localization is crucial to understand protein function in cells or tissues. However, in many cases the role of different subcellular fractions of given proteins along the apical-basal axis of polarized cells has not been investigatedin vivo, partially due to lack of suitable tools. Here, we present the GrabFP system, a nanobody-based toolbox to modify the localization and the dispersal of GFP-tagged proteins along the apical-basal axis of polarized cells. We show that the GrabFP system is an effective and easy-to-implement tool to mislocalize cytosolic and transmembrane GFP-tagged proteins and thereby functionally investigate protein localization along the apical-basal axis. We use the GrabFP system as a tool to study the extracellular dispersal of the Decapentaplegic (Dpp) protein and show that the Dpp gradient forming in the lateral plane of theDrosophilawing disc epithelium is essential for patterning of the wing imaginal disc.
FAM83G/PAWS1 controls cytoskeletal dynamics and cell migration through association with the SH3 adaptor CD2AP
Authors: Cummins Timothy D. , Wu Kevin Z. L. , Bozatzi Polyxeni , Dingwell Kevin S. , Macartney Thomas , Wood Nicola T , Varghese Joby , Gourlay Robert , Campbell David G , Prescott Alan , Griffis Eric , Smith James C , Sapkota Gopal P 
Published: February 2017

AbstractOur previous studies of PAWS1 (ProteinAssociatedWithSMAD1) have suggested that this molecule has roles beyond BMP signalling. To investigate these roles, we have used CRISPR/Cas9 to generate PAWS1 knockout cells. Here, we show that PAWS1 plays a role in the regulation of the cytoskeletal machinery, including actin and focal adhesion dynamics, and cell migration. Confocal microscopy and live cell imaging of actin in U2OS cells indicate that PAWS1 is also involved in cytoskeletal dynamics and organization. Loss of PAWS1 causes severe defects in F-actin organization and distribution as well as in lamellipodial organization, resulting in impaired cell migration. PAWS1 interacts in a dynamic fashion with the actin/cytoskeletal regulator CD2AP at lamellae, suggesting that its association with CD2AP controls actin organization and cellular migration.Summary statementPAWS1/FAM83G controls cell migration by influencing the organisation of F-actin and focal adhesions and the distribution of the actin stress fibre network through its association with CD2AP.
Taenia soliumTAF6 and TAF9 binds to a putative Downstream Promoter Element present inTsTBP1gene core promoter
Authors: Rodríguez-Lima Oscar , García-Gutierrez Ponciano , Jimenez Lucía , Zarain-Herzberg Angel , Lazarini Roberto , Landa Abraham 
Published: February 2017

AbstractWe have cloned and characterized the gene encoding toTaenia soliumTATA binding protein 1 (TsTBP1). It spans 1481 bp and its coding region is interrupted by four introns that possess the consensus donor/acceptor sequences. It produces a protein of 238 amino acids residues, which presented all the classical motives of the TBP1. On the core promoter region we identified putative binding sites for NF1, AP-1, YY1, TAF1/TAF2 and TAF6/TAF9, and the TSS that corresponds to an A+1. Southern and Northern blot analysis showed that TsTBP1 is encoded by a single gene, which produce a messenger of about 1.1 kbp with a higher differential expression in adult than the larval stage. Moreover, two putative TATA boxes were identified at -97 and -69 bp (relative to the TSS), likewise a Downstream Promoter Element (DPE) was located at +27 to +31 bp. EMSA experiments did not show any component of cysticerci nuclear extracts bound to the putative TATA-box elements; in contrast TAF6 and TAF9 bind to the DPE, showing thatTsTBP1is a TATA-less gen. On the other hand, TAF6 and TAF9 were localized on the nucleus from cells ofT. crassicepscysticerci bladder walls. By using the amino acid sequences ofT. soliumTAF6 (TsTAF6) and TAF9 (TsTAF9), we constructed a molecular model showing interaction between DPE-TsTAF6 and TsTAF6-TsTAF9. Finally, anin silicoanalysis of the core promoters ofTaeniidaefamily genes showed that TATA-box and DPE are homologous to the mammalian elements, but not so the Inr. The low identity between TAF9 from cestodes and mammals open the possibility to use it as target to interrupt or modulate the transcription of TATA-box less genes in cestodes as a novel therapeutic strategy.Author summaryNeurocysticercosis still being a health problem in developing countries. Mexico reports a prevalence of 2.5% in the total patients from National Institute of Neurology and Neurosurgery. Several efforts have been made in different fields to studyTaenia solium, and although the Genome Project has been published and released the genomic sequence of this parasite; the transcriptional mechanisms this organism remains unexplored. We isolated and characterizedTaenia soliumTATA-Binding Protein 1 (TsTBP1) gene and TBP-associated factor 6 and 9 cDNAs (TsTAF6andTsTAF9, respectively). Our principal findings are: 1.- Identification of cis and trans elements in the core promoter ofTsTBP1gene. 2.- TheTsTBP1gene is a TATA-less promoter. 3.- Cloning of cDNAs toTsTAF6andTsTAF9, 4.- Identification of a DPE in the core promoter ofTsTBP1gene, which interacts with TAF6 and TAF9, 5.- Construction of a molecular model that shows the interaction between DPE, TAF6, and TAF9; and 6.- A proposal of consensus sequences for TATA-box, Inr and DPE presented onTaeniidaefamily core promoters.
Genome-wide identification of lineage and locus specific variation associated with pneumococcal carriage duration
Authors: Lees John A. , Croucher Nicholas J. , David Goldblatt , Francois Nosten , Julian Parkhill , Claudia Turner , Paul Turner , Stephen D. Bentley 
Published: February 2017

AbstractStreptococcus pneumoniaeis a leading cause of invasive disease in infants, especially in low-income settings. Asymptomatic carriage in the nasopharynx is a prerequisite for disease, and the duration of carriage is an important consideration in modelling transmission dynamics and vaccine response. Existing studies of carriage duration variability are based at the serotype level only, and do not probe variation within lineages or fully quantify interactions with other environmental factors.Here we developed a model to calculate the duration of carriage episodes from longitudinal swab data. By combining these results with whole genome sequence data we estimate that pneumococcal genomic variation accounted for 63% of the phenotype variation, whereas host traits accounted for less than 5%. We further partitioned this heritability into both lineage and locus effects, and quantified the amount attributable to the largest sources of variation in carriage duration: serotype (17%), drug-resistance (9%) and other significant locus effects (7%). For the locus effects, a genome-wide association study identified 16 loci which may have an effect on carriage duration independent of serotype. Hits at a genome-wide level of significance were to prophage sequences, suggesting infection by such viruses substantially affects carriage duration.These results show that both serotype and non-serotype specific effects alter carriage duration in infants and young children and are more important than other environmental factors such as host genetics. This has implications for models of pneumococcal competition and antibiotic resistance, and leads the way for the analysis of heritability of complex bacterial traits.Significance statementOther than serotype, the genetic determinants of pneumococcal carriage duration are unknown. In this study we used longitudinal sampling to measure the duration of carriage in infants, and searched for any associated variation in the pan-genome. While we found that the pathogen genome explains most of the variability in duration, serotype did not fully account for this. Recent theoretical work has proposed the existence of alleles which alter carriage duration to explain the puzzle of continued coexistence of antibiotic-resistant and sensitive strains. Here we have shown that these alleles do exist in a natural population, and also identified candidates for the loci which fulfil this role. Together these findings have implications for future modelling of pneumococcal epidemiology and resistance.
rxncon 2.0: a language for executable molecular systems biology
Authors: Romers Jesper C. , Krantz Marcus 
Published: February 2017

AbstractLarge-scale knowledge bases and models become increasingly important to systematise and interpret empirical knowledge on cellular systems. In signalling networks, as opposed to metabolic networks, distinct modifications of and bonds between components combine into very large numbers of possible configurations, or microstates. These are essentially never measured in vivo, making explicit modelling strategies both impractical and problematic. Here, we presentrxncon2.0, the second generation rxncon language, as a tool to define signal transduction networks at the level of empirical data. By expressing both reactions and contingencies (contextual constraints on reactions) in terms of elemental states, both the combinatorial complexity and the discrepancy to empirical data can be minimised. It works as a higher-level language natural to biologists, which can be compiled into a range of graphical formats or executable models. Taken together, the rxncon language combines mechanistic precision with scalability in a composable and compilable language, that is designed for building executable knowledge bases on the molecular biology of signalling systems.
Genomic analysis ofPelements in natural populations ofDrosophila melanogaster
Authors: Bergman Casey M. , Nelson Michael G. , Bondarenko Vladyslav , Kozeretska Iryna A. 
Published: February 2017

AbstractTheDrosophila melanogaster Ptransposable element provides one of the best cases of horizontal transfer of a mobile DNA sequence in eukaryotes. Invasion of natural populations by thePelement has led to a syndrome of phenotypes known as P-M hybrid dysgenesis that emerges when strains differing in theirPelement composition mate and produce offspring. Despite extensive research on many aspects ofPelement biology, many questions remain about the genomic basis of variation in P-M dysgenesis phenotypes in natural populations. Here we compare gonadal dysgenesis phenotypes and genomicPelement predictions for isofemale strains obtained from three worldwide populations ofD. melanogasterto illuminate the molecular basis of natural variation in cytotype status. We show that the number of predictedPelement insertions in genome sequences from isofemale strains is highly correlated across different bioinformatics methods, but the absolute number of insertions per strain is sensitive to method and filtering strategies. Regardless of method used, we find that the number of euchromaticPelement insertions predicted per strain varies significantly across populations, with strains from a North American population having fewerPelement insertions than strains from populations sampled in Europe or Africa. Despite these geographic differences, numbers of euchromaticPelement insertions are not strongly correlated with the degree of gonadal dysgenesis exhibited by an isofemale strain. Thus, variation inPelement insertion numbers across different populations does not necessarily lead to corresponding geographic differences in gonadal dysgenesis phenotypes. Additionally, we show that pool-seq samples can uncover population differences in the number ofPelement insertions observed from isofemale lines, but that efforts to rigorously detect differences in the number ofPelements across populations using pool-seq data must properly control for read depth per strain. Our work supports the view that euchromaticPelement copy number is not sufficient to explain variation in gonadal dysgenesis across strains ofD. melanogaster, and informs future efforts to decode the genomic basis of geographic and temporal differences inPelement induced phenotypes.
Metabolic diversity of the emerging pathogenic lineages of Klebsiella pneumoniae
Authors: Blin Camille , Passet Virginie , Touchon Marie , Rocha Eduardo P. C. , Brisse Sylvain 
Published: February 2017

SummaryMultidrug resistant and hypervirulent clones of Klebsiella pneumoniae are emerging pathogens. To understand the association between genotypic and phenotypic diversity in this process, we combined genomic, phylogenomic and phenotypic analysis of a diverse set of K. pneumoniae and closely related species. These species were able to use an unusually large panel of metabolic substrates for growth, many of which were shared between all strains. We analysed the substrates used by only a fraction of the strains, identified some of their genetic basis, and found that many could not be explained by the phylogeny of the strains. Puzzlingly, few traits were associated with the ecological origin of the strains. One noticeable exception was the ability to use D‐arabinose, which was much more frequent in hypervirulent strains. The broad carbon and nitrogen core metabolism of K. pneumoniae might contribute to its ability to thrive in diverse environments. Accordingly, even the hypervirulent and multidrug resistant clones have the metabolic signature of ubiquitous bacteria. The apparent few metabolic differences between hypervirulent, multi‐resistant and environmental strains may favour the emergence of dual‐risk strains that combine resistance and hypervirulence.
Encapsulation of Beta‐carotene in Lipid Microparticles Stabilized with Hydrolyzed Soy Protein Isolate: Production Parameters, Alpha‐tocopherol Coencapsulation and Stability Under Stress Conditions
Authors: Brito‐Oliveira Thais C. , Molina Camila V. , Netto Flávia M. , Pinho Samantha C. 
Published: February 2017

AbstractThe objectives of this research were to study the encapsulation of beta‐carotene (BC) in solid lipid microparticles (SLM) of palm stearin (PS) and stabilized with hydrolyzed soy protein isolate (HSPI), and also to investigate the effect of alpha‐tocopherol (TOC) addition to the systems. Through the characterizations of SLM produced with different formulations, it was verified that systems with 5% (w/v) PS, 1.0% (w/v) HSPI, and 0.3% (w/v) xanthan gum (XG) presented the highest stability, with average diameters of approximately 1.2 μm. This formulation was applied for the production of BC‐loaded SLM, with different concentrations of TOC. In SLM containing TOC, nearly 75% of encapsulated BC was preserved after 45 d of storage. The kinetic profiles for degradation of encapsulated BC were fitted to a pseudo‐1st‐order model, and the results showed that the main difference among the systems with different BC:TOC ratios was the residual concentration of BC. The stability of the BC‐loaded SLMs was also studied after stress conditions, and the results showed that the SLMs were able to support thermal treatments over 60 °C but presented low stability after different ionic strength stresses.