bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the influence of surface proteins on probiotic activity of Lactobacillus pentosus HC-2 in Litopenaeus vannamei midgut via Label-free quantitative proteomic analysis
Authors: Du Yang , Fang Han , Liu Mei , Jiang Keyong , Wang Mengqiang , Wang Baojie , Wang Lei 
Published: February 2019

AbstractOur previously work showed that Lactobacillus pentosus HC-2 as probiotic could improve the growth performance, immune response, gut bacteria diversity and disease resistance of Litopenaeus vannamei. However, the probiotic mechanism of was not fully characterized. In the present study, histology and proteomic analysis was performed to explore the influence of HC-2 surface protein on its probiotic effects to L. vannamei after feeding the intact surface proteins or the probiotic treated with lithium chloride (LiCl) to remove non-covalently bound surface proteins or no probiotic for four weeks. Histological observation found that feeding with normal HC-2 obviously improved the intestinal histology and enhanced the protective effect against pathogens damages, but fed with LiCl-treated HC-2 didn’t improve the intestinal environment. A total over 2,764 Peptides and 1,118 uniproteins were identified from L. vannamei midgut, 211 proteins were significant differentially expressed normal HC-2 group compared with control, 510 proteins were significant differentially expressed in LiCl-tread HC-2 group compared with control, and 458 proteins were significant differentially expressed in LiCl-tread HC-2 group compared with normal HC-2 group. GO/KEGG enrichment analysis of the significantly different proteins demonstrated that fed with normal HC-2 mainly induced immune response, metabolic, cell adhesion and cell-cell signaling related proteins up-regulation, which were contributed to bacteria adhesion and colonization in midgut to improve shrimp immune system and growth, but these proteins were suppressed after feeding with deprived surface proteins bacteria. Taken together, these results indicating that the surface proteins were indispensable for HC-2 to execute probiotic effects in midgut of shrimp.
Environmental specificity and evolution in Drosophila-bacteria symbiosis
Authors: Guilhot Robin , Rombaut Antoine , Xuéreb Anne , Howell Kate , Fellous Simon 
Published: February 2019

AbstractEnvironmentally acquired microbial symbionts could contribute to host adaptation to local adaptation like vertically transmitted symbionts do. This scenario necessitates symbionts to have different effects in different environments. In Drosophila melanogaster, communities of extracellular bacterial symbionts vary largely among environments, which could be due to variable effects on phenotype. We investigated this idea with four bacterial strains isolated from the feces of a D. melanogaster lab strain, and tested their effects in two environments: the environment of origin (i.e. the laboratory medium) and a new one (i.e. fresh fruit with live yeast). All bacterial effects on larval and adult traits differed among environments, ranging from very beneficial to marginally deleterious. The joint analysis of larval development speed and adult size further suggests bacteria would affect developmental plasticity more than resource acquisition in males. The context-dependent effects of bacteria we observed, and its underlying mechanisms, sheds light on how environmentally acquired symbionts may contribute to host evolution.
Full-length mRNA sequencing reveals principles of poly(A) tail length control
Authors: Legnini Ivano , Alles Jonathan , Karaiskos Nikos , Ayoub Salah , Rajewsky Nikolaus 
Published: February 2019

SummaryAlthough mRNAs are key molecules for understanding life, there exists no method to determine the full-length sequence of endogenous mRNAs including their poly(A) tails. Moreover, although poly(A) tails can be modified in functionally important ways, there also exists no method to accurately sequence them. Here, we present FLAM-seq, a rapid and simple method for high-quality sequencing of entire mRNAs. We report a cDNA library preparation method coupled to single-molecule sequencing to perform FLAM-seq. Using human cell lines, brain organoids, andC. eleganswe show that FLAM-seq delivers high-quality full-length mRNA sequences for thousands of different genes per sample. We find that (a) 3’ UTR length is correlated with poly(A) tail length, (b) alternative polyadenylation sites and alternative promoters for the same gene are linked to different tail lengths, (c) tails contain a significant number of cytosines. Thus, we provide a widely useful method and fundamental insights into poly(A) tail regulation.
Respiratory syncytial virus activates Rab5a to suppress IRF1-dependent IFN-λ production, subverting the antiviral defense of airway epithelial cells
Authors: Gao Leiqiong , Tang Wei , Xie Jun , Chen Sisi , Ren Luo , Zang Na , Xie Xiaohong , Deng Yu , Liu Enmei 
Published: February 2019

AbstractHuman respiratory syncytial virus (RSV) is a negative-strand RNA virus that causes severe acute pediatric respiratory tract infections worldwide. The limited effective antiviral options and lack of an effective vaccine against RSV highlight the need for a novel anti-viral therapy. One alternative is to identify and target the host factors required for viral infection. All viruses, including RSV, utilize cellular trafficking machinery to fulfill their life cycle in the infected host cells. Rab proteins mediate specific steps in intracellular membrane trafficking through the recruitment and tethering of fusion factors, and docking with actin- or microtubule-based motor proteins. Using RNA interference to knock down Rab proteins, we document that the micropinocytosis-associated Rab5a is required for RSV infection. RSV infection itself induces activation of Rab5a, and inhibition of this activation reduces RSV infection, but the mechanism for this effect remains unknown. Interferon (IFN) signaling plays an important role in innate immunity, and recent studies have identified IFN-λ (lambda), a type III IFN, as the most important IFN for antiviral immune in response to RSV infection of mucosal epithelium. However, how the RSV-induced Rab5a suppresses airway epithelial antiviral immunity has not been unraveled. Here, we show that activated Rab5a inhibits IRF1-induced IFN-λ production and IFN-λ-mediated signal transduction via JAK-STAT1, thereby increasing viral replication. Rab5a knockdown by siRNA resulted in stimulation of IRF1, IFN-λ and JAK-STAT1 expression, and suppressed viral growth. Our results highlight new role for Rab5a in RSV infection, such that its depletion inhibits RSV infection by stimulating the endogenous respiratory epithelial antiviral immunity, which suggests that Rab5a is a potential target for novel therapeutics against RSV infection.Author summaryRSV is the leading cause of lower respiratory tract infection in under 5 years old children. Worldwide. We identified Rab5a as a host factor involved in RSV infection via RNA interference to knock down familiar Rab proteins in human lung epithelial A549 cells infected with RSV. Rab5a belongs to Rab GTPases subfamily, which contributes to intracellular trafficking to promote virus infection. Knockdown or inactive (GDP-bound) Rab5a results in low infection and replication through stimulating IRF1, IFN-λ and JAK-STAT1 expression, and suppressed viral growth. Besides, we propose that the regulation of Rab5a expression during RSV infection might be a viral strategy to promote its infectivity.
A single dose of antibody-drug conjugate cures a stage 1 model of African trypanosomiasis
Authors: MacGregor Paula , Gonzalez-Munoz Andrea L. , Jobe Fatoumatta , Taylor Martin C. , Rust Steven , Sandercock Alan M. , Macleod Olivia J.S. , Van Bocxlaer Katrien , Francisco Amanda F. , D’Hooge Francois , Tiberghien Arnaud , Barry Conor S. , Howard Philip , Higgins Matthew K. , Vaughan Tristan J. , Minter Ralph , Carrington Mark 
Published: February 2019

AbstractInfections of humans and livestock with African trypanosomes are treated with drugs introduced decades ago that are not always fully effective and often have severe side effects. Here, the trypanosome haptoglobin-haemoglobin receptor (HpHbR) has been exploited as a route of uptake for an antibody-drug conjugate (ADC) that is completely effective againstTrypanosoma bruceiin the standard mouse model of infection. Recombinant human anti-HpHbR monoclonal antibodies were isolated and shown to be internalised in a receptor-dependent manner. Antibodies were conjugated to a pyrrolobenzodiazepine (PBD) toxin and killedT. brucei in vitroat picomolar concentrations. A single therapeutic dose (0.25 mg/kg) of a HpHbR antibody-PBD conjugate completely cured aT. bruceimouse infection within 2 days with no re-emergence of infection over a subsequent time course of 77 days. These experiments provide a demonstration of how ADCs can be exploited to treat protozoal diseases that desperately require new therapeutics.Author SummaryHere we show that antibody-drug conjugates (ADCs) can be re-purposed from cancer immunotherapeutics to anti-protozoals by changing the specificity of the immunoglobulin to target a trypanosome cell surface receptor. Trypanosomes were used as a model system due to the availability of receptor null cell lines that allowed the unambiguous demonstration that ADCs targeted to a parasite surface receptor could be specifically internalised via receptor-mediated endocytosis. A single low dose of the resulting ADC was able to cure a stage 1 mouse model of trypanosome infection. We have used toxins and conjugation chemistry that are identical to anti cancer ADCs demonstrating the ability to piggy-back onto the huge research efforts and resources that are being invested in the development of such ADCs.The potential for development of ADCs against a wide range of human pathogens is vast, where only epitope binding sites need vary in order to provide selectivity. This provides a far-reaching opportunity for the rapid development of novel anti-protozoals for the targeted killing of a wide range of pathogens that cause disease worldwide, especially in developing countries.
3D Microstructure of Tendon Collagen Fibrils using Serial Block-Face SEM and a Mechanical Model for Load Transfer
Authors: Safa Babak N. , Peloquin John M. , Natriello Jessica R. , Caplan Jeffrey L. , Elliott Dawn M. 
Published: February 2019

AbstractTendon’s hierarchical structure allows for load transfer between its fibrillar elements at multiple length scales. Tendon microstructure is particularly important, because it includes the cells and their surrounding collagen fibrils, where mechanical interactions can have potentially important physiological and pathological contributions. However, the three-dimensional microstructure and the mechanisms of load transfer in that length scale are not known. It has been postulated that interfibrillar matrix shear or direct load transfer via the fusion/branching of small fibrils are responsible for load transfer, but the significance of these mechanisms is still unclear. Alternatively, the helical fibrils that occur at the microstructural scale in tendon may also mediate load transfer, however, these structures are not well studied due to the lack of a three-dimensional visualization of tendon microstructure. In this study, we used serial block-face scanning electron microscopy (SBF-SEM) to investigate the threedimensional microstructure of fibrils in rat tail tendon. We found that tendon fibrils have a complex architecture with many helically wrapped fibrils. We studied the mechanical implications of these helical structures using finite element modeling and found that frictional contact between helical fibrils can induce load transfer even in the absence of matrix bonding or fibril fusion/branching. This study is significant in that it provides a three-dimensional view of the tendon microstructure and suggests friction between helically wrapped fibrils as a mechanism for load transfer, which is an important aspect of tendon biomechanics.
Ephrin-A5 potentiates netrin-1 axon guidance by enhancing Neogenin availability
Authors: Croteau L.-P. , Kao T.-J. , Kania A. 
Published: February 2019

AbstractAxonal growth cones are guided by molecular cues in the extracellular environment. The mechanisms of combinatorial integration of guidance signals at the growth cone cell membrane are still being unravelled. Limb-innervating axons of vertebrate spinal lateral motor column (LMC) neurons are attracted to netrin-1 via its receptor, Neogenin, and are repelled from ephrin-A5 through its receptor EphA4. The presence of both cues elicits synergistic guidance of LMC axons, but the mechanism of this effect remains unknown. Using fluorescence immunohistochemistry, we show that ephrin-A5 increases LMC growth cone Neogenin protein levels and netrin-1 binding. This effect is enhanced by overexpressing EphA4 and is inhibited by blocking ephrin-A5-EphA4 binding. These effects have a functional consequence on LMC growth cone responses since bath addition of ephrin-A5 increases the responsiveness of LMC axons to netrin-1. Surprisingly, the overexpression of EphA4 lacking its cytoplasmic tail, also enhances Neogenin levels at the growth cone and potentiates LMC axon preference for growth on netrin-1. Since netrins and ephrins participate in a wide variety of biological processes, the enhancement of netrin-1 signalling by ephrins may have broad implications.
Transposable elements contribute to dynamic genome content in maize
Authors: Anderson Sarah N , Stitzer Michelle C , Brohammer Alex B. , Zhou Peng , Noshay Jaclyn M , Hirsch Cory D. , Ross-Ibarra Jeffrey , Hirsch Candice N. , Springer Nathan M 
Published: February 2019

AbstractTransposable elements (TEs) are ubiquitous components of eukaryotic genomes and can create variation in genomic organization. The majority of maize genomes are composed of TEs. We developed an approach to define shared and variable TE insertions across genome assemblies and applied this method to four maize genomes (B73, W22, Mo17, and PH207). Among these genomes we identified 1.6 Gb of variable TE sequence representing a combination of recent TE movement and deletion of previously existing TEs. Although recent TE movement only accounted for a portion of the TE variability, we identified 4,737 TEs unique to one genome with defined insertion sites in all other genomes. Variable TEs are found for all superfamilies and are distributed across the genome, including in regions of recent shared ancestry among individuals. There are 2,380 genes annotated in the B73 genome located within variable TEs, providing evidence for the role of TEs in contributing to the substantial differences in gene content among these genotypes. The large scope of TE variation present in this limited sample of temperate maize genomes highlights the major contribution of TEs in driving variation in genome organization and gene content.Significance StatementThe majority of the maize genome is comprised of transposable elements (TEs) that have the potential to create genomic variation within species. We developed a method to identify shared and non-shared TEs using whole genome assemblies of four maize inbred lines. Variable TEs are found throughout the maize genome and in comparisons of any two genomes we find ~20% of the genome is due to non-shared TEs. Several thousand maize genes are found within TEs that are variable across lines, highlighting the contribution of TEs to gene content variation. This study creates a comprehensive resource for genomic studies of TE variability among four maize genomes, which will enable studies on the consequences of variable TEs on genome function.
A rare variant on a common risk haplotype of HFE causes increased risk of hereditary hemochromatosis
Authors: Glazer Andrew M. , Bastarache Lisa , Hall Lynn , Short Laura , Shields Tiffany , Kroncke Brett M. , Denny Joshua C. , Roden Dan M. 
Published: February 2019

AbstractHereditary hemochromatosis (HH) is an autosomal recessive disorder of excess iron absorption. The most common form, HH1, is caused by loss of function variants in HFE. HFE encodes a cell surface protein that binds to the Transferrin Receptor (TfR1), reducing TfR1’s affinity for the transferrin/iron complex and thereby limiting cellular iron uptake. Two common missense alleles for HH1 have been identified, HFE C282Y and HFE H63D; H63D is considered to be a less penetrant allele. When we deployed Phenotype Risk Scores (PheRS), a method that aggregates multiple symptoms together in Electronic Health Records (EHRs), we identified HFE E168Q as a novel variant associated with HH. E168Q is on the same haplotype as H63D, and in a crystal structure HFE E168 lies at the interface of the HFE-TfR1 interaction and makes multiple salt bridge connections with TfR1. In in vitro cell surface abundance experiments, the HFE E168Q+H63D double mutation surprisingly increased cell surface abundance of HFE by 10-fold compared to wildtype. In coimmunoprecipitation experiments, however, HFE C282Y, E168Q, and E168Q+H63D completely abolished the interaction between HFE and TfR1, while H63D alone only partially reduced binding. These findings provide mechanistic insight to validate the PheRS result that HFE E168Q is an HH1-associated allele and lead to the reclassification of E168Q from a variant of uncertain significance to a pathogenic variant, according to ACMG guidelines. HFE E168Q results in loss of HFE function by disrupting the HFE-TfR1 interaction. In addition, some disease manifestations attributed to H63D may reflect the functional effects of E168Q.
Exercise twice-a-day potentiates skeletal muscle signalling responses associated with mitochondrial biogenesis in humans, which are independent of lowered muscle glycogen content
Authors: Andrade-Souza Victor A. , Ghiarone Thaysa , Sansonio Andre , Silva Kleiton Augusto Santos , Tomazini Fabiano , Arcoverde Lucyana , Fyfe Jackson , Perri Enrico , Saner Nicholas , Kuang Jujiao , Bertuzzi Romulo , Leandro Carol Gois , Bishop David J. , Lima-Silva Adriano E. 
Published: February 2019

AbstractEndurance exercise begun with reduced muscle glycogen stores seems to potentiate skeletal muscle protein abundance and gene expression. However, it is unknown whether this greater signalling responses is due to low muscle glycogenper seor to performing two exercise sessions in close proximity - as a first exercise session is necessary to reduce the muscle glycogen stores. In the present study, we manipulated the recovery duration between a first muscle glycogen-depleting exercise and a second exercise session, such that the second exercise session started with reduced muscle glycogen in both approaches but was performed either two or 15 h after the first exercise session (so-called “twice-a-day” and “once-daily” approaches, respectively). We found that exercise twice-a-day increased the nuclear abundance of transcription factor EB (TFEB) and nuclear factor of activated T cells (NFAT) and potentiated the transcription of peroxisome proliferator-activated receptor-coactivator 1 alpha (PGC-1α), peroxisome proliferator-activated receptor alpha (PPARα) and peroxisome proliferator-activated receptor beta/delta (PPARβ/δ) genes, in comparison with the once-daily exercise. These results suggest that the elevated molecular signalling reported with previous “train-low” approaches can be attributed to performing two exercise sessions in close proximity rather than the reduced muscle glycogen contentper se.The twice-a-day approach might be an effective strategy to induce adaptations related to mitochondrial biogenesis and fat oxidation.
Dynamic architecture of the Escherichia coli Structural Maintenance of Chromosomes (SMC) complex, MukBEF
Authors: Rajasekar Karthik V. , Tang Minzhe , Baker Rachel , Zawadzka Katarzyna , Koczy Oliwia , Wagner Florence , Bolla Jani Reddy , Robinson Carol V. , Arciszewska Lidia K. , Sherratt David J. 
Published: February 2019

AbstractStructural Maintenance of Chromosomes (SMC) complexes use a proteinaceous ring-shaped architecture to organise chromosomes, thereby facilitating chromosome segregation. They utilise cycles of ATP binding and hydrolysis to transport themselves rapidly with respect to DNA, a process requiring protein conformational changes and multiple DNA contacts. We have analysed changes in the architecture of the Escherichia coli SMC complex, MukBEF, as a function of nucleotide binding to MukB and subsequent ATP hydrolysis. This builds upon previous work showing that MukF kleisin directs formation of a MukBEF tripartite ring as a consequence of functional interactions between the C- and N-terminal domains of MukF with the MukB head and neck, respectively (Zawadzka et al., 2018). Using both model truncated substrates and complexes containing full length MukB, we now demonstrate formation of MukBEF ‘dimers of dimers’, dependent on MukF dimerization, MukB head-engagement and MukE, which plays an essential role in organizing MukBEF complexes.
Changes in Ovary Transcriptome and Alternative splicing at estrus from Xiang pigs with Large and Small Litter Size
Authors: Zhang Fuping , Tang Liangting , Ran Xueqin , Mao Ning , Ruan Yiqi , Yi Fanli , Liu Chang , Niu Xi , Huang Shihui , Li Sheng , Wang Jiafu 
Published: February 2019

AbstractBackground/AimsLitter size is one of the most important reproductive traits in pig breeding, which is affected by multiple genes and the environment. Ovaries are the most important reproductive organs and have a profound impact on the reproduction efficiency. Therefore, genetic differences in the ovaries may contribute to the observed differences in litter size. Although QTLs and candidate genes have been reported to affect the litter size in many pig breeds, however, the findings cannot elucidate the marked differences of the reproductive traits between breeds. The aim of present work is to elucidate the mechanisms of the differences for the reproductive traits and identify candidate genes associated with litter size in Xiang pig breed.MethodsThe changes in ovary transcriptome and alternative splicing were investigated at estrus between Xiang pigs with large and small litter size by RNA-seq technology. The RNA-seq results were confirmed by RT-qPCR method.ResultsWe detected 16,219 - 16,285 expressed genes and 12 types of alternative splicing (AS) events in Xiang pig samples. A total of 762 differentially expressed genes were identified by XL (Xiang pig group with larger litter size) vs XS (Xiang pig group with small litter size) sample comparisons. A total of 34 genes were upregulated and 728 genes were downregulated in XL ovary samples compared with the XS samples. Alternative splicing (AS) rates in XL samples were slightly lower than that observed in XS samples. Most of differentially expressed genes were differentially regulated on AS level. Eleven candidate genes were potentially identified to be related to Xiang pig fecundity and litter size, which may be closely related to the gonad development, oocyte maturation or embryo quality.ConclusionThe significant changes in the expression of the protein-coding genes and the level of alternative splicing in estrus ovarian transcriptome between XL and XS groups probably are the molecular mechanisms of phenotypic variation in litter size.