bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tuberculosis prevalence, incidence and prevention in a south african cohort of children living with HIV
Authors: Anyalechi Gloria Ebelechukwu , Bain Rommel , Kindra Gurpreet , Mogashoa Mary , Sogaula Nonzwakazi , Mutiti Anthony , Arpadi Stephen , Rivadeneira Emilia , Abrams Elaine J , Teasdale Chloe A 
Published: October 2022

SUMMARY

Background
We describe tuberculosis (TB) disease among antiretroviral treatment (ART) eligible children living with HIV (CLHIV) in South Africa to highlight TB prevention opportunities.

Methods
In our secondary analysis among 0- to 12-year-old ART-eligible CLHIV in five Eastern Cape Province health facilities from 2012 to 2015, prevalent TB occurred 90 days before or after enrollment; incident TB occurred &gt;90 days after enrollment. Characteristics associated with TB were assessed using logistic and Cox proportional hazards regression with generalized estimating equations.

Results
Of 397 enrolled children, 114 (28.7%) had prevalent TB. Higher-income proxy [adjusted odds ratio (aOR) 1.8 [95% confidence interval (CI) 1.3–2.6] for the highest, 1.6 (95% CI 1.6–1.7) for intermediate]; CD4+ cell count &lt;350 cells/µl [aOR 1.6 (95% CI 1.1–2.2)]; and malnutrition [aOR 1.6 (95% CI 1.1–2.6)] were associated with prevalent TB. Incident TB was 5.2 per 100 person-years and was associated with delayed ART initiation [hazard ratio (HR) 4.7 (95% CI 2.3–9.4)], malnutrition [HR 1.8 (95% CI 1.1–2.7)] and absence of cotrimoxazole [HR 2.3 (95% CI 1.0–4.9)]. Among 362 children with data, 8.6% received TB preventive treatment.

Conclusions
Among these CLHIV, prevalent and incident TB were common. Early ART, cotrimoxazole and addressing malnutrition may prevent TB in these children.
A taxonomic reassessment of native and invasive species ofCorbiculaclams (Bivalvia: Cyrenidae) from the Russian Far East and Korea
Authors: Bespalaya Yulia V , Kropotin Alexander V , Kondakov Alexander V , Aksenova Olga V , Gofarov Mikhail Yu , Kim Sang Ki , Lee Jin Hee , Travina Oksana V , Vikhrev Ilya V , Vinarski Maxim V , Bolotov Ivan N 
Published: October 2022

AbstractCurrently, the validity of many nominal bivalve species of the genus Corbicula endemic to the Russian Far East and South Korea needs a critical reassessment. In this study, we clarify the taxonomic status of Corbicula species of this area based on a combination of molecular genetic, conchological and anatomical data. According to our results, four Corbicula lineages, corresponding to the nominal species Corbicula japonica, Corbicula elatior, Corbicula leana and Corbicula fluminea, can be delineated in samples collected in the Primorye and Khabarovsk regions of Russia and South Korea. Two species endemic to the Russian Far East (i.e. Corbicula finitima and Corbicula lindholmi) are considered here as junior synonyms of the species C. japonica, which is widely distributed in estuarine habitats around the Japanese Archipelago, Sakhalin Island, southern Kurile Islands, Primorye and Khabarovsk regions, Korean Peninsula and China. Three nominal species described from the Lower Amur basin (Corbicula amurensis, Corbicula nevelskoyi and Corbicula sirotskii) appeared to be synonyms of C. elatior, whose range covers the Korean Peninsula, Primorye and Khabarovsk regions and, perhaps, China. We delineated several colour morphs of C. fluminea and C. japonica. The distinctness between these colour morphs can be attributed to both heritable and environmental factors.
Tomato Brown Rugose Fruit Virus Nextstrain Build Version 3: Rise of a Novel Clade
Authors: Botermans Marleen , de Koning Pier P. M. , Oplaat Carla , Fowkes Aimee R. , McGreig Sam , Skelton Anna , Adams Ian P. , Fox Adrian , De Jonghe Kris , Demers Jill E. , Roenhorst Johanna W. , Westenberg Marcel , van de Vossenberg Bart T. L. H. 
Published: October 2022

In the Netherlands, tomato brown rugose fruit virus (ToBRFV; genus Tobamovirus) was first identified in tomato crops in 2019. Since then, the National Plant Protection Organization (NPPO-NL) has performed surveys to track and trace this regulated virus aiming for its eradication. To gain more insight in the epidemiology of ToBRFV, genomes were assembled from Illumina sequence data. Whole-genome phylogenetics was integrated with epidemiological metadata in a Nextstrain build. Two new clades were defined, one of which displayed a rapid increase in comparison to the previous version of the Nextstrain build. This rapid increase could be attributed to the unauthorized application of an isolate of ToBRFV as a cross-protection product. Further analysis of the test results of positive samples from tomato production sites suggests that both deliberate application and accidental introduction had occurred. This report introduces the inclusion of 61 new (near) complete ToBRFV genomes in version three of the Nextstrain build, available from https://nextstrain.nrcnvwa.nl/ToBRFV/20220412 . [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Graphene oxide accelerates diabetic wound repair by inhibiting apoptosis of Ad‐MSCs via Linc00324/miR‐7977/STK4 pathway
Authors: Ji Zhe , Wang Jian , Yang Shuai , Tao Shengjun , Shen Caiqi , Wei Hanxiao , Li Qiang , Jin Peisheng 
Published: October 2022

AbstractMany studies have shown that graphene oxide (GO) promotes proliferation and differentiation of a variety of stem cells. However, its effect on adipose‐derived mesenchymal stem cell (Ad‐MSCs) apoptosis is still unclear. Apoptosis is a significant factor affecting stem cell‐based treatment of diabetic wounds. Therefore, we explored the effect of GO on Ad‐MSC apoptosis and diabetic wound healing. In this study, qRT‐PCR was used to detect Ad‐MSC expression of LncRNAs, miRNAs, and mRNAs under high‐glucose environment. RNA immunoprecipitation (RIP), RNA pull‐down, and luciferase assays were used to detect interactions of specific lncRNAs, miRNAs, and mRNAs. The effects of GO on Ad‐MSC apoptosis were explored by flow cytometry, TUNEL assay, and Western blot. A diabetic wound model was used to explore the function of Linc00324 on Ad‐MSC reparative properties in vivo. As a result, GO inhibited high glucose‐induced apoptosis in Ad‐MSCs, and Linc00324 contributed to the anti‐apoptotic effect of GO. RIP and RNA pull‐down confirmed that Linc00324 directly interacted with miR‐7977, functioning as a miRNA sponge to regulate expression of the miR‐7977 target gene STK4 (MST1) and downstream signaling pathways. In addition, GO reduced the apoptosis of Ad‐MSCs in wounds and promoted wound healing. Taken together, these findings suggest GO may be a superior auxiliary material for Ad‐MSCs to facilitate diabetic wound healing via the Linc00324/miR‐7977/STK4 pathway.
Deep characterization of cancer drugs mechanism of action by integrating large-scale genetic and drug screens
Authors: Sinha Sanju , Sinha Neelam , Ruppin Eytan 
Published: October 2022

AbstractKnowing a drug’s mechanism of action (MOA) is essential for its clinical success by selecting the best indications, likely responders, and combinations. Yet knowledge of many drugs’ MOA remains lacking. Here we present DeepTarget, a computational tool for deep characterization of cancer drugs’ MOA by integrating existing large-scale genetic and drug screens. Spanning ∼1500 drugs across ∼18K possible target genes, DeepTarget predicts: (1) a drug’s primary target(s), (2) whether it specifically targets the wild-type or mutated target forms, and (3) the secondary target(s) that mediate its response when the primary target is not expressed. We first tested and successfully validated DeepTarget in a total of eleven unseen gold-standard datasets, with an average AUC of 0.82, 0.77, and 0.92 for the above three prediction abilities, respectively. We then proceed to use it in a wide range of applications: First, we find that DeepTarget’s predicted specificity of a drug to its target is strongly associated with its success in clinical trials and is higher in its FDA-approved indications. Second, DeepTarget predicts candidate drugs for targeting currently undruggable cancer oncogenes and their mutant forms. Finally, DeepTarget predicts new targets for drugs with unknown MOA and new secondary targets of approved drugs. Taken together, DeepTarget is a new computational framework for accelerating drug prioritization and its target discovery by leveraging large-scale genetic and drug screens.
Annotating and prioritizing human non-coding variants with RegulomeDB
Authors: Dong Shengcheng , Zhao Nanxiang , Spragins Emma , Kagda Meenakshi S. , Li Mingjie , Assis Pedro , Jolanki Otto , Luo Yunhai , Cherry J Michael , Boyle Alan P , Hitz Benjamin C 
Published: October 2022

AbstractNearly 90% of the disease risk-associated variants identified from genome-wide association studies (GWAS) are in non-coding regions of the genome. The annotations obtained from analyzing functional genomics assays can provide additional information to pinpoint causal variants, which are often not the lead variants identified from association studies. However, the lack of available annotation tools limits the use of such data.To address the challenge, we have previously built the RegulomeDB database for prioritizing and annotating variants in non-coding regions1, which has been a highly utilized resource for the research community (Supplementary Fig. 1). RegulomeDB annotates a variant by intersecting its position with genomic intervals identified from functional genomic assays and computational approaches. It also incorporates those hits of a variant into a heuristic ranking score, representing its potential to be functional in regulatory elements.Here we present a newer version of the RegulomeDB web server, RegulomeDB v2.1 (http://regulomedb.org). We improve and boost annotation power by incorporating thousands of newly processed data from functional genomic assays in GRCh38 assembly, and now include probabilistic scores from the SURF algorithm that was the top performing non-coding variant predictor in CAGI 52. We also provide interactive charts and genome browser views to allow users an easy way to perform exploratory analyses in different tissue contexts.
Granule cells affect dendritic tree selection in purkinje cells during cerebellar development
Authors: Kato Mizuki , Schutter Erik De 
Published: October 2022

AbstractThis study investigates the interrelationship between primary dendrite selection of Purkinje cells and migration of their pre-synaptic partner granule cells during cerebellar development. During development of the cerebellar cortex, each Purkinje cell grows more than three dendritic trees, from which a primary tree is selected to develop further, whereas the others completely retract. Experimental studies suggest that this selection process is coordinated by physical and synaptic interactions with granule cells. However, technical limitations hinder a continuous experimental observation of multiple populations. To reveal the mechanism underlying this selection process, we constructed a computational model of dendritic developments and granule cell migrations, using a new computational framework, NeuroDevSim. Comparisons of the resulting morphologies from the model demonstrate the roles of the selection stage in regulating the growth of the selected primary trees. The study presents the first computational model that simultaneously simulates growing Purkinje cells and the dynamics of granule cell migrations, revealing the role of physical and synaptic interactions upon dendritic selection. The model provides new insights about the distinct planar morphology of Purkinje cell dendrites and about roles of the dendritic selection process during the cerebellar development. The model also supports the hypothesis that synaptic interactions by granule cells are likely to be involved in the selection procedure.Author SummaryThe mature structure of a Purkinje cell, the main neuron of the cerebellum, is composed of a large flat dendritic tree composed of a single or sometimes 2 primary dendrites. However, this neuron has multiple similar trees during development, and retracts most of them to select its primary tree. We aim to explore roles of this developmental process as either an important step to attain optimal morphology or merely a redundant step to be eliminated by evolution in the future. We especially focused on environmental interactions on Purkinje cells as criteria to select the dendritic tree, hypothesizing that developing an efficient network with other neurons is one of the main goals of neuronal morphology. We constructed and used computational models to investigate detailed physical interactions and communications between Purkinje cells and their environment. Comparisons of models suggest the role of the selection stage is to obtain favorable growth of primary trees.
Profiling of the β-glucosidases identified in the genome ofPenicillium funiculosum: Insights from genomics, transcriptomics, proteomics and homology modelling studies
Authors: Okereke Omoaruemike Ebele , Gupta Mayank , Ogunyewo Olusola A. , Sharma Kanika , Yazdani Syed Shams 
Published: October 2022

ABSTRACTEnzymatic lignocellulosic biomass conversion to bioethanol is dependent on efficient enzyme systems with β-glucosidase as a key component. In this study, we performed in-depth profiling of the various β-glucosidases present in the genome of the hypercellulolytic fungus;Penicillium funiculosumusing genomics, transcriptomics, proteomics and molecular dynamics simulation approaches. Of the eight β-glucosidase genes identified in theP.funiculosumgenome, three were found to be extracellular, as evidenced by presence of signal peptides and mass spectrometry. Among the three secreted β-glucosidase, two belonged to the GH3 and one belonged to GH1 families. Modelled structures of these proteins predicted a deep and narrow active site for the GH3 β-glucosidases (PfBgl3A andPfBgl3B) and a shallow open active site for the GH1 β-glucosidase (PfBgl1A). The enzymatic assays indicated thatP. funiculosumsecretome showed high β-glucosidase activities with prominent bands on 4-methylumbelliferyl β-D-glucopyranoside (MUG) zymogram. To understand the contributory effect of each of the three secreted β-glucosidases (PfBgls), the corresponding gene was deleted separately and the effect of the deletion on β-glucosidase activity of the secretome was examined. Although not the most abundant β-glucosidase,PfBgl3A was found to be the most significant one as evidenced by a 42 % reduction in β-glucosidase activity in the ΔPfBgl3A strain. To improve the thermostability, two mutants ofPfBgl3A were designed with the help of molecular dynamics (MD) simulation and were expressed inPichia pastorisfor evaluation. ThePfBgl3A mutant (Mutant A) gave 1.4 fold increase in the half-life (T1/2) of the enzyme at 50°C.IMPORTANCECommercially available cellulases are majorly produced fromTrichoderma reesei. However, external supplementation of the cellulase cocktail from this host with exogenous β-glucosidase is often required to achieve desired optimal saccharification of cellulosic feedstocks. This challenge has led to exploration of other cellulase-producing strains because of the importance of this class of enzymes in the cellulose deconstruction machinery. The non-model hypercellulolytic fungusPenicillium funiculosumhas been studied in recent times and identified as a promising source of industrial cellulases. Various genetic interventions targeted at strain improvement for cellulase production have been performed. However, the β-glucosidases of this strain have remained largely understudied. This study, therefore, reports profiling of all the eight β-glucosidases ofP. funiculosumvia molecular and computational approaches and enhancing thermostability of the most promising β-glucosidase via protein engineering. The results of this study set the background for future engineering strategies to transform the fungus into an industrial workhorse.
Brain tissue mechanics is governed by microscale relations of the tissue constituents
Authors: Sáez P. , Borau C. , Antonovaite N. , Franze K. 
Published: October 2022

AbstractLocal mechanical tissue properties are a critical regulator of cell function in the central nervous system (CNS) during development and disorder. However, we still don’t fully understand how the mechanical properties of individual tissue constituents, such as cell nuclei or myelin, determine tissue mechanics. Here we developed a model predicting local tissue mechanics, which induces non-affine deformations of the tissue components. Using the mouse hippocampus and cerebellum as model systems, we show that considering individual tissue components alone, as identified by immunohistochemistry, is not sufficient to reproduce the local mechanical properties of CNS tissue. Our results suggest that brain tissue shows a universal response to applied forces that depends not only on the amount and stiffness of the individual tissue constituents but also on the way how they assemble. Our model may unify current incongruences between the mechanics of soft biological tissues and the underlying constituents and facilitate the design of better biomedical materials and engineered tissues. To this end, we provide a freely-available platform to predict local tissue elasticity upon providing immunohistochemistry images and stiffness values for the constituents of the tissue.
Resource-aware construct design in mammalian cells
Authors: Roberto Di Blasi , Mara Pisani , Fabiana Tedeschi , Masue Marbiah , Karen Polizzi , Simone Furini , Velia Siciliano , Francesca Ceroni 
Published: October 2022

AbstractResource competition can be the cause of unintended coupling between co-expressed genetic constructs. Here we report quantification of the resource load imposed by different mammalian genetic components and identify construct designs with increased performance and reduced resource footprint. We use these to generate improved synthetic circuits and optimise the co-expression of co-transfected cassettes, shedding light on how this can be useful for bioproduction and biotherapeutic applications. This work provides the scientific community with a framework to take resource demand into consideration when designing mammalian constructs to achieve robust and optimised gene expression.
Sequencing and chromosome-scale assembly of the giantPleurodeles waltlgenome
Authors: Brown Thomas , Elewa Ahmed , Iarovenko Svetlana , Subramanian Elaiyaraja , Araus Alberto Joven , Petzold Andreas , Suzuki Miyuki , Suzuki Ken-ichi T. , Hayashi Toshinori , Toyoda Atsushi , Oliveira Catarina , Osipova Ekaterina , Leigh Nicholas D. , Simon Andras , Yun Maximina H. 
Published: October 2022

AbstractThe Iberian ribbed newt (Pleurodeles waltl) constitutes a central model for probing the basis of vertebrate regeneration. Here, we present the sequencing and chromosome-scale assembly of the 20.3GbP. waltlgenome, which exhibits the highest level of contiguity and completeness among giant genome assemblies. We uncover that DNA transposable elements are the major contributors to its expansion, with hAT transposons comprising a large portion of repeats. Several hATs are actively transcribed and differentially expressed during adultP. waltllimb regeneration, along with domesticated hAT transposons of the ZBED transcription factor family. Despite its size, syntenic relationships are conserved. As an example, we show the high degree of conservation of the regeneration-associated Tig1 locus with several neighbouring genes. Together, theP. waltlgenome provides a fundamental resource for the study of regenerative, developmental and evolutionary principles.
3D genome topologies distinguish pluripotent epiblast and primitive endoderm cells in the mouse blastocyst
Authors: Loof Gesa , Szabó Dominik , Garg Vidur , Kukalev Alexander , Zea-Redondo Luna , Kempfer Rieke , Sparks Thomas M. , Zhang Yingnan , Thieme Christoph J , Carvalho Sílvia , Weise Anja , Balachandran Milash , Liehr Thomas , Welch Lonnie R. , Hadjantonakis Anna-Katerina , Pombo Ana 
Published: October 2022

SummaryThe development of embryonic cell lineages is tightly controlled by transcription factors that regulate gene expression and chromatin organisation. To investigate the specialisation of 3D genome structure in pluripotent or extra-embryonic endoderm lineages, we applied Genome Architecture Mapping (GAM) in embryonic stem (ES) cells, extra-embryonic endoderm (XEN) stem cells, and in theirin vivocounterparts, the epiblast (Epi) and primitive endoderm (PrE) cells, respectively. We discover extensive differences in 3D genome topology including the formation domain boundaries that differ between Epi and PrE lineages, bothin vivoandin vitro, at lineage commitment genes. In ES cells,Sox2contacts other active regions enriched for NANOG and SOX2 binding sites. PrE-specific genes, such asLama1andGata6, form repressive chromatin hubs in ES cells.Lama1activation in XEN or PrE cells coincides with its extensive decondensation. Putative binding sites for OCT4 and SNAIL, or GATA4/6, distinguish chromatin contacts unique to embryonic or extra-embryonic lineages, respectively. Overall, 3D genome folding is highly specialised in early development, especially at genes encoding factors driving lineage identity.HighlightsES and XEN cells have specialised 3D genome structuresGAM applied in the blastocyst distinguishes Epi and PrE genome structuresLineage specific genes establish cell-type specific chromatin contactsSpecific chromatin contacts feature putative bindings sites for GATA4/6 in XEN cells and SNAIL in ES cells
Bridging the gap between presynaptic hair cell function and neural sound encoding
Authors: Jaime Tobón Lina María , Moser Tobias 
Published: October 2022

AbstractNeural diversity can expand the encoding capacity of a circuitry. A striking example of diverse structure and function is presented by the afferent synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) in the cochlea. Presynaptic active zones at the pillar IHC side activate at lower IHC potentials than those of the modiolar side that have more presynaptic Ca2+-channels. The postsynaptic SGNs differ in their spontaneous firing rates, sound thresholds and operating ranges. While a causal relationship between synaptic heterogeneity and neural response diversity seems likely, experimental evidence linking synaptic and SGN physiology has remained difficult to obtain. Here, we aimed at bridging this gap byex vivopaired recordings of IHCs and postsynaptic SGN boutons with stimuli and conditions aimed to mimic those ofin vivoSGN-characterization. Synapses with high spontaneous rate of release (SR) were found predominantly on the pillar side of the IHC. These highSRsynapses had larger and more temporally compact spontaneous EPSCs, lower voltage-thresholds, tighter coupling of Ca2+channels and vesicular release sites, shorter response latencies and higher initial release rates. This study indicates that synaptic heterogeneity in IHCs directly contributes to the diversity of spontaneous and sound-evoked firing of SGNs.Significance StatementSound encoding relies on spiral ganglion neurons (SGNs) with diverse spontaneous firing, sound thresholds of firing and sound-intensity range over which SGN firing rate changes. Such functional SGN diversity might originate from different input from afferent synapses with inner hair cells (IHCs). The present study addresses this hypothesis by using recordings from individual IHC-SGN synapses of hearing mice underex vivoconditions aimed to mimic cochlear physiology. The results provide evidence that synaptic heterogeneity in IHCs contributes to SGN firing diversity. Thus, the cochlea employs heterogeneous synapses to decompose sound information into different neural pathways that collectively inform the brain about sound intensity.