bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigenetic regulation in metabolic diseases: mechanisms and advances in clinical study
Authors: Wu Yan-Lin , Lin Zheng-Jun , Li Chang-Chun , Lin Xiao , Shan Su-Kang , Guo Bei , Zheng Ming-Hui , Li Fuxingzi , Yuan Ling-Qing , Li Zhi-hong 
Published: March 2023

AbstractEpigenetics regulates gene expression and has been confirmed to play a critical role in a variety of metabolic diseases, such as diabetes, obesity, non-alcoholic fatty liver disease (NAFLD), osteoporosis, gout, hyperthyroidism, hypothyroidism and others. The term ‘epigenetics’ was firstly proposed in 1942 and with the development of technologies, the exploration of epigenetics has made great progresses. There are four main epigenetic mechanisms, including DNA methylation, histone modification, chromatin remodelling, and noncoding RNA (ncRNA), which exert different effects on metabolic diseases. Genetic and non-genetic factors, including ageing, diet, and exercise, interact with epigenetics and jointly affect the formation of a phenotype. Understanding epigenetics could be applied to diagnosing and treating metabolic diseases in the clinic, including epigenetic biomarkers, epigenetic drugs, and epigenetic editing. In this review, we introduce the brief history of epigenetics as well as the milestone events since the proposal of the term ‘epigenetics’. Moreover, we summarise the research methods of epigenetics and introduce four main general mechanisms of epigenetic modulation. Furthermore, we summarise epigenetic mechanisms in metabolic diseases and introduce the interaction between epigenetics and genetic or non-genetic factors. Finally, we introduce the clinical trials and applications of epigenetics in metabolic diseases.
Notch3 regulates Mybl2 via HeyL to limit proliferation and tumor initiation in breast cancer
Authors: Brahim Sonia , Negulescu Ana-Maria , Geneste Clara , Schott Thomas , Lin Shuheng , Morel Louis-Oscar , Rama Nicolas , Gadot Nicolas , Treilleux Isabelle , Mehlen Patrick , Meurette Olivier 
Published: March 2023

AbstractNotch signaling is a conserved signaling pathway that participates in many aspects of mammary gland development and homeostasis, and has extensively been associated with breast tumorigenesis. Here, to unravel the as yet debated role of Notch3 in breast cancer development, we investigated its expression in human breast cancer samples and effects of its loss in mice. Notch3 expression was very weak in breast cancer cells and was associated with good patient prognosis. Interestingly, its expression was very strong in stromal cells of these patients, though this had no prognostic value. Mechanistically, we demonstrated that Notch3 prevents tumor initiation via HeyL-mediated inhibition of Mybl2, an important regulator of cell cycle. In the mammary glands of Notch3-deficient mice, we observed accelerated tumor initiation and proliferation in a MMTV-Neu model. Notch3-null tumors were enriched in Mybl2 mRNA signature and protein expression. Hence, our study reinforces the anti-tumoral role of Notch3 in breast tumorigenesis.
Immunogenicity and protection of a variant nanoparticle vaccine that confers broad neutralization against SARS-CoV-2 variants
Authors: Logue James , Johnson Robert M. , Patel Nita , Zhou Bin , Maciejewski Sonia , Foreman Bryant , Zhou Haixia , Portnoff Alyse D. , Tian Jing-Hui , Rehman Asma , McGrath Marisa E. , Haupt Robert E. , Weston Stuart M. , Baracco Lauren , Hammond Holly , Guebre-Xabier Mimi , Dillen Carly , Madhangi M. , Greene Ann M. , Massare Michael J. , Glenn Greg M. , Smith Gale , Frieman Matthew B. 
Published: March 2023

AbstractSARS-CoV-2 variants have emerged with elevated transmission and a higher risk of infection for vaccinated individuals. We demonstrate that a recombinant prefusion-stabilized spike (rS) protein vaccine based on Beta/B.1.351 (rS-Beta) produces a robust anamnestic response in baboons against SARS-CoV-2 variants when given as a booster one year after immunization with NVX-CoV2373. Additionally, rS-Beta is highly immunogenic in mice and produces neutralizing antibodies against WA1/2020, Beta/B.1.351, and Omicron/BA.1. Mice vaccinated with two doses of Novavax prototype NVX-CoV2373 (rS-WU1) or rS-Beta alone, in combination, or heterologous prime-boost, are protected from challenge. Virus titer is undetectable in lungs in all vaccinated mice, and Th1-skewed cellular responses are observed. We tested sera from a panel of variant spike protein vaccines and find broad neutralization and inhibition of spike:ACE2 binding from the rS-Beta and rS-Delta vaccines against a variety of variants including Omicron. This study demonstrates that rS-Beta vaccine alone or in combination with rS-WU1 induces antibody-and cell-mediated responses that are protective against challenge with SARS-CoV-2 variants and offers broader neutralizing capacity than a rS-WU1 prime/boost regimen alone. Together, these nonhuman primate and murine data suggest a Beta variant booster dose could elicit a broad immune response to fight new and future SARS-CoV-2 variants.
Identification of a physiologic vasculogenic fibroblast state to achieve tissue repair
Authors: Pal Durba , Ghatak Subhadip , Singh Kanhaiya , Abouhashem Ahmed Safwat , Kumar Manishekhar , El Masry Mohamed S , Mohanty Sujit K. , Palakurti Ravichand , Rustagi Yashika , Tabasum Saba , Khona Dolly K. , Khanna Savita , Kacar Sedat , Srivastava Rajneesh , Bhasme Pramod , Verma Sumit S. , Hernandez Edward , Sharma Anu , Reese Diamond , Verma Priyanka , Ghosh Nandini , Gorain Mahadeo , Wan Jun , Liu Sheng , Liu Yunlong , Castro Natalia Higuita , Gnyawali Surya C. , Lawrence William , Moore Jordan , Perez Daniel Gallego , Roy Sashwati , Yoder Mervin C. , Sen Chandan K. 
Published: March 2023

AbstractTissue injury to skin diminishes miR-200b in dermal fibroblasts. Fibroblasts are widely reported to directly reprogram into endothelial-like cells and we hypothesized that miR-200b inhibition may cause such changes. We transfected human dermal fibroblasts with anti-miR-200b oligonucleotide, then using single cell RNA sequencing, identified emergence of a vasculogenic subset with a distinct fibroblast transcriptome and demonstrated blood vessel forming function in vivo. Anti-miR-200b delivery to murine injury sites likewise enhanced tissue perfusion, wound closure, and vasculogenic fibroblast contribution to perfused vessels in a FLI1 dependent manner. Vasculogenic fibroblast subset emergence was blunted in delayed healing wounds of diabetic animals but, topical tissue nanotransfection of a single anti-miR-200b oligonucleotide was sufficient to restore FLI1 expression, vasculogenic fibroblast emergence, tissue perfusion, and wound healing. Augmenting a physiologic tissue injury adaptive response mechanism that produces a vasculogenic fibroblast state change opens new avenues for therapeutic tissue vascularization of ischemic wounds.
Disease-relevant β2-microglobulin variants share a common amyloid fold
Authors: Wilkinson Martin , Gallardo Rodrigo U. , Martinez Roberto Maya , Guthertz Nicolas , So Masatomo , Aubrey Liam D. , Radford Sheena E. , Ranson Neil A. 
Published: March 2023

Abstractβ2-microglobulin (β2m) and its truncated variant ΔΝ6 are co-deposited in amyloid fibrils in the joints, causing the disorder dialysis-related amyloidosis (DRA). Point mutations of β2m result in diseases with distinct pathologies. β2m-D76N causes a rare systemic amyloidosis with protein deposited in the viscera in the absence of renal failure, whilst β2m-V27M is associated with renal failure, with amyloid deposits forming predominantly in the tongue. Here we use cryoEM to determine the structures of fibrils formed from these variants under identical conditions in vitro. We show that each fibril sample is polymorphic, with diversity arising from a ‘lego-like’ assembly of a common amyloid building block. These results suggest a ‘many sequences, one amyloid fold’ paradigm in contrast with the recently reported ‘one sequence, many amyloid folds’ behaviour of intrinsically disordered proteins such as tau and Aβ.
Insights into pulmonary phosphate homeostasis and osteoclastogenesis emerge from the study of pulmonary alveolar microlithiasis
Authors: Uehara Yasuaki , Tanaka Yusuke , Zhao Shuyang , Nikolaidis Nikolaos M. , Pitstick Lori B. , Wu Huixing , Yu Jane J. , Zhang Erik , Hasegawa Yoshihiro , Noel John G. , Gardner Jason C. , Kopras Elizabeth J. , Haffey Wendy D. , Greis Kenneth D. , Guo Jinbang , Woods Jason C. , Wikenheiser-Brokamp Kathryn A. , Kyle Jennifer E. , Ansong Charles , Teitelbaum Steven L. , Inoue Yoshikazu , Altinişik Göksel , Xu Yan , McCormack Francis X. 
Published: March 2023

AbstractPulmonary alveolar microlithiasis is an autosomal recessive lung disease caused by a deficiency in the pulmonary epithelial Npt2b sodium-phosphate co-transporter that results in accumulation of phosphate and formation of hydroxyapatite microliths in the alveolar space. The single cell transcriptomic analysis of a pulmonary alveolar microlithiasis lung explant showing a robust osteoclast gene signature in alveolar monocytes and the finding that calcium phosphate microliths contain a rich protein and lipid matrix that includes bone resorbing osteoclast enzymes and other proteins suggested a role for osteoclast-like cells in the host response to microliths. While investigating the mechanisms of microlith clearance, we found that Npt2b modulates pulmonary phosphate homeostasis through effects on alternative phosphate transporter activity and alveolar osteoprotegerin, and that microliths induce osteoclast formation and activation in a receptor activator of nuclear factor-κB ligand and dietary phosphate dependent manner. This work reveals that Npt2b and pulmonary osteoclast-like cells play key roles in pulmonary homeostasis and suggest potential new therapeutic targets for the treatment of lung disease.
Retinol dehydrogenase 10 reduction mediated retinol metabolism disorder promotes diabetic cardiomyopathy in male mice
Authors: Wu Yandi , Huang Tongsheng , Li Xinghui , Shen Conghui , Ren Honglin , Wang Haiping , Wu Teng , Fu Xinlu , Deng Shijie , Feng Ziqi , Xiong Shijie , Li Hui , Gao Saifei , Yang Zhenyu , Gao Fei , Dong Lele , Cheng Jianding , Cai Weibin 
Published: March 2023

AbstractDiabetic cardiomyopathy is a primary myocardial injury induced by diabetes with complex pathogenesis. In this study, we identify disordered cardiac retinol metabolism in type 2 diabetic male mice and patients characterized by retinol overload, all-trans retinoic acid deficiency. By supplementing type 2 diabetic male mice with retinol or all-trans retinoic acid, we demonstrate that both cardiac retinol overload and all-trans retinoic acid deficiency promote diabetic cardiomyopathy. Mechanistically, by constructing cardiomyocyte-specific conditional retinol dehydrogenase 10-knockout male mice and overexpressing retinol dehydrogenase 10 in male type 2 diabetic mice via adeno-associated virus, we verify that the reduction in cardiac retinol dehydrogenase 10 is the initiating factor for cardiac retinol metabolism disorder and results in diabetic cardiomyopathy through lipotoxicity and ferroptosis. Therefore, we suggest that the reduction of cardiac retinol dehydrogenase 10 and its mediated disorder of cardiac retinol metabolism is a new mechanism underlying diabetic cardiomyopathy.
Zika virus RNA structure controls its unique neurotropism by bipartite binding to Musashi-1
Authors: Chen Xiang , Wang Yan , Xu Zhonghe , Cheng Meng-Li , Ma Qing-Qing , Li Rui-Ting , Wang Zheng-Jian , Zhao Hui , Zuo Xiaobing , Li Xiao-Feng , Fang Xianyang , Qin Cheng-Feng 
Published: March 2023

AbstractHuman RNA binding protein Musashi-1 (MSI1) plays a critical role in neural progenitor cells (NPCs) by binding to various host RNA transcripts. The canonical MSI1 binding site (MBS), A/GU(1-3)AG single-strand motif, is present in many RNA virus genomes, but only Zika virus (ZIKV) genome has been demonstrated to bind MSI1. Herein, we identified the AUAG motif and the AGAA tetraloop in the Xrn1-resistant RNA 2 (xrRNA2) as the canonical and non-canonical MBS, respectively, and both are crucial for ZIKV neurotropism. More importantly, the unique AGNN-type tetraloop is evolutionally conserved, and distinguishes ZIKV from other known viruses with putative MBSs. Integrated structural analysis showed that MSI1 binds to the AUAG motif and AGAA tetraloop of ZIKV in a bipartite fashion. Thus, our results not only identified an unusual viral RNA structure responsible for MSI recognition, but also revealed a role for the highly structured xrRNA in controlling viral neurotropism.
Cell specialization in cyanobacterial biofilm development revealed by expression of a cell-surface and extracellular matrix protein
Authors: Frenkel Alona , Zecharia Eli , Gómez-Pérez Daniel , Sendersky Eleonora , Yegorov Yevgeni , Jacob Avi , Benichou Jennifer I. C. , Stierhof York-Dieter , Parnasa Rami , Golden Susan S. , Kemen Eric , Schwarz Rakefet 
Published: March 2023

AbstractCyanobacterial biofilms are ubiquitous and play important roles in diverse environments, yet, understanding of the processes underlying the development of these aggregates is just emerging. Here we report cell specialization in formation of Synechococcus elongatus PCC 7942 biofilms—a hitherto unknown characteristic of cyanobacterial social behavior. We show that only a quarter of the cell population expresses at high levels the four-gene ebfG-operon that is required for biofilm formation. Almost all cells, however, are assembled in the biofilm. Detailed characterization of EbfG4 encoded by this operon revealed cell-surface localization as well as its presence in the biofilm matrix. Moreover, EbfG1-3 were shown to form amyloid structures such as fibrils and are thus likely to contribute to the matrix structure. These data suggest a beneficial ‘division of labor’ during biofilm formation where only some of the cells allocate resources to produce matrix proteins—‘public goods’ that support robust biofilm development by the majority of the cells. In addition, previous studies revealed the operation of a self-suppression mechanism that depends on an extracellular inhibitor, which supresses transcription of the ebfG-operon. Here we revealed inhibitor activity at an early growth stage and its gradual accumulation along the exponential growth phase in correlation with cell density. Data, however, do not support a threshold-like phenomenon known for quorum-sensing in heterotrophs. Together, data presented here demonstrate cell specialization and imply density-dependent regulation thereby providing deep insights into cyanobacterial communal behavior.
Deep learning for exploring ultra-thin ferroelectrics with highly improved sensitivity of piezoresponse force microscopy
Authors: Sriboriboon Panithan , Qiao Huimin , Kwon Owoong , Vasudevan Rama K. , Jesse Stephen , Kim Yunseok 
Published: March 2023

AbstractHafnium oxide-based ferroelectrics have been extensively studied because of their existing ferroelectricity, even in ultra-thin film form. However, studying the weak response from ultra-thin film requires improved measurement sensitivity. In general, resonance-enhanced piezoresponse force microscopy (PFM) has been used to characterize ferroelectricity by fitting a simple harmonic oscillation model with the resonance spectrum. However, an iterative approach, such as traditional least squares (LS) fitting, is sensitive to noise and can result in the misunderstanding of weak responses. In this study, we developed the deep neural network (DNN) hybrid with deep denoising autoencoder (DDA) and principal component analysis (PCA) to extract resonance information. The DDA/PCA-DNN improves the PFM sensitivity down to 0.3 pm, allowing measurement of weak piezoresponse with low excitation voltage in 10-nm-thick Hf0.5Zr0.5O2 thin films. Our hybrid approaches could provide more chances to explore the low piezoresponse of the ultra-thin ferroelectrics and could be applied to other microscopic techniques.
Autologous dendritic cell vaccination against HIV-1 induces changes in natural killer cell phenotype and functionality
Authors: Laeremans Thessa , den Roover Sabine , Lungu Cynthia , D’haese Sigrid , Gruters Rob A. , Allard Sabine D. , Aerts Joeri L. 
Published: March 2023

AbstractAlthough natural killer (NK) cells have been studied in connection with dendritic cell (DC)-based vaccination in the field of cancer immunology, their role has barely been addressed in the context of therapeutic vaccination against HIV-1. In this study, we evaluated whether a therapeutic DC-based vaccine consisting of monocyte-derived DCs electroporated with Tat, Rev and Nef encoding mRNA affects NK cell frequency, phenotype and functionality in HIV-1-infected individuals. Although the frequency of total NK cells did not change, we observed a significant increase in cytotoxic NK cells following immunisation. In addition, significant changes in the NK cell phenotype associated with migration and exhaustion were observed together with increased NK cell-mediated killing and (poly)functionality. Our results show that DC-based vaccination has profound effects on NK cells, which highlights the importance of evaluating NK cells in future clinical trials looking at DC-based immunotherapy in the context of HIV-1 infection.
Cardiogenic control of affective behavioural state
Authors: Hsueh Brian , Chen Ritchie , Jo YoungJu , Tang Daniel , Raffiee Misha , Kim Yoon Seok , Inoue Masatoshi , Randles Sawyer , Ramakrishnan Charu , Patel Sneha , Kim Doo Kyung , Liu Tony X. , Kim Soo Hyun , Tan Longzhi , Mortazavi Leili , Cordero Arjay , Shi Jenny , Zhao Mingming , Ho Theodore T. , Crow Ailey , Yoo Ai-Chi Wang , Raja Cephra , Evans Kathryn , Bernstein Daniel , Zeineh Michael , Goubran Maged , Deisseroth Karl 
Published: March 2023

AbstractEmotional states influence bodily physiology, as exemplified in the top-down process by which anxiety causes faster beating of the heart1–3. However, whether an increased heart rate might itself induce anxiety or fear responses is unclear3–8. Physiological theories of emotion, proposed over a century ago, have considered that in general, there could be an important and even dominant flow of information from the body to the brain9. Here, to formally test this idea, we developed a noninvasive optogenetic pacemaker for precise, cell-type-specific control of cardiac rhythms of up to 900 beats per minute in freely moving mice, enabled by a wearable micro-LED harness and the systemic viral delivery of a potent pump-like channelrhodopsin. We found that optically evoked tachycardia potently enhanced anxiety-like behaviour, but crucially only in risky contexts, indicating that both central (brain) and peripheral (body) processes may be involved in the development of emotional states. To identify potential mechanisms, we used whole-brain activity screening and electrophysiology to find brain regions that were activated by imposed cardiac rhythms. We identified the posterior insular cortex as a potential mediator of bottom-up cardiac interoceptive processing, and found that optogenetic inhibition of this brain region attenuated the anxiety-like behaviour that was induced by optical cardiac pacing. Together, these findings reveal that cells of both the body and the brain must be considered together to understand the origins of emotional or affective states. More broadly, our results define a generalizable approach for noninvasive, temporally precise functional investigations of joint organism-wide interactions among targeted cells during behaviour.
Modified variational autoencoder for inversely predicting plasmonic nanofeatures for generating structural color
Authors: Pillai Prajith , Rai Beena , Pal Parama 
Published: March 2023

AbstractWe apply a modified variational autoencoder (VAE) regressor for inversely retrieving the topological parameters of the building blocks of plasmonic composites for generating structural colors as per requirement. We demonstrate results of a comparison study between inverse models based on generative VAEs as well as conventional tandem networks that have been favored traditionally. We describe our strategy for improving the performance of our model by filtering the simulated dataset prior to training. The VAE- based inverse model links the electromagnetic response expressed as the structural color to the geometrical dimensions from the latent space using a multilayer perceptron regressor and shows better accuracy over a conventional tandem inverse model.
A suture anchor-based repair technique for type IV jersey finger injuries: a biomechanical investigation
Authors: Halát Gabriel , Negrin Lukas Leopold , Hoppe Paul Lennart , Unger Ewald , Koch Thomas , Hirtler Lena , Hajdu Stefan 
Published: March 2023

AbstractThe aim of this biomechanical investigation was to evaluate a repair technique for type IV FDP tendon avulsions using a suture anchor, addressing the bony and the tendinous aspect of this injury simultaneously. In 45 distal phalanges from human anatomical specimens the injury was simulated and repairs were performed with a suture anchor using an innovative technique, interosseous sutures and a combination of screws and an interosseous suture. Repetitive loading for 500 cycles simulated postoperative mobilization. Repairs were loaded to failure thereafter. Elongation of the tendon-suture complex, gap formation at the bone-bone contact line and at the bone-tendon insertion line, load at first noteworthy displacement (2 mm), load at failure and the mechanism of failure were assessed. The suture anchor technique was superior biomechanically considering load at failure (mean: 72.8 N), bony gap formation (mean: 0.1 mm) as well as tendinous gap formation (mean: 0.7 mm), implying a preferable stability of the repair. Overall, this study demonstrates good ex vivo mechanical stability for a proposed suture anchor repair technique for type IV FDP tendon avulsion injuries, which might enable early postoperative mobilization in patients. The technique's subcutaneous implant placement and low implant load are expected to reduce potential complications observed in other commonly used repair techniques. This approach warrants further evaluation in vivo.
Zinc oxide nanoparticles induce oxidative stress, genotoxicity, and apoptosis in the hemocytes of Bombyx mori larvae
Authors: Belal Rania , Gad Abir 
Published: March 2023

AbstractThe expanded uses of zinc oxide nanoparticles (ZnO-NPs) have grown rapidly in the field of nanotechnology. Thus, the increased production of nanoparticles (NPs) increases the potential risks to the environment and occupationally exposed humans. Hence, safety and toxicity assessment including genotoxicity of these NPs is indispensable. In the present study, we have evaluated the genotoxic effect of ZnO-NPs on 5th larval instar of Bombyx mori after feeding on mulberry leaves treated with ZnO-NPs at concentrations 50 and 100 μg/ml. Moreover, we evaluated its effects on total and different hemocyte count, antioxidant potential and catalase activity on the hemolymph of treated larvae. Results showed that ZnO-NPs at concentrations of 50 and 100 µg/ml have significantly decreased the total hemocyte count (THC) and different hemocyte count (DHC) except the number of oenocytes as they were significantly increased. Gene expression profile also showed up-regulation of GST, CNDP2 and CE genes suggesting increase in antioxidant activity and alteration in cell viability as well as cell signaling.