bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of the Brazilian version of the Processes of Change Questionnaire in Weight Management in adults with overweight and obesity in Brazil
Authors: de Carvalho Quênia , Ziani Paola Rampelotto , Montezano Bruno Braga , Goularte Jeferson Ferraz , Rosa Adriane R 
Published: March 2023

AbstractIntroductionThis study aimed to analyze the psychometric properties of the Brazilian version of the Processes of Change Questionnaire in Weight Management (P-Weight) questionnaire.MethodsA total of 656 adults participated in the study, including people in weight loss treatment and people from the general community. All participants responded to the Process of Change Questionnaire (P-Weight), the Stages of Change Questionnaire (S-Weight), and the Eating Attitudes Test (EAT-26), which assesses risk of eating disorder used as a measure of external validity. Socio-demographic variables were also investigated.ResultsThe 33-item P-weight questionnaire showed satisfactory psychometric properties with high internal consistency (Cronbach’s alpha=0.959). Exploratory and confirmatory factor analyses revealed a 4-factor model similar to the original Spanish version of P-Weight with a slightly rearrangement of the items (KMO=0.92, df (528, n=328) =8,401.015; p<0.0001). We found significant associations between processes and stages of change (p<0.001) and a moderate correlation between the four subscales of P-weight and EAT-26 (p<0.001). Finally, the mean score of P-Weight were higher in clinical sample compared to the general community, suggesting the sensitivity to discriminate cases and controls (p<0.001).ConclusionThis study showed the validity and reliability of the Brazilian version of the P-Weight scale. Therefore, the P-Weight is readily available to help professionals to employ precision interventions to weight loss considering the patient’s motivational stage in combination with their individual use of the cognitive processes of change.
Wolbachiainfection at least partially rescues the fertility and ovary defects of several newDrosophila melanogaster bag of marblesprotein-coding mutants
Authors: Wenzel Miwa , Aquadro Charles F. 
Published: March 2023

AbstractTheD. melanogasterprotein coding genebag of marbles(bam) plays a key role in early male and female reproduction by forming complexes with partner proteins to promote differentiation in gametogenesis. Like another germline gene,Sex lethal,bamgenetically interacts with the endosymbiontWolbachia, asWolbachiarescues the reduced fertility of abamhypomorphic mutant. Here, we explored the specificity of thebam-Wolbachiainteraction by generating 22 newbammutants, with ten mutants displaying fertility defects. Nine of these mutants trend towards rescue by thewMelWolbachiavariant, with eight statistically significant at the fertility and/or cytological level. In some cases, fertility was increased a striking 20-fold. There is no specificity between the rescue and the known binding regions ofbam, suggestingwMel does not interact with one singularbampartner to rescue the reproductive phenotype. We further tested ifwMel interacts withbamin a non-specific way, by increasingbamtranscript levels or acting upstream in germline stem cells. A fertility assessment of abamRNAi knockdown mutant reveals thatwMel rescue is specific to functionally mutantbamalleles and we find no obvious evidence ofwMel interaction with germline stem cells inbammutants.Author SummaryReproduction in theDrosophila melanogasterfruit fly is dependent on thebag of marbles(bam) gene, which acts early in the process of generating eggs and sperm. Mutations to this gene negatively impact the fertility of the fly, causing it to be sterile or have fewer progeny. Interestingly, we find that the bacteriaWolbachia, which resides within reproductive cells across a wide range of insects, partially restores the fertility and ovary phenotype of severalbammutants of which the resultant Bam protein is altered from wildtype. The protein function of Bam is further suggested to be important by the lack of rescue for a fly that has a fertility defect due to low expression of a non-mutatedbamgene. Previous work makes similar conclusions aboutWolbachiawith another reproductive gene,Sex lethal(Sxl), highlighting the potential for rescue of fertility mutants to occur in a similar way across different genes. An understanding of the ways in whichWolbachiacan affect host reproduction provides us with context with which to frameWolbachia’s impact on host genes, such asbamandSxl,and consider the evolutionary implications ofWolbachia’s infection inD. melanogasterfruit flies.
MetaLLM: Residue-wise Metal ion Prediction Using Deep Transformer Model
Authors: Shishir Fairuz Shadmani , Sarker Bishnu , Rahman Farzana , Shomaji Sumaiya 
Published: March 2023

AbstractProteins bind to metals such as copper, zinc, magnesium, etc., serving various purposes such as importing, exporting, or transporting metal in other parts of the cell as ligands and maintaining stable protein structure to function properly. A metal binding site indicates the single amino acid position where a protein binds a metal ion. Manually identifying metal binding sites is expensive, laborious, and time-consuming. A tiny fraction of the millions of proteins in UniProtKB – the most comprehensive protein database – are annotated with metal binding sites, leaving many millions of proteins waiting for metal binding site annotation. Developing a computational pipeline is thus essential to keep pace with the growing number of proteins. A significant shortcoming of the existing computational methods is the consideration of the long-term dependency of the residues. Other weaknesses include low accuracy, absence of positional information, hand-engineered features, and a pre-determined set of residues and metal ions. In this paper, we propose MetaLLM, a metal binding site prediction technique, by leveraging the recent progress in self-supervised attention-based (e.g. Transformer) large language models (LLMs) and a considerable amount of protein sequences publicly available. LLMs are capable of modelling long residual dependency in a sequence. The proposed MetaLLM uses a transformer pre-trained on an extensive database of protein sequences and later fine-tuned on metal-binding proteins for multi-label metal ions prediction. A 10-fold cross-validation shows more than 90% precision for the most prevalent metal ions.
Aging impairs cold-induced beige adipogenesis and adipocyte metabolic reprogramming
Authors: Holman Corey D. , Sakers Alexander P. , Calhoun Ryan P. , Cheng Lan , Fein Ethan C. , Jacobs Christopher , Tsai Linus , Rosen Evan D. , Seale Patrick 
Published: March 2023

AbstractThe energy-burning capability of beige adipose tissue is a potential therapeutic tool for reducing obesity and metabolic disease, but this capacity is decreased by aging. Here, we evaluate the impact of aging on the profile and activity of adipocyte stem and progenitor cells (ASPCs) and adipocytes during the beiging process. We found that aging increases the expression ofCd9and other fibro-inflammatory genes in fibroblastic ASPCs and blocks their differentiation into beige adipocytes. Fibroblastic ASPC populations from young and aged mice were equally competent for beige differentiationin vitro, suggesting that environmental factors suppress adipogenesisin vivo. Examination of adipocytes by single nucleus RNA-sequencing identified compositional and transcriptional differences in adipocyte populations with age and cold exposure. Notably, cold exposure induced an adipocyte population expressing high levels ofde novolipogenesis (DNL) genes, and this response was severely blunted in aged animals. We further identified natriuretic peptide clearance receptorNpr3, a beige fat repressor, as a marker gene for a subset of white adipocytes and an aging-upregulated gene in adipocytes. In summary, this study indicates that aging blocks beige adipogenesis and dysregulates adipocyte responses to cold exposure and provides a unique resource for identifying cold and aging-regulated pathways in adipose tissue.
Deletion of smooth muscle O-GlcNAc transferase prevents development of atherosclerosis in western diet-fed hyperglycemic ApoE-/-mice in vivo
Authors: Khanal Saugat , Bhavnani Neha , Mathias Amy , Lallo Jason , Gupta Shreya , Ohanyan Vahagn , Ferrell Jessica , Raman Priya 
Published: March 2023

AbstractAccumulating evidence highlights protein O-GlcNAcylation as a putative pathogenic contributor of diabetic vascular complications. We previously reported that elevated protein O-GlcNAcylation correlates with increased atherosclerotic lesion formation and VSMC proliferation in response to hyperglycemia. However, the role of O-GlcNAc transferase (OGT), regulator of O-GlcNAc signaling, in evolution of diabetic atherosclerosis remains elusive. The goal of this study was to determine whether smooth muscle OGT (smOGT) plays a direct role in hyperglycemia-induced atherosclerotic lesion formation and SMC de-differentiation. Using tamoxifen-inducibleMyh11-CreERT2and OGTfl/flmice, we generated smOGTWTand smOGTKOmice, with and without ApoE-null backgrounds. Following STZ-induced hyperglycemia, smOGTWTand smOGTKOmice were kept on standard laboratory diet for study duration. In a parallel study, smOGTWTApoE-/-and smOGTKOApoE-/-were kept on Western diet beginning 8-wks-age. Animals harvested at 14-16-wks-age were used for plasma and tissue collection. Loss of smOGT augmented SM contractile marker expression in aortic vessels of STZ-induced hyperglycemic smOGTKOmice. Consistently, smOGT deletion attenuated atherosclerotic lesion lipid burden (Oil red O), plaque area (H&E), leukocyte (CD45) and smooth muscle cell (ACTA2) abundance in Western diet-induced hyperglycemic smOGTKOApoE-/-mice. This was accompanied with increased SM contractile markers, and reduced inflammatory and proliferative marker expression. Further, smOGT deletion attenuated YY1 and SRF expression (transcriptional regulators of SM contractile genes) in hyperglycemic smOGTKOApoE-/-and smOGTKOmice. These data uncover an atheroprotective outcome of smOGT loss-of-function and suggest a direct regulatory role of OGT-mediated O-GlcNAcylation in VSMC de-differentiation in hyperglycemia.
Cellular heterogeneity of the developing worker honey bee (Apis mellifera) pupa: a single cell transcriptomics analysis
Authors: Patir Anirudh , Raper Anna , Fleming Robert , Henderson Beth EP , Murphy Lee , Henderson Neil C , Clark Emily , Freeman Tom C , Barnett Mark W 
Published: March 2023

AbstractIt is estimated that animals pollinate 87.5% of flowering plants worldwide and that managed honey bees (Apis mellifera) account for 30-50% of this ecosystem service to agriculture. In addition to their important role as pollinators, honey bees are well-established insect models for studying learning and memory, behaviour, caste differentiation, epigenetic mechanisms, olfactory biology, sex determination and eusociality. Despite their importance to agriculture, knowledge of honey bee biology lags behind many other livestock species. In this study we have used scRNA-Seq to map cell types to different developmental stages of the worker honey bee (prepupa at day 11 and pupa at day 15), and sought to determine their gene signatures and thereby provide potential functional annotations for as yet poorly characterized genes. To identify cell type populations we examined the cell-to-cell network based on the similarity of the single-cells’ transcriptomic profiles. Grouping similar cells together we identified 63 different cell clusters of which 15 clusters were identifiable at both stages. To determine genes associated with specific cell populations or with a particular biological process involved in honey bee development, we used gene co-expression analysis. We combined this analysis with literature mining, the honey bee protein atlas and Gene Ontology analysis to determine cell cluster identity. Of the cell clusters identified, 9 were related to the nervous system, 7 to the fat body, 14 to the cuticle, 5 to muscle, 4 to compound eye, 2 to midgut, 2 to hemocytes and 1 to malpighian tubule/pericardial nephrocyte. To our knowledge, this is the first whole single cell atlas of honey bees at any stage of development and demonstrates the potential for further work to investigate their biology of at the cellular level.
Dual role of striatal astrocytes in behavioral flexibility and metabolism in the context of obesity
Authors: Montalban Enrica , Chao Daniela Herrera Moro , Ansoult Anthony , Pham Cuong , Contini Andrea , Castel Julien , Hassouna Rim , Hardonk Marene , Petitbon Anna , Foppen Ewout , Gangarossa Giuseppe , Trifilieff Pierre , Li Dongdong , Luquet Serge , Martin Claire 
Published: March 2023

ABSTRACTBrain circuits involved in metabolic control and reward-associated behaviors are potent drivers of feeding behavior and are both dramatically altered in obesity, a multifactorial disease resulting from genetic and environmental factors. In both mice and human, exposure to calorie-dense food has been associated with increased astrocyte reactivity and pro-inflammatory response in the brain. Although our understanding of how astrocytes regulate brain circuits has recently flourish, whether and how striatal astrocytes contribute in regulating food-related behaviors and whole-body metabolism is still unknown. In this study, we show that exposure to enriched food leads to profound changes in neuronal activity and synchrony. Chemogenetic manipulation of astrocytes activity in the dorsal striatum was sufficient to restore the cognitive defect in flexible behaviors induced by obesity, while manipulation of astrocyte in the nucleus accumbens led to acute change in whole-body substrate utilization and energy expenditure. Altogether, this work reveals a yet unappreciated role for striatal astrocyte as a direct operator of reward-driven behavior and metabolic control.
Oral supplementation of gut microbial metabolite indole-3-acetate alleviates diet-induced steatosis and inflammation in mice
Authors: Ding Yufang , Yanagi Karin , Yang Fang , Callaway Evelyn , Cheng Clint , Hensel Martha E , Menon Rani , Alaniz Robert C. , Lee Kyongbum , Jayaraman Arul 
Published: March 2023

AbstractNon-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in Western countries. There is growing evidence that dysbiosis of the intestinal microbiota and disruption of microbiota-host interactions contribute to the pathology of NAFLD. We previously demonstrated that gut microbiota derived tryptophan metabolite indole-3-acetate (I3A) was decreased in both cecum and liver of high-fat diet-fed mice and attenuated the expression of inflammatory cytokines in macrophages and TNF-a and fatty acid induced inflammatory responses in an aryl-hydrocarbon receptor (AhR) dependent manner in hepatocytes. In this study, we investigated the effect of orally administered I3A in a mouse model of diet induced NAFLD. Western diet (WD)-fed mice given sugar water (SW) with I3A showed dramatically decreased serum ALT, hepatic TG, liver steatosis, hepatocyte ballooning, lobular inflammation, and hepatic production of inflammatory cytokines, compared to WD-fed mice given only SW. Metagenomic analysis show that I3A administration did not significantly modify the intestinal microbiome, suggesting that I3A’s beneficial effects likely reflect the metabolite’s direct actions on the liver. Administration of I3A partially reversed WD induced alterations of liver metabolome and proteome, notably, decreasing expression of several enzymes in hepatic lipogenesis and β- oxidation. Mechanistically, we also show that AMP-activated protein kinase (AMPK) mediates the anti-inflammatory effects of I3A in macrophages. The potency of I3A in alleviating liver steatosis and inflammation clearly demonstrates its potential as a therapeutic modality for preventing the progression of steatosis to NASH.
Intermediate antiparallel fibrils in Aβ40 Dutch mutant aggregation: nanoscale insights from AFM-IR
Authors: Banerjee Siddhartha , Naik Tanmayee , Ghosh Ayanjeet 
Published: March 2023

AbstractCerebral Amyloid Angiopathy (CAA), which involves amyloid deposition in blood vessels leading to fatal cerebral hemorrhage and recurring strokes, is present in the majority Alzheimer’s disease cases. Familial mutations in the amyloid β peptide is correlated to higher risks of CAA, and are mostly comprised of mutations at residues 22 and 23. While the structure of the wild type Aβ peptide has been investigated in great detail, less is known about the structure of mutants involved in CAA and evolutions thereof. This is particularly true for mutations at residue 22, for which detailed molecular structures, as typically determined from Nuclear Magnetic Resonance (NMR) spectroscopy or electron microscopy, do not exist. In this report, we have used nanoscale infrared (IR) spectroscopy augmented with Atomic Force Microscopy (AFM-IR) to investigate structural evolution of the Aβ Dutch mutant (E22Q) at the single aggregate level. We show that that in the oligomeric stage, the structural ensemble is distinctly bimodal, with the two subtypes differing with respect to population of parallel β-sheets. Fibrils on the other hand are structurally homogeneous, with early-stage fibrils distinctly anti parallel in character, which develop parallel β-sheets upon maturation. Furthermore, the antiparallel structure is found to be a persistent feature across different stages of aggregation.
Seed functional ecology in Brazilian rock outcrop vegetation: an integrative synthesis
Authors: Ordóñez-Parra Carlos A. , Medeiros Natália F. , Dayrell Roberta L.C. , Le Stradic Soizig , Negreiros Daniel , Cornelissen Tatiana , Silveira Fernando A. O. 
Published: March 2023

ABSTRACTBackground and AimsRock outcrop vegetation is distributed worldwide and hosts a diverse and unique flora that evolved under harsh environmental conditions. Unfortunately, seed ecology in such ecosystems has received little attention, especially regarding seed traits, germination responses to abiotic factors and the potential role of phylogenetic relatedness on such features Here, we provide the first quantitative and phylogenetically-informed synthesis of the seed functional ecology of Brazilian rock outcrop vegetation, with a particular focus on quartzitic and ironstonecampo rupestre.MethodsUsing a database of functional trait data, we calculated the phylogenetic signal of seven seed traits for 371 taxa and tested whether they varied among growth forms, geographic distribution, and microhabitats. We also conducted meta-analyses that included 4,252 germination records for 102 taxa to assess the effects of light, temperature, and fire-related cues on the germination ofcampo rupestrespecies and explored how the aforementioned ecological groups and seed traits modulate germination responses.Key ResultsAll traits and germination responses showed a moderate-to-strong phylogenetic signal.Campo rupestrespecies responded positively to light and had maximum germination between 20-25 °C. The effect of temperatures beyond this range was moderated by growth form, species geographic distribution, and microhabitat. Seeds exposed to heat shocks above 80 °C lost viability, but smoke accelerated germination. We found a moderating effect of seed mass for in responses to light and heat shocks, with larger, dormant seeds tolerating heat better but less sensitive to light. Species from xeric habitats evolved phenological strategies to synchronise germination during periods of increased soil water availability.ConclusionsPhylogenetic relatedness plays a major role in shaping seed ecology of Brazilian rock outcrop vegetation. Nevertheless, seed traits and germination responses varied significantly between growth forms, species geographic distribution and microhabitats, providing support to the regeneration niche hypothesis and the role of functional traits in shaping germination in these ecosystems.
Interpretation of Predictions in Drug-Gut Bacteria Interactions Using Machine Learning
Authors: Joshi Himanshu , Prakash Meher K 
Published: March 2023

AbstractGut bacteria play a crucial role in host’s metabolism. Both antibiotic and non-antibiotic drugs affect the gut bacteria ecosystem, which negatively affects the host’s health. Also, gut bacteria metabolize drugs, making them ineffective to the target. The structure-activity relationship studies of drugs have the scope to make them more effective, efficient, and specific to the target. Previous machine learning studies use the available data to predict the activity of drugs and gut bacteria on each other, but these models lack interpretability. Herein, we study the drug-gut bacteria interaction using interpretable machine learning models. In this study, we identify the most important physicochemical features of the drug, which decide the drug-gut bacteria interactions with each other. One of the key findings of this work is that the higher-positive charged drug molecules can inhibit the growth of gut bacteria more. In contrast, the higher-negative charged drug molecules have higher possibility to get metabolized by gut bacteria.
Global effects of identity and aging on the human sperm methylome
Authors: de Sena Brandine Guilherme , Aston Kenneth I , Jenkins Timothy G , Smith Andrew D 
Published: March 2023

AbstractAs the average age of fatherhood increases worldwide, so too does the need for understanding effects of aging in male germline cells. Molecular change, including epigenomic alterations, may impact off-spring. Age-associated change to DNA cytosine methylation in the cytosine-guanine (CpG) context is a hallmark of aging tissues, including sperm. Prior studies have led to accurate models that predict a man’s age based on specific methylation features in the DNA of sperm, but the relationship between aging and global DNA methylation in sperm remains opaque. Further clarification requires a more complete survey of the methylome with assessment of variability within and between individuals.We collected sperm methylome data in a longitudinal study of ten healthy fertile men. We used whole-genome bisulfite sequencing of samples collected 10 to 18 years apart from each donor. We found that, overall, variability between donors far exceeds age-associated variation. After controlling for donor identity, we see significant age-dependent genome-wide change to the methylome. Notably, trends of change with age depend on genomic location or annotation, with contrasting signatures that correlate with gene density and proximity to centromeres and promoter regions. These molecular signatures reflect a stable process that begins in early adulthood, progressing steadily through most of the lifespan, and warrants consideration in any future study of the aging sperm epigenome.