bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic signatures of human brain structure: A comparison between GWAS and relatedness-based regression
Authors: Lyu Bingjiang , Tsvetanov Kamen A. , Tyler Lorraine K. , Clarke Alex ,   Cam-CAN, Amos William 
Published: August 2020

AbstractIdentifying the genetic variations impacting human brain structure and their further effects on cognitive functions, is important for our understanding of the fundamental bases of cognition. In this study, we take two different approaches to this issue: classical genome-wide association analysis (GWAS) and a relatedness-based regression approach (REL) to search for associations between genotype and brain structural measures of gray matter and white matter. Instead of searching genetic variants by testing the association between a phenotype trait and the genotype of each single-nucleotide polymorphism (SNP) as in GWAS, REL takes advantage of multiple SNPs within a genomic window as a single measure, which potentially find associations wherever the functional SNP is in linkage disequilibrium (LD) with SNPs that have been sampled. We also conducted a simulation analysis to systemically compare GWAS and REL with respect to different levels of LD. Both methods succeed in identifying genetic variations associated with regional and global brain structural measures and tend to give complementary results due to the different aspects of genetic properties used. Simulation results suggest that GWAS outperforms REL when the signal is relatively weak. However, the collective effects due to local LD boost the performance of REL with increasing signal strength, resulting in better performance than GWAS. Our study suggests that the optimal approach may vary across the genome and that pre-testing for LD could allow GWAS to be preferred where LD is high and REL to be used where LD is low, or the local pattern of LD is complex.
Targeted Transcriptome Analysis using Synthetic Long Read Sequencing Uncovers Isoform Reprograming in the Progression of Colon Cancer
Authors: Liu Silvia , Wu Indira , Yu Yan-Ping , Balamotis Michael , Ren Baoguo , Yehezkel Tuval Ben , Luo Jian-Hua 
Published: August 2020

AbstractDiversity in human gene expression stems, to a large extent, from splicing exons into multiple mRNA isoforms. Characterization of isoforms requires accurate long-read sequencing. However, read lengths, high error rates, low throughput and large input requirements are some of the challenges that remain to be addressed in sequencing technologies.In this study, we used a barcoding-based synthetic long read (SLR) isoform sequencing approach, LoopSeq, to generate sequencing reads sufficiently long and accurate to identify isoforms using standard short read Illumina sequencers. The method identifies isoforms from control RNA samples with 99.4% accuracy and a 0.01% per-base error rate, exceeding the accuracy reported for other long-read sequencing technologies.Applied to targeted transcriptome sequencing of over 10,000 genes from colon cancers and their metastatic counterparts, LoopSeq revealed large scale isoform redistributions from benign colon mucosa to primary colon cancer and metastatic cancer and identified several novel gene fusion isoforms in the colon cancer samples. Strikingly, our data showed that most single nucleotide variants (SNV’s) occurred dominantly in specific isoforms and that some SNVs underwent isoform switching in cancer progression.The ability to use short read sequencers to generate accurate long-read isoform information as the raw unit of transcriptional information holds promise as a new and widely accessible approach in RNA isoform analyses.
BrumiR: A toolkit forde novodiscovery of microRNAs from sRNA-seq data
Authors: Moraga Carol , Sanchez Evelyn , Ferrarini Mariana Galvão , Gutierrez Rodrigo A. , Vidal Elena A. , Sagot Marie-France 
Published: August 2020

AbstractMicroRNAs (miRNAs) are small non-coding RNAs that are key players in the regulation of gene expression. In the last decade, with the increasing accessibility of high-throughput sequencing technologies, different methods have been developed to identify miRNAs, most of which rely on pre-existing reference genomes. However, when a reference genome is absent or is not of high quality, such identification becomes more difficult. In this context, we developed BrumiR, an algorithm that is able to discover miRNAs directly and exclusively from sRNA-seq data. We benchmarked BrumiR with datasets encompassing animal and plant species using real and simulated sRNA-seq experiments. The results demonstrate that BrumiR reaches the highest recall for miRNA discovery, while at the same time being much faster and more efficient than the state-of-the-art tools evaluated. The latter allows BrumiR to analyze a large number of sRNA-seq experiments, from plants or animals species. Moreover, BrumiR detects additional information regarding other expressed sequences (sRNAs, isomiRs, etc.), thus maximizing the biological insight gained from sRNA-seq experiments. Finally, when a reference genome is available, BrumiR provides a new mapping tool (BrumiR2ref) that performs ana posterioriexhaustive search to identify the precursor sequences. The code of BrumiR is freely available athttps://github.com/camoragaq/BrumiR.
Epigenetic change induced byin uterodietary challenge provokes phenotypic variability across multiple generations of mice
Authors: Van de Pette Mathew , Galvao Antonio , Millership Steven J. , To Wilson , Dimond Andrew , Prodani Chiara , McNamara Grainne , Bruno Ludovica , Sardini Alessandro , Webster Zoe , McGinty James , French Paul , Uren Anthony G. , Castillo-Fernandez Juan , John Rosalind M. , Ferguson-Smith Anne C. , Merkenschlager Matthias , Kelsey Gavin , Fisher Amanda G. 
Published: August 2020

AbstractTransmission of epigenetic information between generations occurs in nematodes, flies and plants, mediated by specialised small RNA pathways, histone H3K9me3, H3K27me3, H4K16ac and DNA methylation1-3. In higher vertebrates, epidemiological and experimental evidence supports similar trans-generational effects4,5although the mechanisms that underpin these are incompletely understood6-9. We generated a luciferase reporter knock-in mouse for the imprintedDlk1locus, to visualise and track epigenetic fidelity across generations. We showed that exposure to high-fat diet (HFD) in pregnancy provokes sustained re-expression of the normally silent maternalDlk1allele in offspring, coincident with increased DNA methylation at theDlk1 sDMR. Interestingly, maternalDlk1mis-expression was also evident in the next generation (F2), exclusively in animals derived from F1-exposed females. Oocytes from these females showed altered microRNA and gene expression, without any major changes in underlying DNA methylation, and correctly imprintedDlk1expression resumed in subsequent generations (F3 onwards). Our results reveal how canonical and non-canonical imprinting mechanisms enable the foetal epigenome to adapt toin uterochallenge to modulate the properties of two successive generations of offspring.
Characterization of a novel gene,srpA, conferring resistance to streptogramin A, pleuromutilins, and lincosamides inStreptococcus suis
Authors: Zhang Chaoyang , Liu Lu , Zhang Peng , Cui Jingpo , Qin Xiaoxia , Ma Lichao , Han Kun , Wang Zhanhui , Wang Shaolin , Ding Shuangyang , Shen Zhangqi 
Published: August 2020

AbstractAntimicrobial resistance is undoubtedly one of the greatest global health threats. The emergence of multidrug-resistant (MDR) gram-positive pathogens, like methicillin-resistantStaphylococcus aureus, vancomycin-resistantEnterococcus faecium, and β-lactamase-resistantStreptococcus pneumonia, has severely limited our antibiotic arsenal. Numerous ribosome-targeting antibiotics, especially pleuromutilins, oxazolidinones, and streptogramins, are viewed as promising alternatives against aggressive MDR pathogens. In this study, we identified a new ABC-F family determinant,srpA, inStreptococcus suisby a comparative analysis of whole genome sequences of tiamulin-resistant and -sensitive bacteria. Functional cloning confirmed that the deduced gene can mediate cross-resistance to pleuromutilins, lincosamides, and streptogramin A inS. suisandS. aureus. A sequence alignment revealed thatsrpAshares the highest amino acid identity with Vga(E) (36%) and shows canonical characteristics of ABC-F family members. In SrpA–ribosome docked compounds, the extended loop region of SrpA approaches the valnemulin binding pocket in the ribosome peptidyl-transferase center and competes with bound valnemulin. A detailed mutational analysis of the loop residues confirmed that this domain is crucial for SrpA activity, as substitutions or truncations of this region affect the efficiency and specificity of antibiotic resistance. A ribosome binding assay supported the protective effects of SrpA on the ribosome by preventing antibiotic binding as well as displacing bound drugs. These findings clarify the mechanisms underlying resistance to ribosomal antibiotics.
Innovation in NLR and TLR sensing drives the MHC-II free Atlantic cod immune system
Authors: Jin Xingkun , Morro Bernat , Tørresen Ole K. , Moiche Visila , Solbakken Monica H. , Jakobsen Kjetill S. , Jentoft Sissel , MacKenzie Simon 
Published: August 2020

AbstractThe genome sequencing of Atlantic cod revealed an immune system absent of specific cell surface toll-like receptors (TLRs), major histocompatibility complex (MHC) class II, invariant chain (CD74) and the CD4 (cluster of differentiation 4) receptor. Despite the loss of these major components considered as critical to vertebrate innate and adaptive immune systems the cod system is fully functional, however the underlying mechanisms of the immune response in cod remain largely unknown. In this study,ex vivocod macrophages were challenged with various bacterial and viral microbe-associated molecular patterns (MAMP) to identify major response pathways. Cytosolic MAMP-PRR pathways based upon the NOD-like receptors (NLRs) and RIG-I-like receptors (RLRs) were identified as the critical response pathways. Our analyses suggest that internalization of exogenous ligands through scavenger receptors drives both pathways activating transcription factors like NF-kB (Nuclear factor-kappa B) and interferon regulatory factors (IRFs). Further, ligand-dependent differential expression of a unique TLR25 isoform and multiple NLR paralogues suggests (sub)neofunctionalisation toward specific immune defensive strategies. Our results further demonstrate that the unique immune system of the Atlantic cod provides an unprecedented opportunity to explore the evolutionary history of PRR-based signalling in vertebrate immunity.
Hidden population modes in social brain morphology: Its parts are more than its sum
Authors: Kiesow Hannah , Spreng R. Nathan , Holmes Avram J. , Chakravarty M. Mallar , Marquand Andre F. , Yeo B.T. Thomas , Bzdok Danilo 
Published: August 2020

AbstractThe complexity of social interactions is a defining property of the human species. Many social neuroscience experiments have sought to map ‘perspective taking’, ‘empathy’, and other canonical psychological constructs to distinguishable brain circuits. This predominant research paradigm was seldom complemented by bottom-up studies of the unknown sources of variation that add up to measures of social brain structure; perhaps due to a lack of large population datasets. We aimed at a systematic de-construction of social brain morphology into its elementary building blocks in the UK Biobank cohort (n=~10,000). Coherent patterns of structural co-variation were explored within a recent atlas of social brain locations, enabled through translating autoencoder algorithms from deep learning. The artificial neural networks learned rich subnetwork representations that became apparent from social brain variation at population scale. The learned subnetworks carried essential information about the co-dependence configurations between social brain regions, with the nucleus accumbens, medial prefrontal cortex, and temporoparietal junction embedded at the core. Some of the uncovered subnetworks contributed to predicting examined social traits in general, while other subnetworks helped predict specific facets of social functioning, such as feelings of loneliness. Our population-level evidence indicates that hidden subsystems of the social brain underpin interindividual variation in dissociable aspects of social lifestyle.
NusG is an intrinsic transcription termination factor that stimulates motility and coordinates global gene expression with NusA
Authors: Mandell Zachary F. , Oshiro Reid T. , Yakhnin Alexander V. , Kashlev Mikhail , Kearns Daniel B. , Babitzke Paul 
Published: August 2020

AbstractNusA and NusG are transcription elongation factors that stimulate RNA polymerase pausing inBacillus subtilis. While NusA was known to function as an intrinsic termination factor, the role of NusG in this process had not been explored. To examine the individual and combinatorial roles that NusA and NusG play in intrinsic termination, Term-seq was conducted in wild type, NusA depletion, ΔnusG, and NusA depletion ΔnusGstrains. We determined that NusG functions as an intrinsic termination factor that works alone and cooperatively with NusA to facilitate termination at 88% of the 1,400 identified intrinsic terminators. The loss of both proteins leads to global misregulation of gene expression. Our results indicate that NusG stimulates a sequence-specific pause that assists in the completion of suboptimal terminator hairpins with weak terminal A-U and G-U base pairs at the bottom of the stem. Moreover, the loss of NusG results in flagella and swimming motility defects.
Metabolic potential and survival strategies of microbial communities across extreme temperature gradients on Deception Island volcano, Antarctica
Authors: Bendia Amanda Gonçalves , Lemos Leandro Nascimento , Mendes Lucas William , Signori Camila Negrão , Bohannan Brendan J. M. , Pellizari Vivian Helena 
Published: August 2020

AbstractActive volcanoes in Antarctica, in contrast to the rest of the icy landscape, have remarkable temperature and geochemical gradients that could select for a wide variety of microbial adaptive mechanisms and metabolic pathways. Deception Island is a stratovolcano flooded by the sea, resulting in contrasting ecosystems such as permanent glaciers (<0 °C) and active fumaroles (up to 100 °C). Steep gradients in temperature, salinity and geochemistry over very short distances have been reported for Deception Island, and have been shown to effect microbial community structure and diversity. However, little is known regarding how these gradients affect ecosystem functioning, for example due to inhibition of key metabolic enzymes or pathways. In this study, we used shotgun metagenomics and metagenome-assembled genomes to explore how microbial functional diversity is shaped by extreme geochemical, salinity and temperature gradients in fumarole and glacier sediments. We observed that microbial communities from a 98 °C fumarole harbor specific hyperthermophilic molecular strategies, as well as reductive and autotrophic pathways, while those from <80 °C fumaroles possess more diverse metabolic and survival strategies capable of responding to fluctuating redox and temperature conditions. In contrast, glacier communities showed less diverse metabolic potentials, comprising mainly heterotrophic and carbon pathways. Through the reconstruction of genomes, we were able to clarify putative novel lifestyles of underrepresented taxonomic groups, especially those related to Nanoarchaeota and thermophilic ammonia-oxidizing archaeal lineages. Our results enhance understanding of the metabolic and survival capabilities of different extremophilic lineages of Bacteria and Archaea.
Replay as structural inference in the hippocampal-entorhinal system
Authors: Evans Talfan , Burgess Neil 
Published: August 2020

AbstractModel-based decision making relies on the construction of an accurate representation of the underlying state-space, and localization of one’s current state within it. One way to localize is to recognize the state with which incoming sensory observations have been previously associated. Another is to update a previous state estimate given a known transition. In practice, both strategies are subject to uncertainty and must be balanced with respect to their relative confidences; robust learning requires aligning the predictions of both models over historic observations. Here, we propose a dual-systems account of the hippocampal-entorhinal system, where sensory prediction errors between these models duringonlineexploration of state space initiateofflineprobabilistic inference.Offlineinference computes ametricembedding on grid cells of anassociativeplace graph encoded in the recurrent connections between place cells, achieved by message passing between cells representing non-local states. We provide testable explanations for coordinated place and grid cell ‘replay’ as efficient message passing, and for distortions, partial rescaling and direction-dependent offsets in grid patterns as the confidence weighted balancing of model priors, and distortions to grid patterns as reflecting inhomogeneous sensory inputs across states.Author SummaryMinimising prediction errors between transition and sensory input (observation) models predicts partial rescaling and direction-dependent offsets in grid cell firing patterns.Inhomogeneous sensory inputs predict distortions of grid firing patterns duringonlinelocalisation, and local changes of grid scale duringofflineinference.Principled information propagation duringofflineinference predicts coordinated place and grid cell ‘replay’, where sequences propagate between structurally related features.
Remodeling hydrogen bond interactions results in relaxed specificity of Caspase-3
Authors: Yao Liqi , Swartz Paul , Hamilton Paul , Clark A. Clay 
Published: August 2020

AbstractCaspase enzymes play important roles in apoptosis and inflammation, and the non-identical but overlapping specificity profiles direct cells to different fates. Although all caspases prefer aspartate at the P1 position of the substrate, the caspase-6 subfamily shows preference for valine at the P4 position, while caspase-3 shows preference for aspartate. In comparison to human caspases, caspase-3a from zebrafish has relaxed specificity and demonstrates equal selection for either valine or aspartate at the P4 position. In the context of the caspase-3 conformational landscape, we show that changes in hydrogen bonding near the S3 subsite affect selection of the P4 amino acid. Swapping specificity with caspase-6 requires accessing new conformational space, where each landscape results in optimal binding of DxxD (caspase-3) or VxxD (caspase-6) substrate and simultaneously disfavors binding of the other substrate. Within the context of the caspase-3 conformational landscape, substitutions near the active site result in nearly equal activity against DxxD and VxxD by disrupting a hydrogen bonding network in the substrate binding pocket. The converse substitutions in zebrafish caspase-3a result in increased selection for P4 aspartate over valine. Overall, the data show that evolutionary neofunctionalization resulting in a dual function protease, as in zebrafish caspase-3a, requires fewer amino acid substitutions compared to those required to access new conformational space for swapping substrate specificity, such as between caspases-3 and −6.
Body mass variations relate to fractionated functional brain hierarchies
Authors: Park Bo-yong , Park Hyunjin , Morys Filip , Kim Mansu , Byeon Kyoungseob , Lee Hyebin , Kim Se-Hong , Valk Sofie , Dagher Alain , Bernhardt Boris C. 
Published: August 2020

AbstractVariations in body mass index (BMI) have been suggested to relate to atypical brain organization, yet connectome-level substrates of BMI and their neurobiological underpinnings remain unclear. Studying 325 healthy young adults, we examined association between functional connectome organization and BMI variations. We capitalized on connectome manifold learning techniques, which represent macroscale functional connectivity patterns along continuous hierarchical axes that dissociate low level and higher order brain systems. We observed an increased differentiation between unimodal and heteromodal association networks in individuals with higher BMI, indicative of an increasingly segregated modular architecture and a disruption in the hierarchical integration of different brain system. Transcriptomic decoding and subsequent gene enrichment analyses identified genes previously implicated in genome-wide associations to BMI and specific cortical, striatal, and cerebellar cell types. These findings provide novel insights for functional connectome substrates of BMI variations in healthy young adults and point to potential molecular associations.
Halal food: structured literature review and research agenda
Authors: Secinaro Silvana , Calandra Davide 
Published: August 2020

PurposeThis study reviews and critiques the halal food literature, a growing field of research. In addition, the authors classify the significant themes in this research stream, outline opportunities for future research directions and offer a future research agenda.Design/methodology/approachA sample of 221 scholarly articles published from 1997 to 2020 was investigated using the structured literature review method of Massaro et al. (2016). The authors used the bibliometrix R-package and VOSviewer software to mine information about journals, articles, authors, citations, keywords and countries.FindingsThe analysis reveals five research clusters: halal food and the role of certifications, halal food and awareness, halal food production and quality, halal food in tourism management and halal food and the supply chain. The primary research flow comes from Asia. However, collaborations are also emerging in other continents. In addition, scholars should consider stressing the links among halal food and sustainability, innovation and technology.Research limitations/implicationsThe study analyses this field from a broad perspective, but only considers articles published in the Scopus database. Future research could extend the research methodologies used by, for example, considering mixed method analysis.Originality/valueDespite several studies in the field, no studies have thus far reviewed the literature on halal food to the best of the authors' knowledge. Hence, the presented analysis, using pioneering methods considering sustainability and innovation as priorities, provides a starting point for future research.