bluuebunny/crossref_metadata_2025_split huggingface dataset:
A TetR-like transcriptional regulator in Stenotrophomonas maltophilia involved in fatty acid metabolism is controlled by quorum sensing signals
Authors: Coves Xavier , Huedo Pol , Bravo Marc , Conchillo-Solé Òscar , Gómez Andromeda-Celeste , Esteve-Codina Anna , Dabad Marc , Gut Marta , Daura Xavier , Yero Daniel , Gibert Isidre 
Published: September 2022

ABSTRACTStenotrophomonas maltophilia is an environmental bacterium and it is also an emerging opportunistic multidrug-resistant pathogen. It uses the endogenous DSF quorum sensing (QS) system to coordinate population behaviors and to regulate virulence processes but can also respond to exogenous AHL signals produced by neighboring bacteria. Whole-transcriptome sequencing analyses were performed for S. maltophilia K279a in the exponential and stationary phases as well as in exponential cultures after treatment with exogenous DSF or AHLs. The results revealed that at the beginning of the stationary phase 1673 genes are differentially expressed. COG analysis showed that most of these genes were enriched for energetic metabolism processes and regulation of gene expression. After adding DSF or AHLs, 28 or 82 genes were found deregulated, respectively, 22 of which upregulated by both autoinducers. Interestingly, among these later genes, 14 were also upregulated in the stationary phase. Gene functions regulated by all conditions include lipid and amino acid metabolism, stress response and signal transduction, nitrogen and iron metabolism, and adaptation to microoxic conditions. Among the common top upregulated QS core genes, a putative TetR-like regulator (Smlt2053) was selected for functional characterization. This regulator has been shown to control a narrow regulon, including its own operon. It was found to sense long-chain fatty acids, including the QS signal DSF, and regulate a β-oxidation catabolic pathway. Overall, our findings provide clues on the role that the QS could have in S. maltophilia in the transition from the exponential to the stationary phase and bacterial fitness under high-density growth.IMPORTANCEThe quorum sensing system in Stenotrophomonas maltophilia, in addition to coordinating the bacterial population, controls virulence-associated phenotypes, such as biofilm formation, motility, protease production, and antibiotic resistance mechanisms. Biofilm formation is frequently associated with the persistence and chronic nature of nosocomial infections. In addition, biofilms exhibit high resistance to antibiotics, making treatment of these infections extremely difficult. The importance of studying the metabolic and regulatory systems controlled by quorum sensing autoinducers will make it possible to discover new targets to control pathogenicity mechanisms in S. maltophilia.
Record-matching of STR profiles with fragmentary genomic SNP data
Authors: Kim Jaehee , Rosenberg Noah A. 
Published: September 2022

AbstractIn many forensic settings, identity of a DNA sample is sought from poor-quality DNA, for which the typical STR loci tabulated in forensic databases are not possible to reliably genotype. Genome-wide SNPs, however, can potentially be genotyped from such samples via next-generation sequencing, so that queries can in principle compare SNP genotypes from DNA samples of interest to STR genotype profiles that represent proposed matches. We use genetic record-matching to evaluate the possibility of testing SNP profiles obtained from poor-quality DNA samples to identify exact and relatedness matches to STR profiles. Using 2,504 whole-genome sequences, we show that in some settings, similar match accuracies to those seen with full coverage of the genome are obtained by genetic record-matching for SNP data that represent 5-10% genomic coverage. Thus, if even a fraction of random genomic SNPs can be genotyped by next-generation sequencing, then the potential may exist to test the resulting genotype profiles for matches to profiles consisting exclusively of nonoverlapping STR loci. The result has implications in relation to criminal justice, mass disasters, missing-person cases, studies of ancient DNA, and genomic privacy.
Dectin-1 Stimulation Promotes a Distinct Inflammatory Signature in the Setting of HIV-infection and Aging
Authors: Kumar Archit , Wang Jiawei , Zhou Haowen , Radcliffe Chris , Wyk Brent Vander , Allore Heather G. , Tsang Sui , Barakat Lydia , Mohanty Subhasis , Zhao Hongyu , Shaw Albert C. , Zapata Heidi J. 
Published: September 2022

AbstractDectin-1 is an innate immune receptor that recognizes and binds β-1,3/1,6 glucans on fungi. We evaluated Dectin-1 function in myeloid cells in a cohort of HIV-positive and HIV-negative young and older adults. Stimulation of monocytes with β-D-glucans induced a pro-inflammatory phenotype in monocytes of HIV-infected individuals that was characterized by increased levels of IL-12, TNF-α, and IL-6, with some age-associated cytokine increases also noted. Dendritic cells showed a striking HIV-associated increase in IFN-α production. These increases in cytokine production paralleled increases in Dectin-1 surface expression in both monocytes and dendritic cells that were noted with both HIV and aging. Differential gene expression analysis showed that HIV-positive older adults had a distinct gene signature compared to other cohorts characterized by a robust TNF-α and coagulation response (increased at baseline), a persistent IFN-α and IFN-γ response, and an activated dendritic cell signature/M1 macrophage signature upon Dectin-1 stimulation. Dectin-1 stimulation induced a strong upregulation of MTORC1 signaling in all cohorts, although increased in the HIV-Older cohort (stimulation and baseline). Overall, our study demonstrates that the HIV Aging population has a distinct immune signature in response to Dectin-1 stimulation. This signature may contribute to the pro-inflammatory environment that is associated with HIV and Aging.
Alpha kinase 3 signaling at the M-band maintains sarcomere integrity and proteostasis in striated muscle
Authors: McNamara James W. , Parker Benjamin L. , Voges Holly K. , Mehdiabadi Neda R. , Bolk Francesca , Chung Jin D. , Charitakis Natalie , Molendijk Jeffrey , Lal Sean , Ramialison Mirana , Karavendzas Kathy , Pointer Hayley L. , Syrris Petros , Lopes Luis R. , Elliott Perry M. , Lynch Gordon S. , Mills Richard J. , Hudson James E. , Watt Kevin I. , Porrello Enzo R. , Elliott David A 
Published: September 2022

SUMMARYPathogenic variants in alpha kinase 3 (ALPK3) cause cardiomyopathy and musculoskeletal disease. How ALPK3 mutations result in disease remains unclear because little is known about this atypical kinase. Using a suite of engineered human pluripotent stem cells (hPSCs) we show that ALPK3 localizes to the M-Band of the sarcomere. ALPK3 deficiency disrupted sarcomeric organization and calcium kinetics in hPSC-derived cardiomyocytes and reduced force generation in cardiac organoids. Phosphoproteomic profiling identified ALPK3-dependant phospho-peptides that were enriched for sarcomeric components of the M-band and the ubiquitin-binding protein SQSTM1. Analysis of the ALPK3 interactome confirmed binding to M-band proteins including SQSTM1. Importantly, in hPSC-derived cardiomyocytes modeling ALPK3 deficiency and cardiomyopathic ALPK3 mutations, sarcomeric organization and M-band localization ofSQSTM1 were abnormal. These data suggest ALPK3 has an integral role in maintaining sarcomere integrity and proteostasis in striated muscle. We propose this mechanism may underly disease pathogenesis in patients with ALPK3 variants.
ANKRD26 is a new regulator of type I cytokine receptor signaling in normal and pathological hematopoiesis
Authors: Basso-Valentina Francesca , Donada Alessandro , Manchev Vladimir T , Lisetto Manuel , Balayn Nathalie , Martin Jean Edouard , Muller Delphine , Marin Oyarzun Cecilia Paola , Duparc Hélène , Arkoun Brahim , Cumin Alessandro , Faivre Lionel , Droin Nathalie , Biunno Ida , Balduini Alessandra , Debili Najet , Antony-Debré Iléana , Marty Caroline , Vainchenker William , Plo Isabelle , Favier Remi , Raslova Hana 
Published: September 2022

ABSTRACTSustained ANKRD26 expression associated with germline ANKRD26 mutations causes Thrombocytopenia 2 (THC2), an inherited platelet disorder associated with leukemia predisposition. Some of those patients present also erythrocytosis and/or leukocytosis. Using multiple human-relevant in vitro models (cell lines, primary patient cells and patient-derived iPSCs) we demonstrate for the first time that ANKRD26 is expressed during the early steps of erythroid, megakaryocyte and granulocyte differentiation, and is necessary for progenitor proliferation. As differentiation progresses, ANKRD26 expression is progressively silenced, to complete the cellular maturation of the three myeloid lineages. In primary cells, abnormal ANKRD26 expression in committed progenitors directly impacts the proliferation/differentiation balance for these three cell types. We show that ANKRD26 interacts with and crucially modulates the activity of MPL, EPOR and G-CSFR, three homodimeric type I cytokine receptors that regulate blood cell production. Higher than normal levels of ANKRD26 prevent the receptor internalization, which leads to increased signaling and cytokine hypersensitivity. Altogether these findings show that ANKRD26 overexpression or the absence of its silencing during differentiation are responsible for myeloid blood cell abnormalities in THC2 patients.
Wide Window Acquisition and AI-based data analysis to reach deep proteome coverage for a wide sample range, including single cell proteomic inputs
Authors: Mayer Rupert L. , Matzinger Manuel , Schmücker Anna , Stejskal Karel , Krššáková Gabriela , Berger Frédéric , Mechtler Karl 
Published: September 2022

ABSTRACTA comprehensive proteome map is essential to elucidate molecular pathways and protein functions. Although great improvements in sample preparation, instrumentation and data analysis already yielded impressive results, current studies suffer from a limited proteomic depth and dynamic range therefore lacking low abundant or highly hydrophobic proteins. Here, we combine and benchmark advanced micro pillar array columns (µPAC™) operated at nanoflow with Wide Window Acquisition (WWA) and the AI-based CHIMERYS™ search engine for data analysis to maximize chromatographic separation power, sensitivity and proteome coverage.Our data shows that µPAC™ columns clearly outperform classical packed bed columns boosting peptide IDs by up to 140%. Already at classical narrow isolation widths CHIMERYS™ boosted ID rates by a factor of 2.6 compared to the conventional search engine MS Amanda 2.0. By combining CHIMERYS™ with WWA, even a 4.6-fold increase in ID rates could be achieved.Using our optimized workflow, we were further able to identify more than 10,000 proteins from a single 2 h gradient shotgun analysis. We further investigated the applicability of WWA for single cell inputs and found that the choice of the optimal isolation window width depends on sample input and complexity. Using a short 5.5 cm column and very high flow rates during loading and column equilibration we improved sample throughput to ∼100 samples per day while maintaining high protein ID numbers. We believe that this is especially important for the single cell field where throughput is one of the most limiting factors.Finally, we applied our optimized workflow on immunoprecipitations of Smarca5/SNF2H and found 32 additional interaction partners compared to the original workflow utilizing a packed bed column. These additional interaction partners include previously described interaction partners of Smarca5 like Baz2b as well as undescribed interactors including Arid1a, which is also involved in chromatin remodeling and has been described as key player in neurodevelopmental and malignant disorders.
Ventral temporal and posteromedial sulcal morphology in autism spectrum disorder
Authors: Benitez Javier Ramos , Kannan Sandhya , Hastings William L. , Parker Benjamin J. , Willbrand Ethan H. , Weiner Kevin S. 
Published: September 2022

AbstractTwo recent parallel research tracks link tertiary sulcal morphology—sulci that emerge last in gestation and continue to develop after birth—with functional features of the cerebral cortex and cognition, respectively. The first track identified a relationship between the mid-fusiform sulcus (MFS) in ventral temporal cortex (VTC) and cognition in individuals with Autism Spectrum Disorder (ASD). The second track identified a new tertiary sulcus, the inframarginal sulcus (IFRMS), that serves as a tripartite landmark within the posteromedial cortex (PMC). As VTC and PMC are structurally and functionally different in individuals with ASD compared to neurotypical controls (NTs), here, we integrated these two tracks with a twofold approach. First, we tested if there are morphological differences in VTC and PMC sulci between 50 NTs and 50 individuals with ASD. Second, we tested if tertiary sulcal morphology was linked to cognition in ASD individuals. Our twofold approach replicates and extends recent findings in five ways. First, in terms of replication, the standard deviation (STD) of MFS cortical thickness (CT) was increased in ASDs compared to NTs. Second, MFS length was shorter in ASDs compared to NTs. Third, the CT STD effect extended to other VTC and PMC sulci. Fourth, a subset of VTC and PMC morphological features were correlated between regions in ASD. Fifth, IFRMS depth was negatively associated with ADOS-GS score. These results empirically support a relationship between later-developing, tertiary sulci and ASD, providing a novel framework to study the relationship between brain structure and cognition in additional neurodevelopmental disorders in future studies.Lay SummaryWe observed that some, but not all, morphological features of later-developing tertiary indentations (sulci) in the cerebral cortex differed significantly between neurotypical controls and individuals with autism spectrum disorder (ASD). In ASD, a subset of sulcal morphological features also correlated between brain areas and one feature reflected differences in cognition. Thus, studying these structures provides insight into how individual variability in structure is related to individual variability in cognition in ASD.
Pro-inflammatory chemokines CCL5, CXCL12, and CX3CL1 bind to and activate platelet integrin αIIbβ3 in an allosteric manner
Authors: Takada Yoko K , Fujita Masaaki , Takada Yoshikazu 
Published: September 2022

AbstractPrevious studies showed that pro-inflammatory chemokines CX3CL1 and CXCL12 bound to the allosteric binding site (site 2) of integrins and allosterically activated integrins, in addition to the classical ligand-binding site (site 1). We showed that CCL5 also bound to site 2, in addition to site 1, and activated soluble integrin αvβ3. Platelet integrin αIIbβ3, a fibrinogen receptor, is critical for hemostasis and thrombus formation and activation of αIIbβ3 is a key event for thrombus formation. Activation of αIIbβ3 is known to be mediated exclusively by inside-out signaling. We studied if αIIbβ3 can be allosterically activated. We discovered that CCL5, CXCL12, and CX3CL1 are new ligands for αIIbβ3. Notably they enhanced the binding of monovalent ligand to soluble αIIbβ3 in 1 mM Ca2+by binding to site 2. They activated cell-surface αIIbβ3 on CHO cells quickly (half maximal response <1 min) and at low concentrations (1-10 ng/ml) compared to soluble αIIbβ3, probably because chemokines bind to cell surface proteoglycans. Notably, activation of αIIbβ3 by the chemokines was several times more potent than 1 mM Mn2+. Since CCL5 and CXCL12 are stored in platelet granules and rapidly transported to the surface upon platelet activation, we hypothesized that they are released from the granules and allosterically activate αIIbβ3 by binding to site 2.Transmembrane CX3CL1 on activated endothelial cells likely mediates platelet-endothelial interaction by binding to and activating αIIbβ3. Also, over-produced chemokines during inflammation may trigger αIIbβ3 activation, which is a possible missing link between inflammation and thrombosis.
Transcriptional changes in human palate and skin healing
Authors: Leonardo Trevor R , Chen Lin , Schrementi Megan E , Shi Junhe , Marucha Phillip T , Glass Kimberly , DiPietro Luisa A 
Published: September 2022

AbstractMost human tissue injuries lead to the formation of a fibrous scar and result in the loss of functional tissue. One adult tissue that exhibits a more regenerative response to injury with minimal scarring is the oral mucosa. We generated a microarray gene expression dataset to examine the response to injury from human palate and skin excisional biopsies spanning the first seven days after wounding. Differential expression analyses were performed in each tissue to identify genes overexpressed or underexpressed over time compared to baseline unwounded tissue. To attribute biological processes of interest to these gene expression changes, gene set enrichment analysis was used to identify core gene sets that are enriched over the time-course of the wound healing process with respect to unwounded tissue. This analysis identified gene sets uniquely enriched in either palate or skin wounds and gene sets that are enriched in both tissues in at least one time point after injury. Finally, a cell-deconvolution analysis was performed to better understand the cell type distribution in these tissues and how it changes over the time course of wound healing. This work provides a source of human wound gene expression data that includes two tissue types with distinct regenerative and scarring phenotypes.
COVID-19-associated AKI in hospitalized US patients: incidence, temporal trends, geographical distribution, risk factors and mortality
Authors:   Masthead, Yoo Yun Jae , Wilkins Kenneth J. , Alakwaa Fadhl , Liu Feifan , Torre-Healy Luke A. , Krichevsky Spencer , Hong Stephanie S. , Sakhuja Ankit , Potu Chetan K. , Saltz Joel H. , Saran Rajiv , Zhu Richard L. , Setoguchi Soko , Kane-Gill Sandra L. , Mallipattu Sandeep K. , He Yongqun , Ellison David H. , Byrd James Brian , Parikh Chirag R. , Moffitt Richard A. , Koraishy Farrukh M. 
Published: September 2022

ABSTRACTBackgroundAcute kidney injury (AKI) is associated with mortality in patients hospitalized with COVID-19, however, its incidence, geographic distribution, and temporal trends since the start of the pandemic are understudied.MethodsElectronic health record data were obtained from 53 health systems in the United States (US) in the National COVID Cohort Collaborative (N3C). We selected hospitalized adults diagnosed with COVID-19 between March 6th, 2020, and January 6th, 2022. AKI was determined with serum creatinine (SCr) and diagnosis codes. Time were divided into 16-weeks (P1-6) periods and geographical regions into Northeast, Midwest, South, and West. Multivariable models were used to analyze the risk factors for AKI or mortality.ResultsOut of a total cohort of 306,061, 126,478 (41.0 %) patients had AKI. Among these, 17.9% lacked a diagnosis code but had AKI based on the change in SCr. Similar to patients coded for AKI, these patients had higher mortality compared to those without AKI. The incidence of AKI was highest in P1 (49.3%), reduced in P2 (40.6%), and relatively stable thereafter. Compared to the Midwest, the Northeast, South, and West had higher adjusted AKI incidence in P1, subsequently, the South and West regions continued to have the highest relative incidence. In multivariable models, AKI defined by either SCr or diagnostic code, and the severity of AKI was associated with mortality.ConclusionsUncoded cases of COVID-19-associated AKI are common and associated with mortality. The incidence and distribution of COVID-19-associated AKI have changed since the first wave of the pandemic in the US.
Sodium content of menu items in New York City chain restaurants following enforcement of the sodium warning icon rule, 2015-2017
Authors: Sisti Julia S. , Prasad Divya , Niederman Sarah , Mezzacca Tamar Adjoian , Anekwe Amaka V. , Clapp Jenifer , Farley Shannon M. 
Published: September 2022

AbstractIn 2016, New York City (NYC) began enforcing a sodium warning regulation at chain restaurants, requiring placement of an icon next to any menu item containing ≥2,300 mg sodium. As menu labeling may improve menu nutritional composition, we investigated whether sodium content of menu items changed following enforcement of the sodium warning icon. All menu offerings at 10 quick-service (QSR) and 3 full-service (FSR) chain restaurants were photographed in 2015 (baseline) and 2017 (follow-up) and matched to nutritional information from restaurant websites; items were categorized as being available at both baseline and follow-up, or at only one timepoint. Linear and logistic regression models, respectively, assessed changes in calculated mean sodium-per-serving and the odds of an item containing ≥2,300 mg sodium. At baseline, mean per-serving sodium content was 2,160 mg at FSR and 1,070 mg at QSR, and 40.6% of FSR items and 7.2% of QSR items contained ≥2,300 mg sodium per serving. Sodium content did not differ when comparing all items offered at follow-up to all offered at baseline (21 mg, 95% CI: -60,101), or when comparing new versus discontinued items (17 mg, 95% CI: -154, 187). At follow-up, there was a non-significant increase in the overall likelihood of items requiring a warning icon (OR=1.32, 95% CI: 0.97,1.79). When comparing new versus discontinued items, there was a twofold increase in the odds of requiring a warning icon (OR=2.08, 95% CI: 1.02,4.24). Our findings both highlight high sodium content of menu items at popular chain restaurants and underscore difficulties in motivating restaurants to reduce sodium levels.
Organoid-based single-cell spatiotemporal gene expression landscape of human embryonic development and hematopoiesis
Authors: Chao Yiming , Xiang Yang , Xiao Jiashun , Zhang Shihui , Zheng Weizhong , Wan Xiaomeng , Li Zhuoxuan , Gao Mingze , Wang Gefei , Chen Zhilin , Ebrahimkhani Mo , Yang Can , Wu Angela Ruohao , Liu Pentao , Huang Yuanhua , Sugimura Ryohichi 
Published: September 2022

AbstractSingle-cell level characterization of embryonic development is a major benchmark of human developmental biology. Spatiotemporal analysis of stem-cell-derived embryos offers conceptual and technical advances in the field. Here, we defined the single-cell spatiotemporal gene expression landscape of human embryonic development with stem-cell-derived organoids. We established the human embryonic organoid (HEMO) from expanded potential stem cells and achieved both embryonic and extraembryonic tissues in the same organoid. Time-series single-cell RNA sequencing paired with single-cell resolution spatial revealed human embryonic development signatures such as extraembryonic placenta, yolk sac hematopoiesis neural crest, blood vessels, and cardiac mesoderm. Hematopoietic tissues eventually predominated HEMO with erythropoiesis, mekagaryopiesis, and myelopoiesis. Cell-cell communication network analysis demonstrated that trophoblast-like tissues supplied WNT signaling in neural crest cells to facilitate maturation and migration. Single-cell resolution spatial transcriptomics defined the yolk sac erythro-megakaryopoietic niche. Vitronectin-integrin signaling, a major contributor to megakaryocyte maturation, was predominant in the yolk sac niche in HEMO and to human fetal samples. Overall, our study advances the spatiotemporal analysis of human embryonic development in stem-cell-derived organoids.HighlightsModeling human embryonic development from stem cellsUsed of both 10X Chromium and 10X Visium to define the gene expression landscape of embryonic development and hematopoiesisWNT signaling as a regulator of neural crest maturation and EMTVTN-ITGA2B as the main contributor to Mk maturation within the yolk sac erythro-megakaryopoietic nicheGraphical abstract