bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding the interplay of sleep and aging: Methodological challenges
Authors: Muehlroth Beate E. , Werkle-Bergner Markus 
Published: July 2019

AbstractIn quest of new avenues to explain, predict, and treat pathophysiological conditions during aging, research on sleep and aging has flourished. Despite the great scientific potential to pinpoint mechanistic pathways between sleep, aging, and pathology, only little attention has been paid to the suitability of analytic procedures applied to study these interrelations. On the basis of electrophysiological sleep and structural brain data of healthy younger and older adults, we identify, illustrate, and resolve methodological core challenges in the study of sleep and aging. We demonstrate potential biases in common analytic approaches when applied to older populations. We argue that uncovering age-dependent alterations in the physiology of sleep requires the development of adjusted and individualized analytic procedures that filter out age-independent inter-individual differences. Age-adapted methodological approaches are thus required to foster the development of valid and reliable biomarkers of age-associated cognitive pathologies.
Identification of expression quantitative trait loci in the skeletal muscle of Thoroughbreds reveals heritable variation in expression of genes relevant to cofactor metabolism
Authors: Farries G. , Bryan K. , McGivney C. L. , McGettigan P. A. , Gough K. F. , Browne J.A. , MacHugh D. E. , Katz L. M. , Hill E. W. 
Published: July 2019

SummaryWhile over ten thousand genetic loci have been associated with phenotypic traits and inherited diseases in genome-wide association studies, in most cases only a relatively small proportion of the trait heritability is explained and biological mechanisms underpinning these traits have not been clearly identified. Expression quantitative trait loci (eQTL) are subsets of genomic loci shown experimentally to influence gene expression. Since gene expression is one of the primary determinants of phenotype, the identification of eQTL may reveal biologically relevant loci and provide functional links between genomic variants, gene expression and ultimately phenotype. Skeletal muscle (gluteus medius) gene expression was quantified by RNA-seq for 111 Thoroughbreds (47 male, 64 female) in race training at a single training establishment sampled at two time-points: at rest (n = 92) and four hours after high-intensity exercise (n = 77); n = 60 were sampled at both time points. Genotypes were generated from the Illumina Equine SNP70 BeadChip. Applying a Benjamini-Hochberg corrected P-value threshold (PFDR < 0.05), association tests identified 3,583 cis-eQTL associated with expression of 1,456 genes at rest; 4,992 cis-eQTL associated with the expression of 1,922 genes post-exercise; 1,703 trans-eQTL associated with 563 genes at rest; and 1,219 trans-eQTL associated with 425 genes post-exercise. The gene with the highest cis-eQTL association at both time-points was the endosome-associated-trafficking regulator 1 gene (ENTR1; Rest: PFDR = 3.81 × 10−27, Post-exercise: PFDR = 1.66 × 10−24), which has a potential role in the transcriptional regulation of the solute carrier family 2 member 1 glucose transporter protein (SLC2A1). Functional analysis of genes with significant eQTL revealed significant enrichment for cofactor metabolic processes. These results suggest heritable variation in genomic elements such as regulatory sequences (e.g. gene promoters, enhancers, silencers), microRNA and transcription factor genes, which are associated with metabolic function and may have roles in determining end-point muscle and athletic performance phenotypes in Thoroughbred horses.
The PASTA domains of Bacillus subtilis PBP2B stabilize the interaction of PBP2B with DivIB
Authors: Angeles Danae Morales , Macia-Valero Alicia , Bohorquez Laura C. , Scheffers Dirk-Jan 
Published: July 2019

AbstractBacterial cell division is mediated by a protein complex known as the divisome. Many protein-protein interactions in the divisome have been characterized. In this report, we analyse the role of the PASTA (Penicillin binding protein And Serine Threonine kinase Associated)-domains of Bacillus subtilis PBP2B. PBP2B itself is essential and cannot be deleted, but removing the PBP2B PASTA domains results in impaired cell division and a heat sensitive phenotype. This resembles the deletion of divIB, a known interaction partner of PBP2B. Bacterial two hybrid and co-immunoprecipitation analyses show that the interaction between PBP2B and DivIB is weakened when the PBP2B PASTA domains are removed. Combined, our results show that the PBP2B PASTA domains are required to stabilize the interaction between PBP2B and DivIB.
A computational model tracks whole-lung Mycobacterium tuberculosis infection and predicts factors that inhibit dissemination
Authors: Wessler Timothy , Joslyn Louis R. , Borish H. Jacob , Gideon Hannah P. , Flynn JoAnne L. , Kirschner Denise E. , Linderman Jennifer J. 
Published: July 2019

AbstractMycobacterium tuberculosis (Mtb), the causative infectious agent of tuberculosis (TB), kills more individuals per year than any other infectious agent. Granulomas, the hallmark of Mtb infection, are complex structures that form in lungs, composed of immune cells surrounding bacteria, infected cells, and a caseous necrotic core. While granulomas serve to physically contain and immunologically restrain bacteria growth, some granulomas are unable to control Mtb growth, leading to bacteria and infected cells leaving the granuloma and disseminating, either resulting in additional granuloma formation (local or non-local) or spread to airways or lymph nodes. Dissemination is associated with development of active TB. It is challenging to experimentally address specific mechanisms driving dissemination from TB lung granulomas. Herein, we develop a novel hybrid multi-scale computational model, MultiGran, that tracks Mtb infection within multiple granulomas in an entire lung. MultiGran follows cells, cytokines, and bacterial populations within each lung granuloma throughout the course of infection and is calibrated to multiple non-human primate (NHP) cellular, granuloma, and whole-lung datasets. We show that MultiGran can recapitulate patterns of in vivo local and non-local dissemination, predict likelihood of dissemination, and predict a crucial role for multifunctional CD8+ T cells and macrophage dynamics for preventing dissemination.Author SummaryTuberculosis (TB) is caused by infection with Mycobacterium tuberculosis (Mtb) and kills 3 people per minute worldwide. Granulomas, spherical structures composed of immune cells surrounding bacteria, are the hallmark of Mtb infection and sometimes fail to contain the bacteria and disseminate, leading to further granuloma growth within the lung environment. To date, the mechanisms that determine granuloma dissemination events have not been characterized. We present a computational multi-scale model of granuloma formation and dissemination within primate lungs. Our computational model is calibrated to multiple experimental datasets across the cellular, granuloma, and whole-lung scales of non-human primates. We match to both individual granuloma and granuloma-population datasets, predict likelihood of dissemination events, and predict a critical role for multifunctional CD8+ T cells and macrophage-bacteria interactions to prevent infection dissemination.
A cell-based evaluation of a non-essential amino acid formulation as a non-bioactive control for activation and stimulation of muscle protein synthesis using ex vivo human serum
Authors: Patel Bijal , Pauk Martina , Amigo-Benavent Miryam , Nongonierma Alice B. , Fitzgerald Richard J. , Jakeman Philip M. , Carson Brian P. 
Published: July 2019

AbstractPurposeThe purpose of this study was to compare the effect of treating skeletal muscle cells with media conditioned by postprandial ex vivo human serum fed with either isonitrogenous NEAA or a whey protein hydrolysate (WPH) on stimulating MPS in C2C12 skeletal muscle cells.MethodsBlood was taken from six young healthy males following overnight fast (fasted) and 60 min postprandial (fed) ingestion of either WPH or NEAA (0.33 g.kg-1 Body Mass). C2C12 myotubes were treated with media conditioned by ex vivo human serum (20%) for 4 h. Activation of MPS signalling (phosphorylation of mTOR, P70S6K and 4E-BP1) were determined in vitro by Western Blot and subsequent de novo MPS were determined in vitro by Western Blot and surface sensing of translation technique (SUnSET) techniques, respectively.ResultsMedia conditioned by NEAA fed serum had no effect on protein signalling or MPS compared to fasted, whereas media conditioned by WPH fed serum significantly increased mTOR, P70S6K and 4E-BP1 phosphorylation (p<0.01, p<0.05) compared to fasted serum. Furthermore, the effect of media conditioned by WPH fed serum on protein signalling and MPS was significantly increased (p<0.01, p<0.05) compared to NEAA fed serum.ConclusionIn summary, media conditioned by NEAA fed serum did not result in activation of MPS. Therefore, these in vitro findings suggest the use of isonitrogenous NEAA acts as an effective control for comparing bioactivity of different proteins on activation of MPS. These findings also confirm that activation of MPS in C2C12 myotubes treated with media conditioned by WPH-fed serum is primarily due to circulating EAA.
Evaluation ofTrichoderma harzianummutant lines in the resistance induction against white mold and growth promotion of common bean
Authors: Brandão Renata Silva , Qualhato Thiago Fernandes , Valdisser Paula Arielle Mendes Ribeiro , de C. B. Côrtes Marcio Vinicius , Vieira Pabline Marinho , Silva Roberto Nascimento , Junior Murillo Lobo , Ulhoa Cirano José 
Published: July 2019

ABSTRACTGenetic engineering has brought improvements ofTrichodermaspecies for biotechnological processes such as agriculture. It has previously been reported thatsm1andaquaglyceroporingenes fromTrichoderma harzianumare strongly expressed during pathogens biocontrol. We have previously shown thatSm1plays a significant role in plant disease resistance and aquaporin (AQP) regulate physiological processes and responses related to water stress. Here, we report the evaluation of mutant lines withsm1(deleated) andaqp(overexpressed) inPhaseoulus vulgarisgrowth promotion and disease resistance induction. It was investigated plants physiological and biochemical responses, plant growth promotion and biocontrol ofSclerotinia sclerotiorum, the causal agent of white mold. Treatments includedTrichoderma harzianumwyld type, mutant line overexpressing aquaporin (Aqua), and deletedΔEpl1mutant line. Our results demonstrated that Aqua mutant line increased leaf area in 25%, in comparison to non-treated plants. It also differed from other treatments, in comparison to plants with treatments ALL-42 andΔEpl1, which increased 28% and 91%, respectively (Isso é abstract, ta confuse e extensor. Specific activity of β-1.3 glucanase was higher in plants treated withT. harzianum ΔEpl1mutant isolate, in leaves and roots respectively with 2.07 Umg−1and 2.57 Umg−1. Plants inoculated or not withS. sclerotiorumpresented with 2.27 Umg-1and 2.34 Umg-1of β-1.3 glucanase on average, respectively, but enzymatic activity was higher on leaves when compared to the roots. TheAquamutant demonstrated excellent growth promoting properties. Both mutants ofT. harzianumdo not induce resistance to white mold on common bean plants.
Cross-species epigenetic regulation of nucleus accumbens KCNN3 transcript variants by excessive ethanol drinking and dependence
Authors: Cervera-Juanes Rita , Padula Audrey E. , Wilhem Larry J. , Park Byung , Grant Kathleen A. , Ferguson Betsy , Mulholland Patrick J. 
Published: July 2019

ABSTRACTThe underlying genetic and epigenetic mechanisms driving functional adaptations in neuronal excitability and excessive alcohol intake are poorly understood. Given that small-conductance Ca2+-activated K+ (KCa2 or SK) channels encoded by the KCNN family of genes have emerged from preclinical studies as a crucial target that contributes to heavy drinking and alcohol-induced functional neuroadaptations, we performed a cross-species analysis of KCNN3 methylation, gene expression, and polymorphisms of alcohol-drinking monkeys and alcohol dependent mice. Because of the alternative promoters in KCNN3, we analyzed expression of the different transcript variants that when translated influence surface trafficking and function of KCa2 channels. In heavy drinking rhesus macaques and alcohol dependent C57BL/6J mice, bisulfite sequencing analysis of the nucleus accumbens revealed a differentially methylated region in exon 1A of KCNN3 that overlaps with a predicted promoter sequence. The hypermethylation of KCNN3 in monkey and mouse accumbens paralleled an increase in expression of alternative transcript variants that encode apamin-insensitive and dominant-negative KCa2 channel isoforms. A polymorphic repeat in macaque KCNN3 encoded by exon 1 did not correlate with alcohol drinking. At the protein level, KCa2.3 channel expression in the accumbens was significantly reduced in very heavy drinking monkeys. Together, our cross-species findings on epigenetic dysregulation of KCNN3 by heavy alcohol drinking and dependence represent a complex mechanism that utilizes alternative promoters to impact firing of accumbens neurons. Thus, these results provide support for hypermethylation of KCNN3 by excessive alcohol drinking as a possible key molecular mechanism underlying harmful alcohol intake and alcohol use disorder.
WiPP: Workflow for improved Peak Picking for Gas Chromatography-Mass Spectrometry (GC-MS) data
Authors: Borgsmüller Nico , Gloaguen Yoann , Opialla Tobias , Blanc Eric , Sicard Emilie , Royer Anne-Lise , Le Bizec Bruno , Durand Stéphanie , Migné Carole , Pétéra Mélanie , Pujos-Guillot Estelle , Giacomoni Franck , Guitton Yann , Beule Dieter , Kirwan Jennifer 
Published: July 2019

AbstractLack of reliable peak detection impedes automated analysis of large scale GC-MS metabolomics datasets. Performance and outcome of individual peak-picking algorithms can differ widely depending on both algorithmic approach and parameters as well as data acquisition method. Comparing and contrasting between algorithms is thus difficult. Here we present a workflow for improved peak picking (WiPP), a parameter optimising, multi-algorithm peak detection for GC-MS metabolomics. WiPP evaluates the quality of detected peaks using a machine learning-based classification scheme based on seven peak classes. The quality information returned by the classifier for each individual peak is merged with results from different peak detection algorithms to create one final high quality peak set for immediate down stream analysis. Medium and low quality peaks are kept for further inspection. By applying WiPP to standard compound mixes and a complex biological dataset we demonstrate that peak detection is improved through the novel way to assign peak quality, an automated parameter optimisation, and results integration across different embedded peak picking algorithms. Furthermore, our approach can provide an impartial performance comparison of different peak picking algorithms. WiPP is freely available on GitHub (https://github.com/bihealth/WiPP) under MIT licence.
kASA: Taxonomic Analysis of Metagenomic Data on a Notebook
Authors: Weging Silvio , Gogol-Döring Andreas , Grosse Ivo 
Published: July 2019

AbstractThe taxonomic analysis of sequencing data has become important in many areas of life sciences. However, currently available software tools for that purpose either consume large amounts of RAM or yield an insufficient quality of the results.Here we present kASA, a k-mer based software capable of identifying and profiling metagenomic DNA sequences with high computational efficiency and a user-definable memory footprint. We ensure both high sensitivity and precision by using an amino acid-like encoding of k-mers with a dynamic length of multiple k’s. Custom algorithms and data structures optimized for external memory storage enable for the first time a full-scale metagenomic analysis without compromise on a standard notebook.
Nesprin-2 accumulates at the front of the nucleus during confined cell migration
Authors: Davidson Patricia M. , Battistella Aude , Déjardin Théophile , Betz Timo , Plastino Julie , Borghi Nicolas , Cadot Bruno , Sykes Cécile 
Published: July 2019

SUMMARYThe mechanisms by which cells exert forces on their nuclei to migrate through openings smaller than the nuclear diameter remain unclear. In microfluidic devices, the hourglass shape of the nucleus and its strain patterns as it translocates through narrow constrictions suggest pulling forces. We use CRISPR/Cas9 to fluorescently label nesprin-2 giant, a protein that links the cytoskeleton to the interior of the nucleus. We demonstrate that nesprin-2 giant accumulates at the front of the nucleus during nuclear deformation through narrow constrictions, independently of the nuclear lamina. We find that nesprins are more mobile than lamin A/C, at time scales similar to that of the accumulation. Using artificial constructs, we show that the actin-binding domain of nesprin-2 is necessary and sufficient to generate this accumulation, and that microtubules are not necessary. Actin filaments are organized in a barrel structure around the moving nucleus in the direction of movement, suggesting that this structure is responsible for redistribution of nesprins towards the front of the nucleus. Two-photon ablation and the use of drugs inhibiting the cytoskeleton demonstrate a pulling force on the nucleus from the front of the cell that is dependent on formin and actomyosin contractility. This elastic recoil is significantly reduced when nesprins are reduced at the nuclear envelope. We thus show that actin redistributes nesprin-2 giant towards the front of the nucleus and contributes to pulling the nucleus through narrow constrictions, in concert with myosin.
Atlas of transcriptionally active transposable elements in human adult tissues
Authors: Bogu Gireesh K. , Reverter Ferran , Marti-Renom Marc A. , Snyder Michael P. , Guigó Roderic 
Published: July 2019

AbstractApproximately half of the human genome consists of mobile repetitive DNA sequences known as transposable elements (TEs). They are usually silenced by epigenetic mechanisms, but a few are known to escape silencing at embryonic stages, affecting early human development by regulating nearby protein-coding genes. To investigate transcriptional activity in human adult tissues we systematically investigate the expression landscape of about 4.2 million non-coding TEs in 8,051 RNA-Seq datasets from up to 49 adult tissues and 540 individuals. We show that approximately 79,558 individual TEs (2%). belonging to 856 subfamilies escape epigenetic silencing in adult tissues and become transcriptionally active, often in a very tissue-specific manner. Supporting a role for TEs in the regulation of expression of nearby genes, we found the expression of TEs often correlated with the expression of nearby genes, and significantly stronger when the TEs include eQTLs for the genes. We identified thousands of tissue-elevated, sex-associated TEs in the breast, ethnicity-associated in the skin and age-associated in the tibial artery, where we found a potential implication of two TE subfamilies in atherosclerosis. Our results suggest a functional role of TEs in the regulation of gene expression, support their implication in human phenotypes, and also serve as a comprehensive resource of transcriptionally active TEs in human adult tissues.
A decision support system for technician routing with time windows
Authors: Solano Charris Elyn Lizeth , Montoya-Torres Jairo Rafael , Guerrero-Rueda William 
Published: July 2019

Purpose
The purpose of this paper is to present a decision support system (DSS) for a Colombian public utility company in order to aid decision-making at the operational level regarding route planning and travel time. The aim is to provide a tool to assist technicians that perform interruption and reconnection of domiciliary services for about 2,000 customers a day.

Design/methodology/approach
The real-life problem is modeled as a Single Depot Vehicle Routing Problem with Time Windows (SDVRP-TW), which is a well-known optimization problem in Operations Research/Management Science. A two-stage approach integrated into decision-making software is provided. The first stage considers the clustering of customers generated by a combination of the sweep and the k-means algorithms, while the second phase plans the routing of technicians using the nearest-neighbor and the Or-opt heuristics. The proposed approach is tested using real data sets.

Findings
In comparison with the current route planning approach, the proposed method is able to obtain savings in total travel times, improving operational productivity by 22.2 percent.

Research limitations/implications
Since the analysis is carried out based on mathematical modeling, assumptions about the relationships between variables and elements of the actual complex problem might be simplified. Although the proposed approach aids the route planning, decision makers make the final decisions.

Practical implications
The proposed DSS has a critical impact on actual operational practices at the company. Productivity and service level are improved, while reducing operational costs. The decision-making process itself will be improved so technicians and higher decision makers can focus on performing other tasks.

Originality/value
The real-life problem is modeled using mathematical programming and efficiently solved through a two-stage approach based on simple, quite intuitive, solution procedures that have not been implemented for such services. In addition, as actual data from the company is employed for experimental purposes, the solution approach is tested and its efficiency and efficacy are both validated in a realistic setting, hence providing realistic behavior for decision makers at the company.