bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimizing Exome Captures in Species with Large Genomes Using Species-specific Repetitive DNA Blocker
Authors: Kesälahti Robert , Kumpula Timo A. , Cervantes Sandra , Kujala Sonja T. , Mattila Tiina M. , Tyrmi Jaakko S. , Niskanen Alina K. , Rastas Pasi , Savolainen Outi , Pyhäjärvi Tanja 
Published: April 2024

AbstractLarge and highly repetitive genomes are common. However, research interests usually lie within the non-repetitive parts of the genome, as they are more likely functional, and can be used to answer questions related to adaptation, selection, and evolutionary history. Exome capture is a cost-effective method for providing sequencing data from protein-coding parts of the genes. C0t-1 DNA blockers consist of repetitive DNA and are used in exome captures to prevent the hybridization of repetitive DNA sequences to capture baits or bait-bound genomic DNA. Universal blockers target repetitive regions shared by many species, while species-specific c0t-1 DNA is prepared from the DNA of the studied species, thus perfectly matching the repetitive DNA contents of the species. So far the use of species-specific c0t-1 DNA has been limited to a few model species. Here, we evaluated the performance of blocker treatments in exome captures ofPinus sylvestris, a widely distributed conifer species with a large (> 20 Gbp) and highly repetitive genome. We compared treatment with a commercial universal blocker to treatments with species-specific c0t-1 (30,000 ng and 60,000 ng). Species-specific c0t-1 captured more unique exons than the initial set of targets, reduced sequencing of tandem repeats, and produced more target regions with high read coverage and narrower depth distribution than the universal blocker. Based on our results, we recommend optimizing exome captures by using at least 60,000 ng species-specific c0t-1 DNA. It is relatively easy and fast to prepare and can also be used with existing bait set designs.
Mind Captioning: Evolving descriptive text of mental content from human brain activity
Authors: Horikawa Tomoyasu 
Published: April 2024

AbstractA central challenge in neuroscience is decoding brain activity to uncover mental content comprising multiple components and their interactions. Despite progress in decoding language-related information from human brain activity, generating comprehensive descriptions of complex mental content associated with structured visual semantics remains challenging. We present a method that generates descriptive text mirroring brain representations via semantic features computed by a deep language model. Constructing linear decoding models to translate brain activity induced by videos into semantic features of corresponding captions, we optimized candidate descriptions by aligning their features with brain-decoded features through word replacement and interpolation. This process yielded well-structured descriptions faithfully capturing viewed content, even without relying on the canonical language network, thereby revealing explicit representations of fine-grained structured semantic information outside this network. The method also successfully generalized to verbalize recalled content, demonstrating the potential for non-verbal thought-based brain-to-text communication, which could aid individuals with language expression difficulties.
Evolutionary history of the main extracellular matrix polysaccharides in brown algae
Authors: Hervé Lisa , Bouguerba-Collin Ahlem , Cock J. Mark , Denoeud France , Godfroy Olivier , Brillet-Guéguen Loraine , Barbeyron Tristan , Lipinska Agnieszka P. , Delage Ludovic , Corre Erwan , Drula Elodie , Henrissat Bernard , Czjzek Mirjam , Terrapon Nicolas , Hervé Cécile 
Published: April 2024

AbstractBrown algae belong to the Stramenopiles phylum and are phylogenetically distant from plants and other multicellular organisms. This independent evolutionary history has shaped brown algae with numerous metabolic characteristics specific to this group, including the synthesis of peculiar polysaccharides contained in their extracellular matrix (ECM). Alginates and fucose-containing sulphated polysaccharides (FCSP), the latter including fucans, are the main components of ECMs. However, the metabolic pathways of these polysaccharides remain poorly described due to a lack of genomic data. An extensive genomic dataset has been recently released for brown algae and their close sister species. We performed an expert annotation of key genes involved in ECM-carbohydrate metabolisms, combined with comparative genomics, phylogenetics analyses, and protein modelling. Our analysis indicates that the gene families involved in both the synthesis and degradation of alginate were acquired by the common ancestor of brown algae and their closest sister speciesSchizocladia ischiensis, and subsequently expanded in brown algae. The pathway for the biosynthesis of fucans still remains biochemically unresolved and we identify the most likely fucosyltransferase genes that may harbour a fucan synthase activity in brown algae. Our analysis questions the possible occurrence of FCSPs outside brown algae, notably within their closest sister taxon.
Chloroquine attenuates hypoxia-mediated autophagy to curb thrombosis- anex vivoandin vivostudy
Authors: Bandyopadhyay Propanna , Katakia Yash T. , Mukherjee Sudeshna , Majumder Syamantak , Chowdhury Shibasish , Chowdhury Rajdeep 
Published: April 2024

AbstractBackgroundHypoxia can trigger the activation of blood platelets, leading to thrombosis. If not addressed clinically, it can cause severe complications and fatal consequences as well. The current treatment regime for thrombosis is often palliative and includes long-term administration of anticoagulants, which has the risk of over-bleeding in injury and other secondary effects as well. This demands a deeper understanding of the process and exploration of an alternative therapeutic avenue. Interestingly, recent studies demonstrate that platelets though atypical and enucleated, possess components of autophagy machinery. This cellular homeostatic process though well-studied in non-platelet cells, is under-explored in platelets.MethodsIn this study, we report an activation of autophagy in rat-derived platelets cultured under physiologically relevant hypoxic condition (10% O2)ex vivo. Furthermore, autophagy was triggeredin vivowhen rats were exposed to hypobaric hypoxic conditions. Subsequently, restriction or surgical ligation of the inferior vena cava (IVC) was performed to induce thrombus formation. Post confirming the impact of autophagy induction on platelet functioning, it was inhibited, and then platelet activation and aggregation status were evaluated using light transmission aggregometry, flow cytometry, immunofluorescence and immunoblotting.ResultsHerein, we show that autophagy inhibition with the potent autophagy inhibitor-CQ, a repurposed FDA-approved drug, can significantly reduce platelet activation, both inex vivoandin vivosettings. CQ withdrawal reversed the phenomenon indicating a dynamic effect. Thereafter, in flow restriction or surgical ligation model, interestingly, CQ-pre-treated rats showed reduced clotting ability. Importantly, CQ at the stipulated dose was found to be non-toxic to the tissues, as analyzed through histological staining.ConclusionThus, we propose that the repurpose of the FDA approved drug CQ can attenuate hypoxia-induced thrombosis through inhibition of autophagy and can be explored as an effective therapeutic alternative.HighlightsExposure ofex-vivocultured platelets to physiologically relevant hypoxic condition (O2concentration) can induce autophagy causing them to get activated and eventually aggregate.FDA approved drug chloroquine (CQ) is able to inhibit autophagy in anucleate cellular fragments, platelets, similar to nucleated cells and curb platelet functioning under hypoxic condition in bothex-vivoandin-vivomodel.Flow restriction model mimicking deep vein thrombosis, emphasizes on the effect of CQ on impeding thrombus formation when used at a non-toxic dosage.
Ferroptosis Inhibition Combats Metabolic Derangements and Improves Cardiac Function in Pulmonary Artery Banded Pigs
Authors: Kazmirczak Felipe , Moon Ryan , Vogel Neal T. , Tollison Walt , T.Lahti Matt , Carney John P. , Mendelson Jenna B , Markowski Todd , Higgins LeeAnn , Murray Kevin , Guerrero Candace , Prins Kurt W. 
Published: April 2024

AbstractRight heart failure (RHF) is a leading cause of mortality in multiple cardiovascular diseases and preclinical and human data suggest impaired metabolism is a significant contributor to right-sided cardiac dysfunction. Ferroptosis is a nonapopotic form of cell death driven by impaired metabolism. Rodent data suggests ferroptosis inhibition can restore mitochondrial electron transport chain function and enhance cardiac contractility in left heart failure models, but the effects of ferroptosis inhibition in translational large animal models of RHF are unknown. Here, we showed ferrostatin-1 mediated ferroptosis antagonism improve right heart structure and function in pulmonary artery banded pigs. Molecularly, ferrostatin-1 restored mitochondrial cristae structure and combatted downregulation of electron transport chain proteins. Metabolomics and lipidomics analyses revealed ferrostatin-1 improved fatty acid metabolism. Thus, these translational data suggest ferroptosis may be a therapeutic target for RHF.Graphical Abstract
A cross ancestry genetic study of psychiatric disorders from India
Authors: Holla Bharath , Mahadevan Jayant , Ganesh Suhas , Sud Reeteka , Janardhanan Meghana , Balachander Srinivas , Strom Nora , Mattheisen Manuel , Sullivan Patrick F , Huang Hailiang , Zandi Peter , Benegal Vivek , Reddy YC Janardhan , Jain Sanjeev ,   cVEDA collaborators,   ADBS-CBM consortium,   iPSYCH OCD consortium,   Consortium NORDiC OCD & Related Disorders, Purushottam Meera , Viswanath Biju 
Published: April 2024

AbstractGenome-wide association studies across diverse populations may help validate and confirm genetic contributions to risk of disease. We estimated the extent of population stratification as well as the predictive accuracy of polygenic scores (PGS) derived from European samples to a data set from India. We analysed 2685 samples from two data sets, a population neurodevelopmental study (cVEDA) and a hospital-based sample of bipolar affective disorder (BD) and obsessive-compulsive disorder (OCD). Genotyping was conducted using Illumina’s Global Screening Array.Population structure was examined with principal component analysis (PCA), uniform manifold approximation and projection (UMAP), support vector machine (SVM) ancestry predictions, and admixture analysis. PGS were calculated from the largest available European discovery GWAS summary statistics for BD, OCD, and externalizing traits using two Bayesian methods that incorporate local linkage disequilibrium structures (PGS-CS-auto) and functional genomic annotations (SBayesRC). Our analyses reveal global and continental PCA overlap with other South Asian populations. Admixture analysis revealed a north-south genetic axis within India (FST1.6%). The UMAP partially reconstructed the contours of the Indian subcontinent.The Bayesian PGS analyses indicates moderate-to-high predictive power for BD. This was despite the cross-ancestry bias of the discovery GWAS dataset, with the currently available data. However, accuracy for OCD and externalizing traits was much lower. The predictive accuracy was perhaps influenced by the sample size of the discovery GWAS and phenotypic heterogeneity across the syndromes and traits studied. Our study results highlight the accuracy and generalizability of newer PGS models across ancestries. Further research, across diverse populations, would help understand causal mechanisms that contribute to psychiatric syndromes and traits.
Antibiotic-associated neutropenia is marked by depletion of intestinalLachnospiraceaein pediatric patients
Authors: Fernandez-Sanchez Josaura , Rodgers Rachel , Maknojia Arushana A. , Shaikh Nusrat , Yan Hannah , Mejia Marlyd E. , Hendricks Hope , Jenq Robert R. , Reddy Pavan , Banerjee Ritu , Schraw Jeremy M. , Baldridge Megan T. , King Katherine Y. 
Published: April 2024

AbstractHematologic side effects are associated with prolonged antibiotic exposure in up to 34% of patients. Neutropenia, reported in 10-15% of patients, increases the risk of sepsis and death. Murine studies have established a link between the intestinal microbiota and normal hematopoiesis. We sought to identify predisposing factors, presence of microbiota-derived metabolites, and changes in intestinal microbiota composition in otherwise healthy pediatric patients who developed neutropenia after prolonged courses of antibiotics. In this multi-center study, patients with infections requiring anticipated antibiotic treatment of two or more weeks were enrolled. Stool samples were obtained at the start and completion of antibiotics and at the time of neutropenia. We identified 10 patients who developed neutropenia on antibiotics and 29 controls matched for age, sex, race, and ethnicity. Clinical data demonstrated no association between neutropenia and type of infection or type of antibiotic used; however intensive care unit admission and length of therapy were associated with neutropenia. Reduced intestinal microbiome richness and decreased abundance ofLachnospiraceaefamily members correlated with neutropenia. Untargeted stool metabolomic profiling revealed several metabolites that were depleted exclusively in patients with neutropenia, including members of the urea cycle pathway, pyrimidine metabolism and fatty acid metabolism that are known to be produced byLachnospiraceae. Our study confirms a relationship between intestinal microbiota disruption and abnormal hematopoiesis and identifies taxa and metabolites likely to contribute to microbiota-sustained hematopoiesis. As the microbiome is a key determinant of stem cell transplant and immunotherapy outcomes, these findings are likely to be of broad significance.Key PointsNeutropenia occurred in 17% of patients receiving prolonged antibiotic therapy.We found no association between neutropenia and type of infection or class of antibiotic used.Development of neutropenia after prolonged antibiotic treatment was associated with decreased prevalence ofLachnospiraceaeand Lachnospiraceae metabolites such as citrulline.
Predictors of glycemic worsening in the next year in adults with screen-detected type 2 diabetes
Authors: Aguirre Rebecca Schneider , Hannon Tamara S , Considine Robert V , Patel Yash , Kirkman M Sue , Mather Kieren J 
Published: April 2024

AbstractBackground and AimsIdentifying simple markers of risk for worsening glucose can allow care providers to target therapeutic interventions according to risk of worsening glycemic control. We aimed to determine which routine clinical measures herald near-term glycemic worsening in early type 2 diabetes(T2D).MethodsThe Early Diabetes Intervention Program (EDIP) was a clinical trial in individuals with screen-detected T2D [HbA1C 6.3+0.63%(45+5mmol/mol)]. During the trial some participants experienced worsening fasting blood glucose (FBG). We investigated the time course of FBG, HbA1c, weight, and other clinical factors to determine which might herald glycemic worsening over the next year.ResultsProgressors (62/219, 28.5%) had higher FBG than non-progressors at baseline [118 vs 130mg/dL (6.6 vs 7.2 mmol/L), p=<0.001]. FBG was stable except in the year of progression, when progressors exhibited a large 1-year rise [mean change 14.2mg/dL(0.79 mmol/L)]. Current FBG and antecedent year change in FBG were associated with progression(p<0.01), although the magnitude of change was too small to be of clinical utility (0.19 mg/dL; 0.01 mmol/L). Current or antecedent year change in HbA1c, weight, TG or HDL were not associated with progression. In the year of glycemic worsening, rising glucose was strongly associated with a concurrent increase in weight (p<0.001).ConclusionsElevated FBG but not HbA1c identified individuals at risk for imminent glycemic worsening; the subsequent large rise in glucose was associated with a short-term increase in weight. Glucose and weight surveillance provide actionable information for those caring for patients with early diabetes.HighlightsRecent change in fasting blood sugar is associated with near-term worsening of glycemiaChanges in weight, insulin, HbA1C were not informative for anticipating near-term worsening of glycemiaIncreasing glucose was strongly associated with concurrent weight gain
CBP/P300 BRD Inhibition Reduces Neutrophil Accumulation and Activates Antitumor Immunity in TNBC
Authors: Yuan Xueying , Hao Xiaoxin , Chan Hilda L. , Zhao Na , Pedroza Diego A. , Liu Fengshuo , Le Kang , Smith Alex J. , Calderon Sebastian J. , Lieu Nadia , Soth Michael J. , Jones Philip , Zhang Xiang H.-F. , Rosen Jeffrey M. 
Published: April 2024

AbstractTumor-associated neutrophils (TANs) have been shown to promote immunosuppression and tumor progression, and a high TAN frequency predicts poor prognosis in triple-negative breast cancer (TNBC). Dysregulation of CREB binding protein (CBP)/P300 function has been observed with multiple cancer types. The bromodomain (BRD) of CBP/P300 has been shown to regulate its activity. In this study, we found that IACS-70654, a novel and selective CBP/P300 BRD inhibitor, reduced TANs and inhibited the growth of neutrophil-enriched TNBC models. In the bone marrow, CBP/P300 BRD inhibition reduced the tumor-driven abnormal differentiation and proliferation of neutrophil progenitors. Inhibition of CBP/P300 BRD also stimulated the immune response by inducing an IFN response and MHCI expression in tumor cells and increasing tumor-infiltrated CTLs. Moreover, IACS-70654 improved the response of a neutrophil-enriched TNBC model to docetaxel and immune checkpoint blockade. This provides a rationale for combining a CBP/P300 BRD inhibitor with standard-of-care therapies in future clinical trials for neutrophil-enriched TNBC.SummaryIn neutrophil-enriched triple-negative breast cancer (TNBC) models, CREB binding protein (CBP)/P300 bromodomain (BRD) inhibition reduces tumor growth and systemic neutrophil accumulation while stimulating an antitumor immune response. This improves standard-of-care therapies, suggesting a potential therapeutic benefit of CBP/P300 BRD inhibitors for neutrophil-enriched TNBC.
Targeting of SUMOylation leads to cBAF complex stabilization and disruption of the SS18::SSX transcriptome in Synovial Sarcoma
Authors: Floros Konstantinos V. , Fairchild Carter K. , Li Jinxiu , Zhang Kun , Roberts Jane L. , Kurupi Richard , Hu Bin , Kraskauskiene Vita , Hosseini Nayyerehsadat , Shen Shanwei , Inge Melissa M. , Smith-Fry Kylie , Li Li , Sotiriou Afroditi , Dalton Krista M. , Jose Asha , Abdelfadiel Elsamani I. , Xing Yanli , Hill Ronald D. , Slaughter Jamie M. , Shende Mayuri , Lorenz Madelyn R , Hinojosa Mandy R. , Belvin Benjamin R. , Lai Zhao , Boikos Sosipatros A. , Stamatouli Angeliki M. , Lewis Janina P. , Manjili Masoud H. , Valerie Kristoffer , Li Renfeng , Banito Ana , Poklepovic Andrew , Koblinski Jennifer E. , Siggers Trevor , Dozmorov Mikhail G. , Jones Kevin B. , Radhakrishnan Senthil K. , Faber Anthony C. 
Published: April 2024

AbstractSynovial Sarcoma (SS) is driven by the SS18::SSX fusion oncoprotein. and is ultimately refractory to therapeutic approaches. SS18::SSX alters ATP-dependent chromatin remodeling BAF (mammalian SWI/SNF) complexes, leading to the degradation of canonical (cBAF) complex and amplified presence of an SS18::SSX-containing non-canonical BAF (ncBAF or GBAF) that drives an SS-specific transcription program and tumorigenesis. We demonstrate that SS18::SSX activates the SUMOylation program and SSs are sensitive to the small molecule SAE1/2 inhibitor, TAK-981. Mechanistically, TAK-981 de-SUMOylates the cBAF subunit SMARCE1, stabilizing and restoring cBAF on chromatin, shifting away from SS18::SSX-ncBAF-driven transcription, associated with DNA damage and cell death and resulting in tumor inhibition across both human and mouse SS tumor models. TAK-981 synergized with cytotoxic chemotherapy through increased DNA damage, leading to tumor regression. Targeting the SUMOylation pathway in SS restores cBAF complexes and blocks the SS18::SSX-ncBAF transcriptome, identifying a therapeutic vulnerability in SS, positioning the in-clinic TAK-981 to treat SS.
Massively parallel interrogation of human functional variants modulating cancer immunosurveillance
Authors: Liu Ying , Liu Yongshuo , Niu Xuran , Chen Ang , Li Yizhou , Yu Ying , Liu Zhiheng , Wei Wensheng 
Published: April 2024

SUMMARYAnti-PD-1/PD-L1 immune checkpoint blockade (ICB) therapy has revolutionized clinical cancer treatment, while abnormal PD-L1 or HLA-I expression in patients can significantly impact the therapeutic efficacy. Somatic mutations in cancer cells that modulate these critical immune regulators are closely associated with tumor progression and ICB response. However, a systematic interpretation of cancer immune-related mutations is still lacking. Here, we harnessed the ABEmax system to establish a large-scale sgRNA library encompassing approximately 820,000 sgRNAs that target all feasible Serine/Threonine/Tyrosine residues across the human genome, which systematically unveiled thousands of novel mutations that decrease or augment PD-L1 or HLA-I expression. Notably, we revealed functional mutations that co-regulate PD-L1 and HLA-I expression, represented by the clinically relevant mutation SETD2_Y1666, and verified that it can benefit from immunotherapyin vivo. Our findings generate an unprecedented resource of functional residues regulating cancer immunosurveillance, meanwhile, offer valuable guidance for clinical diagnosis, ICB therapy, and the development of innovative drugs in cancer treatment.
A two-component quasi-icosahedral protein nanocompartment with variable shell composition and irregular tiling
Authors: Dutcher Cassandra A. , Andreas Michael P. , Giessen Tobias W. 
Published: April 2024

AbstractProtein shells or capsids are a widespread form of compartmentalization in nature. Viruses use protein capsids to protect and transport their genomes while many cellular organisms use protein shells for varied metabolic purposes. These protein-based compartments often exhibit icosahedral symmetry and consist of a small number of structural components with defined roles. Encapsulins are a prevalent protein-based compartmentalization strategy in prokaryotes. All encapsulins studied thus far consist of a single shell protein that adopts the viral HK97-fold. Here, we report the characterization of a Family 2B two-component encapsulin fromStreptomyces lydicus. We show the differential assembly behavior of the two shell components and demonstrate their ability to co-assemble into mixed shells with variable shell composition. We determined the structures of both shell proteins using cryo-electron microscopy. Using 3D-classification and crosslinking studies, we highlight the irregular tiling of mixed shells. Our work expands the known assembly modes of HK97-fold proteins and lays the foundation for future functional and engineering studies on two-component encapsulins.