bluuebunny/crossref_metadata_2025_split huggingface dataset:
Obesity-driven mitochondrial dysfunction in human adipose tissue-derived mesenchymal stem/stromal cells involves epigenetic changes
Authors: Eirin Alfonso , Thaler Roman , Glasstetter Logan M. , Xing Li , Zhu Xiang-Yang , Osborne Andrew C. , Mondesir Ronscardy , Bhagwate Aditya V. , Lerman Amir , van Wijnen Andre J. , Lerman Lilach O. 
Published: June 2024

AbstractObesity exacerbates tissue degeneration and compromises the integrity and reparative potential of mesenchymal stem/stromal cells (MSCs), but the underlying mechanisms have not been sufficiently elucidated. Mitochondria modulate the viability, plasticity, proliferative capacity, and differentiation potential of MSCs. We hypothesized that alterations in the 5-hydroxymethylcytosine (5hmC) profile of mitochondria-related genes may mediate obesity-driven dysfunction of human adipose-derived MSCs. MSCs were harvested from abdominal subcutaneous fat of obese and age/sex-matched non-obese subjects (n = 5 each). The 5hmC profile and expression of nuclear-encoded mitochondrial genes were examined by hydroxymethylated DNA immunoprecipitation sequencing (h MeDIP-seq) and mRNA-seq, respectively. MSC mitochondrial structure (electron microscopy) and function, metabolomics, proliferation, and neurogenic differentiation were evaluated in vitro, before and after epigenetic modulation. hMeDIP-seq identified 99 peaks of hyper-hydroxymethylation and 150 peaks of hypo-hydroxymethylation in nuclear-encoded mitochondrial genes from Obese- versus Non-obese-MSCs. Integrated hMeDIP-seq/mRNA-seq analysis identified a select group of overlapping (altered levels of both 5hmC and mRNA) nuclear-encoded mitochondrial genes involved in ATP production, redox activity, cell proliferation, migration, fatty acid metabolism, and neuronal development. Furthermore, Obese-MSCs exhibited decreased mitochondrial matrix density, membrane potential, and levels of fatty acid metabolites, increased superoxide production, and impaired neuronal differentiation, which improved with epigenetic modulation. Obesity elicits epigenetic changes in mitochondria-related genes in human adipose-derived MSCs, accompanied by structural and functional changes in their mitochondria and impaired fatty acid metabolism and neurogenic differentiation capacity. These observations may assist in developing novel therapies to preserve the potential of MSCs for tissue repair and regeneration in obese individuals.
Modeling the potential effects of rooftop solar on household energy burden in the United States
Authors: Forrester Sydney P. , Montañés Cristina Crespo , O’Shaughnessy Eric , Barbose Galen 
Published: June 2024

AbstractPolicymakers at the federal and state level have begun to incorporate energy burden into equity goals and program evaluations, aiming to reduce energy burden below a high level of 6% for lower income households in the United States. Pairing an empirical household-level dataset spanning United States geographies together with modeled hourly energy demand curves, we show that rooftop solar reduces energy burden across a majority of adopters during our study period from a median of 3.3% to 2.6%. For low- and moderate-income adopters (at or below 80% and 120% of area median income, respectively), solar reduces median 2021 energy burden from 7.7% to 6.2%, and 4.1% to 3.3%, respectively. Importantly, solar reduces the rate of high or severe energy burden from 67% of all low-income households before adoption to 52% of households following adoption, and correspondingly from 21% to 13% for moderate-income households. Here, we show rooftop solar can support policy goals to reduce energy burden along with strategies such as weatherization and bill assistance.
Area postrema neurons mediate interleukin-6 function in cancer cachexia
Authors: Sun Qingtao , van de Lisdonk Daniëlle , Ferrer Miriam , Gegenhuber Bruno , Wu Melody , Park Youngkyu , Tuveson David A. , Tollkuhn Jessica , Janowitz Tobias , Li Bo 
Published: June 2024

AbstractInterleukin-6 (IL-6) has been long considered a key player in cancer cachexia. It is believed that sustained elevation of IL-6 production during cancer progression causes brain dysfunctions, which ultimately result in cachexia. However, how peripheral IL-6 influences the brain remains poorly understood. Here we show that neurons in the area postrema (AP), a circumventricular structure in the hindbrain, is a critical mediator of IL-6 function in cancer cachexia in male mice. We find that circulating IL-6 can rapidly enter the AP and activate neurons in the AP and its associated network. Peripheral tumor, known to increase circulating IL-6, leads to elevated IL-6 in the AP, and causes potentiated excitatory synaptic transmission onto AP neurons and AP network hyperactivity. Remarkably, neutralization of IL-6 in the brain of tumor-bearing mice with an anti-IL-6 antibody attenuates cachexia and the hyperactivity in the AP network, and markedly prolongs lifespan. Furthermore, suppression ofIl6ra, the gene encoding IL-6 receptor, specifically in AP neurons with CRISPR/dCas9 interference achieves similar effects. Silencing Gfral-expressing AP neurons also attenuates cancer cachectic phenotypes and AP network hyperactivity. Our study identifies a central mechanism underlying the function of peripheral IL-6, which may serve as a target for treating cancer cachexia.
Inherited C-terminal TREX1 variants disrupt homology-directed repair to cause senescence and DNA damage phenotypes in Drosophila, mice, and humans
Authors: Chauvin Samuel D. , Ando Shoichiro , Holley Joe A. , Sugie Atsushi , Zhao Fang R. , Poddar Subhajit , Kato Rei , Miner Cathrine A. , Nitta Yohei , Krishnamurthy Siddharth R. , Saito Rie , Ning Yue , Hatano Yuya , Kitahara Sho , Koide Shin , Stinson W. Alexander , Fu Jiayuan , Surve Nehalee , Kumble Lindsay , Qian Wei , Polishchuk Oleksiy , Andhey Prabhakar S. , Chiang Cindy , Liu Guanqun , Colombeau Ludovic , Rodriguez Raphaël , Manel Nicolas , Kakita Akiyoshi , Artyomov Maxim N. , Schultz David C. , Coates P. Toby , Roberson Elisha D. O. , Belkaid Yasmine , Greenberg Roger A. , Cherry Sara , Gack Michaela U. , Hardy Tristan , Onodera Osamu , Kato Taisuke , Miner Jonathan J. 
Published: June 2024

AbstractAge-related microangiopathy, also known as small vessel disease (SVD), causes damage to the brain, retina, liver, and kidney. Based on the DNA damage theory of aging, we reasoned that genomic instability may underlie an SVD caused by dominant C-terminal variants in TREX1, the most abundant 3′−5′ DNA exonuclease in mammals. C-terminal TREX1 variants cause an adult-onset SVD known as retinal vasculopathy with cerebral leukoencephalopathy (RVCL or RVCL-S). In RVCL, an aberrant, C-terminally truncated TREX1 mislocalizes to the nucleus due to deletion of its ER-anchoring domain. Since RVCL pathology mimics that of radiation injury, we reasoned that nuclear TREX1 would cause DNA damage. Here, we show that RVCL-associated TREX1 variants trigger DNA damage in humans, mice, and Drosophila, and that cells expressing RVCL mutant TREX1 are more vulnerable to DNA damage induced by chemotherapy and cytokines that up-regulate TREX1, leading to depletion of TREX1-high cells in RVCL mice. RVCL-associated TREX1 mutants inhibit homology-directed repair (HDR), causing DNA deletions and vulnerablility to PARP inhibitors. In women with RVCL, we observe early-onset breast cancer, similar to patients with BRCA1/2 variants. Our results provide a mechanistic basis linking aberrant TREX1 activity to the DNA damage theory of aging, premature senescence, and microvascular disease.
Highly biased agonism for GPCR ligands via nanobody tethering
Authors: Sachdev Shivani , Creemer Brendan A. , Gardella Thomas J. , Cheloha Ross W. 
Published: June 2024

AbstractLigand-induced activation of G protein-coupled receptors (GPCRs) can initiate signaling through multiple distinct pathways with differing biological and physiological outcomes. There is intense interest in understanding how variation in GPCR ligand structure can be used to promote pathway selective signaling (“biased agonism”) with the goal of promoting desirable responses and avoiding deleterious side effects. Here we present an approach in which a conventional peptide ligand for the type 1 parathyroid hormone receptor (PTHR1) is converted from an agonist which induces signaling through all relevant pathways to a compound that is highly selective for a single pathway. This is achieved not through variation in the core structure of the agonist, but rather by linking it to a nanobody tethering agent that binds with high affinity to a separate site on the receptor not involved in signal transduction. The resulting conjugate represents the most biased agonist of PTHR1 reported to date. This approach holds promise for facile generation of pathway selective ligands for other GPCRs.
Structural basis for human mitochondrial tRNA maturation
Authors: Meynier Vincent , Hardwick Steven W. , Catala Marjorie , Roske Johann J. , Oerum Stephanie , Chirgadze Dimitri Y. , Barraud Pierre , Yue Wyatt W. , Luisi Ben F. , Tisné Carine 
Published: June 2024

AbstractThe human mitochondrial genome is transcribed into two RNAs, containing mRNAs, rRNAs and tRNAs, all dedicated to produce essential proteins of the respiratory chain. The precise excision of tRNAs by the mitochondrial endoribonucleases (mt-RNase), P and Z, releases all RNA species from the two RNA transcripts. The tRNAs then undergo 3′-CCA addition. In metazoan mitochondria, RNase P is a multi-enzyme assembly that comprises the endoribonuclease PRORP and a tRNA methyltransferase subcomplex. The requirement for this tRNA methyltransferase subcomplex for mt-RNase P cleavage activity, as well as the mechanisms of pre-tRNA 3′-cleavage and 3′-CCA addition, are still poorly understood. Here, we report cryo-EM structures that visualise four steps of mitochondrial tRNA maturation: 5′ and 3′ tRNA-end processing, methylation and 3′-CCA addition, and explain the defined sequential order of the tRNA processing steps. The methyltransferase subcomplex recognises the pre-tRNA in a distinct mode that can support tRNA-end processing and 3′-CCA addition, likely resulting from an evolutionary adaptation of mitochondrial tRNA maturation complexes to the structurally-fragile mitochondrial tRNAs. This subcomplex can also ensure a tRNA-folding quality-control checkpoint before the sequential docking of the maturation enzymes. Altogether, our study provides detailed molecular insight into RNA-transcript processing and tRNA maturation in human mitochondria.
Comparing costs and climate impacts of various electric vehicle charging systems across the United States
Authors: Horesh Noah , Trinko David A. , Quinn Jason C. 
Published: June 2024

AbstractThe seamless adoption of electric vehicles (EVs) in the United States necessitates the development of extensive and effective charging infrastructure. Various charging systems have been proposed, including Direct Current Fast Charging, Battery Swapping, and Dynamic Wireless Power Transfer. While many studies have evaluated the charging costs and greenhouse gas (GHG) intensity of EVs, a comprehensive analysis comparing these systems and their implications across vehicle categories remains unexplored. This study compares the total cost of ownership (TCO) and GHG-intensity of EVs using these charging systems. Based on nationwide infrastructure deployment simulations, the change to TCO from adopting EVs varies by scenario, vehicle category, and location, with local fuel prices, electricity prices, and traffic volumes dramatically impacting results. Further, EV GHG-intensity depends on local electricity mixes and infrastructure utilizations. This research highlights the responsiveness of EV benefits resulting from technology advancements, deployment decisions, and policymaking.
Revealing the structural evolution of CuAg composites during electrochemical carbon monoxide reduction
Authors: Wang Di , Jung Hyun Dong , Liu Shikai , Chen Jiayi , Yang Haozhou , He Qian , Xi Shibo , Back Seoin , Wang Lei 
Published: June 2024

AbstractComprehending the catalyst structural evolution during the electrocatalytic process is crucial for establishing robust structure/performance correlations for future catalysts design. Herein, we interrogate the structural evolution of a promising Cu-Ag oxide catalyst precursor during electrochemical carbon monoxide reduction. By using extensive in situ and ex situ characterization techniques, we reveal that the homogenous oxide precursors undergo a transformation to a bimetallic composite consisting of small Ag nanoparticles enveloped by thin layers of amorphous Cu. We believe that the amorphous Cu layer with undercoordinated nature is responsible for the enhanced catalytic performance of the current catalyst composite. By tuning the Cu/Ag ratio in the oxide precursor, we find that increasing the Ag concentration greatly promotes liquid products formation while suppressing the byproduct hydrogen. CO2/CO co-feeding electrolysis and isotopic labelling experiments suggest that high CO concentrations in the feed favor the formation of multi-carbon products. Overall, we anticipate the insights obtained for Cu-Ag bimetallic systems for CO electroreduction in this study may guide future catalyst design with improved performance.
Large-area, self-healing block copolymer membranes for energy conversion
Authors: Sproncken Christian C. M. , Liu Peng , Monney Justin , Fall William S. , Pierucci Carolina , Scholten Philip B. V. , Van Bueren Brian , Penedo Marcos , Fantner Georg Ernest , Wensink Henricus H. , Steiner Ullrich , Weder Christoph , Bruns Nico , Mayer Michael , Ianiro Alessandro 
Published: June 2024

AbstractMembranes are widely used for separation processes in applications such as water desalination, batteries and dialysis, and are crucial in key sectors of our economy and society1. The majority of technologically exploited membranes are based on solid polymers and function as passive barriers, whose transport characteristics are governed by their chemical composition and nanostructure. Although such membranes are ubiquitous, it has proved challenging to maximize selectivity and permeability independently, leading to trade-offs between these pertinent characteristics2. Self-assembled biological membranes, in which barrier and transport functions are decoupled3,4, provide the inspiration to address this problem5,6. Here we introduce a self-assembly strategy that uses the interface of an aqueous two-phase system to template and stabilize molecularly thin (approximately 35 nm) biomimetic block copolymer bilayers of scalable area that can exceed 10 cm2 without defects. These membranes are self-healing, and their barrier function against the passage of ions (specific resistance of approximately 1 MΩ cm2) approaches that of phospholipid membranes. The fluidity of these membranes enables straightforward functionalization with molecular carriers that shuttle potassium ions down a concentration gradient with exquisite selectivity over sodium ions. This ion selectivity enables the generation of electric power from equimolar solutions of NaCl and KCl in devices that mimic the electric organ of electric rays.
Early stages of covalent organic framework formation imaged in operando
Authors: Gruber Christoph G. , Frey Laura , Guntermann Roman , Medina Dana D. , Cortés Emiliano 
Published: June 2024

AbstractCovalent organic frameworks (COFs) are a functional material class able to harness, convert and store energy. However, after almost 20 years of research, there are no coherent prediction rules for their synthesis conditions. This is partly because of an incomplete picture of nucleation and growth at the early stages of formation. Here we use the optical technique interferometric scattering microscopy (iSCAT)1–3 for in operando studies of COF polymerization and framework formation. We observe liquid–liquid phase separation, pointing to the existence of structured solvents in the form of surfactant-free (micro)emulsions in conventional COF synthesis. Our findings show that the role of solvents extends beyond solubility to being kinetic modulators by compartmentation of reactants and catalyst. Taking advantage of these observations, we develop a synthesis protocol for COFs using room temperature instead of elevated temperatures. This work connects framework synthesis with liquid phase diagrams and thereby enables an active design of the reaction environment, emphasizing that visualization of chemical reactions by means of light-scattering-based techniques can be a powerful approach for advancing rational materials synthesis.
Descending networks transform command signals into population motor control
Authors: Braun Jonas , Hurtak Femke , Wang-Chen Sibo , Ramdya Pavan 
Published: June 2024

AbstractTo convert intentions into actions, movement instructions must pass from the brain to downstream motor circuits through descending neurons (DNs). These include small sets of command-like neurons that are sufficient to drive behaviours1—the circuit mechanisms for which remain unclear. Here we show that command-like DNs inDrosophiladirectly recruit networks of additional DNs to orchestrate behaviours that require the active control of numerous body parts. Specifically, we found that command-like DNs previously thought to drive behaviours alone2–4in fact co-activate larger populations of DNs. Connectome analyses and experimental manipulations revealed that this functional recruitment can be explained by direct excitatory connections between command-like DNs and networks of interconnected DNs in the brain. Descending population recruitment is necessary for behavioural control: DNs with many downstream descending partners require network co-activation to drive complete behaviours and drive only simple stereotyped movements in their absence. These DN networks reside within behaviour-specific clusters that inhibit one another. These results support a mechanism for command-like descending control in which behaviours are generated through the recruitment of increasingly large DN networks that compose behaviours by combining multiple motor subroutines.
Protein family annotation for the Unified Human Gastrointestinal Proteome by DPCfam clustering
Authors: Barone Federico , Russo Elena Tea , Villegas Garcia Edith Natalia , Punta Marco , Cozzini Stefano , Ansuini Alessio , Cazzaniga Alberto 
Published: June 2024

AbstractTechnological advances in massively parallel sequencing have led to an exponential growth in the number of known protein sequences. Much of this growth originates from metagenomic projects producing new sequences from environmental and clinical samples. The Unified Human Gastrointestinal Proteome (UHGP) catalogue is one of the most relevant metagenomic datasets with applications ranging from medicine to biology. However, the low levels of sequence annotation may impair its usability. This work aims to produce a family classification of UHGP sequences to facilitate downstream structural and functional annotation. This is achieved through the release of the DPCfam-UHGP50 dataset containing 10,778 putative protein families generated using DPCfam clustering, an unsupervised pipeline grouping sequences into single or multi-domain architectures. DPCfam-UHGP50 considerably improves family coverage at protein and residue levels compared to the manually curated repository Pfam. In the hope that DPCfam-UHGP50 will foster future discoveries in the field of metagenomics of the human gut, we release a FAIR-compliant database of our results that is easily accessible via a searchable web server and Zenodo repository.
Visibility forecast in Jiangsu province based on the GCN-GRU model
Authors: Chen Huansang , Xu Yihang , Gao Zhiqiu , Kang Jia , Jiang Yuncong , Li Zheng , Shen Huan 
Published: June 2024

AbstractLow visibility weather easily leads to traffic accidents, posing threats to human life and property. To accurately forecast visibility, we conduct an empirical study focusing on Jiangsu Province. Firstly, we collect the monitoring data from meteorological stations and environmental stations for 2017-2018. Secondly, we analyze the changes in visibility from both spatial and temporal perspectives. Next, the maximum Relevance Minimum Redundancy (mRMR) algorithm is employed to select factors affecting visibility, finding that humidity and $$PM_{2.5}$$

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concentrations are the primary factors. Finally, we propose GCN-GRU (Graph Convolutional Network and Gated Recurrent Unit) model for short-term visibility forecasting, which employs GCN to capture the interactions between stations and uses GRU to learn the interactions between times. Experimental results indicate that GCN-GRU outperforms the standalone GRU model and three machine learning models regarding 6-hour visibility forecasting. Compared to the best competitor, GCN-GRU achieves an average increase of 3.32% in Correlation Coefficient (CORR), a decrease of 17.52% in Root Mean Square Error (RMSE), a reduction of 26.62% in Mean Absolute Percentage Error (MAPE), and a decline of 16.53% in Mean Absolute Error (MAE).
Investigating the confinement effects on masonry behavior based on friction interface
Authors: Ahmed Hafiz Asfandyar , Tanoli Waqas Arshad 
Published: June 2024

AbstractAs a material masonry is anisotropic in nature as it is constituted of various components that differ each other in many ways. Though, the ideas of modeling of concrete are also valid for masonry, still there are difficulties in determining the exact behavior of masonry. The micro modeling (simplified) approach has been adopted in this study for modeling masonry samples subjected to various nature of loadings. The brick masonry units were modeled as discrete elements and linked together by interface element. The coulomb friction model was used to describe the interface element as mortar joint. Damage was assumed to be governed by the compressive strength of both the constituents i.e., mortar and brick. The mechanical properties of the masonry samples were determined by means of variety of tests and those properties then served as input parameters in the constitutive model. The results clearly indicate that numerical model predicted the behavior of the experimentally tested samples, in compression as well as tension prims for both unconfined and confined cases. The proposed model is suitable for modeling any type of brick masonry walls.
Design and analysis of 2D one-way splitter waveguide based on topological photonics
Authors: Mehdipoura Mohammadreza , Moeini Mohammadreza , Ahmadi Vahid , Poursalehi Reza 
Published: June 2024

AbstractWe present a new high-efficiency splitter waveguide design based on photonic topological insulators. The system’s robust edge states allow electromagnetic waves to propagate in the 2D waveguide without backscattering, resulting in almost 100% transmission in the outputs. We also study resonating modes in the structure and show that introducing specific defects can create such modes. We consider four domains with rods of varying magneto-optical properties to provide edge modes in the system. By eliminating rows and columns of rods, we calculate the transmission at the outputs, revealing resonating modes in the middle of the structure with spatial symmetry. Our calculations indicate that the most promising resonating mode occurs when two rods and two columns are eliminated, with a quality factor Q = 1.02 × 106 at frequency f = 8.23 GHz and almost zero transmission at this frequency to the outputs. We further confirm our results using the transmission line resonator model as a semi-analytical model, which agrees well with our findings.