bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutation hot spots for clinical pathogenicity across the SLC6 transporter family
Authors: Huang Jiahui , Digles Daniela , Ecker Gerhard F. 
Published: January 2025

AbstractGenetic mutations of the Solute Carrier 6 (SLC6) family can lead to a diversity of clinal syndromes, such as creatine deficiency. Studying the impact of genetic mutations at the SLC6 family level is valuable not only for their medical significance but also for their conserved sequence and structural features. Within this work, we aim to link the disease-related mutations to their clinical significance from protein-protein interactions (PPIs) perspective, addressing how particular mutations may affect these critical interaction hotspots.In this study, we integrated both curated mutation data from previous work and predictive output from AlphaMissense to examine the entire SLC6 family. The mutations were mapped both onto the sequences and structures of SLC6 transporters. Thereby, a clustering of pathogenic mutations appeared on the surface regions that are likely involved in PPIs. After modeling complexes of SLC6s with potential shared interactors, we assessed these models overall and interface quality. By analyzing the complex interfaces together with the pathogenic mutations, we identified specific hotspots in the interfaces enriched with pathogenic mutations. In-depth examinations of selected PPIs offered insights into how particular mutations may affect these critical interaction hotspots.The hotspots were identified on the ECL3 and ECL4. For instance, Thr394Lys in SLC6A8 was found in the model interfaces, supported by experimental data showing the significant enrichment of the mutated proteins in the ER. Understanding these mutation hotspots can shed light on the broader structure-function relationships of SLC6 transporters and encourage therapeutic interventions targeting protein-protein interactions affected by pathogenic mutations.
LGBTQ+ realities in the biological sciences
Authors: Cooper Katelyn M. , Busch Carly A. , Accorsi Alice , Applewhite Derek A. , Bhanderi Parth B. , da Rocha-Azevedo Bruno , Roy Abhijit Deb , Campanale Joseph P. , Chang Fred , Chipuk Jerry E. , Ligon Lee A. , Luxton G.W. Gant , Graham Austin J. , Hochman-Mendez Camila , Ozugergin Imge , Park Zachory M. , Thomas Claire M. , Valm Alex M. , Zhu Hongxian , Alvania Rebecca S. 
Published: January 2025

AbstractWhile scientific environments have been described as unwelcoming to the LGBTQ+ community, and fields like physics have systematically documented these challenges, the climate in biology workplaces has not been assessed. We conducted the largest survey to date of LGBTQ+ experiences in biology, including 1419 biologists across five professional societies, with 486 identifying as LGBTQ+. Trans and gender non-conforming (TGNC) biologists reported lower belonging and morale within the workplace, professional societies, and the biology community compared to cis, straight biologists. They also reported being less comfortable with the climate of various professional biology environments. While LGBTQ+ biologists report that their workplaces are moderately inclusive, over 20% of all LGBTQ+ biologists and nearly 40% of TGNC biologists experience exclusionary behavior at work. This landmark survey provides the first comprehensive analysis of the LGBTQ+ climate in biology, revealing specific challenges faced by TGNC scientists and identifying interventions to enhance inclusivity for scientists.TeaserClimate study for LGBTQ+ biologists highlights exclusion of trans and gender nonconforming scientists.
Isolation of a novel plant growth-promotingDyellasp. from a Danish natural soil
Authors: Dethier Laura , Jespersen J. Rasmus P. , Lloyd Jemma , Pupi Elena , Zhou Wanru , Liu Fang , Bai Yang , Halkier Barbara Ann , Xu Deyang 
Published: January 2025

AbstractEnvironmental soils are natural reservoirs of unexplored microbes, including potentially beneficial microbes to improve plant performance. Here, we isolated 75 bacterial strains from surface-sterilized roots ofArabidopsis thaliana(Arabidopsis) grown in a natural soil derived from an alder swamp. Culture-dependent isolation of individual strains from the roots followed by monoassociation-based screening identified seven bacteria that promoted Arabidopsis seedling weight. Of those, we identified a new species from theDyellagenus which increased biomass of tomato and Arabidopsis seedlings in agar as well as the shoot biomass of Arabidopsis grown in both the alder swamp soil and potting soil.Dyella sp. A4 specifically promoted the elongation of lateral roots without affecting lateral root number and primary root elongation. The newDyella sp. A4 expands the toolbox of biostimulants for plant growth promotion via modulating root architecture.
Met-ID: An Open-Source Software for Comprehensive Annotation of Multiple On-Tissue Chemical Modifications in MALDI-MSI
Authors: Bjärterot Patrik , Nilsson Anna , Shariatgorji Reza , Vallianatou Theodosia , Kaya Ibrahim , Svenningsson Per , Käll Lukas , Andrén Per E. 
Published: January 2025

ABSTRACTHere, we introduce Met-ID, a graphical interface software designed to efficiently identify metabolites from MALDI-MSI datasets. Met-ID enables annotation ofm/zfeatures from any type of MALDI-MSI experiment, involving either derivatizing or conventional matrices. It utilizes structural information for derivatizing matrices to generate a subset of targets that contain only functional groups specific to the derivatization agent. The software is able to identify multiple derivatization sites on the same molecule, facilitating identification of the derivatized compound. This ability is exemplified by FMP-10, a reactive matrix that assists the covalent charge-tagging of molecules containing phenolic hydroxyl and/or primary or secondary amine groups. Met-ID also permits users to recalibrate data with knownm/zratios, boosting confidence in mass match results. Furthermore, Met-ID includes a database featuring MS2 spectra of numerous chemical standards, consisting of neurotransmitters and metabolites derivatized with FMP-10, alongside peaks for FMP-10 itself, all accessible directly through the software. The MS2 spectral database supports user-uploaded spectra and enables comparison of these spectra with user-provided tissue MS2 spectra for similarity assessment. Although initially installed with basic data, Met-ID is designed to be customizable, encouraging users to tailor the software to their specific needs. While several MSI-oriented software solutions exist, Met-ID stands out as a pioneer in seamlessly combining both MS1 and MS2 functionalities. Developed in alignment with the FAIR Guiding Principles for scientific software, Met-ID is freely available as an open-source tool on GitHub, ensuring wide accessibility and collaboration.
Bcl-2 Oligomerizes Bax on the Mitochondrial Membrane Surface Preventing the Initial Stages of Apoptosis
Authors: Ayscough Sophie E. , Clifton Luke A. , Ådén Jörgen , Köhler Sebastian , Paracini Nicolò , Doutch James , Bragginton Éilís C , Leung Anna. E. , Bogojevic Oliver , Poon Jia-Fei , Nagy Tamás Milán , Wacklin-Knecht Hanna P. , Gröbner Gerhard 
Published: January 2025

AbstractThe Bcl-2 family of proteins control mitochondrial outer membrane (MOM) pore formation, crucial to cellular clearanceviaapoptosis. However, the molecular principles by which opposing family members inhibit, mediate or promote MOM perforation remain elusive. Here, we demonstrate that cell-protecting Bcl-2 directly sequesters cell-killing Bax into a protein-protein complex at the membrane interface preventing Bax forming apoptotic pores. Neutron reflectometry showed Bax association with Bcl-2 occurs through the formation of Bax protein oligomers on the membrane surface. Bax binding to the membrane surface was proportional to the membrane-embedded Bcl-2 suggestive of protein-protein complex formation through both Bcl-2/Bax and Bax/Bax interactions. Bcl-2/Bax sequestration to prevent perforation was observed in membrane models with and without pro-apoptotic cardiolipin present. Our findings shed fundamental new light on the communication of Bcl-2 with its cell-killing relatives at the mitochondriás membraneous exterior to prevent cells from undergoing apoptosis.TeaserMembrane-embedded Bcl-2 sequesters Bax, to prevent the perforation of mitochondrial membranes by Bax which would initiate apoptosis.
Survival Reinforced Transfer Learning for Multicentric Proteomic Subtyping and Biomarker Discovery
Authors: Xie Linhai , Jiang Pei , Chang Cheng 
Published: January 2025

AbstractOmics-based molecular subtyping in large-scale and multicentric cohort studies is a prerequisite for proteomics-driven precision medicine (PDPM). However, keeping the subtypes with robust molecular features and significant associations with prognosis among different cohorts is challenging due to the biological heterogeneity and technical inconsistency. Herein, we propose a subtyping algorithm, named Survival Reinforced Patient Stratification (SRPS), to adapt the known subtypes from the discovery cohort to another by simultaneously preserving the distinct prognosis and molecular characteristics of each subtype. SRPS has been benchmarked on simulated and real-world datasets, where it shows a 12% increase in classification accuracy and possesses the best prognostic discriminations. Moreover, based on the calculated subtype significance score, an ‘unpopular’ protein, Peptidylprolyl Isomerase C (PPIC), was identified as the top-1 remarkable protein for subtyping the hepatocellular carcinoma (HCC) patients with the worst prognosis. Eventually, PPIC was experimentally proved to be a pro-cancer protein in HCC, confirming our work as a practice of interpretable machine learning guided biological discovery in PDPM research.
Alpha-Synuclein co-pathology in Alzheimer’s Disease drives tau accumulation
Authors: Struebing Felix L. , De Vecchi Teodoro , Widmann Jeannine , Song Xiaoxuan , Fierli Federico , Ruf Viktoria , Tang Qilin , Arzberger Thomas , Roeber Sigrun , Koeglsperger Thomas , Windl Otto , Haass Christian , Winkelmann Juliane , Herms Jochen 
Published: January 2025

AbstractThe molecular basis for accelerated cognitive decline seen in Alzheimer’s Disease (AD) cases presenting with cortical alpha-Synuclein (α-Syn) co-pathology is not well understood. We show that such co-pathology brains express higher levels of microtubule-associated protein tau and that increasing α-Syn expression is sufficient to drive tau accumulation. Our results reveal a hitherto unknown link between the pathogenesis of AD and Parkinson’s Disease whereby tau and α-Syn synergistically drive dementia-related pathology.
A novel mouse model of voluntary stretching and its application in breast cancer research
Authors: He Yi , Berrueta Lisbeth , Wang Yan , Badger Gary J. , Langevin Helene M. 
Published: January 2025

AbstractBackgroundStretching exercises such as yoga are recommended for cancer survivors to manage symptoms and promote wellbeing in clinical settings. Although other types of exercise (e.g. running) can reduce the growth of tumors in animal models, the role of stretching on tumor growth remains unclear, and the lack of a preclinical self-stretching model has impeded mechanistic studies on health benefits of stretching. We sought to develop a voluntary stretching animal model to address this research gap and apply it to breast cancer research.MethodsUsing food, water, and enrichment in the home cage as motivators for stretching, a two-week 24/7 behavior monitoring was conducted in a video-based customizable home-cage behavior tracking system, Noldus PhenoTyper, to promote self-stretching in FVB mice. Subsequently, this model was utilized in a comparative study of voluntary stretching and voluntary running on tumor growth and plasma protein profiles in the MET-1 orthotopic mammary tumor FVB mouse model.ResultsThe new voluntary stretching model effectively elicited mouse self-stretching in the custom cage setting in the long-term observation and significantly inhibited tumor growth as effectively as voluntary wheel running. Moreover, plasma proteomic analysis demonstrated that voluntary stretch versus voluntary running distinctly impacted systemic protein profiles, possibly linking to different cellular and molecular mechanisms underlying anti-cancer effects and, potentially, exercise-induced benefits in other health conditions.ConclusionOur work provides the first preclinical voluntary stretching model, which may be well suited to breast cancer research and a valuable research tool to facilitate investigations of stretching health benefits across various research fields.
Single Cell Spatial Transcriptomics Reveals Immunotherapy-Driven Bone Marrow Niche Remodeling in AML
Authors: Gui Gege , Bingham Molly A. , Herzog Julius R. , Wong-Rolle Abigail , Dillon Laura W. , Goswami Meghali , Martin Eddie , Reeves Jason , Kim Sean , Bahrami Arya , Degenhardt Hermann , Zaki George , Divakar Prajan , Schrom Edward C , Calvo Katherine , Hourigan Christopher S. , Hansen Kasper , Zhao Chen 
Published: January 2025

SummaryGiven the successful graft-versus-leukemia cell treatment effect observed with allogeneic hematopoietic stem cell transplant for patients with refractory or relapsed acute myeloid leukemia, immunotherapies have also been investigated in the nontransplant setting. Here, we use a multi-omic approach to investigate spatiotemporal interactions in the bone marrow niche between leukemia cells and immune cells in patients with refractory or relapsed acute myeloid leukemia treated with a combination of the immune checkpoint inhibitor pembrolizumab and hypomethylating agent decitabine. We derived precise segmentation data by extensively training nuclear and membrane cell segmentation models, which enabled accurate transcript assignment and deep learning-feature-based image analysis. To overcome read-depth limitations, we integrated the single-cell RNA sequencing data with single-cell-resolution spatial transcriptomic data from the same sample. Quantifying cell-cell distances between cell edges rather than cell centroids allowed us to conduct a more accurate downstream analysis of the tumor microenvironment, revealing that multiple cell types of interest had global enrichment or local enrichment proximal to leukemia cells after pembrolizumab treatment, which could be associated with their clinical responses. Furthermore, ligand-receptor analysis indicated a potential increase inTWEAKsignaling between leukemia cells and immune cells after pembrolizumab treatment.HighlightsSpatial transcriptomic analysis of R-AML bone marrow niches provides detailed information about intercellular interactions in the tumor microenvironment.Immunotherapy shifts the cell composition of the leukemia neighborhood.Graphical abstract
SpaIM: Single-cell Spatial Transcriptomics Imputation via Style Transfer
Authors: Li Bo , Tang Ziyang , Budhkar Aishwarya , Liu Xiang , Zhang Tonglin , Yang Baijian , Su Jing , Song Qianqian 
Published: January 2025

ABSTRACTSpatial transcriptomics (ST) technologies have revolutionized our understanding of cellular ecosystems. However, these technologies face challenges such as sparse gene signals and limited gene detection capacities, which hinder their ability to fully capture comprehensive spatial gene expression profiles. To address these limitations, we propose leveraging single-cell RNA sequencing (scRNA-seq), which provides comprehensive gene expression data but lacks spatial context, to enrich ST profiles. Herein, we introduce SpaIM, an innovative style transfer learning model that utilizes scRNA-seq information to predict unmeasured gene expressions in ST data, thereby improving gene coverage and expressions. SpaIM segregates scRNA-seq and ST data into data-agnostic contents and data-specific styles, with the contents capture the commonalities between the two data types, while the styles highlight their unique differences. By integrating the strengths of scRNA-seq and ST, SpaIM overcomes data sparsity and limited gene coverage issues, making significant advancements over 12 existing methods. This improvement is demonstrated across 53 diverse ST datasets, spanning sequencing- and imaging-based spatial technologies in various tissue types. Additionally, SpaIM enhances downstream analyses, including the detection of ligand-receptor interactions, spatial domain characterization, and identification of differentially expressed genes. Released as open-source software, SpaIM increases accessibility for spatial transcriptomics analysis. In summary, SpaIM represents a pioneering approach to enrich spatial transcriptomics using scRNA-seq data, enabling precise gene expression imputation and advancing the field of spatial transcriptomics research.
scGraphETM: Graph-Based Deep Learning Approach for Unraveling Cell Type-Specific Gene Regulatory Networks from Single-Cell Multi-Omics Data
Authors: Dong Wenqi , Zhou Manqi , Han Boyu , Wang Fei , Li Yue 
Published: January 2025

AbstractIn the forefront of single-cell multi-omics research, the challenge of elucidating intricate gene regulatory networks (GRNs) at a cellular level is paramount. This study introduces the Single Cell Graph Network Embedded Topic Model (scGraphETM), a novel computational approach aimed at unraveling the complexities of cell-specific GRNs from multiomics single-cell sequencing data. Central to our investigation is the integration of single-cell RNA sequencing and single-cell ATAC sequencing data, leveraging the strengths of both to uncover the underpinnings of cellular regulation. The scGraphETM model innovatively combines a variational autoencoder framework with a graph neural network. By conceptualizing transcription factors (TFs), genes, and regulatory elements (RE) as nodes, and their regulatory interactions as edges, the model adeptly captures the dynamic regulatory interplay within cells. It uniquely incorporates both universal and cell-specific features, enabling the model to generalize across cell populations while also identifying unique regulatory dynamics within individual cells. Our results reveal that scGraphETM surpasses existing methodologies in accurately modeling cell-type clustering, cross-modality imputation and cell-type specific TF-RE relationships.
ECD functions as a novel RNA-binding protein to regulate mRNA splicing
Authors: Raza Mohsin , Rajan Asher Rajkumar , Kalluchi Achyuth , Saleem Irfana , Kennedy Benjamin B. , Bhakat Kishor K. , Band Hamid , Rowley M. Jordan , Band Vimla 
Published: January 2025

AbstractThe human ecdysoneless protein (ECD) plays an essential role in the regulation of cell cycle and cell survival. ECD has been implicated in RNA splicing through its association with the protein components of splicing complex. Here, using electrophoretic mobility shift assay and mutational analysis, we demonstrate that ECD directly binds to RNA through its N-terminal region, specifically using amino acids 135-148. Using enhanced CLIP-seq analyses in human cells, we identified a large repertoire of mRNAs bound to ECD. RNA-seq analyses revealed that ECD depletion in cells leads to widespread RNA splicing aberrations associated with alterations in gene expression. Significantly, we demonstrate that ECD mediates mRNA splicing by directly binding to RNA sequences located near splicing sites. Mechanistically, we demonstrate that ECD directly binds to U5 small nuclear RNA (snRNA), and this interaction is critical for maintaining the expression of key protein components of U5 small nuclear protein (snRNP) complex. Notably, RNA binding defective mutant of ECD fails to rescue downregulated levels of U5 snRNP components or cell proliferation block induced by ECD knockout. Collectively, we provide compelling evidence that ECD regulates RNA splicing by directly associating with RNAs, and the RNA binding activity of ECD is essential for its function.
Performance of an Electroencephalography-Measuring Headband or Actigraphy Compared with Polysomnography in Older Adults with Sleep Disturbances
Authors: Miner Brienne , Pan Yulu , Cho Gawon , Talarczyk Jarett , Chen Anne , Burzynski Chase , Polisetty Lakshmi , Doyle Margaret , Iannone Lynne , Mejnartowicz Slawomir , Breier Richard A. , Gill Thomas M. , Yaggi Henry K. , Knauert Melissa 
Published: January 2025

ABSTRACTStudy ObjectivesIn older adults, self-reported sleep measures may be inaccurate, but polysomnography (PSG) is burdensome. We assessed the performance of an electroencephalography-measuring headband (HB) or actigraphy (ACT) compared with PSG in older adults with sleep disturbances.MethodsSixty-three adults aged ≥60 years who reported symptoms of insomnia and/or daytime sleepiness ≥once/week completed a week-long, home-based protocol during which they wore the HB for seven nights, an actigraph for seven days and nights, and completed a one-night level II unattended PSG. For the current analysis, we compared total sleep time (TST) and wake after sleep onset (WASO) from all three devices on the PSG night. We calculated absolute differences and intraclass correlation coefficients (ICCs) for TST and WASO between HB and ACT, respectively, vs. PSG. We also evaluated the performance of the HB among subgroups of the poorest sleepers according to the presence of sleep apnea, insomnia, poor sleep quality, and periodic limb movements of sleep. Feasibility of the HB was assessed by measures of adherence (i.e., ability to use the HB over seven nights) and usability (i.e., ratings of items from the WEarable Acceptability Range [WEAR] scale).ResultsThe average age was 72.8 [standard deviation 6.6] years, 63.5% were female, and 63.5% identified as non-Hispanic White. On PSG, averages for TST and WASO were 370.1 [93] and 88.9 [63] minutes, respectively. For the HB vs. PSG, mean differences and ICCs were -11.9 minutes and 0.83 [0.74, 0.89] for TST; and -15.5 minutes and 0.65 [0.48, 0.77] for WASO. For ACT vs. PSG, mean differences for TST and WASO were larger, and ICCs showed lower levels of agreement. The HB performed well among the poorest sleepers, with ICCs >0.65 for TST and WASO. On average, participants wore the HB for 6.5 [0.8] nights, and usability was rated highly.ConclusionsThe HB demonstrated good agreement with PSG, outperforming ACT, including among the poorest sleepers. Devices like the HB might provide feasible measures of sleep that are more accurate than ACT and enhance the management of sleep health in older adults with sleep disturbances. Future research should focus on further validation of these devices in habitual sleep environments.