bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bessel beam optical coherence microscopy enables multiscale assessment of cerebrovascular network morphology and function
Authors: Glandorf Lukas , Wittmann Bastian , Droux Jeanne , Glück Chaim , Weber Bruno , Wegener Susanne , El Amki Mohamad , Leitgeb Rainer , Menze Bjoern , Razansky Daniel 
Published: November 2024

AbstractUnderstanding the morphology and function of large-scale cerebrovascular networks is crucial for studying brain health and disease. However, reconciling the demands for imaging on a broad scale with the precision of high-resolution volumetric microscopy has been a persistent challenge. In this study, we introduce Bessel beam optical coherence microscopy with an extended focus to capture the full cortical vascular hierarchy in mice over 1000 × 1000 × 360 μm3 field-of-view at capillary level resolution. The post-processing pipeline leverages a supervised deep learning approach for precise 3D segmentation of high-resolution angiograms, hence permitting reliable examination of microvascular structures at multiple spatial scales. Coupled with high-sensitivity Doppler optical coherence tomography, our method enables the computation of both axial and transverse blood velocity components as well as vessel-specific blood flow direction, facilitating a detailed assessment of morpho-functional characteristics across all vessel dimensions. Through graph-based analysis, we deliver insights into vascular connectivity, all the way from individual capillaries to broader network interactions, a task traditionally challenging for in vivo studies. The new imaging and analysis framework extends the frontiers of research into cerebrovascular function and neurovascular pathologies.
Overexpression of STX11 alleviates pulmonary fibrosis by inhibiting fibroblast activation via the PI3K/AKT/mTOR pathway
Authors: Huang Guichuan , Yang Xiangsheng , Yu Qingyang , Luo Qun , Ju Chunrong , Zhang Bangyan , Chen Yijing , Liang Zihan , Xia Shu , Wang Xiaohua , Xiang Dong , Zhong Nanshan , Tang Xiao Xiao 
Published: November 2024

AbstractFibroblast activation plays an important role in the occurrence and development of idiopathic pulmonary fibrosis (IPF), which is a progressive, incurable, and fibrotic lung disease. However, the underlying mechanism of fibroblast activation in IPF remains elusive. Here, we showed that the expression levels of STX11 and SNAP25 were downregulated in the lung tissues from patients with IPF and mice with bleomycin (BLM)-induced lung fibrosis as well as in the activated fibroblasts. Upregulation of STX11 or SNAP25 suppressed TGF-β1-induced activation of human lung fibroblasts (HLFs) via promoting autophagy. However, they failed to suppress fibroblast actviation when autophagy was blocked with the use of chloroquine (CQ). In addition, STX11 or SNAP25 could inhibit TGF-β1-induced fibroblast proliferation and migration. In vivo, overexpression of STX11 exerted its protective role in the mice with BLM-induced lung fibrosis. STX11 and SNAP25 mutually promoted expression of each other. Co-IP assay indicated that STX11 has an interaction with SNAP25. Mechanistically, STX11-SNAP25 interaction activated fibroblast autophagy and further inhibited fibroblast activation via blocking the PI3K/AKT/mTOR pathway. Overall, the results suggested that STX11-SNAP25 interaction significantly inhibited lung fibrosis by promoting fibroblast autophagy and suppressing fibroblast activation via blocking the PI3K/ATK/mTOR signaling pathway. Therefore, STX11 serves as a promising therapeutic target in IPF.
Bone loss with aging is independent of gut microbiome in mice
Authors: You Xiaomeng , Yan Jing , Herzog Jeremy , Nobakhti Sabah , Campbell Ross , Hoke Allison , Hammamieh Rasha , Sartor R. Balfour , Shefelbine Sandra , Kacena Melissa A. , Chakraborty Nabarun , Charles Julia F. 
Published: November 2024

AbstractEmerging evidence suggests a significant role of gut microbiome in bone health. Aging is well recognized as a crucial factor influencing the gut microbiome. In this study, we investigated whether age-dependent microbial change contributes to age-related bone loss in CB6F1 mice. The bone phenotype of 24-month-old germ-free (GF) mice was indistinguishable compared to their littermates colonized by fecal transplant at 1-month-old. Moreover, bone loss from 3 to 24-month-old was comparable between GF and specific pathogen-free (SPF) mice. Thus, GF mice were not protected from age-related bone loss. 16S rRNA gene sequencing of fecal samples from 3-month and 24-month-old SPF males indicated an age-dependent microbial shift with an alteration in energy and nutrient metabolism potential. An integrative analysis of 16S predicted metagenome function and LC-MS fecal metabolome revealed an enrichment of protein and amino acid biosynthesis pathways in aged mice. Microbial S-adenosyl methionine metabolism was increased in the aged mice, which has previously been associated with the host aging process. Collectively, aging caused microbial taxonomic and functional alteration in mice. To demonstrate the functional importance of young and old microbiome to bone, we colonized GF mice with fecal microbiome from 3-month or 24-month-old SPF donor mice for 1 and 8 months. The effect of microbial colonization on bone phenotypes was independent of the microbiome donors’ age. In conclusion, our study indicates age-related bone loss occurs independent of gut microbiome.
PRMT1-mediated methylation of ME2 promotes hepatocellular carcinoma growth by inhibiting ubiquitination
Authors: Zhang Shuai , Zhang Shuling , Xia Baijuan , Li Xueying , Jiang Hongyu , Feng Su , Xiang Yang , Qiu Ya , Zhou Shi , Luo Peng 
Published: November 2024

AbstractThe mitochondrial malic enzyme 2 (ME2), which is frequently elevated during carcinogenesis and may be a target for cancer therapy, catalyzes the conversion of malate to pyruvate. The processes controlling ME2 activity, however, remain largely unclear. In this work, we show that human hepatocellular carcinoma (HCC) tissues contain high levels of ME2 and that the methylation of ME2 stimulates the growth and migration of HCC cells. Furthermore, we observed that ME2 interacts with protein arginine methyltransferase 1 (PRMT1) and that ME2 enzymatic activity is activated by mutation of ME2 at lysine 67. Mitochondrial respiration was markedly increased by activated ME2, which promoted cell division and carcinogenesis. Furthermore, a negative prognosis for patients was strongly linked with the expression levels of PRMT1 and ME2 R67K in HCC tissues. These findings imply that hepatocellular carcinoma growth is aided by PRMT1-mediated ME2 methylation, that is an essential signaling event that cancer cells need to continue mitochondrial respiration.
ASC specks as a single-molecule fluid biomarker of inflammation in neurodegenerative diseases
Authors: Lobanova Evgeniia , Zhang Yu P. , Emin Derya , Brelstaff Jack , Kahanawita Lakmini , Malpetti Maura , Quaegebeur Annelies , Triantafilou Kathy , Triantafilou Martha , Zetterberg Henrik , Rowe James B. , Williams-Gray Caroline H. , Bryant Clare Elizabeth , Klenerman David 
Published: November 2024

AbstractImmunotherapeutic strategies for Alzheimer’s and Parkinson’s disease would be facilitated by better measures of inflammation. Here we established an ultra-sensitive single-molecule pull-down immunoassay combined with direct stochastic optical reconstruction microscopy (dSTORM) to measure the number, size and shape of individual extracellular inflammasome ASC specks. We assayed human post-mortem brain, serum and cerebrospinal fluid of patients with Parkinson’s and Alzheimer’s as well as healthy elderly. The number of ASC specks increased and showed altered morphology in the blood of early-stage Parkinson’s and Alzheimer’s patients compared to controls, mimicking those found in the brain and cerebrospinal fluid. In serum samples we also measured the number of Aβ, p-tau and α-syn aggregates and formed a composite biomarker of (ASC + p-tau)/Aβ and (ASC + α-syn)/Aβ ratios that distinguished age-matched healthy controls from patients with early-stage Alzheimer’s with AUC of 92% and early-stage Parkinson’s with AUC of 97%. Our findings confirm ASC specks as a fluid candidate biomarker of inflammation for neurodegenerative diseases with blood being the main focus for further development as convenient sample for diagnostics and clinical trials.
A cyclic peptide toolkit reveals mechanistic principles of peptidylarginine deiminase IV regulation
Authors: Bertran M. Teresa , Walmsley Robert , Cummings Thomas , Aramburu Iker Valle , Benton Donald J. , Mora Molina Rocio , Assalaarachchi Jayalini , Chasampalioti Maria , Swanton Tessa , Joshi Dhira , Federico Stefania , Okkenhaug Hanneke , Yu Lu , Oxley David , Walker Simon , Papayannopoulos Venizelos , Suga Hiroaki , Christophorou Maria A. , Walport Louise J. 
Published: November 2024

AbstractPeptidylarginine deiminase IV (PADI4, PAD4) deregulation promotes the development of autoimmunity, cancer, atherosclerosis and age-related tissue fibrosis. PADI4 additionally mediates immune responses and cellular reprogramming, although the full extent of its physiological roles is unexplored. Despite detailed molecular knowledge of PADI4 activation in vitro, we lack understanding of its regulation within cells, largely due to a lack of appropriate systems and tools. Here, we develop and apply a set of potent and selective PADI4 modulators. Using the mRNA-display-based RaPID system, we screen >1012 cyclic peptides for high-affinity, conformation-selective binders. We report PADI4_3, a cell-active inhibitor specific for the active conformation of PADI4; PADI4_7, an inert binder, which we functionalise for the isolation and study of cellular PADI4; and PADI4_11, a cell-active PADI4 activator. Structural studies with PADI4_11 reveal an allosteric binding mode that may reflect the mechanism that promotes cellular PADI4 activation. This work contributes to our understanding of PADI4 regulation and provides a toolkit for the study and modulation of PADI4 across (patho)physiological contexts.
Evasion of antiviral bacterial immunity by phage tRNAs
Authors: Azam Aa Haeruman , Kondo Kohei , Chihara Kotaro , Nakamura Tomohiro , Ojima Shinjiro , Nie Wenhan , Tamura Azumi , Yamashita Wakana , Sugawara Yo , Sugai Motoyuki , Cui Longzhu , Takahashi Yoshimasa , Watashi Koichi , Kiga Kotaro 
Published: November 2024

AbstractRetrons are bacterial genetic elements that encode a reverse transcriptase and, in combination with toxic effector proteins, can serve as antiphage defense systems. However, the mechanisms of action of most retron effectors, and how phages evade retrons, are not well understood. Here, we show that some phages can evade retrons and other defense systems by producing specific tRNAs. We find that expression of retron-Eco7 effector proteins (PtuA and PtuB) leads to degradation of tRNATyr and abortive infection. The genomes of T5 phages that evade retron-Eco7 include a tRNA-rich region, including a highly expressed tRNATyr gene, which confers protection against retron-Eco7. Furthermore, we show that other phages (T1, T7) can use a similar strategy, expressing a tRNALys, to counteract a tRNA anticodon defense system (PrrC170).
Interferometry of quantum correlation functions to access quasiprobability distribution of work
Authors: Hernández-Gómez Santiago , Isogawa Takuya , Belenchia Alessio , Levy Amikam , Fabbri Nicole , Gherardini Stefano , Cappellaro Paola 
Published: November 2024

AbstractThe Kirkwood-Dirac quasiprobability distribution, intimately connected with the quantum correlation function of two observables measured at distinct times, is becoming increasingly relevant for fundamental physics and quantum technologies. This quasiprobability distribution can take non-positive values, and its experimental reconstruction becomes challenging when expectation values of incompatible observables are involved. Here, we use an interferometric scheme aided by an auxiliary system to reconstruct the Kirkwood-Dirac quasiprobability distribution. We experimentally demonstrate this scheme in an electron-nuclear spin system associated with a nitrogen-vacancy center in diamond. By measuring the characteristic function, we reconstruct the quasiprobability distribution of work and analyze the behavior of its first and second moments. Our results clarify the physical meaning of the work quasiprobability distribution in the context of quantum thermodynamics. Finally, we study the uncertainty of measuring the Hamiltonian of the system at two times, via the Robertson-Schrödinger uncertainty relation, for different initial states.
Improving precision of vaccine efficacy evaluation using immune correlate data in time-to-event models
Authors: Dudášová Julie , Valenta Zdeněk , Sachs Jeffrey R. 
Published: November 2024

AbstractUnderstanding potential differences in vaccine-induced protection between demographic subgroups is key for vaccine development. Vaccine efficacy evaluation across these subgroups in phase 2b or 3 clinical trials presents challenges due to lack of precision: such trials are typically designed to demonstrate overall efficacy rather than to differentiate its value between subgroups. This study proposes a method for estimating vaccine efficacy using immunogenicity (instead of vaccination status) as a predictor in time-to-event models. The method is applied to two datasets from immunogenicity sub-studies of vaccine phase 3 clinical trials for zoster and dengue vaccines. Results show that using immunogenicity-based estimation of efficacy in subgroups using time-to-event models is more precise than the standard estimation. Incorporating immune correlate data in time-to-event models improves precision in estimating efficacy (i.e., yields narrower confidence intervals), which can assist vaccine developers and public health authorities in making informed decisions.
Mechanism for Vipp1 spiral formation, ring biogenesis, and membrane repair
Authors: Naskar Souvik , Merino Andrea , Espadas Javier , Singh Jayanti , Roux Aurelien , Colom Adai , Low Harry H. 
Published: November 2024

AbstractThe ESCRT-III-like protein Vipp1 couples filament polymerization with membrane remodeling. It assembles planar sheets as well as 3D rings and helical polymers, all implicated in mitigating plastid-associated membrane stress. The architecture of Vipp1 planar sheets and helical polymers remains unknown, as do the geometric changes required to transition between polymeric forms. Here we show how cyanobacterial Vipp1 assembles into morphologically-related sheets and spirals on membranes in vitro. The spirals converge to form a central ring similar to those described in membrane budding. Cryo-EM structures of helical filaments reveal a close geometric relationship between Vipp1 helical and planar lattices. Moreover, the helical structures reveal how filaments twist—a process required for Vipp1, and likely other ESCRT-III filaments, to transition between planar and 3D architectures. Overall, our results provide a molecular model for Vipp1 ring biogenesis and a mechanism for Vipp1 membrane stabilization and repair, with implications for other ESCRT-III systems.
Structural basis of the mechanism and inhibition of a human ceramide synthase
Authors: Pascoa Tomas C. , Pike Ashley C. W. , Tautermann Christofer S. , Chi Gamma , Traub Michael , Quigley Andrew , Chalk Rod , Štefanić Saša , Thamm Sven , Pautsch Alexander , Carpenter Elisabeth P. , Schnapp Gisela , Sauer David B. 
Published: November 2024

AbstractCeramides are bioactive sphingolipids crucial for regulating cellular metabolism. Ceramides and dihydroceramides are synthesized by six ceramide synthase (CerS) enzymes, each with specificity for different acyl-CoA substrates. Ceramide with a 16-carbon acyl chain (C16 ceramide) has been implicated in obesity, insulin resistance and liver disease and the C16 ceramide-synthesizing CerS6 is regarded as an attractive drug target for obesity-associated disease. Despite their importance, the molecular mechanism underlying ceramide synthesis by CerS enzymes remains poorly understood. Here we report cryo-electron microscopy structures of human CerS6, capturing covalent intermediate and product-bound states. These structures, along with biochemical characterization, reveal that CerS catalysis proceeds through a ping-pong reaction mechanism involving a covalent acyl–enzyme intermediate. Notably, the product-bound structure was obtained upon reaction with the mycotoxin fumonisin B1, yielding insights into its inhibition of CerS. These results provide a framework for understanding CerS function, selectivity and inhibition and open routes for future drug discovery.
Novel BMI cutoff points for obesity diagnosis in older Hispanic adults
Authors: Esparza-Hurtado Natalia , Martagon Alexandro J. , Hart-Vazquez Delia Patricia , Rodríguez-Tadeo Alejandra , González-Arellanes Rogelio 
Published: November 2024

AbstractCurrent body mass index (BMI) cutoff points (≥ 30 kg/m2) underestimate obesity prevalence in older adults. The aim of the present study was to propose new BMI cutoff points for identifying obesity in older Hispanic adults. In this study, new internally derived (ID) BMI cutoff point for obesity in older Hispanic adults was developed by analyzing data from the National Health and Nutrition Survey of 2018–2019 from Mexico. To evaluate the performance/validation of this newly proposed cutoff point, data from the "Study of the 1000", conducted in Northern Mexico, was utilized. Sensitivity, and negative predictive value (NPV) were assessed using receiver operating characteristic analysis, with obesity defined by fat mass index (FMI; ≥ 9.0 kg/m2 for men and ≥ 12.0 kg/m2 for women) as the reference method. The newly proposed ID BMI cutoff point was ≥ 27.2 kg/m2 which demonstrated high sensitivity (≥ 99.4%) and NPV (≥ 99.5%) in the total sample. Furthermore, the prevalence of obesity estimated by the new BMI cutoff point was comparable to that estimated by the FMI. The newly proposed BMI cutoff point provides a more accurate identification of obesity in older Hispanic adults. These findings have implications for improving obesity diagnosis and management in this population.
Solvent and additive-controlled supramolecular isomerism in zinc coordination polymers
Authors: Khorshidi Ghazale , Notash Behrouz 
Published: November 2024

AbstractA new series of Zn(II) supramolecular isomers containing ditopic 1,3-di(pyridin-4-yl)urea (4bpu) ligand were synthesized and characterized by infrared analysis, elemental analysis and TGA as well as single-crystal X-ray diffraction analysis. Four solvent-induced pseudopolymorphic zinc (II) coordination polymers (CPs), namely, {[Zn(4bpu)(OAc)2](CH3OH)}n (1), {[Zn(4bpu)(OAc)2](C2H5OH)}n (2), {[Zn(4bpu)(OAc)2](HOCH2CH2OH)}n (3), and {[Zn(4bpu)(OAc)2](0.5H2O)}n (4), were prepared by the reaction of Zn(OAc)2.2H2O and 4bpu via self-assembly under varying solvent systems. Also, a pair of polymorphic coordination polymers namely, {[Zn(4bpu)(OAc)2](CH3OH)}n (1α) and {[Zn3(4bpu)3(OAc)6](CH3OH)2}n(1β), was prepared in the presence of different organic additives. Single-crystal X-ray diffraction confirmed that 1−4 and 1α display 1D polymeric zig-zag chains and 1β exhibits 1D triple-stranded ladders that were self-assembled through various supramolecular interactions. In addition, a series of dissolution-recrystallization structural transformations (DRST) were performed on these supramolecular isomers.
Expression profile of tsRNAs in white adipose tissue of vitamin D deficiency young male mice with or without obesity
Authors: Jia Qiaowei , Zhao Yan 
Published: November 2024

AbstractThe expression of tsRNA in white adipose tissue (WAT) of VD deficiency male mice with obesity has not been reported. The healthy male C57BL/6J mice aged 4-6 weeks were divided into 4 groups according to the VD3 and fat energy supplement in daily diets. The qPCR verification further demonstrated that tRF5-20-HisGTG-3 were significantly up-regulated and mt-tRF3a-ProTGG was significantly down-regulated not only in HFVDD vs HFVDS, but aslo in HFVDD vs ConVDS. tRF5-22-CysGCA-27 were significantly up-regulated and mt-5'tiRNA-32-SerTGA, mt-5'tiRNA-33-SerTGA and mt-5'tiRNA-33-AlaTGC was significantly down-regulated only in HFVDD vs ConVDS. Enrichment analysis of the qPCR verified DE tsRNAs showed that the 3 up-regulated tsRNAs seemed to be associated with FoxO signaling pathway, GnRH secretion, 2−Oxocarboxylic acid metabolism, Autophagy-animal, Glucagon and insulin signaling pathway, while 4 down-regulated tsRNA seemed to be associated with cell communication, primary metabolic process, metabolic process, response to stimulus, multicellular organismal process, cellular metabolic process, cellular process and biological regulation. The tsRNAs were differentially expressed in VD deficiency with obesity, especially tRF5-20-HisGTG-3, tRF5-22-CysGCA-27, tRF3a-GlyGCC-1, mt-5'tiRNA-33-AlaTGC, mt-5'tiRNA-33-SerTGA, mt-5'tiRNA-32-SerTGA and mt-tRF3a-ProTGG. These tsRNAs seemed to be associated with FoxO signaling pathway, GnRH secretion, 2−oxocarboxylic acid metabolism, autophagy, glucagon and insulin signaling pathway, metabolic process and biological regulation.
Novel reinforcement learning technique based parameter estimation for proton exchange membrane fuel cell model
Authors: Salem Nermin M. , Shaheen Mohamed A. M. , Hasanien Hany M. 
Published: November 2024

AbstractProton Exchange Membrane Fuel Cells (PEMFCs) offer a clean and sustainable alternative to traditional engines. PEMFCs play a vital role in progressing hydrogen-based energy solutions. Accurate modeling of PEMFC performance is essential for enhancing their efficiency. This paper introduces a novel reinforcement learning (RL) approach for estimating PEMFC parameters, addressing the challenges of the complex and nonlinear dynamics of the PEMFCs. The proposed RL method minimizes the sum of squared errors between measured and simulated voltages and provides an adaptive and self-improving RL-based Estimation that learns continuously from system feedback. The RL-based approach demonstrates superior accuracy and performance compared with traditional metaheuristic techniques. It has been validated through theoretical and experimental comparisons and tested on commercial PEMFCs, including the Temasek 1 kW, the 6 kW Nedstack PS6, and the Horizon H-12 12 W. The dataset used in this study comes from experimental data. This research contributes to the precise modeling of PEMFCs, improving their efficiency, and developing wider adoption of PEMFCs in sustainable energy solutions.
Protective effects of Marinobacter nauticus strain GH3 exopolysaccharide on the Oreochromis niloticus model for Alzheimer’s disease
Authors: Abdel-Razik Ghada , Abdelrazik Mohamad , Rashad Alaa , Khalil Wagdy K. B. , Abdel-Gawad Fagr Kh. , Hamed Ahmed A. , El Awady Mohamed E. 
Published: November 2024

AbstractMarinobacter nauticus strain GH3 was isolated from the Red Sea, Sharm Elshiekh, and classified according to cultural attributes, biochemical properties, and the analysis of genetic relationships using 16 S rRNA sequences. A substantial proportion of exopolysaccharides (EPS) in GH3-EPS contained a sulfate content of 25.4%, uronic acid (12.18%), and N-acetylglucosamine (13.6%). The composition of monosaccharides in this fraction consists of glucose, glucoronic acid, arabinose, and xylose by 2:4:3:3, respectively. SEM showed a flower-like shape with white bundles on the GH3-EPS surface. GH3-EPS enhancement of the RAW264.7 macrophage line RAW 264.7 ATTC number J774 cell proliferation via MTT assay for cell viability. GH3-EPS had a high stimulation effect on releasing TNF-alpha and IL-10. Followed by its effect against cyclooxygenase (COX-2) and lipoxygenase (LOX), with IC50s of 14.74 and 19.4 µg/ml, respectively. Antioxidant activity was evaluated for GPx-4, GSS, and MDA with highly significant results, and for DPPH, ABTS, and iron chelating with IC50 (43.51, 31.27, and 84.96 µg/ml, respectively). AChE was inhibited by a mean of 52.92 ± 4.54 and 68.22 ± 5.64 µg/ml. In a fish animal model, GH3-EPS demonstrated a positive treatment effect for AD, supporting biochemical studies, histopathology for some brain parts, and toxicity.