bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic mitochondrial transcription and translation in B cells control germinal centre entry and lymphomagenesis
Authors: Yazicioglu Yavuz F , Marin Eros M , Sandhu Ciaran , Galiani Silvia , Raza Iwan G A , Ali Mohammad , Kronsteiner Barbara , Compeer Ewoud B , Attar Moustafa , Dunachie Susanna J , Dustin Michael L , Clarke Alexander J
Published: July 2022

Germinal centre (GC) B cells undergo proliferation at very high rates in a hypoxic microenvironment, but the cellular processes driving this are incompletely understood. Here we show that the mitochondria of GC B cells are highly dynamic, with significantly upregulated transcription and translation rates associated with the activity of transcription factor mitochondrial A (TFAM). TFAM, whilst also necessary for normal B cell development, is required for entry of activated GC-precursor B cells into the germinal centre reaction, and deletion ofTfamsignificantly impairs GC formation, function, and output. Loss of TFAM in B cells compromises the actin cytoskeleton and impairs cellular motility of GC B cells in response to chemokine signalling, leading to their spatial disorganisation. We show that B cell lymphoma substantially increases mitochondrial translation, and deletion ofTfamin B cells is protective against the development of lymphoma in a c-Myc transgenic model. Finally, we show that pharmacologic inhibition of mitochondrial transcription and translation inhibits growth of GC-derived human lymphoma cells, and induces similar defects in the actin cytoskeleton.
A Quantitative Evaluation of Topological Motifs and Their Coupling in Gene Circuit State Distributions
Authors: Clauss Benjamin , Lu Mingyang
Published: July 2022

One of the major challenges in biology is to understand how gene interactions collaborate to determine overall functions of biological systems. Here, we present a new computational framework that enables systematic, high-throughput, and quantitative evaluation of how small transcriptional regulatory circuit motifs, and their coupling, contribute to functions of a dynamical biological system. We illustrate how this approach can be applied to identify four- node gene circuits, circuit motifs, and motif coupling responsible for various gene expression state distributions, including those derived from single-cell RNA sequencing data. We also identify seven major classes of four-node circuits from clustering analysis of state distributions. The method is applied to establish phenomenological models of gene circuits driving human neuron differentiation, revealing important biologically relevant regulatory interactions. Our study will shed light on a better understanding of gene regulatory mechanisms in creating and maintaining cellular states.
Long range allostery mediates the regulation of plasminogen activator inhibitor-1 by vitronectin
Authors: Kihn Kyle , Marchiori Elisa , Spagnolli Giovanni , Boldrini Alberto , Terruzzi Luca , Lawrence Daniel A. , Gershenson Anne , Faccioli Pietro , Wintrode Patrick L.
Published: July 2022

The serpin plasminogen activator inhibitor 1 (PAI-1) spontaneously undergoes a massive structural change from a metastable, active conformation, with a solvent accessible reactive center loop (RCL), to a stable, inactive or latent conformation in which the RCL has inserted into the central β sheet. Physiologically, conversion to the latent state is regulated by the binding of vitronectin which retards the rate of this latency transition approximately 2-fold. We investigated the effects of vitronectin on the PAI-1 latency transition using all-atom path sampling simulations in explicit solvent. In simulated latency transitions of free PAI-1, the RCL is quite mobile as is the gate, the region that impedes RCL access to the central β sheet. This mobility allows the formation of a transient salt bridge that facilitates the transition, and this finding rationalizes existing mutagenesis results. Vitronectin binding reduces RCL and gate mobility by allosterically rigidifying structural elements over 40 Å away from the binding site thus blocking the transition to the latent conformation. The effects of vitronectin are propagated by a network of dynamically correlated residues including a number of conserved sites that have previously been identified as important for PAI-1 stability. Simulations also revealed a transient pocket populated only in the vitronectin bound state which corresponds to a cryptic drug binding site identified by crystallography. Overall, these results shed new light on regulation of the PAI-1 latency transition by vitronectin and illustrate the potential of path sampling simulations for understanding functional conformational changes in proteins and for facilitating drug discovery.
Discovery of malathion resistance QTL inDrosophila melanogasterusing a bulked phenotyping approach
Authors: Macdonald Stuart J , Long Anthony D
Published: July 2022

Drosophila melanogasterhas proven an effective system with which to understand the evolutionary genetics and molecular mechanisms of insecticide resistance. Insecticide use has left signatures of selection in the fly genome, and both functional and quantitative genetics studies in the system have identified genes and variants associated with resistance. Here, we useD. melanogasterand leverage a bulk phenotyping and pooled sequencing “extreme QTL” approach to genetically dissect variation in resistance to malathion, an organophosphate insecticide. We resolve two QTL (Quantitative Trait Loci), one of which implicates allelic variation at the cytochrome P450 geneCyp6g1, a strong candidate based on previous work. The second shows no overlap with hits from a previous genomewide association study (GWAS) for malathion resistance, recapitulating other studies showing that different strategies for complex trait dissection in flies can yield apparently different architectures. Notably, we see no genetic signal at theAcegene.Aceencodes the target of organophosphate insecticide inhibition, and GWAS have identified strongAce-linked associations with resistance. The absence of QTL implicatingAcehere is most likely because our mapping population does not segregate for several of the known functional polymorphisms impacting resistance atAce, perhaps because our population is derived from flies collected prior to the widespread use of organophosphate insecticides. Our fundamental approach can be an efficient, powerful strategy to dissect genetic variation in resistance traits. Nonetheless, studies seeking to interrogate contemporary insecticide resistance variation may benefit from deriving mapping populations from more recently collected strains.
How does the risk of bias influence the effect sizes of exercise therapy in chronic low back pain randomised controlled trials? A protocol for a meta-epidemiological study
Authors: Innocenti Tiziano , Hayden Jill A , Salvioli Stefano , Giagio Silvia , Piano Leonardo , Cosentino Carola , Brindisino Fabrizio , Feller Daniel , Ogilvie Rachel , Gianola Silvia , Castellini Greta , Bargeri Silvia , Twisk Jos WR , Ostelo Raymond , Chiarotto Alessandro
Published: July 2022

Background and Objectives

Risk of bias is a critical issue to consider when appraising studies. Generally, the higher the risk of bias of a study, the less confidence there will be that the results are valid. Considering that low back pain is recognized to have an extremely high disease burden; exercise therapy is one of the most frequently prescribed interventions for chronic low back pain (CLBP) and that most low back pain trials have methodological limitations that could bias treatment effect estimates; the objective of this study is to explore causal pathways between the sources of risk of bias and estimates of the treatment effect of exercise therapy interventions in CLBP trials.

Methods

The 249 RCTs included in the 2021 Cochrane review publication “Exercise therapy for chronic low back pain” will be included. The risk of bias will be evaluated with the Cochrane Risk of Bias 2 tool (ROB 2). Causal pathways between the exposure (risk of bias domains) and our outcomes of interest (effect sizes for pain and functional limitations) will be explored through univariable and multivariable meta-regression models. These models will be adjusted for potential confounders (sample size, trial registration, incomplete flow chart information and treatment comparisons), exploring relevant interactions within each model. Additional and sensitivity analyses will be performed to explore and test the robustness of the primary analyses.

Ethics and dissemination

A manuscript will be prepared and submitted for publication in an appropriate peer-reviewed journal upon study completion. We believe that the results of this investigation will be relevant to researchers paying more attention to the synthesis of the evidence to translate clinical implications to key stakeholders (healthcare providers and patients).
National and regional prevalence of SARS-CoV-2 antibodies in primary and secondary school children in England: the School Infection Survey, a national open cohort study, November 2021
Authors: Powell Annabel A , Ireland Georgina , Leeson Rebecca , Lacey Andrea , Ford Ben , Poh John , Ijaz Samreen , Shute Justin , Cherepanov Peter , Tedder Richard , Bottomley Christian , Dawe Fiona , Mangtani Punam , Jones Peter , Nguipdop-Djomo Patrick , Ladhani Shamez
Published: July 2022

Background

Risk factors for infection and, therefore, antibody positivity rates will be different in children compared to adults. We aim to estimate national and regional prevalence of SARS-CoV-2 antibodies in primary (4-11-year-olds) and secondary (11-15-year-olds) school children between 10 November and 10 December 2021.

Methods

Cross-sectional surveillance in England using two stage sampling, firstly stratifying into regions and selecting local authorities, then selecting schools according to a stratified sample within selected local authorities. Participants were sampled using a novel oral fluid validated assay for SARS-CoV-2 spike and nucleocapsid IgG antibodies.

Results

4,980 students from 117 state-funded schools (2,706 from 83 primary schools, 2,274 from 34 secondary schools) provided a valid sample. After weighting for age, sex and ethnicity, and adjusting for assay accuracy, the national prevalence of SARS-CoV-2 antibodies in primary school students, who were all unvaccinated, was 40.1% (95%CI; 37.3-43.0). Antibody prevalence increased with age (p<0.001) and were higher in urban than rural schools (p=0.01). In secondary school students, the adjusted, weighted national prevalence of SARS-CoV-2 antibodies was 82.4% (95%CI; 79.5-85.1); including 57.5% (95%CI; 53.9-61.1) in unvaccinated and 97.5% (95%CI; 96.1-98.5) in vaccinated students. Antibody prevalence increased with age (p<0.001), and was not significantly different in urban versus rural students (p=0.1).

Conclusions

Using a validated oral fluid assay, we estimated national and regional seroprevalence of SARS-CoV-2 antibodies in primary and secondary school students. In November 2021, 40% of primary school students and nearly all secondary school students in England had SARS-CoV2 antibodies through a combination of natural infection and vaccination.
Prevalence and Factors Associated with Mental Illness Symptoms among School Students Post Lockdown of the COVID-19 Pandemic in the United Arab Emirates: A Cross-Sectional National Study
Authors: Ghader Nariman Ali , Mheiri Noor Al , Fikri Asma , AbdulRazzak Hira , Saleheen Hassan , Saddik Basema , Aljawarneh Yousef , Dalky Heyam , Banna Ammar Al , Memari Shammah Al , Shehhi Budoor Al , Mazrouei Shereena Al , Hajeri Omniyat Al
Published: July 2022

Data from the United Arab Emirates about the mental health status of the younger population is limited. The current study aimed to assess the prevalence of anxiety, depression, and risk for PTSD among school students post lockdown of the current COVID-19 pandemic. A sample of 3745 students and their parents across the country answered a web-based survey. Parents provided bio-demographic data and students answered questions from the Mood and Feeling Questionnaire (MFQ-Child Self-report), Screen for Child Anxiety Related Disorders (SCARED-Child Version), and Children’s Revised Impact of Event Scale (CRIES-8). Findings showed that the risk for PTSD was the most prevalent (40.6%), followed by symptoms of anxiety (23.3%), and depression (17.1%). For gender differences, symptoms of the three conditions were higher in female students by 6.9%. Moreover, symptoms of depression and anxiety were found to be higher among late adolescents. Further analysis revealed that having medical problems (β = 2.0, p < 0.001) and witnessing the death of a close family member due to COVID-19 (β = 1.7, p < 0.001) were positive predictors associated with PTDS, depression, and anxiety. The study concluded that post COVID-19 lockdown, symptoms of anxiety, depression, and risk for PTSD are prevalent among students in the UAE. Researchers recommend the initiation of a national school mental health screening program and the provision of follow-up services for vulnerable students. Another must-have is the integration of a mental health support system in the emergency and disaster preparedness future plans.
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

Background

Behavioural 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.

Methods

In 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).

Results

Findings 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.

Conclusions

Adolescents 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

The 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

Cancer 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

Acanthamoeba 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

Some 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

Predicting 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

The 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

Motivation

Haplotypes 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.

Results

Here, 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.

Availability

https://github.com/AbeelLab/hat/

Contact

t.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

T-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

Fish 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

Most 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

Superficial 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.
High-resolution simulations of chromatin folding at genomic rearrangements in malignant B cells provide mechanistic insights into proto-oncogene deregulation
Authors: Rico Daniel , Kent Daniel , Karataraki Nefeli , Mikulasova Aneta , Berlinguer-Palmini Rolando , Walker Brian A. , Javierre Biola M. , Russell Lisa J. , Brackley Chris A.
Published: July 2022

Genomic rearrangements are known to result in proto-oncogene deregulation in many cancers, but the link to 3D genome structure remains poorly understood. Here, we used the highly predictive heteromorphic polymer (HiP-HoP) model to predict chromatin conformations at the proto-oncogeneCCND1in healthy and malignant B cells. After confirming that the model gives good predictions of Hi-C data for the nonmalignant human B cell–derived cell line GM12878, we generated predictions for two cancer cell lines, U266 and Z-138. These possess genome rearrangements involvingCCND1and the immunoglobulin heavy locus (IGH), which we mapped using targeted genome sequencing. Our simulations showed that a rearrangement in U266 cells where a singleIGHsuper-enhancer is inserted next toCCND1leaves the local topologically associated domain (TAD) structure intact. We also observed extensive changes in enhancer-promoter interactions within the TAD, suggesting that it is the downstream chromatin remodeling which gives rise to the oncogene activation, rather than the presence of the inserted super-enhancer DNA sequence per se. Simulations of theIGH-CCND1reciprocal translocation in Z-138 cells revealed that an oncogenic fusion TAD is created, encompassingCCND1and theIGHsuper-enhancers. We predicted how the structure and expression ofCCND1changes in these different cell lines, validating this using qPCR and fluorescence in situ hybridization microscopy. Our work demonstrates the power of polymer simulations to predict differences in chromatin interactions and gene expression for different translocation breakpoints.
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

Purpose

The 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/approach

The 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.

Findings

The 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/value

In 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.
Impact of the confirmation bias on returns, expectations and hedging of optimistic and pessimistic traders before and during COVID-19 pandemic
Authors: Trichilli Yousra , Gaadane Sahbi , Boujelbène Abbes Mouna , Masmoudi Afif
Published: July 2022

Purpose

In this paper, the authors investigate the impact of the confirmation bias on returns, expectations and hedging of optimistic and pessimistic traders in the cryptocurrencies, commodities and stock markets before and during COVID-19 periods.

Design/methodology/approach

The authors investigate the impact of the confirmation bias on the estimated returns and the expectations of optimistic and pessimistic traders by employing the financial stochastic model with confirmation bias. Indeed, the authors compute the optimal portfolio weights, the optimal hedge ratios and the hedging effectiveness.

Findings

The authors find that without confirmation bias, during the two sub periods, the expectations of optimistic and pessimistic trader’s seem to convergence toward zero. However, when confirmation bias is particularly strong, the average distance between these two expectations are farer. The authors further show that, with and without confirmation bias, the optimal weights (the optimal hedge ratios) are found to be lower (higher) for all pairs of financial market during the COVID-19 period as compared to the pre-COVID-19 period. The authors also document that the stronger the confirmation bias is, the lower the optimal weight and the higher the optimal hedge ratio. Moreover, results reveal that the values of the optimal hedge ratio for optimistic and pessimistic traders affected or not by the confirmation bias are higher during the COVID-19 period compared to the estimates for the pre-COVID period and inversely for the optimal hedge ratios and the hedging effectiveness index. Indeed, either for optimists or pessimists, the presence of confirmation bias leads to higher optimal hedge ratio, higher optimal weights and higher hedging effectiveness index.

Practical implications

The findings of the study provided additional evidence for investors, portfolio managers and financial analysts to exploit confirmation bias to make an optimal portfolio allocation especially during COVID-19 and non-COVID-19 periods. Moreover, the findings of this study might be useful for investors as they help them to make successful investment decision in potential hedging strategies.

Originality/value

First, this is the first scientific work that conducts a stochastic analysis about the impact of emotional biases on the estimated returns and the expectations of optimists and pessimists in cryptocurrency and commodity markets. Second, the originality of this study stems from the fact that the authors make a comparative analysis of hedging behavior across different markets and different periods with and without the impact of confirmation bias. Third, this paper pays attention to the impact of confirmation bias on the expectations and hedging behavior in cryptocurrencies and commodities markets in extremely stressful periods such as the recent COVID-19 pandemic.
The tourism and hospitality career progression pathway
Authors: Preko Alexander , Anyigba Hod
Published: July 2022

Purpose

The aim of this study was to conduct a comprehensive investigation into declining and emerging occupations and job titles and to develop a national career progression pathway for the tourism and hospitality (T&H) sector.

Design/methodology/approach

Anchored on the Social Cognitive Career Theory, this study used face to face in-depth interviews of 33 industry stakeholders: policymakers, trade association, training providers and beneficiaries (T&H).

Findings

The finding reveals that only the “watchman” occupation was identified as the declining job while majority of the emerging jobs were more related to information technology and environmental occupations (website designers, digital marketers, data analysts, hygienists, and safety and hazard experts).

Practical implications

The findings provide a valuable signal for the growing number of jobs in security services, hygiene and information technology-oriented occupations, which the Ministry of Tourism, Arts and Culture including practitioners including HR directors and general managers should respond timely to and to these growing needs in order to remain competitive in the sector.

Originality/value

This is the first study in context that responded to a call by industry players to fill in a practical knowledge gap in examining declining and emerging jobs and job titles in the T&H sector. The study provides vocational insights into mapping the entry level requirements for the jobs allied with occupations in the national technical and vocational educational training qualifications framework of Ghana at the national level.
The strategic role of firm agility in the relationship between IT capability and firm performance under the COVID-19 outbreak
Authors: Bai Bingfeng , Um Ki-Hyun , Lee Hanna
Published: July 2022

Purpose

Leveraging theory from the dynamic capability literature, this study aims to explore how information technology (IT) capability influences firm agility and subsequently translates into firm performance.

Design/methodology/approach

This study examines the proposed relationships by using survey data from a sample of 296 Chinese retail firms. Structural equation modeling is used to test this study’s hypotheses.

Findings

The following results are produced: the direct effect of IT capability on firm agility is confirmed; firm agility has a direct impact on firm performance; and the indirect effect of IT capability on firm performance via firm agility is demonstrated (i.e. partial mediation).

Originality/value

The catastrophic outbreak of the COVID-19 pandemic has heightened the importance of firm agility more than ever. Although the traumatic event is painful, however, there is nothing like a crisis to offer a tremendous business opportunity. In response to the pandemic circumstance, firms are required to operate their business by reacting to unpredictable and dynamic market changes quickly and efficiently. This study sheds light on why firms should develop their IT capability and how it affects firm performance via firm agility during the COVID-19 outbreak.
Compliance risks for crowdfunding. A neglected aspect of money laundering, terrorist financing and fraud
Authors: Teichmann Fabian , Boticiu Sonia Ruxandra , Sergi Bruno S.
Published: July 2022

Purpose

This study aims to highlight the risks and threats posed by crowdfunding. It also looks at the new European Union regulation on crowdfunding, which is intended to give participants confidence that there will be specific minimum regulatory standards to protect parties against mis-selling issues affecting some platforms.

Design/methodology/approach

This paper is based upon a thorough literature review.

Findings

Crowdfunding is an essential alternative for financing commercial and non-commercial projects. Although it is a fast-growing digital financial tool, it can also be considered extremely risky. It can be an ideal platform for money laundering and can facilitate the financing of terrorism and fraud.

Originality/value

Crowdfunding is still in its infancy, so the literature has not yet sufficiently addressed the compliance risks of crowdfunding. As a result, there is a significant research gap. Thus, this study aims to analyse and propose suggestions to mitigate the risks that all crowdfunding stakeholders may face when deciding to participate in a crowdfunding activity or when they want to set one up.
Analyzing the impact of productive zakat on the welfare of zakat recipients
Authors: Mawardi Imron , Widiastuti Tika , Al Mustofa Muhammad Ubaidillah , Hakimi Fifi
Published: July 2022

Purpose

This study aims to investigate the effects of zakat and business assistance on the growth and well-being of mustahiqs (zakat recipients). This study also investigates the impact of macroeconomic variables on the welfare of mutahiqs.

Design/methodology/approach

The partial least squares-structural equation modelling method is used in this quantitative study, examining data from 137 mustahiqs. The data was collected from seven zakat institutions, which run effective zakat programmes to empower mustahiqs.

Findings

Zakat empowerment programmes and business assistantships positively impact the growth of mustahiqs’ businesses, beneficial to their well-being. Nevertheless, their well-being is unaffected by the proxy of the macroeconomy.

Originality/value

This study adds to the zakat literature by identifying the relationship between zakat, business growth, macroeconomic conditions and mustahiq welfare. Accordingly, this approach was made by combining primary and secondary data. This research offers a unique measure of welfare based on the concept of the Islamic objectives (Maqasid al-Shariah).