bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of biological mechanisms by semantic classifier systems
Authors: Lausser Ludwig , Schmid Florian , Siegle Lea , Hühne Rolf , Buchholz Malte , Kestler Hans A. 
Published: May 2018

AbstractThe interpretability of a classification model is one of its most essential characteristics. It allows for the generation of new hypotheses on the molecular background of a disease. However, it is questionable if more complex molecular regulations can be reconstructed from such limited sets of data. To bridge the gap between complexity and interpretability, we replace the de novo reconstruction of these processes by a hybrid classification approach partially based on existing domain knowledge. Using semantic building blocks that reflect real biological processes these models were able to construct hypotheses on the underlying genetic configuration of the analysed phenotypes. As in the building process, also these hypotheses are composed of high-level biology-based terms. The semantic information we utilise from gene ontology is a vocabulary which comprises the essential processes or components of a biological system. The constructed semantic multi-classifier system consists of expert base classifiers which each select the most suitable term for characterising their assigned problems. Our experiments conducted on datasets of three distinct research fields revealed terms with well-known associations to the analysed context. Furthermore, some of the chosen terms do not seem to be obviously related to the issue and thus lead to new, hypotheses to pursue.Author summaryData mining strategies are designed for an unbiased de novo analysis of large sample collections and aim at the detection of frequent patterns or relationships. Later on, the gained information can be used to characterise diagnostically relevant classes and for providing hints to the underlying mechanisms which may cause a specific phenotype or disease. However, the practical use of data mining techniques can be restricted by the available resources and might not correctly reconstruct complex relationships such as signalling pathways.To counteract this, we devised a semantic approach to the issue: a multi-classifier system which incorporates existing biological knowledge and returns interpretable models based on these high-level semantic terms. As a novel feature, these models also allow for qualitative analysis and hypothesis generation on the molecular processes and their relationships leading to different phenotypes or diseases.
Energy conservation via hydrogen cycling in the methanogenic archaeonMethanosarcina barkeri
Authors: Kulkarni Gargi , Mand Thomas D. , Metcalf William W. 
Published: May 2018

AbstractEnergy conservation via hydrogen cycling, which generates proton motive force by intracellular H2production coupled to extracellular consumption, has been controversial since it was first proposed in 1981. It was hypothesized that the methanogenic archaeonMethanosarcina barkeriis capable of energy conservation via H2cycling, based on genetic data that suggest H2is a preferred, but non-essential, intermediate in the electron transport chain of this organism. Here, we characterize a series of hydrogenase mutants to provide direct evidence of H2cycling.M. barkeriproduces H2during growth on methanol, a phenotype that is lost upon mutation of the cytoplasmic hydrogenase encoded byfrhADGB, although low levels of H2, attributable to the Ech hydrogenase, accumulate during stationary phase. In contrast, mutations that conditionally inactivate the extracellular Vht hydrogenase are lethal when expression of thevhtGACDoperon is repressed. Under these conditions H2accumulates, with concomitant cessation of methane production and subsequent cell lysis, suggesting that the inability to recapture extracellular H2is responsible for the lethal phenotype. Consistent with this interpretation, double mutants that lack both Vht and Frh are viable. Thus, when intracellular hydrogen production is abrogated, loss of extracellular H2consumption is no longer lethal. The common occurrence of both intracellular and extracellular hydrogenases in anaerobic microorganisms suggests that this unusual mechanism of energy conservation may be widespread in nature.ImportanceAdenosine triphosphate (ATP) is required by all living organisms to facilitate essential endergonic reactions required for growth and maintenance. Although synthesis of ATP by substrate-level phosphorylation is widespread and significant, most ATP is made via the enzyme ATP synthase, which is energized by transmembrane chemiosmotic gradients. Therefore, establishing this gradient across the membrane is of central importance to sustaining life. Experimental validation of H2cycling adds to a short list of mechanisms for generating a transmembrane electrochemical gradient that is likely to be widespread, especially among anaerobic microorganisms.
Nothing else matters? Tree characteristics have more effects than biogeoclimatic context on microhabitat diversity and occurrence: a nationwide analysis
Authors: Paillet Yoan , Debaive Nicolas , Archaux Frédéric , Cateau Eugénie , Gilg Olivier , Guilbert Eric 
Published: May 2018

AbstractManaging forests to preserve biodiversity requires a good knowledge not only of the factors driving its dynamics but also of the structural elements that actually support biodiversity. Tree-related microhabitats (cavities, cracks, conks of fungi) are tree-borne features that are reputed to support specific biodiversity for at least a part of species’ life cycles. While several studies have analysed the drivers of microhabitats number and occurrence at the tree scale, they remain limited to a few tree species located in relatively narrow biogeographical ranges. We used a nationwide database of forest reserves where microhabitats were inventoried on more than 22,000 trees. We analysed the effect of tree diameter and living status (alive or dead) on microhabitat number and occurrence per tree, taking into account biogeoclimatic variables and tree genus.We confirmed that larger trees and dead trees bore more microhabitats than their smaller or living counterparts did; we extended these results to a wider range of tree genera and ecological conditions. Contrary to expectations, the total number of microhabitat types per tree barely varied with tree genus – though we did find slightly higher accumulation levels for broadleaves than for conifers – nor did it vary with elevation or soil pH. We observed the same results for the occurrence of individual microhabitat types. However, accumulation levels with diameter and occurrence on dead trees were higher for microhabitats linked with wood decay processes (e.g. dead branches or woodpecker feeding holes) than for other, epixylic, microhabitats such as epiphytes (ivy, mosses and lichens).Promoting large living and dead trees of several tree species may be an interesting, and nearly universal, way to favour microhabitats and enhance the substrates needed to support specific biodiversity. In addition, a better understanding of microhabitat drivers and dynamics at the tree scale may help to better define their role as biodiversity indicators for large-scale monitoring.
Continuous embeddings of DNA sequencing reads, and application to metagenomics
Authors: Menegaux Romain , Vert Jean-Philippe 
Published: May 2018

AbstractWe propose a new model for fast classification of DNA sequences output by next generation sequencing machines. The model, which we call fastDNA, embeds DNA sequences in a vector space by learning continuous low-dimensional representations of the k-mers it contains. We show on metagenomics benchmarks that it outperforms state-of-the-art methods in terms of accuracy and scalability.
Vasculature-associated adipose tissue macrophages dynamically adapt to inflammatory and metabolic challenges
Authors: Silva Hernandez Moura , Báfica André , Rodrigues-Luiz Gabriela Flavia , Chi Jingyi , Alves Santos Patricia d’Emery , Reis Bernardo S. , Hoytema van Konijnenburg David P. , Crane Audrey , Nascimento Arifa Raquel Duque , Martin Patricia , Mendes Daniel Augusto G.B. , Mansur Daniel Santos , Torres Victor , Cadwell Ken , Cohen Paul , Mucida Daniel , Lafaille Juan José 
Published: May 2018

AbstractTissue-resident macrophages comprise the most abundant immune cell population in healthy adipose tissue. Adipose tissue macrophage populations change during metabolic stress and ageing, and are thought to contribute to the pathogenesis of obesity. Here, we studied adipose tissue macrophage subpopulations in the steady state, and in response to nutritional and infectious challenges.Using comprehensive cell-surface-based and gene expression analyses, we found that tissue-resident macrophages from healthy epididymal white adipose tissue (eWAT) tightly associate with blood vessels, displaying a very high endocytic capacity. We refer to these cells as Vasculature-associated Adipose tissue Macrophages (VAMs). Chronic high fat diet (HFD) feeding results in the accumulation of a monocyte-derived CD11c+CD64+double positive (DP) macrophage eWAT population with a predominant anti-inflammatory gene profile, but reduced endocytic function. In contrast, fasting rapidly and reversibly leads to VAM depletion, while acute inflammatory stress induced by pathogens transiently depletes VAMs and simultaneously boosts DP macrophage accumulation. Our results indicate that adipose tissue macrophage populations adapt to metabolic stress and inflammation, suggesting an important role for these cells in restoring homeostasis.
Anti-diuretic activity of a CAPA neuropeptide can compromiseDrosophilachill tolerance
Authors: MacMillan Heath A. , Nazal Basma , Wali Sahr , Yerushalmi Gil Y. , Misyura Lidiya , Donini Andrew , Paluzzi Jean-Paul 
Published: May 2018

AbstractFor insects, chilling injuries that occur in the absence of freezing are often related to a systemic loss of ion and water balance that leads to extracellular hyperkalemia, cell depolarization, and the triggering of apoptotic signalling cascades. The ability of insect ionoregulatory organs (e.g. the Malpighian tubules) to maintain ion balance in the cold has been linked to improved chill tolerance, and many neuroendocrine factors are known to influence ion transport rates of these organs. Injection of micromolar doses of CAPA (an insect neuropeptide) have been previously demonstrated to improveDrosophilacold tolerance, but the mechanisms through which it impacts chill tolerance are unclear, and low doses of CAPA have been demonstrated to cause anti-diuresis in other insects, including dipterans. Here, we provide evidence that low (fM) and high (µM) doses of CAPA impair and improve chill tolerance, respectively,viatwo different effects on Malpighian tubule ion and water transport. While low doses of CAPA are anti-diuretic, reduce tubule K+clearance rates and reduce chill tolerance, high doses facilitate K+clearance from the haemolymph and increase chill tolerance. By quantifying CAPA peptide levels in the central nervous system, we estimated the maximum achievable hormonal titres of CAPA, and found evidence to suggest that CAPA may function as an anti-diuretic peptide inDrosophila. We provide the first evidence of a neuropeptide that can negatively affect cold tolerance in an insect, and the first evidence of CAPA as an anti-diuretic peptide in this ubiquitous insect model.Summary StatementMany insects ion balance in the cold. We show how one neuropeptide can slow ion transport and reduce the cold tolerance of a fly.
The Unreasonable Effectiveness of Convolutional Neural Networks in Population Genetic Inference
Authors: Flagel Lex , Brandvain Yaniv , Schrider Daniel R. 
Published: May 2018

ABSTRACTPopulation-scale genomic datasets have given researchers incredible amounts of information from which to infer evolutionary histories. Concomitant with this flood of data, theoretical and methodological advances have sought to extract information from genomic sequences to infer demographic events such as population size changes and gene flow among closely related populations/species, construct recombination maps, and uncover loci underlying recent adaptation. To date most methods make use of only one or a few summaries of the input sequences and therefore ignore potentially useful information encoded in the data. The most sophisticated of these approaches involve likelihood calculations, which require theoretical advances for each new problem, and often focus on a single aspect of the data (e.g. only allele frequency information) in the interest of mathematical and computational tractability. Directly interrogating the entirety of the input sequence data in a likelihood-free manner would thus offer a fruitful alternative. Here we accomplish this by representing DNA sequence alignments as images and using a class of deep learning methods called convolutional neural networks (CNNs) to make population genetic inferences from these images. We apply CNNs to a number of evolutionary questions and find that they frequently match or exceed the accuracy of current methods. Importantly, we show that CNNs perform accurate evolutionary model selection and parameter estimation, even on problems that have not received detailed theoretical treatments. Thus, when applied to population genetic alignments, CNN are capable of outperforming expert-derived statistical methods, and offer a new path forward in cases where no likelihood approach exists.
Proteomic Analysis of ACE Inhibitory Peptides extracted from Fermented Goat Milk
Authors: Aslam Muhammad Zohaib , Shoukat Sana , Hongfei Zhao , Bolin Zhang 
Published: May 2018

AbstractProtein extracted from goat milk was hydrolyzed with LH (Lactobacillus Helveticus-cicc22171). Angiotensin Converting Enzyme (ACE) inhibitory peptides were purified from fermented samples of goat milk protein with LH by optimizing incubation time to 8 hours (S-8), 16 hours (S-16), 24 hours (S-24) and 36 hours (S-36), via ultrafiltration. Molecular weight cut-off; 10000 Da (PM-10) membrane was used to perform size exclusion chromatography. Sample with 24 h incubation time was considered as best hydrolyzed as compared to others, by applying Nin-Hydrin reaction and SDS-PAGE analysis. ACE inhibitory assay validated the authenticity of S-24 in inhibiting ACE, in vitro. Furthermore, Q executive Hybrid Quadrapole-Orbitrap Mass Spectrometry was used to determine molecular structure and amino acid sequence of ACE inhibitory peptides. Two protein groups VLPVPQKAVPQ and VLPVPQKVVPQ containing PVP, VVP along with one most abundant peptide TQTPVVVPPFLQPEIMGVPKVKE containing VPP has been identified with highest ACE inhibitory activity on the basis of intensity, small structure and higher concentration of hydrophobic and aromatic amino acids. Fermented goat milk containing these novel bioactive peptides, can be used as nutraceuticals to inhibit ACE and control hypertension.
Principal Component Analysis applied directly to Sequence Matrix
Authors: Konishi Tomokazu , Matsukuma Shiori , Fuji Hayami , Nakamura Daiki , Satou Nozomi , Okano Kunihiko 
Published: May 2018

AbstractSequence data is now widely used to observe relationships among organisms. However, understanding structure of the qualitative data is challenging. Conventionally, the relationships are analyzed using a dendrogram that estimates a tree shape. This approach has difficulty in verifying the appropriateness of the tree shape; rather, horizontal gene transfers and mating can make the shape of the relationship as networks. As a connection-free approach, principal component analysis (PCA) is used to summarize the distance matrix, which records distances between each combination of samples. However, this approach is limited regarding the treatment of information of sequence motifs; distances caused by different motifs are mixed up. This hides clues to figure out how the samples are different. As any bases may change independently, sequence is multivariate data essentially. Hence, differences among samples and bases that contribute to the difference should be observed coincidentally. To archive this, the sequence matrix is transferred to boolean vector and directly analyzed by using PCA. The effects are confirmed in diversity of Asiatic lion and human as well as environmental DNA. Resolution of samples and robustness of calculation is improved. Relationship of a direction of difference and causative nucleotides has become obvious at a glance.
Diurnal Chorusing in Nine Species of North American Frogs
Authors: McCallum Malcolm L. , McCallum Jamie L. 
Published: May 2018

AbstractA year-long survey of survey of diurnal frog calling behavior was conducted at the Red River Research and Education Park in Shreveport (Caddo Parish), Louisiana to investigate the prevalence of daytime breeding choruses in the species present at the park. We determined that 60% (9/15) of species known from the area participated in daytime breeding choruses. Four of these were new species reports for the behavior. One species was identified entirely based on a daytime chorus from outside the normal breeding season. Although we believe daytime chorusing is widespread in frogs, several species did not diurnally chorus during our study. Diurnal calling may be an important indicator of the peak breeding season for a species and it may also be a useful tool at times when night surveys are impossible.
Enhancement of Transgene Expression by NF-Y and CTCF
Authors: Zimmerman Devon , Patel Krupa , Hall Matthew , Elmer Jacob 
Published: May 2018

AbstractIf a transgene is effectively delivered to a cell, its expression may still be limited by epigenetic mechanisms that silence the transgene. Indeed, once the transgene reaches the nucleus, it may be bound by histone proteins and condensed into heterochromatin or associated with repressor proteins that block transcription. In this study, we sought to enhance transgene expression by adding binding motifs for several different epigenetic enzymes either upstream or downstream of two promoters (CMV and EF1α). Screening these plasmids revealed that luciferase expression was enhanced 10-fold by the addition of a CCAAT box just upstream of the EF1α promoter to recruit nuclear transcription factor Y (NF-Y), while inserting a CCCTC-binding factor (CTCF) motif downstream of the EF1α promoter enhanced expression 14-fold (14.03 ± 6.54). ChIP assays confirmed that NF-Y and CTCF bound to the motifs that were added to each plasmid, but the presence of NF-Y and CTCF did not significantly affect the levels of histone acetylation (H3K9ac). Overall, these result show that transgene expression from the EF1α promoter can be significantly increased with motifs that recruit NF-Y or CTCF.
Remodeling of epigenome and transcriptome landscapes with aging in mice reveals widespread induction of inflammatory responses
Authors: Benayoun Bérénice A. , Pollina Elizabeth A. , Singh Param Priya , Mahmoudi Salah , Harel Itamar , Casey Kerriann M. , Dulken Ben W. , Kundaje Anshul , Brunet Anne 
Published: May 2018

AbstractAging is accompanied by the functional decline of tissues. However, a systematic study of epigenomic and transcriptomic changes across tissues during aging is missing. Here we generated chromatin maps and transcriptomes from 4 tissues and one cell type from young, middle-age, and old mice, yielding 143 high-quality datasets. We focused specifically on chromatin marks linked to gene expression regulation and cell identity: histone H3 trimethylation at lysine 4 (H3K4me3), a mark enriched at promoters, and histone H3 acetylation at lysine 27 (H3K27ac), a mark enriched at active enhancers. Epigenomic and transcriptomic landscapes could easily distinguish between ages, and machine learning analysis showed that specific epigenomic states could predict transcriptional changes during aging. Analysis of datasets from all tissues identified recurrent age-related chromatin and transcriptional changes in key processes, including the upregulation of immune system response pathways such as the interferon signaling pathway. The upregulation of interferon response pathway with age was accompanied by increased transcription of various endogenous retroviral sequences. Pathways deregulated during mouse aging across tissues, notably innate immune pathways, were also deregulated with aging in other vertebrate species – African turquoise killifish, rat, and humans – indicating common signatures of age across species. To date, our dataset represents the largest multi-tissue epigenomic and transcriptomic dataset for vertebrate aging. This resource identifies chromatin and transcriptional states that are characteristic of youthful tissues, which could be leveraged to restore aspects of youthful functionality to old tissues.
PsEst3, a new psychrophilic esterase from the Arctic bacterium Paenibacillus sp. R4: crystallization and X-ray crystallographic analysis
Authors: Kim Hyun , Park Ae Kyung , Lee Jun Hyuck , Shin Seung Chul , Park Hyun , Kim Han-Woo 
Published: May 2018

Esterases are very useful biocatalysts in industry: they hydrolyze esters and split them into a carboxylic acid and an alcohol. The psychrophilic esterase PsEst3 was obtained from Paenibacillus sp. R4, which was isolated from the active layer of the permafrost in Council, Alaska. PsEst3 was successfully overexpressed using a psychrophilic chaperonin co-expression system and was purified by nickel-affinity and size-exclusion chromatography. Recombinant PsEst3 was crystallized at 290 K using the hanging-drop vapour-diffusion method. X-ray diffraction data were collected to 2.1 Å resolution. The crystal was determined to belong to space group P4132 or P4332, with unit-cell parameters a = b = c = 145.33 Å. Further crystallographic analysis needs to be conducted to investigate the structure and function of this esterase.
Explaining and tackling the informal economy: a dual informal labour market approach
Authors: Williams Colin Charles , Bezeredi Slavko 
Published: May 2018

PurposeTo transcend the long-standing debate regarding whether workers are driven into the informal economy by either their involuntary “exclusion” or voluntary “exit” from the formal economy, the purpose of this paper is to propose and evaluate the existence of a dual informal labour market composed of an exit-driven “upper tier” and an exclusion-driven “lower-tier” of informal workers, and to explore its policy implications.Design/methodology/approachTo do so, data are reported from a 2015 survey of the informal economy conducted in South-East Europe involving 6,019 face-to-face interviews in Bulgaria, Croatia and FYR Macedonia.FindingsIdentifying a dual informal labour market with three exit-driven informal workers for every exclusion-driven informal worker, a multinomial logit regression analysis reveals that, compared to the exclusion-driven “lower tier”, the exit-driven “upper tier” is significantly more likely to be populated by the formally employed, retired and those not struggling financially. Participation is not affected by the perceived severity of penalties and likely risks of detection, but relative to those in the exclusion-driven “lower tier”, there is a significant correlation between those doing so for exit rationales and their lack of both horizontal trust and vertical trust in formal institutions.Practical implicationsThe outcome is a call to transcend the conventional deterrence approach of increasing the penalties and risks of detection. Instead, to tackle those driven by exit rationales, tackling both the lack of horizontal trust that other citizens are operating in a compliant manner and the lack of vertical trust in formal institutions is advocated. To tackle exclusion-driven informal workers, meanwhile, a focus upon the macro-level economic and social conditions which lead to their participation is required.Originality/valueThis is the first paper to empirically evaluate the existence of a dual informal labour market and to evaluate its policy implications.