bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of the interactive effects of labile and recalcitrant organic matter on microbial growth and metabolism
Authors: Quigley Lauren N. M. , Edwards Abigail , Steen Andrew D. , Buchan Alison 
Published: January 2019

AbstractGeochemical models typically represent organic matter (OM) as consisting of multiple, independent pools of compounds, each accessed by microorganisms at different rates. However, recent findings indicate that organic compounds can interact within microbial metabolisms. The relevance of interactive effects within marine systems is debated and a mechanistic understanding of its complexities, including microbe-substrate relationships, is lacking. As a first step toward uncovering mediating processes, the interactive effects of distinct pools of OM on the growth and respiration of marine bacteria, individual strains and a simple, constructed community of Roseobacter lineage members were tested. Isolates were provided with natural organic matter (NOM) and different concentrations (1, 4, 40, 400 μM-C) and forms of labile organic matter (acetate, casamino acids, tryptone, coumarate). The microbial response to the mixed substrate regimes was assessed using viable counts and respiration in two separate experiments. Two marine bacteria and a six-member constructed community were assayed with these experiments. Both synergistic and antagonistic growth responses were evident for all strains, but all were transient. The specific substrate conditions promoting a response, and the direction of that response, varied amongst species. These findings indicate that the substrate conditions that result in OM interactive effects are both transient and species-specific and thus influenced by both the composition and metabolic potential of a microbial community.
The landscape of SNCA transcripts across synucleinopathies: New insights from long reads sequencing analysis
Authors: Tseng Elizabeth , Rowell William J , Glenn Omolara-Chinue , Hon Ting , Barrera Julio , Kujawa Steve , Chiba-Falek Ornit 
Published: January 2019

AbstractDysregulation of alpha-synuclein expression has been implicated in the pathogenesis of synucleinopathies, in particular Parkinson’s Disease (PD) and Dementia with Lewy bodies (DLB). Previous studies have shown that the alternatively spliced isoforms of the SNCA gene are differentially expressed in different parts of the brain for PD and DLB patients. Similarly, SNCA isoforms with skipped exons can have a functional impact on the protein domains. The large intronic region of the SNCA gene was also shown to harbor structural variants that affect transcriptional levels. Here we apply the first study of using long read sequencing with targeted capture of both the gDNA and cDNA of the SNCA gene in brain tissues of PD, DLB, and control samples using the PacBio Sequel system. The targeted full-length cDNA (Iso-Seq) data confirmed complex usage of known alternative start sites and variable 3’ UTR lengths, as well as novel 5’ starts and 3’ ends not previously described. The targeted gDNA data allowed phasing of up to 81% of the ~114kb SNCA region, with the longest phased block excedding 54 kb. We demonstrate that long gDNA and cDNA reads have the potential to reveal long-range information not previously accessible using traditional sequencing methods. This approach has a potential impact in studying disease risk genes such as SNCA, providing new insights into the genetic etiologies, including perturbations to the landscape the gene transcripts, of human complex diseases such as synucleinopathies.
Genetic Nature or Genetic Nurture? Quantifying Bias in Analyses Using Polygenic Scores
Authors: Trejo Sam , Domingue Benjamin W. 
Published: January 2019

AbstractSummary statistics from a genome-wide association study (GWAS) can be used to generate a polygenic score (PGS). For complex, behavioral traits, the correlation between an individual’s PGS and their phenotype may contain bias alongside the causal effect of the individual’s genes (due to geographic, ancestral, and/or socioeconomic confounding). We formalize the recent introduction of a different source of bias in regression models using PGSs: the effects of parental genes on offspring outcomes, also known as genetic nurture. GWAS do not discriminate between the various pathways through which genes influence outcomes, meaning existing PGSs capture both direct genetic effects and genetic nurture effects. We construct a theoretical model for genetic effects and show that, unlike other sources of bias in PGSs, the presence of genetic nurture biases PGS coefficients from both naïve OLS (between-family) and family fixed effects (within-family) regressions. This bias is in opposite directions; while naïve OLS estimates are biased upwards, family fixed effects estimates are biased downwards. We quantify this bias for a given trait using two novel parameters that we identify and discuss: (1) the genetic correlation between the direct and nurture effects and (2) the ratio of the SNP heritabilities for the direct and nurture effects.
Comparative analyses of chromatin landscape in white adipose tissue suggest humans may have less beigeing potential than other primates
Authors: Swain-Lenz Devjanee , Berrio Alejandro , Safi Alexias , Crawford Gregory E. , Wray Gregory A. 
Published: January 2019

AbstractHumans carry a much larger percentage of body fat than other primates. Despite the central role of adipose tissue in metabolism, little is known about the evolution of white adipose tissue in primates. Phenotypic divergence is often caused by genetic divergence in cis-regulatory regions. We examined the cis-regulatory landscape of fat during human origins by performing comparative analyses of chromatin accessibility in human and chimpanzee adipose tissue using macaque as an outgroup. We find that many cis-regulatory regions that are specifically closed in humans are under positive selection, located near genes involved with lipid metabolism, and contain a short sequence motif involved in the beigeing of fat, the process in which white adipocytes are transdifferentiated into beige adipocytes. While the primary role of white adipocytes is to store lipids, beige adipocytes are thermogeneic. The collective closing of many putative regulatory regions associated with beiging of fat suggests an adaptive mechanism that increases body fat in humans.
Chaperone-mediated ordered assembly of the SAGA and NuA4 transcription co-activator complexes
Authors: Elías-Villalobos Alberto , Toullec Damien , Faux Céline , Séveno Martial , Helmlinger Dominique 
Published: January 2019

AbstractTranscription initiation involves the coordinated activities of large multimeric complexes that are organized into functional modules. Little is known about the mechanisms and pathways that govern their assembly from individual components. We report here several principles governing the assembly of the highly conserved SAGA and NuA4 co-activator complexes. Using fission yeast, which contain two functionally non-redundant paralogs of the shared Tra1 subunit, we demonstrate that Tra1 contributes to scaffolding the entire NuA4 complex. In contrast, within SAGA, Tra1 specifically promotes the incorporation of the de-ubiquitination module (DUB), defining an ordered assembly pathway. Biochemical and functional analyses elucidated the mechanism by which Tra1 assemble differentially into SAGA or NuA4 and identified a small, conserved region of Spt20 that is both necessary and sufficient to anchor Tra1 within SAGA. Finally, we establish that Hsp90 and its cochaperone TTT are required for Tra1 de novo incorporation into both SAGA and NuA4, indicating that Tra1, a pseudokinase of the PIKK family, shares a dedicated chaperone machinery with its cognate kinases. Overall, our work brings mechanistic insights into the de novo assembly of transcriptional complexes through ordered pathways and reveals the contribution of dedicated chaperones to this process.
In vivo structure of the Legionella type II secretion system by electron cryotomography
Authors: Ghosal Debnath , Kim Ki Woo , Zheng Huaixin , Kaplan Mohammed , Vogel Joseph P. , Cianciotto Nicholas P. , Jensen Grant J. 
Published: January 2019

AbstractThe type II secretion system (T2SS) is a multi-protein envelope-spanning assembly that translocates a wide range of virulence factors, enzymes and effectors through the outer membrane (OM) of many Gram-negative bacteria. Here, using electron cryotomography and subtomogram averaging methods, we present the first in situ structure of an intact T2SS, imaged within the human pathogen Legionella pneumophila. Although the T2SS has only limited sequence and component homology with the evolutionarily-related Type IV pilus (T4P) system, we show that their overall architectures are remarkably similar. Despite similarities, there are also differences, including for instance that the T2SS-ATPase complex is usually present but disengaged from the inner membrane, the T2SS has a much longer periplasmic vestibule, and it has a short-lived flexible pseudopilus. Placing atomic models of the components into our ECT map produced a complete architectural model of the intact T2SS that provides new insights into the structure and function of its components, its position within the cell envelope, and the interactions between its different subcomplexes. Overall, these structural results strongly support the piston model for substrate extrusion.
The genomic architecture of introgression among sibling species of bacteria
Authors: Cavassim Maria Izabel A , Moeskjær Sara , Moslemi Camous , Fields Bryden , Bachmann Asger , Vilhjálmsson Bjarni , Schierup Mikkel H , Young J Peter W , Andersen Stig U 
Published: January 2019

AbstractBackgroundGene transfer between bacterial species is an important mechanism for adaptation. For example, sets of genes that confer the ability to form nitrogen-fixing root nodules on host plants have frequently moved betweenRhizobiumspecies. It is not clear, though, whether such transfer is exceptional, or if frequent inter-species introgression is typical. To address this, we sequenced the genomes of 196 isolates of theRhizobium leguminosarumspecies complex obtained from root nodules of white clover (Trifolium repens).ResultsCore gene phylogeny placed the isolates into five distinct genospecies that show high intra-genospecies recombination rates and remarkably different demographic histories. Most gene phylogenies were largely concordant with the genospecies, indicating that recent gene transfer between genospecies was rare. In contrast, very similar symbiosis gene sequences were found in two or more genospecies, suggesting recent horizontal transfer. The replication and conjugative transfer genes of the plasmids carrying the symbiosis genes showed a similar pattern, implying that introgression occurred by conjugative plasmid transfer. The only other regions that showed strong phylogenetic discordance with the genospecies classification were two small chromosomal clusters, one neighbouring a conjugative transfer system. Phage-related sequences were observed in the genomes, but appeared to have very limited impact on introgression.ConclusionsIntrogression among these closely-related species has been very limited, confined to the symbiosis plasmids and a few chromosomal islands. Both introgress through conjugative transfer, but have been subject to different types of selective forces.
Buffer Therapy in Acute Metabolic Acidosis: Effects on Acid-Base Status and Glomerular Permeability
Authors: Schnapauff Jan , Piros David , Rippe Anna , Bentzer Peter , Clyne Naomi , Öberg Carl M. 
Published: January 2019

ABSTRACTBackground:Correction of acute metabolic acidosis using sodium bicarbonate is effective, but has been hypothesized to exacerbate intra-cellular acidosis causing cellular dysfunction. The effects of acidemia and bicarbonate therapy on the cellular components of the glomerular filtration barrier, crucial for the integrity of the renal filter, are as yet unknown. Controversy persists regarding the most appropriate method to assess acid-base status: the “Stewart approach” or the “Siggaard-Andersen approach” using the standard base excess (SBE).Methods:Here we performed physiological studies in anesthetized Sprague-Dawley rats during severe metabolic acidosis (HCl iv 6 mmol kg-1) and following bicarbonate (2.5 mmol kg-1) administration. We assessed glomerular permeability using sieving coefficients of polydisperse fluorescein isothiocyanate (FITC)-Ficoll 70/400. Acid-base status was evaluated using SBE, standard bicarbonate, total CO2, the Stewart-Fencl strong ion difference (ΔSID = Na – Cl – 38) and a theoretical model of plasma and erythrocyte strong ion difference.Results:Our data show that neither acidosis nor its correction with NaHCO3altered glomerular permeability. We identified ΔSID as a strong estimator of plasma base excess (as assessed using the Van Slyke equation).In silicomodeling indicates that changes in the strong ion difference in erythrocytes would explain their buffering effect by means of a shift of anions from the extracellular fluid.Conclusion:These data demonstrate a remarkable tolerance of the glomerular filter to severe acute acidosis and bicarbonate therapy. Our results also cast light on the buffer mechanism in erythrocytes and the ability of different acid-base parameters to evaluate the extent of an acid-base disorder.IMPORTANCE STATEMENTMetabolic acidosis is a frequent complication of acute kidney injury in critically ill patients and is associated with a high risk of mortality. Correction of acidosis using sodium bicarbonate is simple and effective, but could possibly induce intracellular acidosis causing cellular dysfunction. The effects of acidemia and subsequent bicarbonate treatment on the cellular components of the glomerular filtration barrier, crucial for the integrity of the renal filter, are unknown. We show that neither severe acidemia nor bicarbonate therapy appear to have negative effects on glomerular permeability. Our analysis also highlights the buffering effects of erythrocytes, which appear to be mediated by a shift of strong anions into the red cells, increasing the strong ion difference in the extracellular fluid.
Spread of pathological α-synuclein from urogenital nerves initiates multiple system atrophy-like symptoms
Authors: Wang Xuejing , Ma Mingming , Wu Erxi , Teng Dongyang , Yuan Xin , Zhou Lebo , Zhang Rui , Yao Jing , Chen Yongkang , Xia Danhao , Teng Robert K.F. , Wang Fengfei , Huang Jason H. , Yue Zhenyu , Zhang Zhuohua , Teng Junfang , Tang Beisha , Ding Xuebing 
Published: January 2019

AbstractMultiple system atrophy (MSA) is a fatal adult-onset movement disorder with autonomic failures, especially urogenital dysfunction. The neuropathological feature of MSA is the accumulation of misfolded α-synuclein (α-Syn) in the nervous system. Here, we show that misfolded α-Syn exist in nerve terminals in detrusor (DET) and external urethral sphincter (EUS) of patients with MSA. Moreover, α-Syn preformed fibrils inoculated into the EUS or DET in TgM83+/− mice initiated the transmission of misfolded α-Syn from the lower urinary tract to brain, and these mice developed α-Syn inclusion pathology through micturition reflex pathways along with urinary dysfunction and motor impairments. These findings indicate that spreading of misfolded α-Syn from the autonomic control of the lower urinary tract to the brain via micturition reflex pathways induces autonomic failure and motor impairments. These results provide important new insights into the pathogenesis of MSA as well as highlight potential targets for early detection and therapeutics.
Chemogenetic inhibition of a monosynaptic projection from the basolateral amygdala to the ventral hippocampus selectively reduces appetitive, but not consummatory, alcohol drinking-related behaviors
Authors: Bach Eva C. , Ewin Sarah E. , Heaney Chelcie F. , Carlson Hannah N. , Almonte Antoine G. , Chappell Ann M. , Raab-Graham Kimberly F. , Weiner Jeffrey L. 
Published: January 2019

ABSTRACTAlcohol use disorder (AUD) and anxiety/stressor disorders frequently co-occur and this dual diagnosis represents a major health and economic problem worldwide. The basolateral amygdala (BLA) is a key brain region that is known to contribute to the etiology of both disorders. Although many studies have implicated BLA hyperexcitability in the pathogenesis of AUD and comorbid conditions, relatively little is known about the specific efferent projections from this brain region that contribute to these disorders. Recent optogenetic studies have shown that the BLA sends a strong monosynaptic excitatory projection to the ventral hippocampus (vHC) and that this circuit modulates anxiety- and fear-related behaviors. However, it is not known if this pathway influences alcohol drinking-related behaviors. Here, we employed a rodent operant drinking regimen that procedurally separates appetitive (e.g. seeking) and consummatory (e.g. intake) behaviors, chemogenetics, and brain region-specific microinjections, to determine if BLA-vHC circuitry influences alcohol drinking-related measures. We first confirmed prior optogenetic findings that silencing this circuit reduced anxiety-like behaviors on the elevated plus-maze. We then demonstrated that inhibiting the BLA-vHC pathway significantly reduced appetitive alcohol drinking-related behaviors while having no effect on consummatory measures. Sucrose seeking measures were also reduced following chemogenetic inhibition of this circuit. Taken together, these findings provide the first indication that the BLA-vHC circuit may regulate appetitive alcohol drinking-related behaviors and add to a growing body of evidence suggesting that dysregulation of this pathway may contribute to the pathophysiology of AUD and anxiety/stressor-related disorders.HIGHLIGHTSThe basolateral amygdala sends a monosynaptic glutamatergic projection to the ventral hippocampusInhibiting this circuit reduces anxiety-like behaviors in male Long Evans ratsInhibition of this pathway also decreases operant alcohol seeking-related behaviors
Chemsex: origins of the word, a history of the phenomenon and a respect to the culture
Authors: Stuart David 
Published: January 2019

Purpose
The purpose of this paper is to clarify the origins, use and meaning of the term “chemsex”.

Design/methodology/approach
The approach used here is one born of personal experiences and reflection.

Findings
The term chemsex has a definition and a purpose that promotes culturally competent care for a marginalized group of vulnerable people.

Research limitations/implications
This is a qualitative, personal, point-of-view piece which may be of value in broadening understandings and responses amongst public health and academic activities.

Practical implications
The findings can be used to develop a sense of community and support amongst men who have sex with men in a chemsex setting, and to provide some background and context for professionals working in this field.

Originality/value
This paper is amongst the first, if not the first, of its nature to be published in an academic journal.
Two-phase investigation of water-Al2O3 nanofluid in a micro concentric annulus under non-uniform heat flux boundary conditions
Authors: Toghraie Davood , Mashayekhi Ramin , Arasteh Hossein , Sheykhi Salman , Niknejadi Mohammadreza , Chamkha Ali J. 
Published: January 2019

Purpose
This is a 3D numerical study of convective heat transfer through a micro concentric annulus governing non-uniform heat flux boundary conditions employing water-Al2O3 nanofluid. The nanofluid is modeled using two-phase mixture model, as it has a good agreement to experimental results.

Design/methodology/approach
Half of the inner pipe surface area of the annulus section of a double pipe heat exchanger is exposed to a constant heat flux which two models are considered to divide the exposing surface area to smaller ones considering the fact that in all cases half of the inner pipe surface area has to be exposed to the heat flux: in model (A), the exposing surface area is divided radially to two parts (A1), four parts (A2) and eight parts (A3) by covering the whole length of the annulus and in model (B) the exposing surface area is divided axially to two parts (B1), four parts (B2) and eight parts (B3) by covering half of the annulus radially.

Findings
The results reveal that model (B) leads to higher Nusselt numbers compared to model (A); however, at Reynolds number 10, model (A3) exceeds model (B3). The average Nusselt number is increased up to 142 and 83 per cent at models (A3) with Reynolds number 10 and model (B3) with Reynolds number 1000, respectively.

Originality/value
This paper is a two-phase investigation of water-Al2O3 nanofluid in a micro concentric annulus under non-uniform heat flux boundary conditions.
Review of tribological behavior of graphene coatings on piston rings in engines
Authors: Acunaş Karagöz Zeynep Burcu , Demirtaş Selman , Kaleli Hakan , Yüksek Levent , Çıtak Emre 
Published: January 2019

Purpose
This study aims to find out friction and wear characteristics of graphene and graphene coating deposited by the Chemical Vapor Deposition (CVD) process on Honda GX270 engine (nodular cast iron) piston rings experimentally investigated under boundary lubricated conditions.

Design/methodology/approach
This study consists of two stages: tribotest and engine tests. First test was conducted through a reciprocating tribotest machine and second test was conducted through an engine bench with a duration of 75h. Engine piston ring was coated with graphene by two different methods: transfer method and direct CVD method.

Findings
Graphene has been demonstrated to be a potential and promising candidate for wear- and scratch-resistant coating because it is the thinnest, lightest and strongest known nanomaterial. In this case, the ability of a mono-layer graphene film to withstand high pressure differences (6 atm) indicates its mechanical robustness. It can effectively prevent or reduce mechanical failure by strengthening and toughening the loaded surface as well as by transferring the stress throughout the structure. The positive tribological outcomes of the graphene reinforced material under various dynamic loads revealed the potential of graphene-based coatings in macro - and micro-tribology.

Originality/value
This study fulfils an identified need to study for automotive industry a coating which is wear and scratch resistant.