bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dermatopontin-expressing fibroblasts mediate an essential skin macrophage niche
Authors: Vollmers Apple Cortez , Wu Sunny Z. , Altieri Anthony , McCartney Erika E. , Bender Hannah , Lee Wyne P. , Zhang Juan , Hu Crystal , Uttarwar Salil , Vander Heiden Jason A. , Davidson Christopher , Chung Yein , Ortiz Willie , Long Michael , Asuncion Raymond , Yang Yeqing Angela , Jiang Jean X. , Modrusan Zora , Krishnamurty Akshay T. , Fu Wenxian , Müller Sören , Buechler Matthew B. , Turley Shannon J. 
Published: November 2024

AbstractFibroblasts are present in all tissues and are crucial for maintaining tissue homeostasis. We previously identified fibroblasts marked byDermatopontin(Dpt) but their role in supporting macrophage homeostasis remains unclear. Here, we generated novel mesenchymal lineage-restricted genetic tools to targetDptexpressing fibroblasts and elucidate their role in supporting skin macrophages. Transcriptional profiling, flow cytometry, and in situ hybridization uncovered two broad populations of F4/80-expressing skin macrophages, denoted by high expression of CD206 and CD64 (CD206hiCD64+), or CD11c. Targeted depletion ofDpt+ fibroblasts resulted in a profound loss of both macrophage populations. Conditional deletion of colony-stimulating factor-1 (Csf1)inDpt+ fibroblasts revealed that CD206hiCD64+, and not CD11c+, macrophages are acutely dependent on fibroblast-derivedCsf1, consistent with their higher expression of theCsf1receptor. FollowingCsf1deletion inDpt+ fibroblasts, loss of CD206hiCD64+ macrophages were observed across the dermis, dermal white adipose tissue (dWAT), and adventitia, accompanied by a modest upregulation of fibroblast-related and extracellular matrix (ECM) genes and structural changes to the skin. Alterations to the skin network upon loss of fibroblast-derivedCsf1and CD206hiCD64+ macrophages led to a significant delay in wound healing. We also demonstrate the CSF1-CSF1R signaling pathway is functionally relevant in human systemic sclerosis, or scleroderma, as elevated levels of CSF1 produced by fibroblasts and an increased abundance of macrophages both correlate with disease severity. Our findings demonstrate the role ofDpt+ fibroblasts in regulating aCsf1-dependent macrophage niche in skin and orchestrating responses in injury and disease.
Interpretable AI in Tissue Engineering: XGBoost and SHAP for PLGA Scaffold Biocompatibility
Authors: Rafat Md Tanzim 
Published: November 2024

AbstractThe refinement of scaffold materials is essential in tissue engineering to promote cellular growth and tissue regeneration. This study applied Extreme Gradient Boosting (XGBoost) and SHapley Additive exPlanations (SHAP) to predict and interpret the biocompatibility of poly(lactic-co-glycolic acid) (PLGA)-based scaffolds. A dataset of 10,010 synthetic samples was analyzed, examining key scaffold features such as Young’s Modulus, Ultimate Tensile Strength, Strain at Failure, Compressive Modulus, Pore Size, Porosity, and Degradation Time. The XGBoost model demonstrated high predictive accuracy with a Root Mean Square Error (RMSE) of 2.59. SHAP analysis identified Young’s Modulus, Strain at Failure, and Ultimate Tensile Strength as the most influential factors affecting biocompatibility. These findings highlight the critical role of mechanical properties in scaffold performance, particularly in cell adhesion and tissue integration. This research offers a data-driven framework for optimizing scaffold designs and integrating machine learning predictions with biological insights for improved tissue engineering applications.
Reconciling competing models on the roles of condensates and soluble complexes in transcription factor function
Authors: Bremer Anne , Lang Walter H. , Kempen Ryan P. , Sweta Kumari , Taylor Aaron B. , Borgia Madeleine B. , Ansari Aseem Z. , Mittag Tanja 
Published: November 2024

AbstractPhase separation explains the exquisite spatial and temporal regulation of many biological processes, but the role of transcription factor–mediated condensates in gene regulation is contentious, requiring head-to-head comparison of competing models. Here, we focused on the prototypical yeast transcription factor Gcn4 and assessed two models for gene transcription activation, i.e., mediated via soluble complexes or transcriptional condensates. Both models rely on the ability of transcription factors and coactivators to engage in multivalent interactions. Unexpectedly, we found that propensity to form homotypic Gcn4 condensates does not correlate well with transcriptional activity. Contrary to prevailing models, binding to DNA suppresses Gcn4 phase separation. Notably, the ability of Gcn4 to form soluble complexes with coactivator subunit Med15 closely mirrored the propensity to recruit Med15 into condensates, indicating that these properties are intertwined and cautioning against interpretation of mutational data without head-to-head comparisons. However, Gcn4 variants with the highest affinity for Med15 do not function as well as expected and instead have activities that reflect their abilities to phase separate with Med15. These variants therefore indeed form cellular condensates, and those attenuate activity. Our results show that transcription factors can function as soluble complexes as well as condensates, reconciling two seemingly opposing models, and have implications for other phase-separating systems.Highlights-Homotypic phase separation propensities of Gcn4 variants do not predictin vivoactivities well.-DNA binding leads to solubilization of GCN4 condensates, which is reversed by Med15 association.-The abilities to co-phase separate and form soluble complexes with Med15 are highly intertwined.-Variants with high affinities for Med15 form condensates that attenuate function.
Diverse priming outcomes under conditions of very rare precursor B cells
Authors: Madden Patrick J. , Marina-Zárate Ester , Rodrigues Kristen A. , Steichen Jon M. , Shil Monolina , Ni Kaiyuan , Michaels Katarzyna Kaczmarek , Maiorino Laura , Upadhyay Amit A. , Saha Swati , Pradhan Arpan , Kalyuzhiny Oleksandr , Liguori Alessia , Lopez Paul G. , Phung Ivy , Phelps Nicole , Georgeson Erik , Alavi Nushin , Kubitz Michael , Lu Danny , Eskandarzadeh Saman , Metz Amanda , Rodriguez Oscar L. , Shields Kaitlyn , Schultze Steven , Smith Melissa L. , Healy Brandon S. , Lim Deuk , Lewis Vanessa R. , Ben-Akiva Elana , Pinney William , Gregory Justin , Xiao Shuhao , Carnathan Diane G. , Kasturi Sudhir Pai , Watson Corey T. , Bosinger Steven E. , Silvestri Guido , Schief William R. , Irvine Darrell J , Crotty Shane 
Published: November 2024

SUMMARYRare B cells can have special pathogen-recognition features giving them the potential to make outsized contributions to protective immunity. However, rare naive B cells infrequently participate in immune responses. We investigated how germline-targeting vaccine antigen delivery and adjuvant selection affect priming of exceptionally rare BG18-like HIV broadly neutralizing antibody-precursor B cells (~1 in 50 million) in non-human primates. Only escalating dose (ED) priming immunization using the saponin adjuvant SMNP elicited detectable BG18-like cells in germinal centers (GCs). All groups had strong GC responses, but only ED+SMNP and bolus+SMNP induced BG18-like memory B cells in >50% of animals. One group had vaccine-specific GC responses equivalent to ED+SMNP, but BG18-like memory B cells were rarely detected. Following homologous boosting, BG18-like memory B cells were more frequent in a bolus priming group, but had lower somatic hypermutation and affinities. This outcome was inversely associated with post-prime antibody titers, suggesting antibody feedback can significantly influence rare precursor B cell responses.
TheSalmonellapathogenicity island 1-encoded small RNA InvR mediates post-transcriptional feedback control of the activator HilA inSalmonella
Authors: Hou Yutong , Kim Kyungsub , Cakar Fatih , Golubeva Yekaterina A. , Slauch James M. , Vanderpool Carin K. 
Published: November 2024

ABSTRACTSalmonellaPathogenicity Island 1 (SPI1) encodes a type three secretion system (T3SS) essential forSalmonellainvasion of intestinal epithelial cells. Many environmental and regulatory signals control SPI1 gene expression, but in most cases, the molecular mechanisms remain unclear. Many of these regulatory signals control SPI1 at a post-transcriptional level and we have identified a number of small RNAs (sRNAs) that control the SPI1 regulatory circuit. The transcriptional regulator HilA activates expression of the genes encoding the SPI1 T3SS structural and primary effector proteins. Transcription ofhilAis controlled by the AraC-like proteins HilD, HilC, and RtsA. ThehilAmRNA 5’ untranslated region (UTR) is ~350-nuclotides in length and binds the RNA chaperone Hfq, suggesting it is a likely target for sRNA-mediated regulation. We used the rGRIL-seq (reverse global sRNA target identification by ligation and sequencing) method to identify sRNAs that bind to thehilA5’ UTR. The rGRIL-seq data, along with genetic analyses, demonstrate that the SPI1-encoded sRNA InvR base pairs at a site overlapping thehilAribosome binding site. HilD and HilC activate bothinvRandhilA. InvR in turn negatively regulates the translation of thehilAmRNA. Thus, the SPI1-encoded sRNA InvR acts as a negative feedback regulator of SPI1 expression. Our results suggest that InvR acts to fine-tune SPI1 expression and prevent overactivation ofhilAexpression, highlighting the complexity of sRNA regulatory inputs controlling SPI1 andSalmonellavirulence.IMPORTANCESalmonellaTyphimurium infections pose a significant public health concern, leading to illnesses that range from mild gastroenteritis to severe systemic infection. Infection is initiated and requires a complex apparatus that the bacterium uses to invade the intestinal epithelium. Understanding howSalmonellaregulates this system is essential for addressing these infections effectively. Here we show that the small RNA (sRNA) InvR imposes negative feedback regulation on expression of the invasion system. This work underscores the role of sRNAs inSalmonella’scomplex regulatory network, offering new insights into how these molecules contribute to bacterial adaptation and pathogenesis.
Structural insights into cholesterol sensing by the LYCHOS-mTORC1 pathway
Authors: Yu Shang , Ding Jin-hui , Wang Weize , Wang Jia-le , Zuo Peng , Yang Ao , Dai Zonglin , Yin Yuxin , Sun Jin-peng , Liang Ling 
Published: November 2024

AbstractThe mechanistic target of rapamycin complex 1 (mTORC1) pathway regulates cellular metabolism and growth by coordinating nutrient resources, including cholesterol, and its aberrant activation is linked to various age-related diseases. LYCHOS is a cholesterol sensor on the lysosome and bound to the GATOR1 complex, a GTPase-activating protein for the Rag GTPase, at high cholesterol concentrations, thereby activating the protein kinase mTORC1. However, how LYCHOS senses cholesterol and transduces signal to GATOR1 remain largely unknown. Here we report six cryo-electron microscopy structures of human LYCHOS, depicting five distinct states. These are categorized into a contracted state when complexed with a sufficient amount of the cholesterol analogue cholesteryl hemisuccinate (CHS), and an expanded state when CHS is deficient. The structure forms a homodimer, within each monomer the transmembrane region is divided into a permease-like domain (PLD) and a GPCR-like domain (GLD) with two clearly defined adjacent cholesterol binding sites between them. The PLD shares a conserved Na+/H+antiporter (NhaA) fold, which much resembles plant auxin transporter PINs. Cholesterol locates between PLD and GLD and cholesterol binding induces a translation of GLD towards PLD and exposes the cytosolic extension of transmembrane 15, which mediates the interaction between LYCHOS and GATOR1. Strikingly, structure-guided mutations of Gly702 in GLD of LYCHOS increase its affinity for cholesterol, leading to sustained mTORC1 activation in cells. This indicates that LYCHOS’s moderate affinity for cholesterol is crucial as a cholesterol sensor. Our results not only showed a solute carrier mechanistically coordinates a GPCR domain, elucidating the structural mechanism of cholesterol sensing by the mTORC1 pathway on the lysosome; but also provides a structural basis for developing inhibitors that selectively target to mTORC1 pathway to treat age-related diseases by blocking LYCHOS in its expanded state.
Involvement of Hepatitis B Core–Related Antigen in Viral Genome Integration in Patients With Prior Hepatitis B Virus Infection
Authors: Saito Tomoya , Suzuki Rigel , Rahman Akhinur , Mori Kento , Rajib Samiul Alam , Kobayashi Nobuhiro , Ichikawa Takaya , Orimo Tatsuya , Kakisaka Tatsuhiko , Liang Lihan , Nao Naganori , Suzuki Saori , Tamura Tomokazu , Satou Yorifumi , Taketomi Akinobu , Fukuhara Takasuke 
Published: November 2024

AbstractBackgroundThe incidence of non-B non-C hepatocellular carcinoma (NBNC-HCC), which is negative for hepatitis B surface antigen and hepatitis C virus antibodies, is on the rise. Relatively high numbers of NBNC-HCC patients are hepatitis B core antibody (HBcAb) positive, suggesting that previous HBV infection may play a role in NBNC-HCC development, though the exact mechanisms are unclear. This study aimed to investigate whether HBV genomes are integrated into the host genome of HBcAb-positive NBNC-HCC cases and how these integrations may contribute to cancer development and progression.MethodsHBV detection PCR using HBV-specific primers on DNA extracted from HBcAb-positive NBNC-HCC tissue samples was performed. Positive samples were further examined for HBV integration sites using viral DNA–capture sequencing. Additionally, hepatitis B core-related antigen (HBcrAg) serum levels were measured to assess whether they could be predictive for HBV detection PCR results.ResultsAmong 90 HBcAb-positive NBNC-HCC samples, HBV genome amplification was detected in 18 samples, and elevated HBcrAg levels were associated with the HBV detection PCR results. Seventeen of these samples exhibited HBV integration. The HBV genome was integrated near theTERTgene in 7 samples, resulting in significantly increasedTERTmRNA levels; in theKMT2Bgene (2 samples); and downstream ofLOC441666(2 samples).ConclusionThe integration sites we identified in our samples have been previously reported in HBV-related HCC, suggesting that HBV integration may also contribute to hepatocarcinogenesis in HBcAb-positive NBNC-HCC. Furthermore, HBcrAg could serve as a potential, noninvasive marker for detecting HBV integration in these cases.
A high-quality phased genome assembly of stinging nettle,Urtica dioicassp.dioica
Authors: Hirabayashi Kaede , Dumigan Christopher R. , Ku•ka Matúš , Percy Diana M. , Guerriero Gea , Cronk Quentin , Deyholos Michael K. , Todesco Marco 
Published: November 2024

AbstractStinging nettles (Urtica dioica) have a long history of association with human civilization, having been used as a source of textile fibres, food and medicine. Here, we present a chromosome-level, phased genome assembly for a diploid female clone ofUrtica dioicafrom Romania. Using a combination of PacBio HiFi, Oxford Nanopore and Illumina sequencing, and Hi-C long-range interaction data (using a novel Hi-C protocol presented here), we assembled two haplotypes of 574.9 Mbp (contig N50 = 10.9 Mbp, scaffold N50 = 44.0 Mbp) and 521.2 Mbp (contig N50 = 13.5 Mbp, scaffold N50 = 48.0 Mbp), with assembly BUSCO scores of 92.6% and 92.3%. We annotated 20,333 and 20,140 genes for each haplotype, covering over 90% of the complete BUSCO genes and including two copies of a gene putatively encoding the neurotoxic peptide urthionin, which could contribute to nettle’s characteristic sting. Despite its relatively small size, the nettle genome displays very high levels of repetitiveness, with transposable elements comprising more than 60% of the genome, as well as considerable structural variation. This genome assembly represents an important resource for the nettle community and will enable the investigation of the genetic basis of the many interesting characteristics of this species.
FARFOOD: A database of potential interactions between food compounds and drugs
Authors: Nevado-Bulnes Ana María , Benitez Dixan Agustin , Cumplido-Laso Guadalupe , Carvajal-González Jose María , Mulero-Navarro Sonia , Román Angel-Carlos 
Published: November 2024

SummaryNutrition is a fundamental aspect in human life development, both from a socio-economic and medical perspective. In recent years, new personalized approaches have been added to the biochemical study of nutrients. These approaches consider both the effect of foods on the body and the role of genes in metabolizing or digesting different nutrients. Although drug-food interactions have been known for decades, there is a lack of studies that address these processes in a comprehensive way, using structural and computational biochemistry techniques. In this paper we develop a method to predict potential interactions between foods and drugs based on the structural similarity between food compounds and medications. Our results have produced a database and an app to consult potential interactions between drugs and foods that we have called FARFOOD. Additionally, we validated two of these potential interactions with widely used drugs (lisinopril and bupropion) through structural docking between the ligand protein and the food compounds that are structurally similar to the drug. Moreover, patient surveys are used in the lisinopril and bupropion cases in addition to allopurinol to assess the possible effects of the potentially interacting foods on the symptoms of the conditions for which the medication is prescribed. In summary, this manuscript presents an interesting computational resource for predictive food-drug interaction analysis.
Age-related differences in psychopathology within sex chromosome trisomies
Authors: Roybal Melissa R. , Liu Siyuan , Larsen Isabella G. , Wass Anastasia , Schaffer Lukas , Ajumobi Tiffany , Whitman Ethan T. , Warling Allysa , Clasen Liv , Blumenthal Jonathan , Rau Srishti , Raznahan Armin 
Published: November 2024

AbstractSex chromosome trisomies (SCTs) are a group of genetic disorders characterized by presence of a supernumerary sex chromosome, resulting in karyotypes other than XX or XY. These include XXX (Trisomy X), XXY (Klinefelter syndrome), and XYY (Jacobs syndrome). Sex chromosome trisomies have been linked to increased risk for psychopathology; however, this relationship warrants additional research. Specifically, little is known regarding potential age-related variation in risk for psychopathology and how this may differ across karyotypes and subdomains of psychopathology, which has relevance for psychoeducation, personalized care, and mechanistic research. Thus, we used the Child Behavior Checklist (CBCL) to estimate age-related variation in psychopathology in a large cross-sectional sample of individuals with SCTs (n = 201) and euploidic controls (n = 304) spanning the age range of 5-18 years. We found that elevations of psychopathology in SCT were significantly associated with age in a manner that varied as a combined function of the karyotype and CBCL scale being considered. Post hoc tests revealed there is a uniquely pronounced age-associated increase in severity of social problems in XYY, alongside a lack of statistical evidence for age-related variation in the severity of psychopathology for other CBCL domains and SCT karyotypes. Our findings are relevant for advancing the personalization of clinical assessment and monitoring in SCTs. They also highlight potential windows of dynamic risk emergence for closer clinical and biological study, as well as opportunities to provide intervention to mitigate future risk.
A multi-model analysis of risk factors influencing hippocampus degree centrality in Han Chinese adults who lost their only child
Authors: Cao Yang , Guo Min , Wang Yuxin , Luo Yifeng 
Published: November 2024

AbstractObjectiveThis study explores the relationship between Hippocampus Degree Centrality (DC) values and various risk factors in Han Chinese adults who have lost their only child, a phenomenon known as “shidu”. Our goal is to develop statistical models that have the potential to predict DC values and enhance clinical diagnosis and intervention strategies for Post-Traumatic Stress Disorder (PTSD) in these parents.MethodsParticipants were recruited from a PTSD survey conducted in Jiangsu Province, China, between September 2016 and March 2017. The survey included Han Chinese parents who had lost their only child to causes such as traffic accidents, explosions, suicide, cancer, and sudden death. Of the 237 participants, we focused on PTSD cases that met specific criteria, excluding individuals with adrenal disorders to eliminate confounding effects. After obtaining informed consent for follow-up assessments, we analyzed data from 109 eligible participants, examining a range of statistical models - linear, flexible, LASSO, ridge, and logistic regression - to identify correlations between DC values and various risk factors.ResultsCortisol, gender, BMI, and memory capability are key contributors associated with DC values in Han Chinese adults who have experienced the trauma of losing their only child. We found that cortisol levels are negatively correlated with DC values in males, and are positively correlated in females (p-value = 0.017), which forms a gender-specific correlation. Additionally, BMI (p-value = 0.011) and memory scores (p-value = 0.157) indicate that physiological and cognitive factors can influence the hippocampus.ConclusionLinear and logistic models incorporating cortisol, gender, BMI, and memory capability show the greatest potential for clinical application in diagnosing DC abnormalities. These abnormalities are key indicators of stress levels and neurocognitive function in “shidu” parents, offering valuable insights for PTSD diagnosis and intervention strategies.