bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tree‐Ring Insights Into Past and Future Streamflow Variations in Beijing, Northern China
Authors: Cao Honghua , Chen Feng , Hu Mao , Hou Tiyuan , Zhao Xiaoen , Wang Shijie , Zhang Heli 
Published: January 2025

AbstractAs the largest city in northern China and the capital of China, the rapid increases in Beijing’s water consumption in recent years have made water resources provision an increasing problem. To rationally allocate water resources, it is important to obtain long‐term runoff information in Beijing. In this study we develop a 236‐year chronology of tree‐ring widths based on cores from Pinus tabuliformis from four sampling sites. The resulting regression model reconstructs December–July runoff of the Yongding River in Beijing, with 49.5% of the variance explained, back to 1786 CE. Among the last 236 years, 1868, 1956, 1991, 1998, 2018, and 2021 were extremely high runoff years; and 1900, 1906, 1999, and 2000 were extremely low runoff years. Comparison of the runoff reconstruction results with climate grid data demonstrated a large magnitude of climate change in North China during the study period. Linkage analysis between the reconstructed runoff and large‐scale water vapor indicated that the high runoff years occurred during negative phases of the Pacific Decadal Oscillation, which may be influenced by the East Asian Summer Monsoon. Projections indicate that the flow of the Yongding River will increase in the future. Supported by policies such as the Ecological Water Supply and South‐to‐North Water Diversion, regional vegetation productivity and Yongding River runoff have increased substantially since 2000. Vegetation growth interacts with runoff volume. It is unclear how long these increases will continue.
More than just a name? From magnetic to optical skyrmions and the topology of light
Authors: Chen Jian , Forbes Andrew , Qiu Cheng-Wei 
Published: January 2025

AbstractTopology is usually perceived intrinsically immutable for a given object. We argue that optical topologies do not immediately enjoy such benefits. Using ‘optical skyrmions’ as an example, we show that they will exhibit varying textures and topological invariants (skyrmion numbers), depending on how to construct the skyrmion vector when projecting from real to parameter space. We demonstrate the fragility of optical skyrmions under a ubiquitous scenario--simple reflection off an optical mirror. Optical topology is not without benefit, but it must not be assumed.
Discoidin domain receptor 2 is an important modulator of BMP signaling during heterotopic bone formation
Authors: Wu Fashuai , Ge Chunxi , Pan Haichun , Han Yuanyuan , Mishina Yuji , Kaartinen Vesa , Franceschi Renny T. 
Published: January 2025

AbstractBone morphogenetic proteins are essential for bone regeneration/fracture healing but can also induce heterotopic ossification (HO). Understanding accessory factors modulating BMP signaling would provide both a means of enhancing BMP-dependent regeneration while preventing HO. This study focuses on the ability of the collagen receptor, discoidin domain receptor 2 (DDR2), to regulate BMP activity. As will be shown, induction of bone formation by subcutaneous BMP2 implants is severely compromised in Ddr2-deficient mice. In addition, Ddr2 deficiency attenuates HO in mice expressing the ACVR1 mutation associated with human fibrodysplasia ossificans progressiva. In cells migrating into BMP2 implants, DDR2 is co-expressed with GLI1, a skeletal stem cell marker, and DDR2/GLI1-positive cells participate in BMP2-induced bone formation where they contribute to chondrogenic and osteogenic lineages. Consistent with this distribution, conditional knockout of Ddr2 in Gli1-expressing cells inhibited bone formation to the same extent seen in globally Ddr2-deficient animals. This response was explained by selective inhibition of Gli1+ cell proliferation without changes in apoptosis. The basis for this DDR2 requirement was explored further using bone marrow stromal cells. Although Ddr2 deficiency inhibited BMP2-dependent chondrocyte and osteoblast differentiation and in vivo, bone formation, early BMP responses including SMAD phosphorylation remained largely intact. Instead, Ddr2 deficiency reduced the nuclear/cytoplasmic ratio of the Hippo pathway intermediates, YAP and TAZ. This suggests that DDR2 regulates Hippo pathway-mediated responses to the collagen matrix, which subsequently affect BMP responsiveness. In summary, DDR2 is an important modulator of BMP signaling and a potential therapeutic target both for enhancing regeneration and treating HO.
Vitamin D sensitizes cervical cancer to radiation-induced apoptosis by inhibiting autophagy through degradation of Ambra1
Authors: zhang Zhaoming , Yu Xinyue , Cheng Guanghui 
Published: January 2025

AbstractCervical cancer (CC) is becoming a major health issue globally, and radiotherapy plays a crucial role in its treatment. However, the prognosis of some patients remains poor due to tumor resistance to the therapy. This study aimed to explore whether vitamin D could confer a more radiosensitive phenotype in CC based on our previous findings and detection using the database. We found that vitamin D sensitized vitamin D receptor (VDR)-positive CC cells (Siha and Caski) to the cytotoxic effects of radiation in vivo and in vitro. We examined conventional radiation-induced cell death, such as DNA damage and cell cycle arrest, in vitamin D–treated cells to detect the underlying mechanism, but no association was observed between them. Subsequently, our proteome analysis exhibited that autophagy was reduced in irradiated CCs treated with vitamin D, and apoptosis displayed the opposite effect. Moreover, we confirmed that vitamin D-pretreated irradiated cells displayed reduced autophagy activity mediated by the Ambra1 downregulation, and the elevation of apoptosis was attributed to the activation of caspase 8. Importantly, the pharmacological inhibition of caspases or the Ambra1 overexpression could restore tumor proliferation under the vitamin D and radiation combination treatment. Hence, the aforementioned findings revealed the essential impact of vitamin D in terms of enhancing radiosensitivity in CC meditated by inhibiting autophagy and proposed the addition of vitamin D as a viable strategy to improve the therapeutic efficacy of VDR-positive CC.
Remodelling of the immune landscape by IFNγ counteracts IFNγ-dependent tumour escape in mouse tumour models
Authors: Lau Vivian W. C. , Mead Gracie J. , Varyova Zofia , Mazet Julie M. , Krishnan Anagha , Roberts Edward W. , Prota Gennaro , Gileadi Uzi , Midwood Kim S. , Cerundolo Vincenzo , Gérard Audrey 
Published: January 2025

AbstractLoss of IFNγ-sensitivity by tumours is thought to be a mechanism enabling evasion, but recent studies suggest that IFNγ-resistant tumours can be sensitised for immunotherapy, yet the underlying mechanism remains unclear. Here, we show that IFNγ receptor-deficient B16-F10 mouse melanoma tumours are controlled as efficiently as WT tumours despite their lower MHC class I expression. Mechanistically, IFNγ receptor deletion in B16-F10 tumours increases IFNγ availability, triggering a remodelling of the immune landscape characterised by inflammatory monocyte infiltration and the generation of ‘mono-macs’. This altered myeloid compartment synergises with an increase in antigen-specific CD8+ T cells to promote anti-tumour immunity against IFNγ receptor-deficient tumours, with such an immune crosstalk observed around blood vessels. Importantly, analysis of transcriptomic datasets suggests that similar immune remodelling occurs in human tumours carrying mutations in the IFNγ pathway. Our work thus serves mechanistic insight for the crosstalk between tumour IFNγ resistance and anti-tumour immunity, and implicates this regulation for future cancer therapy.
Experimental identification of topological defects in 2D colloidal glass
Authors: Vaibhav Vinay , Bera Arabinda , Liu Amelia C. Y. , Baggioli Matteo , Keim Peter , Zaccone Alessio 
Published: January 2025

AbstractTopological defects are singularities within a field that cannot be removed by continuous transformations. The definition of these irregularities requires an ordered reference configuration, calling into question whether they exist in disordered materials, such as glasses. However, recent work suggests that well-defined topological defects emerge in the dynamics of glasses, even if they are not evident in the static configuration. In this study, we reveal the presence of topological defects in the vibrational eigenspace of a two-dimensional experimental colloidal glass. These defects strongly correlate with the vibrational features and spatially correlate with each other and structural “soft spots”, more prone to plastic flow. This work experimentally confirms the existence of topological defects in disordered systems revealing the complex interplay between topology, disorder, and dynamics.
Gene-editing in patient and humanized-mice primary muscle stem cells rescues dysferlin expression in dysferlin-deficient muscular dystrophy
Authors: Escobar Helena , Di Francescantonio Silvia , Smirnova Julia , Graf Robin , Müthel Stefanie , Marg Andreas , Zhogov Alexej , Krishna Supriya , Metzler Eric , Petkova Mina , Daumke Oliver , Kühn Ralf , Spuler Simone 
Published: January 2025

AbstractDystrophy-associated fer-1-like protein (dysferlin) conducts plasma membrane repair. Mutations in the DYSF gene cause a panoply of genetic muscular dystrophies. We targeted a frequent loss-of-function, DYSF exon 44, founder frameshift mutation with mRNA-mediated delivery of SpCas9 in combination with a mutation-specific sgRNA to primary muscle stem cells from two homozygous patients. We observed a consistent >60% exon 44 re-framing, rescuing a full-length and functional dysferlin protein. A new mouse model harboring a humanized Dysf exon 44 with the founder mutation, hEx44mut, recapitulates the patients’ phenotype and an identical re-framing outcome in primary muscle stem cells. Finally, gene-edited murine primary muscle stem-cells are able to regenerate muscle and rescue dysferlin when transplanted back into hEx44mut hosts. These findings are the first to show that a CRISPR-mediated therapy can ameliorate dysferlin deficiency. We suggest that gene-edited primary muscle stem cells could exhibit utility, not only in treating dysferlin deficiency syndromes, but also perhaps other forms of muscular dystrophy.
Mitigating CaCO3 crystal nucleation and growth through continuous ion displacement via alternating electric fields
Authors: Liu Yiming , Xiao Minhao , Huang Xiaochuan , Park Jane , Hoffman Matthew E. , Feng Yuren , An Alicia Kyoungjin , Li Qilin , Hoek Eric M. V. , Jassby David 
Published: January 2025

AbstractMineral crystal formation poses a challenge on surfaces (e.g., heat exchangers, pipes, membranes, etc.) in contact with super-saturated fluids. Applying alternating currents (AC) to such surfaces can prevent surface crystallization under certain conditions. Here, we demonstrate that ion displacement induced by periodic charging and discharging of the electrical double layer (EDL) inhibits both heterogeneous and homogeneous nucleation (and crystal growth) of CaCO3. Titanium sheets (meant to simulate metallic heat exchanger surfaces) are immersed in super-saturated CaCO3 solutions with a saturation index >11. We show that at relatively high AC frequencies, incomplete EDL formation leads to an alternating electric field that propagates far into the bulk solution, inducing rapid ion migration that overwhelms the Brownian motion of ions. Electrochemical characterization reveals EDL charging/discharging under AC conditions that greatly inhibits precipitation. Operating at 4 Vpp, 0.1–10 Hz reduces turbidity by over 96% and reduces CaCO3 coverage on the metal plates by over 92%. Based on electrokinetic and crystallization models, the ion displacement velocity (exceeding the mean Brownian velocity) and displacement length disrupts ion collision and crystal nucleation. Overall, the technique has potential for preventing mineral crystal formation in heat exchangers and many other industrially relevant systems.
Deep learning and genome-wide association meta-analyses of bone marrow adiposity in the UK Biobank
Authors: Xu Wei , Mesa-Eguiagaray Ines , Morris David M. , Wang Chengjia , Gray Calum D. , Sjöström Samuel , Papanastasiou Giorgos , Badr Sammy , Paccou Julien , Li Xue , Timmers Paul R. H. J. , Timofeeva Maria , Farrington Susan M. , Dunlop Malcolm G. , Semple Scott I. , MacGillivray Tom , Theodoratou Evropi , Cawthorn William P. 
Published: January 2025

AbstractBone marrow adipose tissue is a distinct adipose subtype comprising more than 10% of fat mass in healthy humans. However, the functions and pathophysiological correlates of this tissue are unclear, and its genetic determinants remain unknown. Here, we use deep learning to measure bone marrow adiposity in the femoral head, total hip, femoral diaphysis, and spine from MRI scans of approximately 47,000 UK Biobank participants, including over 41,000 white and over 6300 non-white participants. We then establish the heritability and genome-wide significant associations for bone marrow adiposity at each site. Our meta-GWAS in the white population finds 67, 147, 134, and 174 independent significant single nucleotide polymorphisms, which map to 54, 90, 43, and 100 genes for the femoral head, total hip, femoral diaphysis, and spine, respectively. Transcriptome-wide association studies, colocalization analyses, and sex-stratified meta-GWASes in the white participants further resolve functional and sex-specific genes associated with bone marrow adiposity at each site. Finally, we perform a multi-ancestry meta-GWAS to identify genes associated with bone marrow adiposity across the different bone regions and across ancestry groups. Our findings provide insights into BMAT formation and function and provide a basis to study the impact of BMAT on human health and disease.
Immune correlates of early clearance of Mycobacterium tuberculosis among tuberculosis household contacts in Indonesia
Authors: Setiabudiawan Todia P. , Apriani Lika , Verrall Ayesha J. , Utami Fitria , Schneider Marion , Indrati Agnes R. , Halim Pauline P. , Kaplonek Paulina , Malca Hadar , Lee Jessica Shih-Lu , Moorlag Simone J. C. F. M. , de Bree L. Charlotte J. , Mourits Vera P. , Joosten Leo A. B. , Netea Mihai G. , Alisjahbana Bachti , McNamara Ryan P. , Alter Galit , van Laarhoven Arjan , Ussher James E. , Sharples Katrina , Koeken Valerie A. C. M. , Hill Philip C. , van Crevel Reinout 
Published: January 2025

AbstractSome individuals, even when heavily exposed to an infectious tuberculosis patient, do not develop a specific T-cell response as measured by interferon-gamma release assay (IGRA). This could be explained by an IFN-γ-independent adaptive immune response, or an effective innate host response clearing Mycobacterium tuberculosis (Mtb) without adaptive immunity. In heavily exposed Indonesian tuberculosis household contacts (n = 1347), a persistently IGRA negative status was associated with presence of a BCG scar, and - especially among those with a BCG scar - with altered innate immune cells dynamics, higher heterologous (Escherichia coli-induced) proinflammatory cytokine production, and higher inflammatory proteins in the IGRA mitogen tube. Neither circulating concentrations of Mtb-specific antibodies nor functional antibody activity associated with IGRA status at baseline or follow-up. In a cohort of adults in a low tuberculosis incidence setting, BCG vaccination induced heterologous innate cytokine production, but only marginally affected Mtb-specific antibody profiles. Our findings suggest that a more efficient host innate immune response, rather than a humoral response, mediates early clearance of Mtb. The protective effect of BCG vaccination against Mtb infection may be linked to innate immune priming, also termed ‘trained immunity’.
A higher order PUF complex is central to regulation of C. elegans germline stem cells
Authors: Qiu Chen , Crittenden Sarah L. , Carrick Brian H. , Dillard Lucas B. , Costa Dos Santos Stephany J. , Dandey Venkata P. , Dutcher Robert C. , Viverette Elizabeth G. , Wine Robert N. , Woodworth Jennifer , Campbell Zachary T. , Wickens Marvin , Borgnia Mario J. , Kimble Judith , Hall Traci M. Tanaka 
Published: January 2025

AbstractPUF RNA-binding proteins are broadly conserved stem cell regulators. Nematode PUF proteins maintain germline stem cells (GSCs) and, with key partner proteins, repress differentiation mRNAs, including gld-1. Here we report that PUF protein FBF-2 and its partner LST-1 form a ternary complex that represses gld-1 via a pair of adjacent FBF binding elements (FBEs) in its 3′UTR. One LST-1 molecule links two FBF-2 molecules via motifs in the LST-1 intrinsically-disordered region; the gld-1 FBE pair includes a well-established ‘canonical’ FBE and a newly-identified noncanonical FBE. Remarkably, this FBE pair drives both full RNA repression in GSCs and full RNA activation upon differentiation. Discoveries of the LST-1–FBF-2 ternary complex, the gld-1 adjacent FBEs, and their in vivo significance predict an expanded regulatory repertoire of different assemblies of PUF-partner-RNA higher order complexes in nematode GSCs. This also suggests analogous PUF controls may await discovery in other biological contexts and organisms.
A simple model for Behavioral Time Scale Synaptic Plasticity (BTSP) provides content addressable memory with binary synapses and one-shot learning
Authors: Wu Yujie , Maass Wolfgang 
Published: January 2025

Abstract
Recent experimental studies in the awake brain have identified a rule for synaptic plasticity that is instrumental for the instantaneous creation of memory traces in area CA1 of the mammalian brain: Behavioral Time scale Synaptic Plasticity. This one-shot learning rule differs in five essential aspects from previously considered plasticity mechanisms. We introduce a transparent model for the core function of this learning rule and establish a theory that enables a principled understanding of the system of memory traces that it creates. Theoretical predictions and numerical simulations show that our model is able to create a functionally powerful content-addressable memory without the need for high-resolution synaptic weights. Furthermore, it reproduces the repulsion effect of human memory, whereby traces for similar memory items are pulled apart to enable differential downstream processing. Altogether, our results create a link between synaptic plasticity in area CA1 of the hippocampus and its network function. They also provide a promising approach for implementing content-addressable memory with on-chip learning capability in highly energy-efficient crossbar arrays of memristors.
Functional protein mining with conformal guarantees
Authors: Boger Ron S. , Chithrananda Seyone , Angelopoulos Anastasios N. , Yoon Peter H. , Jordan Michael I. , Doudna Jennifer A. 
Published: January 2025

AbstractMolecular structure prediction and homology detection offer promising paths to discovering protein function and evolutionary relationships. However, current approaches lack statistical reliability assurances, limiting their practical utility for selecting proteins for further experimental and in-silico characterization. To address this challenge, we introduce a statistically principled approach to protein search leveraging principles from conformal prediction, offering a framework that ensures statistical guarantees with user-specified risk and provides calibrated probabilities (rather than raw ML scores) for any protein search model. Our method (1) lets users select many biologically-relevant loss metrics (i.e. false discovery rate) and assigns reliable functional probabilities for annotating genes of unknown function; (2) achieves state-of-the-art performance in enzyme classification without training new models; and (3) robustly and rapidly pre-filters proteins for computationally intensive structural alignment algorithms. Our framework enhances the reliability of protein homology detection and enables the discovery of uncharacterized proteins with likely desirable functional properties.
ZIC1 is a context-dependent medulloblastoma driver in the rhombic lip
Authors: Lee John J. Y. , Tao Ran , You Zhen , Haldipur Parthiv , Erickson Anders W. , Farooq Hamza , Hendriske Liam D. , Abeysundara Namal , Richman Cory M. , Wang Evan Y. , Das Gupta Neha , Hadley Jennifer , Batts Melissa , Mount Christopher W. , Wu Xiaochong , Rasnitsyn Alex , Bailey Swneke , Cavalli Florence M. G. , Morrissy Sorana , Garzia Livia , Michealraj Kulandaimanuvel Antony , Visvanathan Abhi , Fong Vernon , Palotta Jonelle , Suarez Raul , Livingston Bryn G. , Liu Miao , Luu Betty , Daniels Craig , Loukides James , Bendel Anne , French Pim J. , Kros Johan M. , Korshunov Andrey , Kool Marcel , Chico Ponce de León Fernando , Perezpeña-Diazconti Mario , Lach Boleslaw , Singh Sheila K. , Leary Sarah E. S. , Cho Byung-Kyu , Kim Seung-Ki , Wang Kyu-Chang , Lee Ji-Yeoun , Tominaga Teiji , Weiss William A. , Phillips Joanna J. , Dai Shizhong , Zadeh Gelareh , Saad Ali G. , Bognár László , Klekner Almos , Pollack Ian F. , Hamilton Ronald L. , Ra Young-shin , Grajkowska Wieslawa A. , Perek-Polnik Marta , Thompson Reid C. , Kenney Anna M. , Cooper Michael K. , Mack Stephen C. , Jabado Nada , Lupien Mathieu , Gallo Marco , Ramaswamy Vijay , Suva Mario L. , Suzuki Hiromichi , Millen Kathleen J. , Huang L. Frank , Northcott Paul A. , Taylor Michael D. 
Published: January 2025

Abstract
Transcription factors are frequent cancer driver genes, exhibiting noted specificity based on the precise cell of origin. We demonstrate that ZIC1 exhibits loss-of-function (LOF) somatic events in group 4 (G4) medulloblastoma through recurrent point mutations, subchromosomal deletions and mono-allelic epigenetic repression (60% of G4 medulloblastoma). In contrast, highly similar SHH medulloblastoma exhibits distinct and diametrically opposed gain-of-function mutations and copy number gains (20% of SHH medulloblastoma). Overexpression of ZIC1 suppresses the growth of group 3 medulloblastoma models, whereas it promotes the proliferation of SHH medulloblastoma precursor cells. SHH medulloblastoma ZIC1 mutants show increased activity versus wild-type ZIC1, whereas G4 medulloblastoma ZIC1 mutants exhibit LOF phenotypes. Distinct ZIC1 mutations affect cells of the rhombic lip in diametrically opposed ways, suggesting that ZIC1 is a critical developmental transcriptional regulator in both the normal and transformed rhombic lip and identifying ZIC1 as an exquisitely context-dependent driver gene in medulloblastoma.
Exploring the effects of perceived social support and psychological distress through mediation and multigroup analyses in work-related quality of life
Authors: Yılmaz Sıdıka Ece , Çıtak Şenel 
Published: January 2025

AbstractWork-related quality of life has emerged as a central focus in the field of occupational health due to its impact on individual well-being and overall quality of life. So, it is crucial to enhance the current theory by conducting a study on the concept across different sectors. Also, the specific mechanisms through which perceived social support influences work-related quality of life remain underexplored. The role of psychological distress as a potential mediator in this relationship has not been investigated. Thus, the study aimed to explore the mediating role of psychological distress in this relationship, while also examining potential gender differences. The study, conducted with 401 teachers through a questionnaire, utilized the AMOS program for data analysis. The findings supported the direct effects among the variables and the mediating role of psychological distress. Additionally, the impact of psychological distress on work-related quality of life was found to be higher for females, but no differences for other paths. The study contributes to the literature by addressing the gap in understanding the mechanisms regarding work-related quality of life. The results highlight the importance of considering psychological distress and gender differences in interventions aimed at improving work-related quality of life.