bluuebunny/crossref_metadata_2025_split huggingface dataset:
OBMeta: a comprehensive web server to analyze and validate gut microbial features and biomarkers for obesity-associated metabolic diseases
Authors: Xu Cuifang , Huang Jiating , Gao Yongqiang , Zhao Weixing , Shen Yiqi , Luo Feihong , Yu Gang , Zhu Feng , Ni Yan 
Published: August 2023

AbstractGut dysbiosis is closely associated with obesity and related metabolic diseases including type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD). The gut microbial features and biomarkers have been increasingly investigated in recent studies, which require further validation due to the limited sample size and various confounding factors that may affect microbial compositions. So far, it lacks a comprehensive bioinformatics pipeline providing automated statistical analysis and integrating independent studies for cross validation simultaneously. OBMeta aims to streamline the standard metagenomics data analysis from diversity analysis, comparative analysis, functional analysis, to co-abundance network analysis. In addition, a curated database has been established with a total of 88 public research projects, covering three different phenotypes (Obesity, T2D, and NAFLD) and more than five different intervention strategies (exercise, diet, probiotics, medication, and surgery). With OBMeta, users can not only analyze their own research projects, but also search and match public datasets of interest for cross-project validation. Moreover, OBMeta provides cross-phenotype and cross-intervention-based advanced validation that maximally supports preliminary findings from an individual study. To summarize, OBMeta is a comprehensive web server to analyze and validate gut microbial features and biomarkers for obesity-associated metabolic diseases. OBMeta is freely available at:http://obmeta.met-bioinformatics.cn/.Abstract Figure
Long-term Prediction of Severe Hypoglycemia in Type 2 Diabetes Based on Multi-view Co-training
Authors: Agraz Melih , Deng Yixiang , Karniadakis George Em , Mantzoros Christos Socrates 
Published: August 2023

AbstractBackgroundPatients with type 2 diabetes mellitus (T2DM) who have severe hypoglycemia (SH) poses a considerable risk of long-term death, demanding urgent medical attention. Accurate prediction of SH remains challenging due to its multifactorial nature, contributed from factors such as medications, lifestyle choices, and metabolic measurements.MethodIn this study, we propose a systematic approach to improve the robustness and accuracy of SH predictions using machine learning models, guided by clinical feature selection. Our focus is on developing one-year SH prediction models using both semi-supervised learning and supervised learning algorithms. Utilizing the clinical trial, namely Action to Control Cardiovascular Risk in Diabetes, which involves electronic health records for over 10,000 individuals, we specifically investigate adults with T2DM who are at an increased risk of cardiovascular complications.ResultsOur results indicate that the application of a multi-view co-training method, incorporating the random forest algorithm, improves the specificity of SH prediction, while the same setup with Naive Bayes replacing random forest demonstrates better sensitivity. Our framework also provides interpretability of machine learning (XAI) models by identifying key predictors for hypoglycemia, including fast plasma glucose, hemoglobin A1c, general diabetes education, and NPH or L insulins.ConclusionBy enhancing prediction accuracy and identifying crucial predictive features, our study contributes to advancing the understanding and management of hypoglycemia in this population.
Developing a male-specific counselling curriculum for HIV treatment in Malawi
Authors: Mphande Misheck , Robson Isabella , Hubbard Julie , Chikuse Elijah , Lungu Eric , Phiri Khumbo , Cornell Morna , Phiri Sam , Coates Thomas J , Dovel Kathryn 
Published: August 2023

AbstractMen living with HIV in sub-Saharan Africa have sub-optimal engagement in antiretroviral therapy (ART) Programs. Generic ART counselling curriculum in Malawi does not meet men’s needs and should be tailored to men.We developed a male-specific ART counselling curriculum, adapted from the Malawi Ministry of Health (MOH) curriculum based on literature review of men’s needs and motivations for treatment. The curriculum was piloted through group counselling with men in 6 communities in Malawi, with focus group discussion (FGD) conducted immediately afterward (n=85 men) to assess knowledge of ART, motivators and barriers to care, and perceptions of the male-specific curriculum. Data were analysed in Atlas.ti using grounded theory. We conducted a half-day meeting with MOH and partner stakeholders to finalize the curriculum (n=5).The male-specific curriculum adapted three existing topics from generic counselling curriculum (status disclosure, treatment as prevention, and ART side effects) and added four new topics (how treatment contributes to men’s goals, feeling healthy on treatment, navigating health systems, and self-compassion for the cyclical nature of lifelong treatment. Key motivators for men were embedded throughout the curriculum and included: family wellbeing, having additional children, financially stability, and earning/keeping respect. During the pilot, men reported having little understanding of how ART contributed to their personal goals prior to the male-specific counselling. Men were most interested in additional information about treatment as prevention, benefits of disclosure/social support beyond their sexual partner, how to navigate health systems, and side effects with new regimens. Respondents stated that the male-specific counselling challenged the idea that men were incapable of overcoming treatment barriers and lifelong medication.Male-specific ART counselling curriculum is needed to address men’s specific needs. In Malawi context, topics should include: how treatment contributes to men’s goals, navigating health systems, self-compassion/patience for lifelong treatment, and taking treatment while healthy.
Main Manuscript for Microbiome single cell atlases generated with a benchtop instrument
Authors: Li Xiangpeng , Xu Linfeng , Demaree Benjamin , Noecker Cecilia , Bisanz Jordan E. , Weisgerber Daniel W. , Modavi Cyrus , Turnbaugh Peter J. , Abate Adam R. 
Published: August 2023

AbstractSingle cell sequencing is useful for resolving complex systems into their composite cell types and computationally mining them for unique features that are masked in pooled sequencing. However, while commercial instruments have made single cell analysis widespread for mammalian cells, analogous tools for microbes are limited. Here, we present EASi-seq (Easily Accessible Single microbe sequencing). By adapting the single cell workflow of the commercial Mission Bio Tapestri instrument, this method allows for efficient sequencing of individual microbes’ genomes. EASi-seq allows thousands of microbes to be sequenced per run and, as we show, can generate detailed atlases of human and environmental microbiomes. The ability to capture large shotgun genome datasets from thousands of single microbes provides new opportunities in discovering and analyzing species subpopulations. To facilitate this, we develop a companion bioinformatic pipeline that clusters genome by sequence similarity, improving whole genome assembly, strain identification, taxonomic classification, and gene annotation. In addition, we demonstrate integration of metagenomic contigs with the EASi-seq datasets to reduce capture bias and increase coverage. Overall, EASi-seq enables high quality single cell genomic data for microbiome samples using an accessible workflow that can be run on a commercially available platform.
Leveraging fine-scale population structure reveals conservation in genetic effect sizes between human populations across a range of human phenotypes
Authors: Hu Sile , Ferreira Lino A. F. , Shi Sinan , Hellenthal Garrett , Marchini Jonathan , Lawson Daniel J. , Myers Simon R. 
Published: August 2023

AbstractAn understanding of genetic differences between populations is essential for avoiding confounding in genome-wide association studies (GWAS) and understanding the evolution of human traits. Polygenic risk scores constructed in one group perform poorly in highly genetically-differentiated populations, for reasons which remain controversial. We developed a statistical ancestry inference pipeline able to decompose ancestry both within and between countries, and applied it to the UK Biobank data. This identifies fine-scale patterns of genetic relatedness not captured by standard and widely used principal components (PCs), and allows fine-scale population stratification correction that removes both false positive and false negative associations for traits with geographic correlations. We also develop and apply ANCHOR, an approach leveraging segments of distinct ancestries within individuals to estimate similarity in underlying causal effect sizes between groups, using an existing PGS. Applying ANCHOR to >8000 people of mixed African and European ancestry, we demonstrate that estimated causal effect sizes are highly similar across these ancestries for 26 of 29 quantitative molecular and non-molecular phenotypes (mean correlation 0.98 +/-0.08), providing evidence that gene-environment and gene-gene interactions do not play major roles in the poor prediction of European-ancestry PRS scores in African populations for these traits, contradicting previous findings. Instead our results provide optimism that shared causal mutations operate similarly in different groups, focussing the challenge of improving GWAS “portability” between groups on joint fine-mapping.
The stromal side of cytochromeb6fcomplex regulates state transitions
Authors: Riché Alexis , Dumas Louis , Malesinski Soazig , Bossan Guillaume , Madigou Céline , Zito Francesca , Alric Jean 
Published: August 2023

AbstractIn oxygenic photosynthesis, state transitions distribute light energy between Photosystem I and Photosystem II. This regulation involves the reduction of the plastoquinone pool, activation of the STT7 protein kinase by cytochromeb6fcomplex, phosphorylation and migration of Light Harvesting Complexes II (LHCII). Here we show the C-term of cytb6subunit acts on phosphorylation of STT7 and state transitions. We used site-directed mutagenesis of the chloroplastpetBgene to truncate (remove L215b6) or elongate (add G216b6) the cytb6subunit. Modified complexes are devoid of hemeciand degraded by FTSH protease, revealing that salt bridge formation between cytb6(PetB) and subunit IV (PetD) is key to the assembly of the complex. In double mutants where FTSH is inactivated, modified cytb6fare accumulated but the phosphorylation cascade is blocked. We also replaced the arginine interacting with hemecipropionate (R207Kb6). In this modified complex, hemeciis present but the kinetics of phosphorylation are slower. We show that highly phosphorylated forms of STT7 are accumulated transiently after reduction of the PQ pool, and represent the active forms of the protein kinase. 96% protein coverage using phosphoproteomics showed 4 new phosphorylated peptides in the kinase domain of STT7. Phosphorylation of the LHCII targets is favored at the expense of the protein kinase, and the migration of LHCII towards PSI is the limiting step for state transitions.Significance statementState transitions are regulatory mechanisms that optimize the quantum yield of photosynthesis.Chlamydomonas reinhardtiiis the choice organism to study this regulation at the molecular level. Our study describes an unprecedented mechanism of stereochemical changes at the Qisite of the cytochromeb6fcomplex that trigger STT7 protein kinase activation through autophosphorylation.
Identifying small-molecules binding sites in RNA conformational ensembles with SHAMAN
Authors: Panei F. P. , Gkeka P. , Bonomi M. 
Published: August 2023

AbstractThe rational targeting of RNA with small molecules is hampered by our still limited understanding of RNA structural and dynamic properties. Mostin silicotools for binding site identification rely on static structures and therefore cannot face the challenges posed by the dynamic nature of RNA molecules. Here, we present SHAMAN, a computational technique to identify potential small-molecule binding sites in RNA structural ensembles. SHAMAN enables exploring the conformational landscape of RNA with atomistic molecular dynamics and at the same time identifying RNA pockets in an efficient way with the aid of probes and enhanced-sampling techniques. In our benchmark composed of large, structured riboswitches as well as small, flexible viral RNAs, SHAMAN successfully identified all the experimentally resolved pockets and ranked them among the most favorite probe hotspots. Overall, SHAMAN sets a solid foundation for future drug design efforts targeting RNA with small molecules, effectively addressing the long-standing challenges in the field.
Whole genome structural predictions reveal hidden diversity in putative oxidative enzymes of the lignocellulose degrading ascomyceteParascedosporium putredinisNO1
Authors: Scott Conor JR , Leadbeater Daniel R , Oates Nicola C , James Sally R , Newling Katherine , Li Yi , McGregor Nicholas GS , Bird Susannah , Bruce Neil C 
Published: August 2023

AbstractEconomic valorisation of lignocellulose is paramount to realising a true circular bioeconomy; however, this requires the development of systems and processes to expand the repertoire of bioproducts beyond current renewable fuels, chemicals, and sustainable materials.Parascedosporium putredinisNO1 is an ascomycete that thrived at the later stages of a wheat- straw composting community culture, indicating a propensity to degrade recalcitrant lignin- enriched biomass, but exists within an underrepresented and underexplored fungal lineage. This strain has proven an exciting candidate for the identification of new enzymes targeting recalcitrant components of lignocellulose following the recent discovery of a new lignin β-ether linkage cleaving enzyme.The first genome for the genusParascedosporiumforP. putredinisNO1 genome was sequenced, assembled, and annotated. The genome is 39 Mb in size, consisting of 21 contigs annotated to contain 9.998 protein-coding sequences. The carbohydrate-active enzyme (CAZyme) repertoire was compared to 2570 ascomycete genomes and in detail withTrichoderma reesei,Fusarium oxysporum,and sister taxaScedosporium boydii.Significant expansion in the oxidative auxiliary activity class of CAZymes was observed in theP. putredinisNO1 genome resulting from increased sequences encoding putative lytic polysaccharide monooxygenases (LPMOs), oxidative enzymes acting within LPMO redox systems, and lignin-degrading laccases.P. putredinisNO1 scored above the 95thpercentile for AA gene density across the ascomycete phylum, suggesting a primarily oxidative strategy for lignocellulose breakdown. Novel structure-based searching approaches were employed, revealing 17 new sequences with structural similarity to LPMO, laccase, and peroxidase sequences and which are potentially new lignocellulose-degrading enzymes.ImportanceAn annotated reference genome has revealedP. putredinisNO1 as a useful resource for the identification of new lignocellulose degrading enzymes for biorefining of woody plant biomass. Utilising a ‘structure-omics’ based searching strategy, new potentially lignocellulose-active sequences were identified that would have been missed by traditional sequence searching methods. These new identifications, alongside the discovery of novel enzymatic functions from this underexplored lineage with the recent discovery of a new phenol oxidase that cleaves the main structural β-O-4 linkage in lignin fromP. putredinisNO1 highlights the underexplored and poorly represented family Microascaceae as particularly interesting candidates worthy of further exploration toward the valorisation of high value biorenewable products.
Aging is associated with functional and molecular changes in distinct hematopoietic stem cell subsets
Authors: Somuncular Ece , Hauenstein Julia , Su Tsu-Yi , Dumral Özge , Gustafsson Charlotte , Tzortzis Efthymios , Forlani Aurora , Johansson Anne-Sofie , Månsson Robert , Luc Sidinh 
Published: August 2023

AbstractAge is a risk factor for hematologic malignancies. Attributes of the aging hematopoietic system include increased myelopoiesis, impaired adaptive immunity, and a functional decline of the hematopoietic stem cells (HSCs) that maintain hematopoiesis. Changes in the composition of diverse HSC subsets have been suggested to be responsible for age-related alterations, however, the underlying regulatory mechanisms are incompletely understood in the context of HSC heterogeneity. In this study, we investigated how distinct HSC subsets, separated by CD49b, functionally and molecularly change their behavior with age. We demonstrate that blood lineage differentiation progressively shifts to a higher myeloid cellular output in both lymphoid-biased and myeloid-biased HSC subsets during aging. In parallel, we show that HSCs selectively undergo age-dependent gene expression and gene regulatory molecular changes in a progressive manner, which is initiated already in the pre-adult stage. Overall, our studies suggest that aging intrinsically alters both cellular and molecular properties of HSCs.Highlights:With age a gradual shift towards myeloid differentiation occurs in both myeloid-biased and lymphoid-biased enriched HSC subsets.Age-related molecular changes preferentially occur in HSCs.Functionally distinct HSC subsets with high transcriptional similarity can be distinguished on the epigenetic level.HSC aging is associated with a progressive increase in chromatin accessibility.
Development and Analytical Evaluation of a Point-of-Care Electrochemical Biosensor for Rapid and Accurate SARS-CoV-2 Detection
Authors: Meshesha Mesfin , Sardar Anik , Supekar Ruchi , Bhattacharjee Lopamudra , Chatterjee Soumyo , Halder Nyancy , Mohanta Kallol , Pal Biplab 
Published: August 2023

AbstractThe COVID-19 pandemic has underscored the critical need for rapid and accurate screening and diagnostic methods for potential respiratory viruses. Existing COVID-19 diagnostic approaches face limitations either in terms of turnaround time or accuracy. In this study, we present an electrochemical biosensor that offers nearly instantaneous and precise SARS-CoV-2 detection, suitable for point-of-care and environmental monitoring applications. The biosensor employs a stapled hACE-2 N-terminal alpha helix peptide to functionalize an in-situ grown polypyrrole conductive polymer on a nitrocellulose membrane backbone through a chemical process. We assessed the biosensor’s analytical performance using heat-inactivated omicron and delta variants of the SARS-CoV-2 virus in artificial saliva (AS) and nasal swabs (NS) samples diluted in a strong ionic solution. Virus identification was achieved through electrochemical impedance spectroscopy (EIS) and frequency analyses. The assay demonstrated a limit of detection of 40 TCID50/mL, with 95% sensitivity and 100% specificity. Notably, the biosensor exhibited no cross-reactivity when tested against the influenza virus. The entire testing process using the biosensor takes less than a minute. In summary, our biosensor exhibits promising potential in the battle against pandemic respiratory viruses, offering a platform for the creation of rapid, compact, portable, and point-of-care devices capable of multiplexing various viruses. This groundbreaking development has the capacity to significantly bolster our readiness and response to future viral outbreaks.
A novel PEX14/PEX5 interface links peroxisomal protein import and receptor recycling
Authors: Emmanouilidis Leonidas , Sehr Jessica , Reglinski Katharina , Gaussmann Stefan , Goricanec David , Kordon Jonathan , Menezes Filipe , Waithe Dominic , Hublitz Philip , Bader Verian , Winklhofer Konstanze F. , Jung Martin , Schliebs Wolfgang , Eggeling Christian , Erdmann Ralf , Sattler Michael 
Published: August 2023

AbstractNewly synthesized peroxisomal proteins are recognized in the cytosol by the cycling receptor PEX5 and directed to a docking complex comprising PEX14 and PEX13 at the peroxisomal membrane. After cargo translocation, the unloaded PEX5 is recycled in an ATP-dependent manner. Receptor docking involves the WxxxF-motifs in the N-terminal domain (NTD) of PEX5 that are recognized by the N-terminal domain of PEX14. Here, we combine biochemical methods and NMR spectroscopy to identify a novel binding interface between human PEX5 and PEX14. The interaction involves the PEX5 C-terminal cargo-binding TPR domain and a conserved IPSWQI peptide motif in the C-terminal intrinsically disordered region of PEX14. The three-dimensional structure of the PEX14 IPSWQI peptide bound the PEX5 TPR domain, shows the PEX14 interaction is non-overlapping with PTS1 binding to the TPR domain. Notably, PEX14 IPSWQI motif binding to a hinge region in the TPR domain shows a more open supercoil of the TPR fold that resembles the apo conformation in the absence of PTS1 peptide. Mutation of binding site residues in PEX5 or PEX14 leads to a partial protein import defect and decrease of the steady-state-concentration of PEX5. This resembles the mutant phenotype of cells affected in receptor recycling, suggesting a role in this process.
The punctate localisation of the yeast sterol transporter Ysp2p is determined by three dimerisation interfaces in its C-terminus
Authors: Alli-Balogun Ganiyu O. , Ivanović Lazar , Kukulski Wanda , Levine Tim P. 
Published: August 2023

AbstractSterol lipids traffic between intracellular compartments by vesicular and non-vesicular routes. Sterol traffic from the plasma membrane to the endoplasmic reticulum (ER), so-called retrograde traffic, particularly depends on a non-vesicular mechanism, being transported by the ubiquitous family ofLipid transfer proteinsAnchored atMembrane contact sites (LAMs, also called GRAMD1/Asters in humans, VASt in plants). LAMs are similar to many lipid transfer proteins in that they localise to membrane contact sites and carry lipids between two organelles. In yeast, the major LAM active at ER-plasma membrane contact sites is Ysp2p, which has a uniquely punctate distribution in the cortical ER. Here, we have comprehensively dissected how Ysp2p achieves its distinctive punctate localisation. We show that the PHGRAMdomain of Ysp2p has membrane binding properties similar to its human counterpart GRAMD1B, but that this is not important for punctate localisation of Ysp2p. Instead, all regions necessary for the punctate localisation of Ysp2p at membrane contacts are present in ∼200 residues at the C-terminus of Ysp2p, with a critical region being a small ý-sheet that we predict homodimerises. We also study the role of punctate localisation of Ysp2 in its function in retrograde sterol traffic, and show that function does not require the punctate localisation, but instead requires a polybasic region adjacent to the sterol transfer domain. Finally, to investigate the interaction of the polybasic region with the plasma membrane, we examine contacts populated by the Ysp2 C-terminus by electron tomography, and find that they consist of generic cortical ER.