bluuebunny/crossref_metadata_2025_split huggingface dataset:
White Matter Microstructure in Habit and Reward Circuits in Anorexia Nervosa: Insights from a Neurite Orientation Dispersion and Density Imaging Study
Authors: Murray Stuart B. , Cabeen Ryan P. , Jann Kay , Tadayonnejad Reza , Strober Michael , Feusner Jamie D. 
Published: July 2022

AbstractBackgroundBehavioural features of anorexia nervosa (AN) suggest abnormalities in reward and habit. Neuroimaging evidence suggests morphometric and functional perturbations within these circuits, although fewer studies have assessed white matter characteristics in AN, and no studies to date have assessed white matter microstructure in AN.MethodsIn this brain imaging study, 29 female adolescents with partially or fully weight-restored AN and 27 healthy controls, all between 10-19 years, underwent whole-brain multi-shell diffusion tensor imaging. Utilizing neurite orientation dispersion and density imaging methods, we investigated group differences in white matter neurite density, orientation dispersion, and myelin density in tracts between prominent nodes of the reward circuit (ventral tegmental area (VTA) to nucleus accumbens (NAcc)) and the habit circuit (sensory motor area (SMA) to putamen).ResultsFindings revealed reduced neurite (F=5.20, p=0.027) and myelin density (F=5.39, p=0.025) in the left VTA-NAcc tract, and reduced orientation dispersion in the left (F=7.00, p=0.011) and right (F=6.77, p=0.012) VTA-NAcc tract. There were no significant group differences in the SMA-putamen tract. Significant relationships, after corrections, were not evident between tract microstructure and reward responsiveness, compulsive behaviours, illness duration, or BMI.ConclusionsAdolescents with AN exhibit less dense, undermyelinated, and less dispersed white matter tracts connecting prominent reward system nodes, which may signify underutilization of this part of the reward circuit. These results provide a detailed examination of white matter microstructure in tracts underlying instrumental behavioral phenotypes contributing to illness in AN.
Active mRNA degradation by EXD2 nuclease elicits recovery of transcription after genotoxic stress
Authors: Sandoz Jérémy , Cigrang Max , Catez Philippe , Donnio Lise-Marie , Elly Clèmence , Berico Pietro , Braun Cathy , Alekseev Sergey , Egly Jean-Marc , Mari-Giglia Guiseppina , Compe Emmanuel , Coin Frédéric 
Published: July 2022

AbstractThe transcriptional response to genotoxic stress involves gene expression arrest, followed by recovery of mRNA synthesis (RRS) after DNA repair. Using a small-scale RNA interference screen, we found that the lack of the EXD2 nuclease impaired RRS and decreased cell survival after UV irradiation, without affecting DNA repair. Overexpression of wild-type, but not nuclease-dead EXD2, restored RRS and cell survival. We observed that UV irradiation triggered recruitment of EXD2 to chromatin where the nuclease transiently interacts with RNA Polymerase II (RNAPII) to promote the degradation of nascent mRNAs synthesized at the time of genotoxic attack. Reconstitution of the EXD2-RNAPII partnership on a transcribed DNA template in vitro showed that EXD2 primarily interacts with an elongation-blocked RNAPII and efficiently digest mRNA. Overall, our data highlight a crucial new step in the transcriptional response to genotoxic attack in which EXD2 interacts with elongation-stalled RNAPII on chromatin to degrade the associated nascent mRNA, allowing transcription restart after DNA repair.
Identification of prognostic biomarkers for suppressing tumorigenesis and metastasis of Hepatocellular carcinoma through transcriptome analysis
Authors: Mishra Divya , Mishra Ashish , Singh M.P. 
Published: July 2022

AbstractCancer is one of the deadliest diseases developed through tumorigenesis and could be fatal if reached at metastatic phase. The novality of present investigation is to explore the prognostic biomarkers in hepatocellular carcinoma (HCC) that could develop glioblastoma multiforme (GBM) due to metastasis. The analysis was done using RNA-Seq datasets for both HCC (PRJNA494560 and PRJNA347513) and GBM (PRJNA494560 and PRJNA414787) from Gene Expression Omnibus (GEO). This study identified 13 hub genes found to be overexpressed in both GBM and HCC. Promoter methylation study showed these genes to be hypomethylated. Validation through genetic alteration and missense mutations resulted in chromosomal instability leading to improper chromosome segregation causing aneuploidy. A 13-gene predictive model was obtained and validated using KM plot. These hub genes could be prognostic biomarkers and potential therapeutic targets, inhibition of which could suppress tumorigenesis and metastasis.
Acanthamoeba polyphaga de novo transcriptome and its dynamics during Mimivirus infection
Authors: Nuri Reut , Feldmesser Ester , Fridmann-Sirkis Yael , Keren-Shaul Hadas , Nevo Reinat , Minsky Abraham , Reich Ziv 
Published: July 2022

AbstractAcanthamoeba polyphaga mimivirus (Mimivirus) is a giant virus that infects Acanthamoeba species – opportunistic human pathogens. We applied long- and short-read sequencing to generate a de novo transcriptome of the host and followed the dynamics of both host and virus transcriptomes over the course of infection. The assembled transcriptome of the host included 22,604 transcripts and 13,043 genes, with N50 = 2,372 nucleotides. Functional enrichment analysis revealed major changes in the host transcriptome, namely, enrichment in downregulated genes associated with cytoskeleton homeostasis and DNA replication, repair, and nucleotide synthesis. These modulations, together with those implicated by other enriched processes, indicate cell cycle arrest, an event we demonstrated experimentally. We also observed upregulation of host genes associated with transcription, secretory pathways and, as reported here for the first time, peroxisomes and the ubiquitin-proteasome system. In Mimivirus, the early stages of infections were marked by upregulated genes related to DNA replication, transcription, translation, and nucleotide metabolism, and the later stages, by enrichment in genes associated with lipids metabolism, carbohydrates, and proteases. Some of the changes observed in the amoebal transcriptome likely point to Mimivirus infection causing the dismantling of the host cytoskeleton, the translocation of endoplasmic reticulum membranes to viral factory areas, and cell cycle arrest.
Frameshift Mutations in the Microevolution and Macroevolution of Viruses
Authors: Ji Yu-Fei , Shao Jian-Wei , Chen Rui-Xu , Gong Huan-Yu , Sun Ming-Hui , Li Guo-Hui , Chen Ji-Ming 
Published: July 2022

ABSTRACTSome nucleotide insertions or deletions (indels) in open reading frames of virus genes lead to frameshift mutations (FSMs), which can drastically change amino acid sequences. Most FSMs are deleterious and inhibited by natural selection, but some FSMs could aid viruses in adapting to new hosts, escaping immunity, or changing viral pathogenicity or transmissibility. Surprisingly, various fundamental aspects of FSMs in virus evolution remain unknown. In this report, we identified 679 FSMs in the genomes of viruses from 13 randomly selected animal virus families using randomly selected sequences. The 679 FSMs were formed with 1−5 indels, and most (89.4%) FSMs were fixed through the compensatory mechanism with two indels. Each FSM changed 3−209 (mean=15.4, median=13) amino acid residues. FSM frequencies were usually higher in viral sequences with lower sequence identities and steeply increased when sequence identities declined to 60.0%−69.9% or 70.0%−79.9%. This suggests that FSMs are more important to the macroevolution (i.e., inter-species evolution, including speciation) than to the microevolution (i.e., intra-species evolution) of viruses. This study provided novel evidence for the hopeful monster hypothesis in evolutionary biology. Furthermore, we found that FSMs occurred at different frequencies among genes in the same virus genomes and among virus families. Collectively, this study revealed multiple fundamental features of FSMs in virus evolution for the first time and provided novel insights into the mechanisms of macroevolution and speciation.
Predicting the unpredictable: heatwaves and history of variability shape phytoplankton community thermal responses within one generation
Authors: Santelia Maria Elisabetta , Listmann Luisa , Schnell Stefanie , Schaum Elisa 
Published: July 2022

AbstractPredicting the effect of increased thermal unpredictability, for example in the shape of heatwaves on phytoplankton metabolic responses is ripe with challenges. While single genotypes in laboratory environments will respond to environmental fluctuations in predictable and repeatable ways, it is difficult to relate rapid evolutionary responses of whole communities to their ecological history. Previously experienced environments, including fluctuations therein, can shape an organism’s specific niche as well as their responses to further environmental changes. This is a testable hypothesis as long as samples can be obtained where the environmental history is known, sufficiently diverse, and not obscured by confounding parameters such as day length and precipitation patterns. Here, we tested immediate (i.e. within one generation) metabolic temperature responses of natural phytoplankton assemblages from two thermally distinct regions in the Baltic Sea: the warmer and less predictable Kiel Area, and the overall colder and more predictable Bornholm Basin. Our approach allows us to investigate effects on immediate physiological time scales (responses curves), ecological and evolutionary processes on longer time scales (seasonal differences between basins) as well as mid-term responses during a natural occurring heatwave. We found evidence for a higher degree of phenotypic plasticity in samples from unpredictable environments (Kiel Area).
ABC-transporter CFTR folds with high fidelity through a modular, stepwise pathway
Authors: Im Jisu , Hillenaar Tamara , Yeoh Hui Ying , Sahasrabudhe Priyanka , Mijnders Marjolein , van Willigen Marcel , van der Sluijs Peter , Braakman Ineke 
Published: July 2022

ABSTRACTThe question how proteins fold is especially pointed for large multidomain, multispanning membrane proteins with complex topologies. We have uncovered the sequence of events that encompass proper folding of the ABC transporter CFTR in live cells, by combining kinetic radiolabeling with protease-susceptibility assays. We found that CFTR folds in two clearly distinct stages. The first, co-translational, stage involves folding of the 2 transmembrane domains TMD1 and TMD2, plus one nucleotide-binding domain, NBD1. The second stage is a simultaneous, post-translational increase in protease resistance for both TMDs and NBD2 caused by assembly of these domains onto NBD1.Our technology probes every 2-3 residues (on average) in CFTR. This in-depth analysis at amino-acid level allows detailed analysis of domain folding and importantly also the next level: the assembly of the domains to native, folded CFTR. Defects and changes brought about by medicines, chaperones or mutations also are amenable to analysis. We here show that the DXD motif in NBD1 that was identified to be required for export of CFTR from the ER turned out to be required for proper domain folding and assembly instead, upstream of transport. CFTR mutated in this motif phenocopies the misfolding and degradation of the well-known disease-causing mutant F508del that established cystic fibrosis as protein-folding disease. The highly modular process of domain folding and stepwise domain assembly explains the relatively high fidelity of folding and the importance of a step-wise folding process for such complex proteins.
HAT: Haplotype Assembly Tool using short and error-prone long reads
Authors: Shirali Hossein Zade Ramin , Urhan Aysun , Assis de Souza Alvaro , Singh Akash , Abeel Thomas 
Published: July 2022

AbstractMotivationHaplotypes are the set of alleles cooccurring on a single chromosome and inherited together to the next generation. Because a monoploid reference genome loses this co-occurrence information, its usability is limited to associate phenotypes with allelic combinations of genotypes. Therefore, methods to reconstruct the complete haplotypes from DNA sequencing data are crucial. Recently, several attempts have been made at haplotype reconstructions, but significant limitations remain. High-quality continuous haplotypes cannot be created reliably, particularly when there are few differences between the homologous chromosomes.ResultsHere, we introduce HAT, a haplotype assembly tool that exploits short and long reads along with a reference genome to reconstruct haplotypes. HAT tries to take advantage of the accuracy of short reads and the length of the long reads to reconstruct haplotypes. We tested HAT on the aneuploid yeast strain Saccharomyces pastorianus CBS1483 and multiple simulated polyploid data sets of the same strain, showing that it outperforms existing tools.Availabilityhttps://github.com/AbeelLab/hat/Contactt.abeel@tudelft.nl
Extracellular vesicle microRNAs contribute to Notch signaling pathway in T-Cell Acute Lymphoblastic Leukemia
Authors: Colangelo Tommaso , Panelli Patrizio , Mazzarelli Francesco , Tamiro Francesco , Melocchi Valentina , Palumbo Orazio , Rossi Giovanni , Giambra Vincenzo , Bianchi Fabrizio 
Published: July 2022

AbstractT-cell acute lymphoblastic leukemia (T-ALL) is an aggressive T-cell malignancy characterized by genotypically-defined and phenotypically divergent cell populations, governed by adaptive landscapes. Clonal expansions are associated to genetic and epigenetic events, and modulation of external stimuli that affect the hierarchical structure of subclones and support the dynamics of leukemic subsets. Recently, small extracellular vesicles (sEV) such exosomes were also shown to play a role in leukemia. Here, by coupling miRNome, bulk and single cell transcriptome profiling, we found that T-ALL-secreted sEV contain NOTCH1-dependent microRNAs (EV-miRs), which control oncogenic pathways acting as autocrine stimuli and ultimately promoting the expansion/survival of highly proliferative cell subsets of human T-cell leukemias. Of interest, we found that NOTCH1-dependent EV-miRs mostly comprised members of miR-17-92a cluster and paralogues, which rescued in vitro the proliferation of T-ALL cells blocked by γ-secretase inhibitors (GSI) and regulate network of genes characterizing patients with relapsed/refractory early T-cell progenitor (ETP) ALLs. All these findings suggest that NOTCH1 dependent EV-miRs may sustain the growth/survival of immunophenotypically defined cell populations, altering the cell heterogeneity and the dynamics of T-cell leukemias in response to conventional therapies.
Midgut bacterial microbiota of 12 fish species from a marine protected area in the Aegean Sea (Greece)
Authors: Kormas Konstantinos , Nikouli Eleni , Kousteni Vasiliki , Damalas Dimitrios 
Published: July 2022

ABSTRACTFish microbiome science is progressing fast, but it is biased toward farmed or laboratory fish species against natural fish populations, which remain considerably underinvestigated. We analysed the midgut bacterial microbiota of 45 specimens of 12 fish species collected from the Gyaros Island marine protected area (Aegean Sea, Greece). The species belong to seven taxonomic families and are either herbivores or omnivores. Mucosa midgut bacterial diversity was assessed by amplicon metabarcoding of the 16S rRNA V3–V4 gene region. A total of 854 operational taxonomic units were identified. In each fish species, between 2 and 18 OTUs dominated with cumulative relative abundance ≥70%. Most of the dominating bacterial taxa have been reported to occur both in wild and farmed fish populations. The midgut bacterial communities were different among the 12 fish, except forPagrus pagrusandPagellus erythrinus, which belong to the Sparidae family. No differentiation of the midgut bacterial microbiota was found based on feeding habits, i.e., omnivorous vs. carnivorous. Comparing wild and farmedP. pagrusmidgut bacterial microbiota revealed considerable variation between them. Our results expand the gut microbiota of wild fish and support the host species effect as the more likely factor shaping intestinal bacterial microbiota.
Multi-ancestry GWAS of major depression aids locus discovery, fine-mapping, gene prioritisation, and causal inference
Authors: Meng Xiangrui , Navoly Georgina , Giannakopoulou Olga , Levey Daniel , Koller Dora , Pathak Gita , Koen Nastassja , Lin Kuang , Rentería Miguel E. , Feng Yanzhe , Gaziano J. Michael , Stein Dan J. , Zar Heather J. , Campbell Megan L. , van Heel David A. , Trivedi Bhavi , Finer Sarah , McQuillin Andrew , Bass Nick , Chundru V. Kartik , Martin Hilary , Huang Qin Qin , Valkovskaya Maria , Kuo Po-Hsiu , Chen Hsi-Chung , Tsai Shih-Jen , Liu Yu-Li , Kendler Kenneth S. , Peterson Roseann E. , Cai Na , Fang Yu , Sen Srijan , Scott Laura , Burmeister Margit , Loos Ruth , Preuss Michael , Actkins Ky’Era V. , Davis Lea K. , Uddin Monica , Wani Agaz , Wildman Derek , Ursano Robert J. , Kessler Ronald C. , Kanai Masahiro , Okada Yukinori , Sakaue Saori , Rabinowitz Jill , Maher Brion , Uhl George , Eaton William , Cruz-Fuentes Carlos S. , Martinez-Levy Gabriela A. , Campos Adrian I. , Millwood Iona Y. , Chen Zhengming , Li Liming , Wassertheil-Smoller Sylvia , Jiang Yunxuan , Tian Chao , Martin Nicholas G. , Mitchell Brittany L. , Byrne Enda M. , Wray Naomi R. , Awasthi Swapnil , Coleman Jonathan R. I. , Ripke Stephan ,   PGC MDD Working Group,   China Kadoorie Biobank Collaborative Group,   the 23andMe Research Team,   Genes & Health Research Team, Sofer Tamar , Walters Robin G. , Polimanti Renato , Dunn Erin C. , Stein Murray B. , Gelernter Joel , Lewis Cathryn , Kuchenbaecker Karoline 
Published: July 2022

AbstractMost genome-wide association studies (GWAS) of major depression (MD) have been conducted in samples of European ancestry. Here we report a multi-ancestry GWAS of MD, adding data from 21 studies with 88,316 MD cases and 902,757 controls to previously reported data from individuals of European ancestry. This includes samples of African (36% of effective sample size), East Asian (26%) and South Asian (6%) ancestry and Hispanic/Latinx participants (32%). The multi-ancestry GWAS identified 190 significantly associated loci, 53 of them novel. For previously reported loci from GWAS in European ancestry the power-adjusted transferability ratio was 0.6 in the Hispanic/Latinx group and 0.3 in each of the other groups. Fine-mapping benefited from additional sample diversity: the number of credible sets with ≤5 variants increased from 3 to 12. A transcriptome-wide association study identified 354 significantly associated genes, 205 of them novel. Mendelian Randomisation showed a bidirectional relationship with BMI exclusively in samples of European ancestry. This first multi-ancestry GWAS of MD demonstrates the importance of large diverse samples for the identification of target genes and putative mechanisms.
Superficial white matter across the lifespan: volume, thickness, change, and relationship with cortical features
Authors: Schilling Kurt G , Archer Derek , Rheault Francois , Lyu Ilwoo , Huo Yuankai , Cai Leon Y , Bunge Silvia A , Weiner Kevin S , Gore John C , Anderson Adam W , Landman Bennett A 
Published: July 2022

AbstractSuperficial white matter (SWM) represents a significantly understudied part of the human brain, despite comprising a large portion of brain volume and making up a majority of cortical structural connections. Using multiple, high-quality, datasets with large sample sizes (N=2421, age range 5-100) in combination with methodological advances in tractography, we quantified features of SWM volume and thickness across the brain and across the lifespan. We address four questions: (1) How does U-fiber volume change with age? (2) What does U-fiber thickness look like across the brain? (3) How does SWM thickness change with age? (4) Are there relationships between SWM thickness and cortical features? Our main findings are that (1) SWM volume shows unique volumetric trajectories with age that are distinct from gray matter and other white matter trajectories; (2) SWM thickness varies across the brain, with patterns robust across individuals and across the population at the region-level and vertex-level; (3) SWM shows nonlinear changes across the lifespan that vary across regions; and (4) SWM thickness is associated with cortical thickness and curvature. For the first time, we show that SWM volume follows a similar trend as overall white matter volume, peaking at a similar time in adolescence, leveling off throughout adulthood, and decreasing with age thereafter. Notably, the relative fraction of total brain volume of SWM continuously increases with age, and consequently takes up a larger proportion of total white matter volume, unlike the other tissue types that decrease with respect to total brain volume. This study represents the first characterization of SWM features across the lifespan and provides the background for characterizing normal aging and insight into the mechanisms associated with SWM development and decline.
Environmental control for X-ray nanotomography
Authors: Holler Mirko , Aidukas Tomas , Heller Lars , Appel Christian , Phillips Nicholas W. , Müller-Gubler Elisabeth , Guizar-Sicairos Manuel , Raabe Jörg , Ihli Johannes 
Published: July 2022

The acquisition speed and spatial resolution of X-ray nanotomography have continuously improved over the last decades. Coherent diffraction-based techniques breach the 10 nm resolution barrier frequently and thus pose stringent demands on sample positioning accuracy and stability. At the same time there is an increasing desire to accommodate in situ or operando measurements. Here, an environmental control system for X-ray nanotomography is introduced to regulate the temperature of a sample from room temperature up to 850°C in a controlled atmospheric composition. The system allows for a 360° sample rotation, permitting tomographic studies in situ or operando free of missing wedge constraints. The system is implemented and available at the flOMNI microscope at the Swiss Light Source. In addition to the environmental control system itself, the related modifications of flOMNI are described. Tomographic measurements of a nanoporous gold sample at 50°C and 600°C at a resolution of sub-20 nm demonstrate the performance of the device.
Improving handwritten digit recognition using hybrid feature selection algorithm
Authors: Chin Fung Yuen , Lem Kong Hoong , Wong Khye Mun 
Published: July 2022

PurposeThe amount of features in handwritten digit data is often very large due to the different aspects in personal handwriting, leading to high-dimensional data. Therefore, the employment of a feature selection algorithm becomes crucial for successful classification modeling, because the inclusion of irrelevant or redundant features can mislead the modeling algorithms, resulting in overfitting and decrease in efficiency.Design/methodology/approachThe minimum redundancy and maximum relevance (mRMR) and the recursive feature elimination (RFE) are two frequently used feature selection algorithms. While mRMR is capable of identifying a subset of features that are highly relevant to the targeted classification variable, mRMR still carries the weakness of capturing redundant features along with the algorithm. On the other hand, RFE is flawed by the fact that those features selected by RFE are not ranked by importance, albeit RFE can effectively eliminate the less important features and exclude redundant features.FindingsThe hybrid method was exemplified in a binary classification between digits “4” and “9” and between digits “6” and “8” from a multiple features dataset. The result showed that the hybrid mRMR + support vector machine recursive feature elimination (SVMRFE) is better than both the sole support vector machine (SVM) and mRMR.Originality/valueIn view of the respective strength and deficiency mRMR and RFE, this study combined both these methods and used an SVM as the underlying classifier anticipating the mRMR to make an excellent complement to the SVMRFE.