bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigenetic priming of an epithelial enhancer by p63 and CTCF controls expression of a skin-restricted gene XP33
Authors: Smirnov Artem , Lena Anna Maria , Tosetti Giulia , Yang Xue , Cappello Angela , Helmer Citterich Manuela , Melino Gerry , Candi Eleonora 
Published: December 2023

AbstractThe transcription factor p63 is a renowned master regulator of gene expression of stratified epithelia. While multiple proteins have been identified as p63 bona fide targets, little is known about non-coding RNAs (ncRNAs) whose transcription is controlled by p63. Here, we describe a skin-specific non-coding RNA XP33 as a novel target of p63. XP33 levels are increased during keratinocyte differentiation in vitro, while its depletion results in decreased expression of late cornified gene LCE2D. By using publicly available multi-omics data, we show that CTCF and p63 establish an epithelial enhancer to prime XP33 transcription in a tissue-restricted manner. XP33 promoter and enhancer form a chromatin loop exclusively in keratinocytes but not in other cell types. Moreover, the XP33 enhancer is occupied by differentiation-specific factors that control XP33 transcription. Altogether, we identify a tissue-specific non-coding RNA whose expression is epigenetically regulated by p63 and CTCF.
The societal economic impact of vision impairment in adults 40 years and above: findings from the National Eye Survey of Trinidad and Tobago
Authors: Braithwaite T. , Bailey H. , Bartholomew D. , Maharaj V. , Fraser A. , Deomansingh F. , Ramsewak S. S. , Tripathi V. , Sharma S. , Singh D. , Ramsewak S. S. , Bourne R. R. A. , Gray A. 
Published: December 2023

Abstract
Background
Understanding and mitigating the societal economic impact of vision impairment (VI) is important for achieving the Sustainable Development Goals.

Aim
To estimate the prevalent societal economic impact of presenting VI in Trinidad and Tobago using bottom-up cost and utilisation data from the 2014 National Eye Survey of Trinidad and Tobago.

Methods
We took a societal perspective to combine comprehensive, individual-level cost and utilisation data, with population-based prevalence estimates for VI, and additional data from a contemporaneous national eyecare system survey. We included direct (medical and non-medical) and indirect (productivity loss) costs, and intangible losses in total cost estimates, presented in 2014 Trinidad & Tobago (TT) dollars and UK sterling equivalent. We considered but excluded transfer payments and dead weight losses. Sensitivity analyses explored impact on total cost of parameter uncertainty and assumptions.

Results
Individual utilisation and cost data were available for 65.5% (n = 2792/4263) and 59.0% (n = 2516/4263) eligible participants aged ≥40 years, respectively. Participant mean age was 58.4(SD 11.8, range 40–103) years, 56.3% were female. We estimated total societal cost of VI in 2014 at UK£365,650,241 (TT$3,842,324,655), equivalent to £675 per capita (population ≥40 years). Loss of wellbeing accounted for 73.3%. Excluding this, the economic cost was UK£97,547,222 (TT$1,025,045,399), of which indirect costs accounted for 70.5%, followed by direct medical costs (17.9%), and direct non-medical costs (11.6%).

Conclusion
This study provides a comprehensive estimate of the economic impact of vision loss in a Caribbean country, and highlights the extent to which affected individuals and their families bear the societal economic cost of vision impairment.
Phospholipids are imported into mitochondria by VDAC, a dimeric beta barrel scramblase
Authors: Jahn Helene , Bartoš Ladislav , Dearden Grace I. , Dittman Jeremy S. , Holthuis Joost C. M. , Vácha Robert , Menon Anant K. 
Published: December 2023

AbstractMitochondria are double-membrane-bounded organelles that depend critically on phospholipids supplied by the endoplasmic reticulum. These lipids must cross the outer membrane to support mitochondrial function, but how they do this is unclear. We identify the Voltage Dependent Anion Channel (VDAC), an abundant outer membrane protein, as a scramblase-type lipid transporter that catalyzes lipid entry. On reconstitution into membrane vesicles, dimers of human VDAC1 and VDAC2 catalyze rapid transbilayer translocation of phospholipids by a mechanism that is unrelated to their channel activity. Coarse-grained molecular dynamics simulations of VDAC1 reveal that lipid scrambling occurs at a specific dimer interface where polar residues induce large water defects and bilayer thinning. The rate of phospholipid import into yeast mitochondria is an order of magnitude lower in the absence of VDAC homologs, indicating that VDACs provide the main pathway for lipid entry. Thus, VDAC isoforms, members of a superfamily of beta barrel proteins, moonlight as a class of phospholipid scramblases - distinct from alpha-helical scramblase proteins - that act to import lipids into mitochondria.
Human and mouse neutrophils share core transcriptional programs in both homeostatic and inflamed contexts
Authors: Hackert Nicolaj S. , Radtke Felix A. , Exner Tarik , Lorenz Hanns-Martin , Müller-Tidow Carsten , Nigrovic Peter A. , Wabnitz Guido , Grieshaber-Bouyer Ricardo 
Published: December 2023

AbstractNeutrophils are frequently studied in mouse models, but the extent to which findings translate to humans remains poorly defined. In an integrative analysis of 11 mouse and 13 human datasets, we find a strong correlation of neutrophil gene expression across species. In inflammation, neutrophils display substantial transcriptional diversity but share a core inflammation program. This program includes genes encoding IL-1 family members, CD14, IL-4R, CD69, and PD-L1. Chromatin accessibility of core inflammation genes increases in blood compared to bone marrow and further in tissue. Transcription factor enrichment analysis implicates members of the NF-κB family and AP-1 complex as important drivers, and HoxB8 neutrophils with JunB knockout show a reduced expression of core inflammation genes in resting and activated cells. In independent single-cell validation data, neutrophil activation by type I or type II interferon, G-CSF, and E. coli leads to upregulation in core inflammation genes. In COVID-19 patients, higher expression of core inflammation genes in neutrophils is associated with more severe disease. In vitro treatment with GM-CSF, LPS, and type II interferon induces surface protein upregulation of core inflammation members. Together, we demonstrate transcriptional conservation in neutrophils in homeostasis and identify a core inflammation program shared across heterogeneous inflammatory conditions.
Structural plasticity for neuromorphic networks with electropolymerized dendritic PEDOT connections
Authors: Janzakova Kamila , Balafrej Ismael , Kumar Ankush , Garg Nikhil , Scholaert Corentin , Rouat Jean , Drouin Dominique , Coffinier Yannick , Pecqueur Sébastien , Alibart Fabien 
Published: December 2023

AbstractNeural networks are powerful tools for solving complex problems, but finding the right network topology for a given task remains an open question. Biology uses neurogenesis and structural plasticity to solve this problem. Advanced neural network algorithms are mostly relying on synaptic plasticity and learning. The main limitation in reconciling these two approaches is the lack of a viable hardware solution that could reproduce the bottom-up development of biological neural networks. Here, we show how the dendritic growth of PEDOT:PSS-based fibers through AC electropolymerization can implement structural plasticity during network development. We find that this strategy follows Hebbian principles and is able to define topologies that leverage better computing performances with sparse synaptic connectivity for solving non-trivial tasks. This approach is validated in software simulation, and offers up to 61% better network sparsity on classification and 50% in signal reconstruction tasks.
The separation pin distinguishes the pro– and anti–recombinogenic functions of Saccharomyces cerevisiae Srs2
Authors: Meir Aviv , Raina Vivek B. , Rivera Carly E. , Marie Léa , Symington Lorraine S. , Greene Eric C. 
Published: December 2023

AbstractSrs2 is an Sf1a helicase that helps maintain genome stability in Saccharomyces cerevisiae through its ability to regulate homologous recombination. Srs2 downregulates HR by stripping Rad51 from single–stranded DNA, and Srs2 is also thought to promote synthesis–dependent strand annealing by unwinding D–loops. However, it has not been possible to evaluate the relative contributions of these two distinct activities to any aspect of recombination. Here, we used a structure–based approach to design an Srs2 separation–of–function mutant that can dismantle Rad51–ssDNA filaments but is incapable of disrupting D–loops, allowing us to assess the relative contributions of these pro– and anti–recombinogenic functions. We show that this separation–of–function mutant phenocopies wild–type SRS2 in vivo, suggesting that the ability of Srs2 to remove Rad51 from ssDNA is its primary role during HR.
Structures of human prostaglandin F2α receptor reveal the mechanism of ligand and G protein selectivity
Authors: Lv Xiuqing , Gao Kaixuan , Nie Jia , Zhang Xin , Zhang Shuhao , Ren Yinhang , Sun Xiaoou , Li Qi , Huang Jingrui , Liu Lijuan , Zhang Xiaowen , Zhang Weishe , Liu Xiangyu 
Published: December 2023

AbstractProstaglandins and their receptors regulate various physiological processes. Carboprost, an analog of prostaglandin F2α and an agonist for the prostaglandin F2-alpha receptor (FP receptor), is clinically used to treat postpartum hemorrhage (PPH). However, off-target activation of closely related receptors such as the prostaglandin E receptor subtype EP3 (EP3 receptor) by carboprost results in side effects and limits the clinical application. Meanwhile, the FP receptor selective agonist latanoprost is not suitable to treat PPH due to its poor solubility and fast clearance. Here, we present two cryo-EM structures of the FP receptor bound to carboprost and latanoprost-FA (the free acid form of latanoprost) at 2.7 Å and 3.2 Å resolution, respectively. The structures reveal the molecular mechanism of FP receptor selectivity for both endogenous prostaglandins and clinical drugs, as well as the molecular mechanism of G protein coupling preference by the prostaglandin receptors. The structural information may guide the development of better prostaglandin drugs.
Structure of the complete Saccharomyces cerevisiae Rpd3S-nucleosome complex
Authors: Markert Jonathan W. , Vos Seychelle M. , Farnung Lucas 
Published: December 2023

AbstractAcetylation of histones is a key post-translational modification that guides gene expression regulation. In yeast, the class I histone deacetylase containing Rpd3S complex plays a critical role in the suppression of spurious transcription by removing histone acetylation from actively transcribed genes. The S. cerevisiae Rpd3S complex has five subunits (Rpd3, Sin3, Rco1, Eaf3, and Ume1) but its subunit stoichiometry and how the complex engages nucleosomes to achieve substrate specificity remains elusive. Here we report the cryo-EM structure of the complete Rpd3S complex bound to a nucleosome. Sin3 and two copies of subunits Rco1 and Eaf3 encircle the deacetylase subunit Rpd3 and coordinate the positioning of Ume1. The Rpd3S complex binds both trimethylated H3 tails at position lysine 36 and makes multiple additional contacts with the nucleosomal DNA and the H2A–H2B acidic patch. Direct regulation via the Sin3 subunit coordinates binding of the acetylated histone substrate to achieve substrate specificity.
Contractile ring mechanosensation and its anillin-dependent tuning during early embryogenesis
Authors: Hsu Christina Rou , Sangha Gaganpreet , Fan Wayne , Zheng Joey , Sugioka Kenji 
Published: December 2023

AbstractCytokinesis plays crucial roles in morphogenesis. Previous studies have examined how tissue mechanics influences the position and closure direction of the contractile ring. However, the mechanisms by which the ring senses tissue mechanics remain largely elusive. Here, we show the mechanism of contractile ring mechanosensation and its tuning during asymmetric ring closure of Caenorhabditis elegans embryos. Integrative analysis of ring closure and cell cortex dynamics revealed that mechanical suppression of the ring-directed cortical flow is associated with asymmetric ring closure. Consistently, artificial obstruction of ring-directed cortical flow induces asymmetric ring closure in otherwise symmetrically dividing cells. Anillin is vital for mechanosensation. Our genetic analysis suggests that the positive feedback loop among ring-directed cortical flow, myosin enrichment, and ring constriction constitutes a mechanosensitive pathway driving asymmetric ring closure. These findings and developed tools should advance the 4D mechanobiology of cytokinesis in more complex tissues.
Multi-ancestry study of the genetics of problematic alcohol use in over 1 million individuals
Authors: Zhou Hang , Kember Rachel L. , Deak Joseph D. , Xu Heng , Toikumo Sylvanus , Yuan Kai , Lind Penelope A. , Farajzadeh Leila , Wang Lu , Hatoum Alexander S. , Johnson Jessica , Lee Hyunjoon , Mallard Travis T. , Xu Jiayi , Johnston Keira J. A. , Johnson Emma C. , Nielsen Trine Tollerup , Galimberti Marco , Dao Cecilia , Levey Daniel F. , Overstreet Cassie , Byrne Enda M. , Gillespie Nathan A. , Gordon Scott , Hickie Ian B. , Whitfield John B. , Xu Ke , Zhao Hongyu , Huckins Laura M. , Davis Lea K. , Sanchez-Roige Sandra , Madden Pamela A. F. , Heath Andrew C. , Medland Sarah E. , Martin Nicholas G. , Ge Tian , Smoller Jordan W. , Hougaard David M. , Børglum Anders D. , Demontis Ditte , Krystal John H. , Gaziano J. Michael , Edenberg Howard J. , Agrawal Arpana ,   Million Veteran Program, Zhao Hongyu , Justice Amy C. , Stein Murray B. , Kranzler Henry R. , Gelernter Joel 
Published: December 2023

AbstractProblematic alcohol use (PAU), a trait that combines alcohol use disorder and alcohol-related problems assessed with a questionnaire, is a leading cause of death and morbidity worldwide. Here we conducted a large cross-ancestry meta-analysis of PAU in 1,079,947 individuals (European, N = 903,147; African, N = 122,571; Latin American, N = 38,962; East Asian, N = 13,551; and South Asian, N = 1,716 ancestries). We observed a high degree of cross-ancestral similarity in the genetic architecture of PAU and identified 110 independent risk variants in within- and cross-ancestry analyses. Cross-ancestry fine mapping improved the identification of likely causal variants. Prioritizing genes through gene expression and chromatin interaction in brain tissues identified multiple genes associated with PAU. We identified existing medications for potential pharmacological studies by a computational drug repurposing analysis. Cross-ancestry polygenic risk scores showed better performance of association in independent samples than single-ancestry polygenic risk scores. Genetic correlations between PAU and other traits were observed in multiple ancestries, with other substance use traits having the highest correlations. This study advances our knowledge of the genetic etiology of PAU, and these findings may bring possible clinical applicability of genetics insights—together with neuroscience, biology and data science—closer.
Fatty acid profiling and oxidative stability of biscuits available in the market of the city of Ludhiana, India
Authors: Kaur Prabhjot , Choudhary Monika , Sharma Sanjula 
Published: December 2023

AbstractIndia has occupied third position in biscuit manufacturing with an average production of 1.95 million tonnes. The major ingredients in biscuit manufacturing are refined wheat flour, sugar and fat. Fat to be used must be chosen carefully as it affects quality of final product in terms of fatty acid composition and oxidative stability. Therefore, the present work was planned to study fatty acid profile of highly consumed baked products of biscuit family such as biscuits and cookies available in market. The study was carried out to do fatty acid profiling of a range of highly consumed baked products of biscuit family as a primary objective and also, to determine oxidative stability of these products by analysing peroxide value and free fatty acid content. The most commonly consumed packaged and unpackaged bakery products were selected and were bought from the local market of Ludhiana city on the basis of a survey conducted on 200 subjects. The selected products were analysed for fatty acid composition and oxidative stability using standard methods. Fatty acid profiling of 22 bakery products of biscuit family was done. Palmitic acid was the most abundant among all fatty acids in packaged and unpackaged samples. Peroxide value of all the products even after storage period of three months was found below the permissible limits (< 10 meq/kg). Free fatty acids value of all the products also did not cross acceptable level of 0.5 percent. Out of total selected eight brands, six were national and two were international. Amount of palmitic acid was higher in the products belonging to local brands.
Exploring the therapeutic potential of sodium deoxycholate tailored deformable-emulsomes of etodolac for effective management of arthritis
Authors: Sharma Gajanand , Mahajan Akanksha , Thakur Kanika , Kaur Gurjeet , Goni Vijay G. , Kumar Muniramiah Vinod , Barnwal Ravi Pratap , Singh Gurpal , Singh Bhupinder , Katare O. P. 
Published: December 2023

AbstractThe current piece of research intends to evaluate the potential of combining etodolac with deformable-emulsomes, a flexible vesicular system, as a promising strategy for the topical therapy of arthritis. The developed carrier system featured nanometric dimensions (102 nm), an improved zeta potential (− 5.05 mV), sustained drug release (31.33%), and enhanced drug deposition (33.13%) of DE-gel vis-à-vis conventional system (10.34% and 14.71%). The amount of permeation of the developed nano formulation across skin layers was demonstrated through CLSM and dermatokinetics studies. The safety profile of deformable-emulsomes has been investigated through in vitro HaCaT cell culture studies and skin compliance studies. The efficacy of the DE-gel formulation was sevenfold higher in case of Xylene induced ear edema model and 2.2-folds in CFA induced arthritis model than that of group treated with conventional gel (p < 0.01). The main technological rationale lies in the use of phospholipid and sodium deoxycholate-based nanoscale flexible lipoidal vesicles, which effectively encapsulate drug molecules within their interiors. This encapsulation enhances the molecular interactions and facilitates the transportation of the drug molecule effectively to the target-site. Hence, these findings offer robust scientific evidence to support additional investigation into the potential utility of flexible vesicular systems as a promising drug delivery alternative for molecules of this nature.
Acute kidney injury interacts with VKORC1 genotype on initiative warfarin dose among heart surgery recipients: a real-world research
Authors: Xiong Liang , Yu Feng , Ge Weihong , Xu Hang 
Published: December 2023

AbstractPatients who receive heart valve surgery need anticoagulation prophylaxis to reduce the risk of thrombosis. Warfarin often is a choice but its dosage varies due to gene and clinical factors. We aim to study, among them, if there is an interaction between acute kidney injury and two gene polymorphisms from this study. We extracted data of heart valve surgery recipients from the electronic health record (EHR) system of a medical center. The primary outcome is about the average daily dose of warfarin, measured as an additive interaction effect (INTadd) between acute kidney injury (AKI) and warfarin-related gene polymorphisms. The confounders, including age, sex, body surface area (BSA), comorbidities (i.e., atrial fibrillation [AF], hypertension [HTN], congestive heart failure [CHF]), serum albumin level, warfarin-relevant gene polymorphism (i.e., CYP2C9, VKORC1), prosthetic valve type (i.e., metal, bio), and warfarin history were controlled via a multivariate-linear regression model. The study included 200 patients, among whom 108 (54.00%) are female. Further, the mean age is 54.45 years, 31 (15.50%) have CHF, and 40 (20.00%) patients were prescribed concomitant amiodarone, which potentially overlays with the warfarin prophylaxis period. During the follow-up, AKI occurred in 30 (15.00%) patients. VKORC1 mutation (1639G>A) occurred in 25 (12.50%) patients and CYPC29 *2 or *3 mutations presented in 20 patients (10.00%). We found a significant additive interaction effect between AKI and VKORC1 (− 1.17, 95% CI − 1.82 to − 0.53, p = 0.0004). This result suggests it is probable that there is an interaction between acute kidney injury and the VKORC1 polymorphism for the warfarin dose during the initial period of anticoagulation prophylaxis.
Increase of nesting habitat suitability for green turtles in a warming Mediterranean Sea
Authors: Mancino Chiara , Hochscheid Sandra , Maiorano Luigi 
Published: December 2023

AbstractClimate change is reshaping global ecosystems at an unprecedented rate, with major impacts on biodiversity. Therefore, understanding how organisms can withstand change is key to identify priority conservation objectives. Marine ectotherms are being extremely impacted because their biology and phenology are directly related to temperature. Among these species, sea turtles are particularly problematic because they roam over both marine and terrestrial habitats throughout their life cycles. Focusing on green turtles (Chelonia mydas) in the Mediterranean Sea, we investigated the future potential changes of nesting grounds through time, assuming that marine turtles would shift their nesting locations. We modeled the current distribution of nesting grounds including both terrestrial and marine variables, and we projected the potential nesting distribution across the Mediterranean basin under alternative future greenhouse gas emission scenario (2000–2100). Our models show an increase in nesting probability in the western Mediterranean Sea, irrespective of the climate scenario we consider. Contrary to what is found in most global change studies, the worse the climate change scenario, the more suitable areas for green turtles will potentially increase. The most important predictors were anthropogenic variables, which negatively affect nesting probability, and sea surface temperature, positively linked to nesting probability, up to a maximum of 24–25 °C. The importance of the western Mediterranean beaches as potential nesting areas for sea turtles in the near future clearly call for a proactive conservation and management effort, focusing on monitoring actions (to document the potential range expansion) and threat detection.
Improving nonalcoholic fatty liver disease classification performance with latent diffusion models
Authors: Hardy Romain , Klepich Joe , Mitchell Ryan , Hall Steve , Villareal Jericho , Ilin Cornelia 
Published: December 2023

AbstractIntegrating deep learning with clinical expertise holds great potential for addressing healthcare challenges and empowering medical professionals with improved diagnostic tools. However, the need for annotated medical images is often an obstacle to leveraging the full power of machine learning models. Our research demonstrates that by combining synthetic images, generated using diffusion models, with real images, we can enhance nonalcoholic fatty liver disease (NAFLD) classification performance even in low-data regime settings. We evaluate the quality of the synthetic images by comparing two metrics: Inception Score (IS) and Fréchet Inception Distance (FID), computed on diffusion- and generative adversarial network (GAN)-generated images. Our results show superior performance for the diffusion-generated images, with a maximum IS score of 1.90 compared to 1.67 for GANs, and a minimum FID score of 69.45 compared to 100.05 for GANs. Utilizing a partially frozen CNN backbone (EfficientNet v1), our synthetic augmentation method achieves a maximum image-level ROC AUC of 0.904 on a NAFLD prediction task.