bluuebunny/crossref_metadata_2025_split huggingface dataset:
High Genetic Potential for Proteolytic Decomposition in Northern Peatland Ecosystems
Authors: Graham Emily B. , Yang Fan , Bell Sheryl , Hofmockel Kirsten S. 
Published: July 2018

AbstractNitrogen (N) is a scarce nutrient commonly limiting primary productivity. Microbial decomposition of complex carbon (C) into small organic molecules (e.g., free amino acids) has been suggested to supplement biologically-fixed N in high latitude peatlands. We evaluated the microbial (fungal, bacterial, and archaeal) genetic potential for organic N depolymerization in peatlands at Marcell Experimental Forest (MEF) in northern Minnesota. We used guided gene assembly to examine the abundance and diversity of protease genes; and further compared to those of N-fixing (nifH) genes in shotgun metagenomic data collected across depth at two distinct peatland environments (bogs and fens). Microbial proteases greatly outnumberednifHgenes with the most abundant gene families (archaeal M1 and bacterial Trypsin) each containing more sequences than all sequences attributed tonifH. Bacterial protease gene assemblies were diverse and abundant across depth profiles, indicating a role for bacteria in releasing free amino acids from peptides through depolymerization of older organic material and contrasting the paradigm of fungal dominance in depolymerization in forest soils. Although protease gene assemblies for fungi were much less abundant overall than for bacteria, fungi were prevalent in surface samples and therefore may be vital in degrading large soil polymers from fresh plant inputs during early stage of depolymerization. In total, we demonstrate that depolymerization enzymes from a diverse suite of microorganisms, including understudied bacterial and archaeal lineages, are likely to play a substantial role in C and N cycling within northern peatlands.ImportanceNitrogen (N) is a common limitation on primary productivity, and its source remains unresolved in northern peatlands that are vulnerable to environmental change. Decompositionof complex organic matter into free amino acids has been proposed as an important N source, but the genetic potential of microorganisms mediating this process has not been examined. Such information can elucidate possible responses of northern peatlands to environmental change. We show high genetic potential for microbial production of free amino acids across a range of microbial guilds. In particular, the abundance and diversity of bacterial genes encoding proteolytic activity suggests a predominant role for bacteria in regulating productivity and contrasts a paradigm of fungal dominance of organic N decomposition. Our results expand our current understanding of coupled carbon and nitrogen cycles in north peatlands and indicate that understudied bacterial and archaeal lineages may be central in this ecosystem’s response to environmental change.
Specific activation of HIV-1 from monocytic reservoir cells by bromodomain inhibitor in humanized mice in vivo
Authors: Li Guangming , Zhang Zheng , Reszka-Blanco Natalia , Li Feng , Chi Liqun , Ma Jianping , Jeffrey Jerry , Cheng Liang , Su Lishan 
Published: July 2018

ABSTRACTThe combination antiretroviral therapy (cART) effectively suppresses HIV-1 infection and enables HIV-infected individuals to live long productive lives. However, the persistence of HIV-1 reservoir cells with latent or low-replicating HIV-1 in patients under cART make HIV-1 infection an incurable disease. Recent studies have focused on the development of strategies such as epigenetic modulators to activate and purge these reservoirs. Bromodomain inhibitors (BETi) are epigenetic modulating compounds able to activate viral transcription in HIV-1 latency cell lines in a positive transcription elongation factor b (P-TEFb)-dependent manner. Little is known about the efficacy of activating HIV-1 reservoir cells under cART by BETi in vivo. In this study, we seek to test the potential of a BETi (I-BET151) in activating HIV-1 reservoir cells under effective cART in humanized mice in vivo. We discover that I-BET151 efficiently activates HIV-1 transcription in monocytic cells, but not in CD4+T cells, during suppressive cART in vivo. We further reveal that HIV-1 proviruses in monocytic cells are more sensitive to I-BET151 treatment than in T cells in vitro. Finally, we demonstrate that I-BET151-activated viral transcription in monocytic cells is dependent on both CDK2 and CDK9, whereas only CDK9 is involved in activation of HIV-1 by I-BET151 in T cells. Our findings indicate a role of myeloid cells in HIV-1 persistence, and highlights the limitation of measuring or targeting T cell reservoirs alone in terms of HIV-1 cure, as well as provides a potential strategy to reactivate monocytic reservoirs during cART.IMPORTANCEIt has been reported the low level of active P-TEFb critically contributes to the maintenance of HIV-1 latency or low-replication in HIV-1 reservoir cells under cART. Bromodomain inhibitors are used to activate HIV-1 replication in vitro but their effect on activation of the HIV-1 resevoirs with cART in vivo is not clear. We found that BETi (I-BET151) treatment reactivated HIV-1 gene expression in humanized mice during suppressive cART. Interestingly, I-BET151 preferentially reactivated HIV-1 gene expression in monocytic cells, but not in CD4 T cells. Furthermore, I-BET151 significantly increased HIV-1 transcription in monocytic cells, but not in latently infected CD4 T cells, via CDK2-dependent mechanisms. Our findings suggest that BETi can preferentially activate monocytic HIV-1 reservoir cells, and a combination of latency reversal agents targeting different cell types and pathways is needed to achieve reactivation of different HIV-1 reservoir cells during cART.
Examination of AustralianStreptococcus suisIsolates From Clinically Affected Pigs in a Global Context and the Genomic Characterisation of ST1 as a Predictor of Virulence
Authors: O’Dea Mark A , Laird Tanya , Abraham Rebecca , Jordan David , Lugsomya Kittitat , Fitt Laura , Gottschalk Marcello , Truswell Alec , Abraham Sam 
Published: July 2018

AbstractStreptococcus suisis a major zoonotic pathogen that causes severe disease in both humans and pigs. In this study, we investigatedS. suisfrom 148 cases of clinical disease in pigs from 46 pig herds over a period of seven years. These isolates underwent whole genome sequencing, genome analysis and antimicrobial susceptibility testing. Genome sequence data of Australian isolates was compared at the core genome level to clinical isolates from overseas. Results demonstrated eight predominant multi-locus sequence types and two majorcpsgene types (cps2 and 3). At the core genome level Australian isolates clustered predominantly within one large clade consisting of isolates from the UK, Canada and North America. In particular, serotype 2 MLST25 strains were very closely associated with Canadian and North American strains. A very small proportion of Australian swine isolates (5%) were phylogenetically associated with south-east Asian and UK isolates, many of which were classified as causing systemic disease, and derived from cases of human and swine disease. In addition, we show that ST1 clones carry a constellation of putative virulence genes not present in other Australian STs, and that this is mirrored in overseas ST1 clones. Based on this dataset we provide a comprehensive outline of the currentS. suisclones associated with disease in Australian pigs and their global context, and discuss the implications this has on antimicrobial therapy, potential vaccine candidates and public health.ImportanceIn this study, we examine in detail, the genomic characteristics of 148Streptococcus suisisolates from clinically diseased Australian pigs. We report the antimicrobial susceptibility profiles, virulence gene analysis and relationship to isolates from other regions of the world. We also demonstrate that ST1 clones, regardless of serotype, carry a large array of putative virulence genes while maintaining a small total gene content. This compilation of data has major ramifications for vaccine development, and refines the understanding of the distribution of various strains of this potentially-fatal zoonotic agent in the global pig industry
Fungal polysaccharopeptides reduce obesity by richness of specific microbiota and modulation of lipid metabolism
Authors: Li Xiaojun , Chen Peng , Zhang Peng , Chang Yifan , Cui Mingxu , Duan Jinyou 
Published: July 2018

AbstractThe prevalence of obesity and related disorders has vastly increased throughout the world and prevention of such circumstances thus represents a major challenge. Here, we show that protein-bound β-glucan (PBG), one representative of Coriolus versicolor polysaccharopeptides which are broadly used as immune boosters and clinically implicated in treatment of cancers and chronic hepatitis, could be a potent anti-obesity agent. PBG could reduce obesity and metabolic inflammation in mice fed with a high-fat diet (HFD). Gut microbiota analysis revealed that PBG markedly increased the abundance of Akkermansia muciniphila although it didn’t rescue HFD-induced change in the Firmicutes to Bacteroidetes ratio. It appeared that PBG altered host physiology and created an intestinal microenvironment favorable for A. muciniphila colonization. Fecal transplants from PBG-treated animals in part reduced obesity in recipient HFD-fed mice. Further, PBG was shown to promote lipid metabolism in microbiota-depleted mice. Thus, our data highlights that PBG might exert its anti-obesity effects through a mirobiota-dependent (richness of specific microbiota) and -independent (modulation of lipid metabolism) manner. The fact that Coriolus versicolor polysaccharopeptides are approved oral immune boosters in cancers and chronic hepatitis with well-established safety profiles may accelerate the development of PBG as a novel drug for obesity treatment.
A multiscale analysis of DNA phase separation: From atomistic to mesoscale level
Authors: Sun Tiedong , Mirzoev Alexander , Minhas Vishal , Korolev Nikolay , Lyubartsev Alexander P. , Nordenskiöld Lars 
Published: July 2018

ABSTRACTDNA condensation and phase separation is of utmost importance for DNA packing in vivo with important applications in medicine, biotechnology and polymer physics. The presence of hexagonally ordered DNA is observed in virus capsids, sperm heads and in dinoflagellates. Rigorous modelling of this process in all-atom MD simulations is presently difficult to achieve due to size and time scale limitations. We used a hierarchical approach for systematic multiscale coarse-grained (CG) simulations of DNA phase separation induced by the three-valent cobalt(III)-hexammine (CoHex3+). Solvent-mediated effective potentials for a CG model of DNA were extracted from all-atom MD simulations. Simulations of several hundred 100-bp-long CG DNA oligonucleotides in the presence of explicit CoHex3+ ions demonstrated aggregation to a liquid crystalline hexagonally ordered phase. Following further coarse-graining and extraction of effective potentials, we conducted modelling at mesoscale level. In agreement with electron microscopy observations, simulations of an 10.2-kbp-long DNA molecule showed phase separation to either a toroid or a fibre with distinct hexagonal DNA packing. The mechanism of toroid formation is analysed in detail. The approach used here is based only on the underlying all-atom force field and uses no adjustable parameters and may be generalized to modelling chromatin up to chromosome size.
Rewiring of transcription factor binding in differentiating human embryonic stem cells is constrained by DNA sequence repeat symmetry
Authors: Goldshtein Matan , Lukatsky David B. 
Published: July 2018

ABSTRACTWe analyze design principles of transcription factor (TF) recognition by genomic DNA in differentiating human embryonic stem cells for 36 TFs and five histone modifications in four developmental layers, using the data recently measured by Tsankov et al. This analysis reveals that DNA sequence repeat symmetry plays a central role in defining TF-DNA binding preferences across different developmental layers. In particular, we find that different TFs bind similar symmetry patterns within a given developmental layer. While the TF cluster content undergoes modifications upon transitions between different developmental layers, most TFs possess dominant preferences for similar DNA repeat symmetry types. Histone modifications also exhibit strong preferences for similar DNA repeat symmetry patterns, with the symmetry strength differentiating between different histone modifications. Overall, our findings show that despite the enormous sequence complexity of the TF-DNA binding landscape in differentiating human embryonic stem cells, this landscape can be quantitatively characterized in simple terms, using the notion of DNA sequence repeat symmetry.
RNA-Dependent Amplification of Mammalian mRNA Encoding Extracellular Matrix Components: Identification of Chimeric RNA Intermediates for α1, β1, and γ1 Chains of Laminin
Authors: Volloch Vladimir , Rits Sophia , Olsen Bjorn 
Published: July 2018

ABSTRACTThe aim of the present study was to test for the occurrence of key elements predicted by the previously postulated mammalian RNA-dependent mRNA amplification model in a tissue producing massive amounts of extracellular matrix proteins. At the core of RNA-dependent mRNA amplification, until now only described in one mammalian system, is the self-priming of an antisense strand and extension of its 3’ terminus into a sense-oriented RNA containing the protein-coding information of a conventional mRNA. The resulting product constitutes a new type of biomolecule. It is chimeric in that it contains covalently connected antisense and sense sequences in a hairpin configuration. Cleavage of this chimeric intermediate in the loop region of a hairpin structure releases mRNA which contains an antisense segment in its 5’UTR; depending on the position of self-priming, the chimeric end product may encode the entire protein or its C-terminal fragment. The occurrence of such composite chimeric molecules is unique for this type of mRNA amplification and represents a conclusive “identifier” of this process. We report here the detection, by next generation sequencing, of such chimeric junction sequences for mRNAs molecules encoding αl, β1, and γ1 chains of laminin in cells of the extracellular matrix-generating Engelbreth-Holm-Swarm (EHS) mouse tumor, best known for producing extraordinarily large amounts of “Matrigel”.
TheDrosophilachromodomain protein Kismet activates steroid hormone receptor transcription to govern axon pruning and memoryin vivo
Authors: Latcheva Nina K. , Viveiros Jennifer M. , Marenda Daniel R. 
Published: July 2018

SummaryAxon pruning is critical for the proper synapse elimination required for sculpting precise neural circuits. Though axon pruning has been described in the literature for decades, relatively little is known about the molecular and cellular mechanisms that govern axon pruningin vivo. Here, we show that the epigenetic reader Kismet (Kis) binds to cisregulatory elements of the steroid hormone receptorEcdysone Receptor(EcR) gene inDrosophilaneurons. Kis is required to activateEcRtranscription at these elements and promote H3K36 di- and tri-methylation and H4K16 acetylation. We show that exogenous EcR can rescue axon pruning and memory defects associated with loss of Kis, and that the histone deacetylase inhibitor SAHA can rescue these phenotypes. EcR protein abundance is a cell-autonomous, rate-limiting step required to initiate axon pruning inDrosophila,and our data suggests that this step is under epigenetic control.Highlights (bullet points up to 4)The chromodomain reader Kismet activates transcription of the steroid hormone receptorEcR-B1in theDrosophilato initiate developmental axon pruning.Kismet promotes H3K36 di- and tri-methylation and H4K16 acetylation at theEcRlocus and upstream cis-regulatory sites.Axon pruning and memory defects associated with loss of Kismet are significantly rescued by general HDAC inhibition.
Interplay of primary sequence and RNA secondary structure in determining 5′ splice site choice
Authors: Tosto Frances Anne , Shilo Asaf , Rausch Jason W. , Le Grice Stuart F. J. , Misteli Tom 
Published: July 2018

AbstractSelective use of 5′ splice sites is a common mechanism by which pre-mRNAs are alternatively spliced. Whereas the sequence requirements of 5′ splice site choice have been well characterized, other important determinants remain poorly defined. Here we apply a combination of structural mapping by SHAPE-MaP and targeted mutational analysis in a cell-based system to comprehensively probe the interplay of primary sequence, secondary RNA structure, regulatory elements and linear splice site position to determine mechanisms of splice site choice in vivo. Using the disease-causing alternative 5′ splice site selection in LMNA in the premature aging disorder Hutchinson-Gilford Progeria Syndrome as a model system, we identify RNA secondary structural elements near the alternative 5′ splice sites. We show that splice site choice is significantly influenced by the structural context of the available splice sites. While local structure alone is not sufficient to account for splice site selection, the choice of 5′ splice sites depends on the structural stability of the 5′ splice site region which is conferred by downstream elements. In addition, relative positioning of the competing sites within the primary sequence of the pre-mRNA is a predictor of 5′ splice site usage, with the distal position favored over the proximal, regardless of sequence composition. Together, these results reveal an intricate interplay amongst RNA sequence, secondary structure and splice site position in determining 5′ splice site choice.
Temporal and spatial variation in distribution of fish environmental DNA in England’s largest lake
Authors: Handley Lori Lawson , Read Daniel S. , Winfield Ian J. , Kimbell Helen , Johnson Harriet , Li Jianlong , Hahn Christoph , Blackman Rosetta , Wilcox Rose , Donnelly Rob , Szitenberg Amir , Hänfling Bernd 
Published: July 2018

AbstractEnvironmental DNA offers great potential as a biodiversity monitoring tool. Previous work has demonstrated that eDNA metabarcoding provides reliable information for lake fish monitoring, but important questions remain about temporal and spatial repeatability, which is critical for understanding the ecology of eDNA and developing effective sampling strategies. Here, we carried out comprehensive spatial sampling of England’s largest lake, Windermere, during summer and winter to 1) examine repeatability of the method, 2) compare eDNA results with contemporary gill-net survey data, 3) test the hypothesis of greater spatial structure of eDNA in summer compared to winter due to differences in water mixing between seasons, and 4) compare the effectiveness of shore and offshore sampling for species detection. We find broad consistency between results from three sampling events in terms of species detection and abundance, with eDNA detecting more species than established methods and being significantly correlated to rank abundance determined by long-term data. As predicted, spatial structure was much greater in the summer, reflecting less mixing of eDNA than in the winter. For example Arctic charr, a deep-water species, was only detected in deep, mid-lake samples in the summer, while littoral or benthic species such as minnow and stickleback were more frequently detected in shore samples. By contrast in winter, the eDNA of these species was more uniformly distributed. This has important implications for design of sampling campaigns, for example, deep-water species could be missed and littoral/benthic species overrepresented by focusing exclusively on shoreline samples collected in the summer.
Evaluation of the antifibrotic potency by knocking down SPARC, CCR2 and SMAD3
Authors: Ding Weifeng , Pu Weilin , Jiang Shuai , Ma Yanyun , Liu Qingmei , Wu Wenyu , Chu Haiyan , Zou Hejian , Jin Li , Wang Jiucun , Zhou Xiaodong 
Published: July 2018

AbstractThe genes of SPARC, CCR2, and SMAD3 are implicated in orchestrating inflammation and fibrosis in scleroderma and other fibrotic disorders. Aim of the studies was to examine synergistic effect of inhibition of these genes in treating fibrosis. The peptide nanoparticles were used to deliver the siRNAs in bleomycin-induced fibrotic mice. Triple combination of siRNAs targeting on Sparc, Ccr2 and Smad3 achieved favorable anti-inflammatory and anti-fibrotic effects. Inhibition of inflammation was evidenced by reduced inflammatory cells and proinflammatory cytokines in the BALF and/or the tissues. Activation of fibroblasts was suppressed in mouse tissues in which α-Sma and collagens were significantly reduced. Aberrant expression of the genes in fibroblasts, monocytes/macrophage, endothelial and epithelial cells were reinstalled after the treatment. In addition, transcriptome profiles indicated that some bleomycin-induced alterations of multiple biological pathways were recovered to varying degrees by the treatment. The results indicated that the triple combination of siRNAs systemically reinstated multiple biopathways, probably through controlling on different cell types including fibroblasts, monocytes/macrophages, endothelial cells and others. The multi-target-combined therapeutic approach examined herein may represent a novel and effective therapy for fibrosis.
Archival research considerations for CRSP data
Authors: Francis Rick N. , Mubako Grace , Olsen Lori 
Published: July 2018

Purpose
This study aims to remind researchers that measurement errors and inappropriate inferences may result from improperly combining and adjusting certain Center for Research in Security Prices (CRSP) measures.

Design/methodology/approach
In addition to real-world working examples, the study uses earnings announcements data to examine the effects of improperly combining and adjusting CRSP measures.

Findings
This study assists researchers with the following two considerations when using CRSP data: stand-alone share prices adjusted with CRSP adjustment factors are inaccurate in the presence of property dividend, spin-off and rights offering events; and ignoring covertly missing stock returns may create misleading test results. The primary objectives of the study are to help researchers increase the integrity of their studies and the probability of publication.

Research limitations/implications
Inadequate consideration for the two issues discussed in the paper may change the researcher’s statistical inferences.

Originality/value
Archival researchers who overtly address and discuss the existence of these issues achieve two important and related benefits. First, the researcher increases his or her credibility with editors and reviewers, which enhances the probability of a published study. Second, the researcher increases his or her perceived technical competency, which potentially affects promotion and tenure decisions, editorial membership decisions, co-authorship opportunities and other professional effects. Doctoral students will find this study to be particularly useful.