bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of poverty on mental illness: Emerging evidence of a causal relationship
Authors: Marchi Mattia , Alkema Anne , Xia Charley , Thio Chris H. L. , Chen Li-Yu , Schalkwijk Winni , Galeazzi Gian M. , Ferrari Silvia , Pingani Luca , Kweon Hyeokmoon , Evans-Lacko Sara , Hill W. David , Boks Marco P. 
Published: May 2023

AbstractThe link between poverty and mental illness has sparked discussions concerning the poverty role as a risk factor for poor mental health. If poverty has as a causal role in mental illness, it would have profound implications for our comprehension of mental well-being and guide efforts to address the increasing incidence of mental health disorders.Building on the recent breakthrough discovery of heritability of poverty traits and utilizing large-scale genome-wide association studies of mental illness, we used Genomic Structural Equation Modeling (GSEM) and Mendelian randomization (MR) to examine the evidence of a causal relationship between poverty and mental illness. A common factor of poverty was derived from household income (HI), occupational income (OI), and social deprivation (SD). The causal effect of poverty was examined on 9 mental illnesses: attention deficit and hyperactivity disorder (ADHD), anorexia nervosa (AN), anxiety disorders (ANX), autism spectrum disorders (ASD), bipolar disorder (BD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and schizophrenia (SZ), while accounting for the influence of cognitive ability (CA).Our analysis highlights HI as the measure of poverty with the strongest correlation with the common factor, when compared to OI and SD. Using the common factor of poverty, bidirectional MR provided evidence that mental illness leads to poverty, consistent with the existing paradigm. What is new is evidence that higher levels of poverty likely pose a causal factor in developing ADHD (Inverse Variance Weighted Odds Ratio per Standard Deviation change [IVW OR]=3.43[95%CI:2.95-3.99]), MDD (IVW OR=1.49[95%CI:1.29-1.72]), and SZ (IVW OR=1.53[95%CI:1.35-1.73]), but exerts a protective effect against AN (IVW OR=0.50[95%CI:0.40-0.62]). The direct effect of poverty on mental illness remained following adjustment for CA, albeit with reduced effect sizes.Our research indicates that higher poverty levels are likely causal risk factors for MDD and SZ, but protective against AN. Notably, CA explains a significant portion of the impact of poverty, aligning with prior reports that highlight the contribution of impaired cognitive function to severe mental illnesses. Although individuals’ skills and abilities tied to earning capacity may be the variables with the actual causal effect of poverty on mental illness, our findings warrant further investigations into interventions targeting poverty and cognitive abilities to advance mental health.
Uniform Manifold Approximation and Projection-based Assessment of Chronic Kidney Disease Aetiologies based on Urinary Peptidomics
Authors: Mavrogeorgis Emmanouil , He Tianlin , Mischak Harald , Latosinska Agnieszka , Vlahou Antonia , Schanstra Joost P. , Catanese Lorenzo , Amann Kerstin , Huber Tobias B. , Beige Joachim , Rupprecht Harald , Siwy Justyna 
Published: May 2023

AbstractBackgroundThe impact of artificial intelligence combined with advanced techniques is ever-increasing in the biomedical field appearing promising, among others, in chronic kidney disease (CKD) diagnosis. However, existing models are often single-aetiology specific. Proposed here is a pipeline for the development of single models able to distinguish and spatially visualize multiple CKD aetiologies.MethodsAcquired were from the Human Urinary Proteome Database the urinary peptide data of 1850 healthy control (HC) and CKD (diabetic kidney disease-DKD, IgA nephropathy-IgAN, vasculitis) participants. The uniform manifold approximation and projection (UMAP) method was coupled to a support vector machine (SVM) algorithm. Binary (DKD, HC) and multiclass (DKD, HC, IgAN, vasculitis) classifications were performed, including or skipping the UMAP step. Last, the pipeline was compared to the current state-of-the-art single-aetiology CKD urinary models.FindingsIn an independent test set, the developed models (including the UMAP step) achieved 90.35% and 70.13% overall predictive accuracies, respectively, for the binary and the multiclass classifications (96.14% and 85.06%, skipping the UMAP step). Overall, the HC class was distinguished with the highest accuracy. The different classes displayed a tendency to form distinct clusters in the 3D-space based on their disease state.InterpretationUrinary peptide data appear to potentially be an effective basis for CKD aetiology differentiation. The UMAP step may provide a unique visualization advantage capturing the relevant molecular (patho)physiology. Further studies are warranted to validate the pipeline’s clinical potential in the presented as well as other CKD aetiologies or even other diseases.
Population context drives cell-to-cell variability in interferon response in epithelial cells
Authors: Metz-Zumaran Camila , Doldan Patricio , Muraca Francesco , Keser Yagmur , Lukas Pascal , Kuropka Benno , Küchenhoff Leonie , Talemi Soheil Rastgou , Höfer Thomas , Freund Christian , Cavalcanti-Adam Elisabetta Ada , Graw Frederik , Stanifer Megan , Boulant Steeve 
Published: May 2023

AbstractIsogenic cells respond in a heterogeneous manner to interferon. Using a micropatterning approach combined with high-content imaging and spatial analyses, we characterized how the population context (position of a cell with respect to the neighboring cells) of human intestinal epithelial cells affects single cell response to interferons. We identified that cells at the edge of a cellular colony are significantly more responsive than cells embedded within this colony. We determined that this spatial heterogeneity in IFN response was the result of the polarized basolateral distribution of the IFN receptors making cells located in the center of a cellular colony not responsive to ectopic IFN stimulation. We could demonstrate that this population context driven cell-to-cell variability influences the outcome of viral infection as cells embedded in a cellular colony are not protected by interferons and therefore more susceptible to infection. Our data highlights that the behavior of individual isolated cells does not directly translate to their behavior in a population, placing the population context as a key driver of cell-to-cell heterogeneity in IFN response.
ClearX9-Stem™: an efficient, affordable & sustainable stem cell culture medium for biotech and cell-cultivated meat industries
Authors: Gautam Sumit , Verma Neeraj , Manvati Siddharth , Dhar Pawan K. 
Published: May 2023

ABSTRACTStem cells are extraordinary cells with a unique ability of self-renewal and differentiation into various cell types such as muscle, nerve, bone, and blood cells. Historically, they have found significant applications in the biotech and pharma sectors. To grow and maintain stem cells artificially, researchers use basal media formulations supplemented with nutrients and growth factors, with Fetal bovine serum (FBS) as the key component of the culture medium. However, to maintain this supply every year, millions of pregnant cows are slaughtered for preparing FBS. The process of harvesting FBS also raises concerns about contamination with pathogens, animal proteins that may interfere with cellular behavior and ethical considerations regarding animal welfare. To overcome these limitations, here we report ClearX9-Stem™ - an affordable, sustainable, effective, and ethical replacement for an FBS-enriched stem cell culture medium. A specialized ClearX9-Stem™ cell culture medium formulation was designed to grow chicken embryonic fibroblast (SL-29) in the absence of FBS. Based on the results obtained, ClearX9-Stem™ is undergoing further refinement to meet the growing academic and industrial demand for serum-free culture media formulations. In the future, there is a need to customize and optimize ClearX9-Stem™ for the scalable growth of cells in bioreactors.HIGHLIGHTSClearX9-Stem™ provides good nutritional support for the growth of chicken embryonic fibroblast cells.ClearX9-Stem™ cell growth performance is comparable to the serum-enriched culture mediumClearX9-Stem™ maintains a healthy morphological profile of cells during divisionClearX9-Stem™ generates a stress-free environment within cellsClearX9-Stem™ does not require animal slaughter and reduces the environmental footprintClearX9-Stem™ has applications in the biotechnology, pharma, and cell-cultivated meat industries
The sequestration of miR-642a-3p by a complex formed by HIV-1 Gag and human Dicer increases AFF4 expression and viral production
Authors: Alpuche-Lazcano Sergio P. , Dunkley Owen R. S. , Scarborough Robert J. , Daniels Sylvanne M. , Daher Aïcha , Truchi Marin , Estable Mario C. , Mari Bernard , Mouland Andrew J. , Gatignol Anne 
Published: May 2023

ABSTRACTMicro (mi)RNAs are critical regulators of gene expression in human cells, the functions of which can be affected during viral replication. Here, we show that the human immunodeficiency virus type 1 (HIV-1) structural precursor Gag protein interacts with the miRNA processing enzyme Dicer. RNA immunoprecipitation and sequencing experiments show that Gag modifies the retention of a specific miRNA subset without affecting Dicer’s pre- miRNA processing activity. Among the retained miRNAs, miR-642a-3p shows an enhanced occupancy on Dicer in the presence of Gag and is predicted to target AFF4 mRNA, which encodes an essential scaffold protein for HIV-1 transcriptional elongation. miR-642a-3p gain- or loss-of-function negatively or positively regulates AFF4 protein expression at mRNA and protein levels with concomitant modulations of HIV-1 production, consistent with an antiviral activity. By sequestering miR-642a-3p with Dicer, Gag enhances AFF4 expression and HIV- 1 production without affecting miR-642a-3p levels. These results identify miR-642a-3p as a strong suppressor of HIV-1 replication and uncover a novel mechanism by which a viral structural protein directly disrupts an miRNA function for the benefit of its own replication.IMPORTANCE:Virus-host relationships occur at different levels and the human immunodeficiency virus type 1 (HIV-1) can modify the expression of microRNAs in different cells. Here, we identify a virus- host interaction between the HIV-1 structural protein Gag and the miRNA-processing enzyme Dicer. Gag does not affect the microRNA processing function of Dicer but affects the functionality of a subset of microRNAs that are enriched on the Dicer-Gag complex compared to on Dicer alone. We show that miR-642a-3p, the most enriched microRNA on the Dicer- Gag complex targets and degrades AFF4 mRNA coding for a protein from the super transcription elongation complex, essential for HIV-1 and cellular transcription. Interestingly, the silencing capacity by miR-642a-3p is hindered by Gag and heightened in its absence, consequently affecting HIV-1 transcription. These findings unveil a new paradigm that a microRNA function rather than its abundance can be affected by a viral protein through its enhanced retention on Dicer.
Vascular Endothelial-derived SPARCL1 Exacerbates Viral Pneumonia Through Pro-Inflammatory Macrophage Activation
Authors: Zhao Gan , Gentile Maria E. , Xue Lulu , Cosgriff Christopher V. , Weiner Aaron I. , Adams-Tzivelekidis Stephanie , Wong Joanna , Li Xinyuan , Kass-Gergi Sara , Holcomb Nicolas P. , Basal Maria C. , Stewart Kathleen M. , Planer Joseph D. , Cantu Edward , Christie Jason D. , Crespo Maria M. , Mitchell Michael J. , Meyer Nuala J. , Vaughan Andrew E. 
Published: May 2023

AbstractInflammation upon infectious lung injury is a double-edged sword: while tissue-infiltrating immune cells and cytokines are necessary to control infection, these same factors often aggravate injury. Full appreciation of both the sources and targets of inflammatory mediators is required to facilitate strategies to maintain antimicrobial effects while minimizing off-target epithelial and endothelial damage. Recognizing that the vasculature is centrally involved in tissue responses to injury and infection, we observed that pulmonary capillary endothelial cells (ECs) exhibit dramatic transcriptomic changes upon influenza injury punctuated by profound upregulation ofSparcl1. Endothelial deletion and overexpression of SPARCL1 implicated this secreted matricellular protein in driving key pathophysiologic symptoms of pneumonia, which we demonstrate result from its effects on macrophage polarization. SPARCL1 induces a shift to a pro-inflammatory “M1-like” phenotype (CD86+CD206-), thereby increasing associated cytokine levels. Mechanistically, SPARCL1 acts directly on macrophagesin vitroto induce the pro-inflammatory phenotype via activation of TLR4, and TLR4 inhibitionin vivoameliorates inflammatory exacerbations caused by endothelialSparcl1overexpression. Finally, we confirmed significant elevation of SPARCL1 in COVID-19 lung ECs in comparison with those from healthy donors. Survival analysis demonstrated that patients with fatal COVID-19 had higher levels of circulating SPARCL1 protein compared to those who recovered, indicating the potential of SPARCL1 as a biomarker for prognosis of pneumonia and suggesting that personalized medicine approaches might be harnessed to block SPARCL1 and improve outcomes in high-expressing patients.
dsSurvival 2.0: Privacy enhancing survival curves for survival models in the federated DataSHIELD analysis system
Authors: Banerjee Soumya , Bishop Tom R.P. 
Published: May 2023

AbstractObjectiveSurvival models are used extensively in biomedical sciences, where they allow the investigation of the effect of exposures on health outcomes. It is desirable to use diverse data sets in survival analyses, because this offers increased statistical power and generalisability of results. However, there are often challenges with bringing data together in one location or following an analysis plan and sharing results.DataSHIELD is an analysis platform that helps users to overcome these ethical, governance and process difficulties. It allows users to analyse data remotely, using functions that are built to restrict access to the detailed data items (federated analysis).Previous works have provided survival modelling functionality in DataSHIELD (dsSurvival package), but there is a requirement to provide functions that offer privacy enhancing survival curves that retain useful information.ResultsWe introduce an enhanced version of the dsSurvival package which offers privacy enhancing survival curves for DataSHIELD. Different methods for enhancing privacy were evaluated for their effec-tiveness in enhancing privacy while maintaining utility. We demonstrated how our selected method could enhance privacy in different scenarios using real survival data. The details of how DataSHIELD can be used to generate survival curves can be found in the associated tutorial.
Colonization and Dissemination ofKlebsiella pneumoniaeis Dependent on Dietary Carbohydrates
Authors: Hecht Aaron L. , Harling Lisa C. , Friedman Elliot S. , Tanes Ceylan , Lee Junhee , Firrman Jenni , Tu Vincent , Liu LinShu , Bittinger Kyle , Goulian Mark , Wu Gary D. 
Published: May 2023

AbstractDysbiosis of the gut microbiota is increasingly appreciated as both a consequence and precipitant of human disease. The outgrowth of the bacterial familyEnterobacteriaceaeis a common feature of dysbiosis, including the human pathogenKlebsiella pneumoniae. Dietary interventions have proven efficacious in the resolution of dysbiosis, though the specific dietary components involved remain poorly defined. Based on a previous human diet study, we hypothesized that dietary nutrients serve as a key resource for the growth of bacteria found in dysbiosis. Through human sample testing, andex-vivo, andin vivomodeling, we find that nitrogen is not a limiting resource for the growth ofEnterobacteriaceaein the gut, contrary to previous studies. Instead, we identify dietary simple carbohydrates as critical in colonization ofK. pneumoniae. We additionally find that dietary fiber is necessary for colonization resistance againstK. pneumoniae, mediated by recovery of the commensal microbiota, and protecting the host against dissemination from the gut microbiota during colitis. Targeted dietary therapies based on these findings may offer a therapeutic strategy in susceptible patients with dysbiosis.
From interaction networks to interfaces: Scanning intrinsically disordered regions using AlphaFold2
Authors: Bret Hélène , Andreani Jessica , Guerois Raphaël 
Published: May 2023

AbstractThe revolution brought about by AlphaFold2 and the performance of AlphaFold2-Multimer open promising perspectives to unravel the complexity of protein-protein interaction networks. Nevertheless, the analysis of interaction networks obtained from proteomics experiments does not systematically provide the delimitations of the interaction regions. This is of particular concern in the case of interactions mediated by intrinsically disordered regions, in which the interaction site is generally small. Using a dataset of protein-peptide complexes involving intrinsically disordered protein regions that are non-redundant with the structures used in AlphaFold2 training, we show that when using the full sequences of the proteins involved in the interaction networks, AlphaFold2-Multimer only achieves 40% success rate in identifying the correct site and structure of the interface. By delineating the interaction region into fragments of decreasing size and combining different strategies for integrating evolutionary information, we managed to raise this success rate up to 90%. Beyond the correct identification of the interaction site, our study also explores specificity issues. We show the advantages and limitations of using the AlphaFold2 confidence score to discriminate between alternative binding partners, a task that can be particularly challenging in the case of small interaction motifs.
Three genes controlling streptomycin susceptibility inAgrobacterium fabrum
Authors: Howarth Robyn E. , Pattillo Curtis M. , Griffitts Joel S. , Calvopina-Chavez Diana G. 
Published: May 2023

ABSTRACTStreptomycin is a commonly used antibiotic for its efficacy against diverse bacteria. The plant pathogenAgrobacterium fabrumis a model for studying pathogenesis and interkingdom gene transfer. Streptomycin-resistant variants ofA. fabrumare commonly employed in genetic analyses, yet mechanisms of resistance and susceptibility to streptomycin in this organism have not previously been investigated. We observe that resistance to a high concentration of streptomycin arises at high frequency inA. fabrumand we link this trait to the presence of a chromosomal gene (strB) encoding a putative aminoglycoside phosphotransferase. We show howstrB, along withrpsL(encoding ribosomal protein S12) andrsmG(encoding a 16S rRNA methyltransferase) modulate streptomycin sensitivity inA. fabrum.
Heterogeneous subpopulations of GABAAR-responding neurons coexist in physiological and pathological mature neuronal networks at increasing scales of complexity
Authors: Colombi I. , Rastogi M. , Parrini M. , Alberti M. , Chiappalone M. , Nanni M. , Contestabile A. , Cancedda L. 
Published: May 2023

ABSTRACTGABA is the main inhibitory neurotransmitter in adults. Depolarizing/excitatory GABA responses have been well characterized at the level of neuronal-populationaverageduring typicalneurodevelopmentand partially in pathology. However, no investigation has specifically assessed whether amosaicismof cells with either depolarizing/excitatory or hyperpolarizing/inhibitory GABAergic responses exists inadultanimals in health/disease. Here, we showed that such mosaicism is present both in adult WT and Down syndrome (DS) mice, as assessed at increasing scales of neuronal-network complexity (cultures, brain- slices, behaving mice). Nevertheless, WT mice presented a lower percentage of cells with depolarizing GABA than DS mice. Restoring the mosaicism of hyperpolarizing and depolarizing GABA-responding neurons to WT levels rescued anxiety behaviour in DS mice. We also found heterogeneous GABAergic responses in mature control and trisomic human iPSC-derived neurons. Thus, a heterogeneous population of GABA-responding cells exists in physiological/pathological conditions in mature mouse and human neurons, possibly contributing to disease-associated behaviours.
Cation permeability and pore dynamics in TRPV1 ion channels
Authors: García-Ávila Miriam , Tello-Marmolejo Javier , Rosenbaum Tamara , Islas León D. 
Published: May 2023

AbstractThe Transient Receptor Vanilloid 1 (TRPV1) is a non-selective ion channel, which is activated by several chemical ligands and heat. We have previously shown that activation of TRPV1 by different ligands result in single-channel openings with different conductance, suggesting that the selectivity filter is highly dynamic. TRPV1 is weakly voltage-dependent, here we sought to explore whether the permeation of different monovalent ions could influence the voltage-dependence of this ion channel. By using single-channel recordings, we show that TRPV1 channels undergo rapid transitions to closed states that are directly connected to the open state, which may result from structural fluctuations of their selectivity filters. Moreover, we demonstrate that the rates of these transitions are strongly influenced by the permeant ion, suggesting that ion permeation regulates the voltage dependence of these channels.
Modeling kidney development, disease, and plasticity with clonal expandable nephron progenitor cells and nephron organoids
Authors: Huang Biao , Zeng Zipeng , Li Hui , Li Zexu , Chen Xi , Guo Jinjin , Zhang Chennan C. , Schreiber Megan E. , Vonk Ariel C. , Xiang Tianyuan , Patel Tadrushi , Li Yidan , Parvez Riana K. , Der Balint , Chen Jyun Hao , Liu Zhenqing , Thornton Matthew E. , Grubbs Brendan H. , Diao Yarui , Dou Yali , Gnedeva Ksenia , Lindström Nils O. , Ying Qilong , Pastor-Soler Nuria M. , Fei Teng , Hallows Kenneth R. , McMahon Andrew P. , Li Zhongwei 
Published: May 2023

SUMMARYNephron progenitor cells (NPCs) self-renew and differentiate into nephrons, the functional units of the kidney. Here we report manipulation of p38 and YAP activity creates a synthetic niche that allows the long-term clonal expansion of primary mouse and human NPCs, and induced NPCs (iNPCs) from human pluripotent stem cells. Cultured iNPCs resemble closely primary human NPCs, generating nephron organoids with abundant distal convoluted tubule cells, which are not observed in published kidney organoids. The synthetic niche reprograms differentiated nephron cells into NPC state, recapitulating the plasticity of developing nephronin vivo. Scalability and ease of genome-editing in the cultured NPCs allow for genome-wide CRISPR screening, identi-fying novel genes associated with kidney development and disease. A rapid, efficient, and scala-ble organoid model for polycystic kidney disease was derived directly from genome-edited NPCs, and validated in drug screen. These technological platforms have broad applications to kidney development, disease, plasticity, and regeneration.