bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leisure-time physical activity motives and perceived gains for individuals with spinal cord injury
Authors: Watson Paul K. , Stendell Laura , Quel de Oliveira Camila , Middleton James W. , Arora Mohit , Davis Glen M. 
Published: July 2024

Abstract
Study design
Longitudinal cross-sectional.

Objectives
To examine motives to, and perceived gains from, leisure-time physical activity (LTPA) in people with spinal cord injury (SCI).

Setting
Community.

Methods
One hundred and five physically active individuals with SCI undertook an online survey and a semi-structured interview. The Exercise Motives and Gains Inventory was used to examine the movies towards, and the gains from LTPA, and the Leisure-time Physical Activity Questionnaire was administered via interview to gather LTPA data. A cross-sectional analysis, which included descriptive, inferential, and regression statistics, was conducted on all participants, physical activity (PA) guideline adherers and PA guideline non-adherers.

Results
The most common motives for LTPA were improvements in health and fitness, management of appearance and weight, and avoidance of illness. The most common gains from LTPA included improved health, fitness, strength and endurance, increased nimbleness, and enjoyment and revitalisation.

Conclusions
Whilst health enhancement appears to be a significant motivator for LTPA, other psychosocial aspects, such as affiliation and revitalisation, appear to influence engagement and volume of LTPA. Regular LTPA should be encouraged for its health benefits, and emphasis should be placed on promoting its ability to reduce illness, facilitate affiliation, and manage stress.
Whole genome sequencing study of identical twins discordant for psychosis
Authors: Ormond Cathal , Ryan Niamh M. , Hedman Anna M. , Cannon Tyrone D. , Sullivan Patrick F. , Gill Michael , Hultman Christina , Heron Elizabeth A. , Johansson Viktoria , Corvin Aiden 
Published: July 2024

AbstractMonozygotic (MZ) twins are often thought to have identical genomes, but recent work has shown that early post-zygotic events can result in a spectrum of DNA variants that are different between MZ twins. Such variants may explain phenotypic discordance and contribute to disease etiology. Here we performed whole genome sequencing in 17 pairs of MZ twins discordant for a psychotic disorder (schizophrenia, schizoaffective disorder or bipolar disorder). We examined various classes of rare variants that are discordant within a twin pair. We identified four genes harboring rare, predicted deleterious missense variants that were private to an affected individual in the cohort. Variants in FOXN1 and FLOT2 would have been categorized as damaging from recent schizophrenia and bipolar exome sequencing studies. Additionally, we identified four rare genic copy number variants (CNVs) private to an affected sample, two of which overlapped genes that have shown evidence for association with schizophrenia or bipolar disorder. One such CNV was a 3q29 duplication previously implicated in autism and developmental delay. We have performed the largest MZ twin study for discordant psychotic phenotypes to date. These findings warrant further investigation using other analytical approaches.
TOX2 nuclear-cytosol translocation is linked to leukemogenesis of acute T-cell leukemia by repressing TIM3 transcription
Authors: Li Anzhou , Zhang Junbao , Zhan Liangping , Liu Xiufeng , Zeng Xiliang , Zhu Qian , Wang Zifeng , Li Jiang 
Published: July 2024

AbstractNuclear factors TOX and TOX2 upregulate TIM3 expression and lead to T-cell exhaustion in malignancies. Here, we demonstrate two distinct TIM3 expression patterns (high & low) with high TOX and TOX2 levels in T-cell acute lymphoblastic leukemia (T-ALL) specimens and cell lines. However, the mechanisms regulated by TOX and TIM3 signaling in leukemogenesis are unclear. We found that TOX and TOX2 proteins each directly upregulated HAVCR2 transcription, while the cellular localization of TOX2 was different in Jurkat and MOLT3 cells (nucleus) and lymphoblastic cell T2 and normal T cells (cytoplasm). Nuclear TOX and TOX2 formed a protein complex and repressed HAVCR2 promoter activity by recruiting transcriptional corepressor LCOR and deacetylase HDAC3. The nuclear-cytosol translocation of TOX2 was deacetylation-dependent and cooperatively mediated by deacetylase Sirt1 and kinase TBK1. Radiation damage induced TOX2 nuclear translocation and decreased Sirt1, TIM3, and caspase 1 expression in normal T cells. Accordingly, knockdown of TOX, TOX2 or LCOR; HDAC3 inhibition; or TIM3 overexpression induced Jurkat cell apoptosis in vitro and slow growth in vivo. Thus, our findings demonstrate a novel regulatory mechanism involving TOX-TOX2 and the TIM3 pathway in the leukemogenesis of T-ALL.
Endoplasmic reticulum stress—a key guardian in cancer
Authors: Zhang Wenlong , Shi Yidan , Oyang Linda , Cui Shiwen , Li Shizhen , Li Jinyun , Liu Lin , Li Yun , Peng Mingjing , Tan Shiming , Xia Longzheng , Lin Jinguan , Xu Xuemeng , Wu Nayiyuan , Peng Qiu , Tang Yanyan , Luo Xia , Liao Qianjin , Jiang Xianjie , Zhou Yujuan 
Published: July 2024

AbstractEndoplasmic reticulum stress (ERS) is a cellular stress response characterized by excessive contraction of the endoplasmic reticulum (ER). It is a pathological hallmark of many diseases, such as diabetes, obesity, and neurodegenerative diseases. In the unique growth characteristic and varied microenvironment of cancer, high levels of stress are necessary to maintain the rapid proliferation and metastasis of tumor cells. This process is closely related to ERS, which enhances the ability of tumor cells to adapt to unfavorable environments and promotes the malignant progression of cancer. In this paper, we review the roles and mechanisms of ERS in tumor cell proliferation, apoptosis, metastasis, angiogenesis, drug resistance, cellular metabolism, and immune response. We found that ERS can modulate tumor progression via the unfolded protein response (UPR) signaling of IRE1, PERK, and ATF6. Targeting the ERS may be a new strategy to attenuate the protective effects of ERS on cancer. This manuscript explores the potential of ERS-targeted therapies, detailing the mechanisms through which ERS influences cancer progression and highlighting experimental and clinical evidence supporting these strategies. Through this review, we aim to deepen our understanding of the role of ER stress in cancer development and provide new insights for cancer therapy.
Sequence-to-sequence translation from mass spectra to peptides with a transformer model
Authors: Yilmaz Melih , Fondrie William E. , Bittremieux Wout , Melendez Carlo F. , Nelson Rowan , Ananth Varun , Oh Sewoong , Noble William Stafford 
Published: July 2024

AbstractA fundamental challenge in mass spectrometry-based proteomics is the identification of the peptide that generated each acquired tandem mass spectrum. Approaches that leverage known peptide sequence databases cannot detect unexpected peptides and can be impractical or impossible to apply in some settings. Thus, the ability to assign peptide sequences to tandem mass spectra without prior information—de novo peptide sequencing—is valuable for tasks including antibody sequencing, immunopeptidomics, and metaproteomics. Although many methods have been developed to address this problem, it remains an outstanding challenge in part due to the difficulty of modeling the irregular data structure of tandem mass spectra. Here, we describe Casanovo, a machine learning model that uses a transformer neural network architecture to translate the sequence of peaks in a tandem mass spectrum into the sequence of amino acids that comprise the generating peptide. We train a Casanovo model from 30 million labeled spectra and demonstrate that the model outperforms several state-of-the-art methods on a cross-species benchmark dataset. We also develop a version of Casanovo that is fine-tuned for non-enzymatic peptides. Finally, we demonstrate that Casanovo’s superior performance improves the analysis of immunopeptidomics and metaproteomics experiments and allows us to delve deeper into the dark proteome.
Multilevel neurium-mimetic individualized graft via additive manufacturing for efficient tissue repair
Authors: Kong Lingchi , Gao Xin , Yao Xiangyun , Xie Haijiao , Kang Qinglin , Sun Wei , You Zhengwei , Qian Yun , Fan Cunyi 
Published: July 2024

AbstractComplicated peripheral nerve injuries or defects, especially at branching sites, remain a prominent clinical challenge after the application of different treatment strategies. Current nerve grafts fail to match the expected shape and size for delicate and precise branched nerve repair on a case-by-case basis, and there is a lack of geometrical and microscale regenerative navigation. In this study, we develop a sugar painting-inspired individualized multilevel epi-/peri-/endoneurium-mimetic device (SpinMed) to customize natural cues, featuring a selectively protective outer sheath and an instructive core, to support rapid vascular reconstruction and consequent efficient neurite extension along the defect area. The biomimetic perineurium dictates host-guest crosslinking in which new vessels secrete multimerin 1 binding to the fibroin filler surface as an anchor, contributing to the biological endoneurium that promotes Schwann cell homing and remyelination. SpinMed implantation into rat sciatic nerve defects yields a satisfactory outcome in terms of structural reconstruction, with sensory and locomotive function restoration. We further customize SpinMed grafts based on anatomy and digital imaging, achieving rapid repair of the nerve trunk and branches superior to that achieved by autografts and decellularized grafts in a specific beagle nerve defect model, with reliable biosafety. Overall, this intelligent art-inspired biomimetic design offers a facile way to customize sophisticated high-performance nerve grafts and holds great potential for application in translational regenerative medicine.
Modular RNA motifs for orthogonal phase separated compartments
Authors: Stewart Jaimie Marie , Li Shiyi , Tang Anli A. , Klocke Melissa Ann , Gobry Martin Vincent , Fabrini Giacomo , Di Michele Lorenzo , Rothemund Paul W. K. , Franco Elisa 
Published: July 2024

AbstractRecent discoveries in biology have highlighted the importance of protein and RNA-based condensates as an alternative to classical membrane-bound organelles. Here, we demonstrate the design of pure RNA condensates from nanostructured, star-shaped RNA motifs. We generate condensates using two different RNA nanostar architectures: multi-stranded nanostars whose binding interactions are programmed via linear overhangs, and single-stranded nanostars whose interactions are programmed via kissing loops. Through systematic sequence design, we demonstrate that both architectures can produce orthogonal (distinct and immiscible) condensates, which can be individually tracked via fluorogenic aptamers. We also show that aptamers make it possible to recruit peptides and proteins to the condensates with high specificity. Successful co-transcriptional formation of condensates from single-stranded nanostars suggests that they may be genetically encoded and produced in living cells. We provide a library of orthogonal RNA condensates that can be modularly customized and offer a route toward creating systems of functional artificial organelles for the task of compartmentalizing molecules and biochemical reactions.
Programmable DNA pyrimidine base editing via engineered uracil-DNA glycosylase
Authors: Yi Zongyi , Zhang Xiaoxue , Wei Xiaoxu , Li Jiayi , Ren Jiwu , Zhang Xue , Zhang Yike , Tang Huixian , Chang Xiwen , Yu Ying , Wei Wensheng 
Published: July 2024

AbstractDNA base editing technologies predominantly utilize engineered deaminases, limiting their ability to edit thymine and guanine directly. In this study, we successfully achieve base editing of both cytidine and thymine by leveraging the translesion DNA synthesis pathway through the engineering of uracil-DNA glycosylase (UNG). Employing structure-based rational design, exploration of homologous proteins, and mutation screening, we identify a Deinococcus radiodurans UNG mutant capable of effectively editing thymine. When fused with the nickase Cas9, the engineered DrUNG protein facilitates efficient thymine base editing at endogenous sites, achieving editing efficiencies up to 55% without enrichment and exhibiting minimal cellular toxicity. This thymine base editor (TBE) exhibits high editing specificity and significantly restores IDUA enzyme activity in cells derived from patients with Hurler syndrome. TBEs represent efficient, specific, and low-toxicity approaches to base editing with potential applications in treating relevant diseases.
Evidence for multi-fragmentation and mass shedding of boulders on rubble-pile binary asteroid system (65803) Didymos
Authors: Pajola M. , Tusberti F. , Lucchetti A. , Barnouin O. , Cambioni S. , Ernst C. M. , Dotto E. , Daly R. T. , Poggiali G. , Hirabayashi M. , Nakano R. , Epifani E. Mazzotta , Chabot N. L. , Della Corte V. , Rivkin A. , Agrusa H. , Zhang Y. , Penasa L. , Ballouz R.-L. , Ivanovski S. , Murdoch N. , Rossi A. , Robin C. , Ieva S. , Vincent J. B. , Ferrari F. , Raducan S. D. , Campo-Bagatin A. , Parro L. , Benavidez P. , Tancredi G. , Karatekin Ö. , Trigo-Rodriguez J. M. , Sunshine J. , Farnham T. , Asphaug E. , Deshapriya J. D. P. , Hasselmann P. H. A. , Beccarelli J. , Schwartz S. R. , Abell P. , Michel P. , Cheng A. , Brucato J. R. , Zinzi A. , Amoroso M. , Pirrotta S. , Impresario G. , Bertini I. , Capannolo A. , Caporali S. , Ceresoli M. , Cremonese G. , Dall’Ora M. , Gai I. , Casajus L. Gomez , Gramigna E. , Manghi R. Lasagni , Lavagna M. , Lombardo M. , Modenini D. , Palumbo P. , Perna D. , Tortora P. , Zannoni M. , Zanotti G. 
Published: July 2024

AbstractAsteroids smaller than 10 km are thought to be rubble piles formed from the reaccumulation of fragments produced in the catastrophic disruption of parent bodies. Ground-based observations reveal that some of these asteroids are today binary systems, in which a smaller secondary orbits a larger primary asteroid. However, how these asteroids became binary systems remains unclear. Here, we report the analysis of boulders on the surface of the stony asteroid (65803) Didymos and its moonlet, Dimorphos, from data collected by the NASA DART mission. The size-frequency distribution of boulders larger than 5 m on Dimorphos and larger than 22.8 m on Didymos confirms that both asteroids are piles of fragments produced in the catastrophic disruption of their progenitors. Dimorphos boulders smaller than 5 m have size best-fit by a Weibull distribution, which we attribute to a multi-phase fragmentation process either occurring during coalescence or during surface evolution. The density per km2 of Dimorphos boulders ≥1 m is 2.3x with respect to the one obtained for (101955) Bennu, while it is 3.0x with respect to (162173) Ryugu. Such values increase once Dimorphos boulders ≥5 m are compared with Bennu (3.5x), Ryugu (3.9x) and (25143) Itokawa (5.1x). This is of interest in the context of asteroid studies because it means that contrarily to the single bodies visited so far, binary systems might be affected by subsequential fragmentation processes that largely increase their block density per km2. Direct comparison between the surface distribution and shapes of the boulders on Didymos and Dimorphos suggest that the latter inherited its material from the former. This finding supports the hypothesis that some asteroid binary systems form through the spin up and mass shedding of a fraction of the primary asteroid.
Aging drives cerebrovascular network remodeling and functional changes in the mouse brain
Authors: Bennett Hannah C. , Zhang Qingguang , Wu Yuan-ting , Manjila Steffy B. , Chon Uree , Shin Donghui , Vanselow Daniel J. , Pi Hyun-Jae , Drew Patrick J. , Kim Yongsoo 
Published: July 2024

AbstractAging is frequently associated with compromised cerebrovasculature and pericytes. However, we do not know how normal aging differentially impacts vascular structure and function in different brain areas. Here we utilize mesoscale microscopy methods and in vivo imaging to determine detailed changes in aged murine cerebrovascular networks. Whole-brain vascular tracing shows an overall ~10% decrease in vascular length and branching density with ~7% increase in vascular radii in aged brains. Light sheet imaging with 3D immunolabeling reveals increased arteriole tortuosity of aged brains. Notably, vasculature and pericyte densities show selective and significant reductions in the deep cortical layers, hippocampal network, and basal forebrain areas. We find increased blood extravasation, implying compromised blood-brain barrier function in aged brains. Moreover, in vivo imaging in awake mice demonstrates reduced baseline and on-demand blood oxygenation despite relatively intact neurovascular coupling. Collectively, we uncover regional vulnerabilities of cerebrovascular network and physiological changes that can mediate cognitive decline in normal aging.
Structure of the MlaC-MlaD complex reveals molecular basis of periplasmic phospholipid transport
Authors: Wotherspoon Peter , Johnston Hannah , Hardy David J. , Holyfield Rachel , Bui Soi , Ratkevičiūtė Giedrė , Sridhar Pooja , Colburn Jonathan , Wilson Charlotte B. , Colyer Adam , Cooper Benjamin F. , Bryant Jack A. , Hughes Gareth W. , Stansfeld Phillip J. , Bergeron Julien R. C. , Knowles Timothy J. 
Published: July 2024

AbstractThe Maintenance of Lipid Asymmetry (Mla) pathway is a multicomponent system found in all gram-negative bacteria that contributes to virulence, vesicle blebbing and preservation of the outer membrane barrier function. It acts by removing ectopic lipids from the outer leaflet of the outer membrane and returning them to the inner membrane through three proteinaceous assemblies: the MlaA-OmpC complex, situated within the outer membrane; the periplasmic phospholipid shuttle protein, MlaC; and the inner membrane ABC transporter complex, MlaFEDB, proposed to be the founding member of a structurally distinct ABC superfamily. While the function of each component is well established, how phospholipids are exchanged between components remains unknown. This stands as a major roadblock in our understanding of the function of the pathway, and in particular, the role of ATPase activity of MlaFEDB is not clear. Here, we report the structure of E. coli MlaC in complex with the MlaD hexamer in two distinct stoichiometries. Utilising in vivo complementation assays, an in vitro fluorescence-based transport assay, and molecular dynamics simulations, we confirm key residues, identifying the MlaD β6-β7 loop as essential for MlaCD function. We also provide evidence that phospholipids pass between the C-terminal helices of the MlaD hexamer to reach the central pore, providing insight into the trajectory of GPL transfer between MlaC and MlaD.
Mapping the molecular landscape of Lotus japonicus nodule organogenesis through spatiotemporal transcriptomics
Authors: Ye Keyi , Bu Fengjiao , Zhong Liyuan , Dong Zhaonian , Ma Zhaoxu , Tang Zhanpeng , Zhang Yu , Yang Xueyong , Xu Xun , Wang Ertao , Lucas William J. , Huang Sanwen , Liu Huan , Zheng Jianshu 
Published: July 2024

AbstractLegumes acquire nitrogen-fixing ability by forming root nodules. Transferring this capability to more crops could reduce our reliance on nitrogen fertilizers, thereby decreasing environmental pollution and agricultural production costs. Nodule organogenesis is complex, and a comprehensive transcriptomic atlas is crucial for understanding the underlying molecular events. Here, we utilized spatial transcriptomics to investigate the development of nodules in the model legume, Lotus japonicus. Our investigation has identified the developmental trajectories of two critical regions within the nodule: the infection zone and peripheral tissues. We reveal the underlying biological processes and provide gene sets to achieve symbiosis and material exchange, two essential aspects of nodulation. Among the candidate regulatory genes, we illustrate that LjNLP3, a transcription factor belonging to the NIN-LIKE PROTEIN family, orchestrates the transition of nodules from the differentiation to maturation. In summary, our research advances our understanding of nodule organogenesis and provides valuable data for developing symbiotic nitrogen-fixing crops.
A gate tunable transmon qubit in planar Ge
Authors: Sagi Oliver , Crippa Alessandro , Valentini Marco , Janik Marian , Baghumyan Levon , Fabris Giorgio , Kapoor Lucky , Hassani Farid , Fink Johannes , Calcaterra Stefano , Chrastina Daniel , Isella Giovanni , Katsaros Georgios 
Published: July 2024

AbstractGate-tunable transmons (gatemons) employing semiconductor Josephson junctions have recently emerged as building blocks for hybrid quantum circuits. In this study, we present a gatemon fabricated in planar Germanium. We induce superconductivity in a two-dimensional hole gas by evaporating aluminum atop a thin spacer, which separates the superconductor from the Ge quantum well. The Josephson junction is then integrated into an Xmon circuit and capacitively coupled to a transmission line resonator. We showcase the qubit tunability in a broad frequency range with resonator and two-tone spectroscopy. Time-domain characterizations reveal energy relaxation and coherence times up to 75 ns. Our results, combined with the recent advances in the spin qubit field, pave the way towards novel hybrid and protected qubits in a group IV, CMOS-compatible material.
Human-centred physical neuromorphics with visual brain-computer interfaces
Authors: Wang Gao , Marcucci Giulia , Peters Benjamin , Braidotti Maria Chiara , Muckli Lars , Faccio Daniele 
Published: July 2024

AbstractSteady-state visual evoked potentials (SSVEPs) are widely used for brain-computer interfaces (BCIs) as they provide a stable and efficient means to connect the computer to the brain with a simple flickering light. Previous studies focused on low-density frequency division multiplexing techniques, i.e. typically employing one or two light-modulation frequencies during a single flickering light stimulation. Here we show that it is possible to encode information in SSVEPs excited by high-density frequency division multiplexing, involving hundreds of frequencies. We then demonstrate the ability to transmit entire images from the computer to the brain/EEG read-out in relatively short times. High-density frequency multiplexing also allows to implement a photonic neural network utilizing SSVEPs, that is applied to simple classification tasks and exhibits promising scalability properties by connecting multiple brains in series. Our findings open up new possibilities for the field of neural interfaces, holding potential for various applications, including assistive technologies and cognitive enhancements, to further improve human-machine interactions.