bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence and correlates of anxiety and depression among female sex workers in Dire Dawa city Administration, Eastern Ethiopia
Authors: Yesuf Yassin Mohammed , Mekonnen Dawit , Teklu Hareg , Kebede Sebsibew Atikaw 
Published: February 2023

AbstractBackgroundThe mental health states of Female Sex Workers (FSWs) are least explored. The present study examined the levels of anxiety and depression as well as associated factors among FSWs in Dire Dawa city.MethodsCross-sectional explanatory sequential mixed-method research design was used. Snowball technique was used to recruit respondents. Beck Anxiety Inventory and Patient Health Questionnaire were used to measure anxiety and depression, respectively. Valid questionnaires were collected from 292 respondents (81% response rate) and interviews were made with six FSWs. Data collected through the questionnaire were analyzed using frequency, percentage, independent sample t-test, ANOVA, Pearson correlation and multiple linear regression while thematic analysis was used to analyze the qualitative data.ResultsThe prevalence rates of anxiety and depression were 43.5% and 69.8%, respectively. Psychosocial and demographic variables were important correlates explaining 56% (F=43.324, p=<0.01, R2=.557) and 23% (F=10.319, p<0.01, R2=.228) of the variations in anxiety and depression, respectively. Specifically,Khatuse (β= .371, t=8.744, p<0.01), violence (β= .272, t= 6.521, p<0.01), stigma (β= .258, t= 5.427, p<0.01), tobacco use (β=.200, t= 3.837, p<0.01) and alcohol use (β= -.136, t= -3.327, p<0.01) were significantly correlated with anxiety. Besides, violence (β= .298, t= 5.439, p<0.01), alcohol use (β= -.162, t= 3.011, p<0.01), stigma (β= .160, t= 2.549, p<0.05), andKhatuse (β= .151, t= 2.915, p<0.01) were significantly associated with depression. The qualitative findings substantiated the survey results.ConclusionFrom the findings it is concluded that FSWs in Dire Dawa city were experiencing higher levels of anxiety and depression where psychosocial were important correlates of FSWs’ mental health. Therefore, organizations that are working with and/or concerned about FSWs need to provide evidence-based mental health and psychosocial interventions.
Genetic evidence that high BMI in childhood has a protective effect on intermediate diabetes traits, including measures of insulin sensitivity and secretion
Authors: Hawkes Gareth , Beaumont Robin N , Tyrrell Jessica , Power Grace M , Wood Andrew , Laakso Markku , Silva Lilian Fernandes , Boehnke Michael , Yin Xianyong , Richardson Tom G , Davey Smith George , Frayling Timothy M 
Published: February 2023

AbstractDetermining how high body-mass index (BMI) at different time points influences the risk of developing type two diabetes (T2D), and affects insulin secretion and insulin sensitivity, is critical. By estimating childhood BMI in 441,761 individuals in the UK Biobank, we identified which genetic variants had larger effects on adulthood BMI than on childhood BMI, and vice-versa. All genome-wide significant genetic variants were then used to separate the independent genetic effects of high childhood BMI from high adulthood BMI on the risk of T2D and insulin related phenotypes using Mendelian randomisation and studies of T2D, and oral and intravenous measures of insulin secretion and sensitivity. We found that a 1.s.d. (= 1.97kg/m2) higher childhood BMI, corrected for the independent genetic liability to adulthood BMI, was associated with a protective effect for seven measures of insulin sensitivity and secretion, including an increased insulin sensitivity index (β = 0.15 [0.067, 0.225], p = 2.79×10−4), and reduced fasting glucose (β = -0.053 [-0.089, -0.017], p = 4.31×10−3). There was however little to no evidence of a direct protective effect on T2D (OR = 0.94 [0.85 - 1.04], p = 0.228), independently of genetic liability to adulthood BMI. Our results thus cumulatively provide evidence of the protective effect of higher childhood BMI on insulin secretion and sensitivity, which are crucial intermediate diabetes traits. However, we stress that our results should not currently lead to any change in public health or clinical practice, given the uncertainty in biological pathway of these effects, and the limitations of this type of study.Research in ContextHigh BMI in adulthood is associated with higher risk of type two diabetes, coupled with lower insulin sensitivity and secretion.Richardson et al [2020] used genetics to show that high BMI in childhood does not appear to increase the risk of type diabetes independently from its effect on adult BMI.We asked: does high childhood BMI affect insulin related traits such as fasting glucose and insulin sensitivity, independently of adulthood BMI?We used genetics to show that high childhood BMI has a protective effect on seven insulin sensitivity and secretion traits, including fasting glucose and measures of insulin sensitivity and secretion, independently of adulthood BMI.Our work has the potential to turn conventional understanding on its head – high BMI in childhood improves insulin sensitivity (when adjusting for knock on effects to high adult BMI) and opens up important questions about plasticity in childhood and compensatory mechanisms.
The seminal odorant binding protein Obp56g is required for mating plug formation and male fertility inDrosophila melanogaster
Authors: Brown Nora C. , Gordon Benjamin , McDonough-Goldstein Caitlin E. , Misra Snigdha , Findlay Geoffrey D. , Clark Andrew G. , Wolfner Mariana F. 
Published: February 2023

AbstractInDrosophila melanogasterand other insects, the seminal fluid proteins (SFPs) and male sex pheromones that enter the female with sperm during mating are essential for fertility and induce profound post-mating effects on female physiology and behavior. The SFPs inD. melanogasterand other taxa include several members of the large gene family known as odorant binding proteins (Obps). Previous work inDrosophilahas shown that someObpgenes are highly expressed in the antennae and can mediate behavioral responses to odorants, potentially by binding and carrying these molecules to odorant receptors. These observations have led to the hypothesis that the seminal Obps might act as molecular carriers for pheromones or other compounds important for male fertility in the ejaculate, though functional evidence in any species is lacking. Here, we used RNAi and CRISPR/Cas9 generated mutants to test the role of the seven seminal Obps inD. melanogasterfertility and the post-mating response (PMR). We found thatObp56gis required for male fertility and the induction of the PMR, whereas the other six genes had no effect on fertility when mutated individually.Obp56gis expressed in the male’s ejaculatory bulb, an important tissue in the reproductive tract that synthesizes components of the mating plug. We found males lackingObp56gfail to form a mating plug in the mated female’s reproductive tract, leading to ejaculate loss and reduced sperm storage. We also examined the evolutionary history of these seminalObpgenes, as several studies have documented rapid evolution and turnover of SFP genes across taxa. We found extensive lability in gene copy number and evidence of positive selection acting on two genes,Obp22aandObp51a. Comparative RNAseq data from the male reproductive tract of multipleDrosophilaspecies revealed thatObp56gshows high male reproductive tract expression only in species of themelanogasterandobscuragroups, though conserved head expression in all species tested. Together, these functional and expression data suggest thatObp56gmay have been co-opted for a reproductive function over evolutionary time.
SaLTy: a novelStaphylococcus aureusLineage Typer
Authors: Cheney Liam , Payne Michael , Kaur Sandeep , Lan Ruiting 
Published: February 2023

AbstractStaphylococcus aureusasymptomatically colonises 30% of humans and in 2017 was associated with 20,000 deaths in the USA alone. DividingS. aureusinto smaller sub-groups can reveal the emergence of distinct sub-populations with varying potential to cause infections. Despite multiple molecular typing methods categorising such sub-groups, they do not take full advantage ofS. aureusWGS when describing the fundamental population structure of the species.In this study, we developedStaphylococcus aureusLineage Typing (SaLTy), which rapidly divides the species into 61 phylogenetically congruent lineages. Alleles of three core genes were identified that uniquely define the 61 lineages and were used for SaLTy typing. SaLTy was validated on 5,000 genomes and 99.12% (4,956/5,000) of isolates were assigned the correct lineage.We compared SaLTy lineages to previously calculated clonal complexes (CCs) from BIGSdb (n=21,173). SALTy improves on CCs by grouping isolates congruently with phylogenetic structure. SaLTy lineages were further used to describe the carriage ofStaphylococcalchromosomal cassette containingmecA(SCCmec) which is carried by methicillin-resistantS. aureus(MRSA). Most lineages had isolates lacking SCCmecand the four largest lineages varied in SCCmecover time. Classifying isolates into SaLTy lineages, which were further SCCmectyped, allowed SaLTy to describe high-level MRSA epidemiologyWe provide SALTy as a simple typing method that defines phylogenetic lineages (https://github.com/LanLab/SaLTy). SALTy is highly accurate and can quickly analyse large amounts ofS. aureusWGS. SALTy will aid the characterisation ofS. aureuspopulations and the ongoing surveillance of sub-groups that threaten human health.
Evidence for a sensorimotor prediction process in action observation
Authors: Hilt Pauline M. , Gueugneau Nicolas , Fadiga Luciano , Pozzo Thierry , Papaxanthis Charalambos 
Published: February 2023

AbstractThe mirror neurons network in the human brain is activated both during the observation of action and the execution of the same action, facilitating thus the transformation of visual information into motor representations, to understand the actions and intentions of others. How this transformation takes place, however, is still under debate. One prevailing theory,direct matching, assumes a direct correspondence between the visual information of the actor’s movement and the activation of the motor representations in the observer’s motor cortex that would produce the same movement. Alternatively, thepredictive codingtheory postulates that, during action observation, motor predictions (e.g., position, velocity) are generated and compared to the visual information of the actor’s movement. Here, we experimentally interrogate these two hypotheses during a locomotion task. The motor prediction process was assessed by measuring the timing of imagined movements: the participants had to imagine walking, forward or backward, for 9 m (linear path). Action observation was assessed by measuring time estimation in an inference locomotor task (the same 9 m linear path): after perceiving an actor walking forward or backward for 3 m, the vision of the observer was occluded and he/she had to estimate when the actor would reach the end of the 9 m path. We manipulated the timing processes during the two tasks by creating sensory illusions via peripheral mechanical muscle vibration on leg muscles, which has provided consistent results in the literature (acceleration of forward and deceleration of backward locomotion). We found that sensory illusions specifically affected the timing processes of both locomotion inference and mental locomotion, suggesting the involvement of sensorimotor predictions, common to both tasks. These findings seem to support the predictive coding hypothesis.
A novel cryopreservation and biobanking strategy to study lymphoid tissue stromal cells in human disease
Authors: Brandstadter Joshua D , De Martin Angelina , Lütge Mechthild , Ferreira Antonio , Gaudette Brian T , Stanossek Yves , Wang Shumei , Gonzalez Michael V , Camiolo Edward , Wertheim Gerald , Austin Bridget , Allman David , Lim Megan S , Fajgenbaum David C , Aster Jon C , Ludewig Burkhard , Maillard Ivan 
Published: February 2023

AbstractNon-hematopoietic lymph node stromal cells (LNSCs) regulate lymphocyte trafficking, survival, and function for key roles in host defense, autoimmunity, alloimmunity, and lymphoproliferative disorders. However, study of LNSCs in human diseases is complicated by a dependence on viable lymphoid tissues, which are most often excised prior to establishment of a specific diagnosis. Here, we demonstrate that cryopreservation can be used to bank lymphoid tissue for the study of LNSCs in human disease. Using human tonsils, lymphoid tissue fragments were cryopreserved for subsequent enzymatic digestion and recovery of viable non-hematopoietic cells. Flow cytometry and single-cell transcriptomics identified comparable proportions of LNSC cell types in fresh and cryopreserved tissue. Moreover, cryopreservation had little effect on transcriptional profiles, which showed significant overlap between tonsils and lymph nodes. The presence and spatial distribution of transcriptionally defined cell types was confirmed by in situ analyses. Our broadly applicable approach promises to greatly enable research into the roles of LNSC in human disease.
Marine Picoplankton Metagenomes from Eleven Vertical Profiles Obtained by the Malaspina Expedition in the Tropical and Subtropical Oceans
Authors: Sánchez Pablo , Sebastián Marta , Pernice Massimo , Rodríguez-Martínez Raquel , Pesant Stephane , Agustí Susana , Gojobori Takashi , Logares Ramiro , Sala María Montserrat , Vaqué Dolors , Massana Ramon , Duarte Carlos M. , Acinas Silvia G. , Gasol Josep M. 
Published: February 2023

ABSTRACTThe Ocean microbiome has a crucial role on Earth’s biogeochemical cycles, but also represents a tremendous potential for biological applications as part of the bluebiotechnology. During the last decade, global cruises such asTaraOceans or the Malaspina Expedition have expanded our knowledge on the diversity and genetic repertoire of marine microbes. Nevertheless, there is still a gap of knowledge on broad scale patterns between photic and bathypelagic dark ocean microbes derived from the lack of detailed vertical profiles covering contrasting oceans depth regions. Here we present a dataset of 76 microbial metagenomes of the picoplankton size fraction (0.2-3.0 μm) collected in 11 stations along the Malaspina Expedition circumnavigation that cover vertical profiles sampling at 7 depths, from the surface to the 4000 m deep (or the sea floor in shallower waters). This Malaspina Microbial Vertical Profiles metagenomes (MProfile) dataset produced 1.66 Tbp of raw DNA sequences that assembled into a total 25.3 Gbp. After gene prediction and annotation, we built a 46.3 million non-redundant gene compendium with their corresponding annotations (M-GeneDB-VP), clustered at 95% sequence similarity. This dataset will be a valuable resource for exploring the functional and taxonomic connectivity between the photic and bathypelagic tropical and subtropical ocean at a global scale, while increasing our general knowledge on the Ocean microbiome.
Sulcal morphology of posteromedial cortex substantially differs between humans and chimpanzees
Authors: Willbrand Ethan H. , Maboudian Samira A. , Kelly Joseph P. , Parker Benjamin J. , Foster Brett L. , Weiner Kevin S. 
Published: February 2023

AbstractRecent studies identify a surprising coupling between evolutionarily new sulci and the functional organization of human posteromedial cortex (PMC). Yet, no study has compared this modern PMC sulcal patterning between humans and non-human hominoids. To fill this gap in knowledge, we first manually defined 918 sulci in 120 chimpanzee (Pan Troglodytes) hemispheres and 1619 sulci in 144 human hemispheres. We uncovered four new PMC sulci, and quantitatively identified species differences in incidence, depth, and surface area. Interestingly, some PMC sulci are more common in humans and others, in chimpanzees. Further, we found that the prominent marginal ramus of the cingulate sulcus differs significantly between species. Contrary to classic observations, the present results reveal that the surface anatomy of PMC substantially differs between humans and chimpanzees — findings which lay a foundation for better understanding the evolution of neuroanatomical-functional and neuroanatomical-behavioral relationships in this highly expanded region of the human cerebral cortex.
Medial prefrontal cortex stimulation abolishes implicit reactions to threats and prevents the return of fear
Authors: Manassero Eugenio , Concina Giulia , Caraig Maria Clarissa Chantal , Sarasso Pietro , Salatino Adriana , Ricci Raffaella , Sacchetti Benedetto 
Published: February 2023

AbstractDown-regulating emotional overreactions toward threats is fundamental for developing treatments for anxiety and post-traumatic disorders. The prefrontal cortex (PFC) is critical for top-down modulatory processes, and despite previous studies adopting repetitive Transcranial Magnetic Stimulation (rTMS) over this region provided encouraging results in enhancing extinction, no studies have hitherto explored the effects of stimulating the medial PFC (mPFC) on threat memory and generalization. Here we showed that rTMS applied before threat memory retrieval abolishes implicit reactions to learned and novel stimuli in humans. These effects were not due to inhibition of electrodermal reactivity and enduringly persisted one week later in the absence of rTMS. No effects were detected on explicit recognition. Critically, we observed stronger attenuation of defensive responses in subjects stimulated over the mPFC than the dlPFC. Our findings uncover a prefrontal region whose modulation can permanently hamper implicit reactions to learned dangers, representing an advance to long-term deactivating overreactions to threats.
The anti-leprosy drug clofazimine reduces polyQ toxicity through activation of PPARγ
Authors: Li Xuexin , Hernandez Ivo , Häggblad Maria , Lidemalm Louise , Brautigam Lars , Lucas Jose J. , Carreras-Puigvert Jordi , Hühn Daniela , Fernandez-Capetillo Oscar 
Published: February 2023

SUMMARYPolyQ diseases are autosomal dominant neurodegenerative disorders caused by the expansion of CAG repeats. While of slow progression, these diseases are ultimately fatal and lack effective therapies. Here, we present our results from a High-Throughput chemical screen oriented to find drugs that lower the toxicity of a protein containing the first exon from the Huntington’s disease protein huntingtin (HTT) harboring 94 glutamines (Htt-Q94). Our screening identified the anti-leprosy drug clofazimine as a hit, which was subsequently validated in several in vitro models as well as in a zebrafish model of polyQ toxicity. Computational analyses of transcriptional signatures, together with molecular modeling and biochemical assays revealed that clofazimine is an agonist of the peroxisome proliferator activated receptor gamma (PPARγ), previously suggested as a potential therapy for HD by stimulating mitochondrial biogenesis. Accordingly, clofazimine rescued the mitochondrial dysfunction triggered by Htt-Q94expression. Together, our results support the potential of clofazimine repurposing for the treatment of PolyQ diseases.
Mechanism of sensor kinase CitA transmembrane signaling
Authors: Zhang Xizhou Cecily , Xue Kai , Salvi Michele , Schomburg Benjamin , Mehrens Jonas , Giller Karin , Stopp Marius , Weisenburger Siegfried , Böning Daniel , Sandoghdar Vahid , Unden Gottfried , Becker Stefan , Andreas Loren B. , Griesinger Christian 
Published: February 2023

AbstractMembrane bound histidine kinases (HKs) are ubiquitous sensors of extracellular stimuli in bacteria. Here, we used solid-state NMR in conjunction with crystallography, solution NMR and distance measurements to investigate the transmembrane signaling mechanism of a paradigmatic citrate sensing membrane embedded HK, CitA. Citrate binding in the sensory extracytoplasmic PAS domain (PASp) causes the linker to transmembrane helix 2 (TM2) to adopt a helical conformation. This triggers a piston-like pulling of TM2 and a quaternary structure rearrangement in the cytosolic PAS domain (PASc). Crystal structures of PASc reveal both anti-parallel and parallel dimer conformations. An anti-parallel to parallel transition upon citrate binding agrees with interdimer distances measured in the lipid embedded protein using a site-specific19F label in PASc. These data show how Angstrom scale structural changes in the sensor domain are transmitted across the membrane to be converted and amplified into a nm scale shift in the linker to the phosphorylation subdomain of the kinase.One-Sentence SummaryTransmembrane signal transduction of a PAS-domain containing histidine kinase occurs via a piston-like pulling of a transmembrane helix, and amplification by cytoplasmic PAS domain dimer rearrangement.
BiGPICC: a graph-based approach to identifying carcinogenic gene combinations from mutation data
Authors: Oles Vladyslav , Dash Sajal , Anandakrishnan Ramu 
Published: February 2023

ABSTRACTGenome data from cancer patients represents relationships between the presence of a gene mutation and cancer occurrence in a patient. Different types of cancer in human are thought to be caused by combinations of two to nine gene mutations. Identifying these combinations through traditional exhaustive search requires the amount of computation that scales exponentially with the combination size and in most cases is intractable even for cutting-edge supercomputers.We propose a parameter-free heuristic approach that leverages the intrinsic topology of gene-patient mutations to identify carcinogenic combinations. The biological relevance of the identified combinations is measured by using them to predict the presence of tumor in previously unseen samples. The resulting classifiers for 16 cancer types perform on par with exhaustive search results, and score the average of 80.1% sensitivity and 91.6% specificity for the best choice of hit range per cancer type. Our approach is able to find higher-hit carcinogenic combinations targeting which would take years of computations using exhaustive search.
TLR7 activation at epithelial barriers promotes emergency myelopoiesis and lung anti-viral immunity
Authors: Jackson William D , Giacomassi Chiara , Ward Sophie , Owen Amber , Luis Tiago C. , Spear Sarah , Woollard Kevin J , Johansson Cecilia , Strid Jessica , Botto Marina 
Published: February 2023

SummaryMonocytes are heterogeneous innate effector leukocytes generated in the bone marrow and released into circulation in a CCR2-dependent manner. During infection or inflammation myelopoiesis is modulated to rapidly meet demand for more effector cells. Danger signals from peripheral tissues can influence this process. Herein we demonstrate that repetitive TLR7 stimulation via the epithelial barriers drove a potent emergency bone marrow monocyte response. This process was unique to TLR7 activation and occurred independently of the canonical CCR2 and CX3CR1 axes or prototypical cytokines. The monocytes egressing the bone marrow had an immature Ly6C-high profile and differentiated into vascular Ly6C-low monocytes and tissue macrophages in multiple organs. They displayed a blunted cytokine response to further TLR7 stimulation and reduced lung viral load after RSV and influenza virus infection. These data provide insights into the emergency myelopoiesis likely to occur in response to the encounter of single-stranded RNA viruses at barrier sites.