bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of host factors for Rift Valley Fever Phlebovirus
Authors: Balaraman Velmurugan , Indran Sabarish V. , Li Yonghai , Meekins David A. , Jakkula Laxmi U.M.R. , Liu Heidi , Hays Micheal P. , Souza-Neto Jayme A. , Gaudreault Natasha N. , Hardwidge Philip R. , Wilson William C. , Weber Friedemann , Richt Juergen A. 
Published: September 2023

AbstractBackgroundRift Valley fever phlebovirus (RVFV) is a zoonotic pathogen that causes Rift Valley fever (RVF) in livestock and humans. Currently, there is no licensed human vaccine or antiviral drug to control RVF. Although multiple species of animals and humans are vulnerable to RVFV infection, host factors affecting susceptibility are not well understood.MethodologyTo identify the host factors or genes essential for RVFV replication, we conducted a CRISPR-Cas9 knock-out screen in human A549 cells. We then validated the putative genes using siRNA-mediated knockdowns and CRISPR-Cas9-mediated knockout studies, respectively. The role of a candidate gene in the virus replication cycle was assessed by measuring intracellular viral RNA accumulation, and the virus titers by plaque assay or TCID50assay.FindingsWe identified approximately 900 genes with potential involvement in RVFV infection and replication. Further evaluation of the effect of six genes on viral replication using siRNA-mediated knockdowns found that silencing two genes (WDR7 and LRP1) significantly impaired RVFV replication. For further analysis, we focused on theWDR7gene since the role ofLRP1in RVFV replication was previously described in detail. Knock-out A549 cell lines were generated and used to dissect the effect ofWRD7on RVFV and another bunyavirus, La Crosse encephalitis virus (LACV). We observed significant effects ofWDR7knock-out cells on both intracellular RVFV RNA levels and viral titers. At the intracellular RNA level,WRD7affected RVFV replication at a later phase of its replication cycle (24h) when compared to LACV which was affected an earlier replication phase (12h).ConclusionIn summary, we have identifiedWDR7as an essential host factor for the replication of two relevant bunyaviruses, RVFV and LACV. Future studies will investigate the mechanistic role by whichWDR7facilitates Phlebovirus replication.Authors SummaryRift Valley fever phlebovirus is a high consequence pathogen that infects multiple animal species and also humans. Currently, there are no control measures available to treat RVF in humans and to prevent the incursion of Rift Valley fever virus into non-endemic countries. RVFV poses a significant threat to animal and human health in countries where it is endemic. RVFV replication depends on the host’s machinery to complete its replication cycle. Therefore, one way to control virus replication is to disrupt the interaction between the virus and the host proteins important for replication. In this study, we identified a host factor, the WDR7 gene, that is critical for RVFV replication. The identification of this host factor is important as it can potentially lead to the development of antiviral strategies to control Rift Valley fever in both humans and animals.
Organic matter degradation in the deep, sulfidic waters of the Black Sea: Insights into the ecophysiology of novel anaerobic bacteria
Authors: Yadav Subhash , Koenen Michel , Bale Nicole J , Reitsma Wietse , Engelmann Julia C , Damsté Jaap S. Sinninghe , Villanueva Laura 
Published: September 2023

AbstractOur knowledge about the physiology of deep sea (>1,000 m) microorganisms involved in organic matter (OM) degradation is still scare due to the lack of available isolates, especially from sulfidic environments. In this study, we successfully cultivated and characterized the physiology of a wide range of novel piezotolerant anaerobic bacteria affiliated with the phylaFusobacteriota,Bacillota,Spirochaetota,Bacteroidota,Cloacimonadota,Planctomycetota,MycoplasmatotaandChloroflexotainvolved in OM degradation in deep sulfidic waters of the Black Sea. The novel taxa are specialized in degrading specific types of OM and cover a wide range of physiological categories, including primary degraders, fermenters, and terminal oxidizers. This is the first report which demonstrates this for such a diverse physiological group from any sulfidic marine habitat. Collectively, this study provides a step forward in our understanding of the microbes thriving in the extreme conditions of the deep sulfidic waters of the Black Sea.
A resource for probing influences of perinatal factors on neurodevelopment in 3-10-years-old Chinese children
Authors: Wang Yin-Shan , Su Xue-Ting , Ke Li , He Qing-Hua , Chang Da , Nie JingJing , Luo XinLi , Chen Fumei , Xu Jihong , Zhang Cai , Zhang Shudong , Zhang Shuyue , An Huiping , Guo Rui , Yue Suping , Duan Wen , Jia Shichao , Yang Sijia , Yu Yankun , Zhao Yang , Zhou Yang , Chen Li-Zhen , Fan Xue-Ru , Gao Peng , Lv Chenyu , Wu Ziyun , Zhao Yunyan , Quan Xi , Zhao Feng , Mu Yanchao , Yan Yu , Xu Wenchao , Liu Jie , Xing Lixia , Chen Xiaoqin , Wu Xiang , Zhao Lanfeng , Huang Zhijuan , Ren Yanzhou , Hao Hongyan , Li Hui , Wang Jing , Dong Qing , Chen Yanli , Huang Ruiwang , Liu Siman , Wang Yun , Dong Qi , Zuo Xi-Nian 
Published: September 2023

ABSTRACTAdverse perinatal factors can disrupt the normal development of the brain, with potential long-term impacts on children’s overall development. Currently, the neuropathological mechanisms by which these factors lead to various neurodevelopmental disorders (NDDs) remain largely unknown. An open resource that integrate perinatal factors with brain and mental health development is essential for investigating NDD-related aetiology. In this Data Descriptor, we introduce a multicentre database containing information on perinatal factors that influence children’s brain-mind development, namely, periCBD, that combines neuroimaging and behavioural phenotypes with perinatal factors associated with a high incidence of NDDs at county/region/central district hospitals. PeriCBD was designed to establish a platform for the investigation of individual differences in brain-mind development among children aged 3–10 years are associated with perinatal factors. Ultimately, our goal was to develop an early prediction and screening model for NDDs that leverages normative data to facilitate NDD aetiology research. Herein, we provide a systematic overview of the data acquisition/cleaning/quality control/sharing, processes of periCBD and present preliminary brain-mind associations.
BRG1/BRM inhibitor targets AML stem cells and exerts superior preclinical efficacy combined with BET or Menin inhibitor
Authors: Fiskus Warren , Piel Jessica , Collins Mike , Hentemann Murphy , Cuglievan Branko , Mill Christopher P. , Birdwell Christine E. , Das Kaberi , Davis John A. , Hou Hanxi , Jain Antrix , Malovannaya Anna , Kadia Tapan M. , Daver Naval , Sasaki Koji , Takahashi Koichi , Hammond Danielle , Reville Patrick , Wang Jian , Loghavi Sanam , Sen Rwik , Ruan Xinjia , Su Xiaoping , Flores Lauren B. , DiNardo Courtney D. , Bhalla Kapil N. 
Published: October 2023

AbstractBRG1 (SMARCA4) and BRM (SMARCA2) are the core ATPases of chromatin remodeling BAF (BRG1/BRM-associated factor) complexes, which enable transcription factors/co-factors to modulate gene-expressions, mediating growth, differentiation-arrest and survival of AML cells. In AML with MLL1r (MLL1 rearrangement) or mutant (mt) NPM1, although monotherapy with Menin inhibitor (MI) induces clinical remissions, most patients either fail to respond or relapse. FHD-286 is a selective BRG1/BRM inhibitor, undergoing clinical development in AML. Here, FHD-286 induced differentiation and lethality in AML cells with MLL1r or mtNPM1, reducing chromatin accessibility and repressing c-Myc, PU.1 and CDK4/6. Whereas FHD-286 monotherapy reduced AML burden, leukemia-initiating potential and improved survival, FHD-286 combinations with MI, BET inhibitor, decitabine or venetoclax was significantly more effective in reducing AML burden and improved survival, without significant toxicity, in xenograft models of AML with MLL1r or mtNPM1. These findings highlight promising FHD-286-based combinations for therapy of AML with MLL1r or mtNPM1.Statement of SignificanceInhibition of BRG1/BRM ATPases by FHD-286 reduced chromatin accessibility, repressed c-Myc, PU.1 and CDK4/6, inducing differentiation, leukemia-initiating potential and lethality in AML stem-progenitor cells. FHD-286-based combinations with Menin or BET inhibitor or decitabine reduced AML burden and improved survival in xenograft models of AML with MLL rearrangement or mutant NPM1.
Transcriptome-wide RNA structure probing with temporal resolution
Authors: Wang Danyang , Tang Yongkang , Li Ang , Sun Lei , Kleiner Ralph E. 
Published: September 2023

ABSTRACTReactive small-molecule probes are widely used for RNA structure probing, however current approaches largely measure average RNA transcript dynamics and do not resolve structural differences that occur during folding or transcript maturation. Here, we present SNIPER-seq, an RNA structure probing method relying upon metabolic labeling with 2’-aminodeoxycytidine, structure-dependent 2’-amino reaction with an aromatic isothiocyanate, and high-throughput RNA sequencing. Our method maps cellular RNA structure transcriptome-wide with temporal resolution enabling determination of transcript age-dependent RNA structural dynamics. We benchmark our approach against known RNA structures and investigate the dynamics of human 5S rRNA during ribosome biogenesis, revealing specific structural changes in 5S rRNA loops that occur over the course of several hours. Taken together, our work sheds light on the maturation and coordinated conformational changes that take place during ribosome biogenesis and provides a general strategy for surveying evolving RNA structural dynamics across the transcriptome.
Pervasive morphological responses to climate change in bird body and appendage size
Authors: Ryding Sara , McQueen Alexandra , Klaassen Marcel , Tattersall Glenn J. , Symonds Matthew R.E. 
Published: October 2023

AbstractChanges to body size and shape have been identified as potential adaptive responses to climate change, but the pervasiveness of these responses is questioned. To address this, we measured body and appendage size from 5013 museum bird skins of ecologically and evolutionary diverse species. We found that morphological change is a shared response to climate change across birds. Birds increased bill surface area, tarsus length, and relative wing length through time, consistent with expectations of increasing appendage size in warmer climates. Furthermore, birds decreased in absolute wing length, consistent with the expectation of decreasing body size in warmer climates. Interestingly, these trends were generally consistent across different diets, foraging habitats, and migratory and thermoregulatory behaviours. Shorter-term responses to hot weather were contrary to long-term effects for appendages. Overall, our findings support that morphological adaptation is a widespread response to climate change in birds that is independent of other ecological traits.
Commensal myeloid crosstalk in neonatal skin regulates long-term cutaneous type 17 inflammation
Authors: Dhariwala Miqdad O. , DeRogatis Andrea M. , Okoro Joy N. , Weckel Antonin , Tran Victoria M. , Habrylo Irek , Ojewumi Oluwasunmisola T. , Tammen Allison E. , Leech John M. , Merana Geil R. , Carale Ricardo O. , Barrere-Cain Rio , Hiam-Galvez Kamir J. , Spitzer Matthew H. , Scharschmidt Tiffany C. 
Published: October 2023

AbstractEarly life microbe-immune interactions at barrier surfaces have lasting impacts on the trajectory towards health versus disease. Monocytes, macrophages and dendritic cells are primary sentinels in barrier tissues, yet the salient contributions of commensal-myeloid crosstalk during tissue development remain poorly understood. Here, we identify that commensal microbes facilitate accumulation of a population of monocytes in neonatal skin. Transient postnatal depletion of these monocytes resulted in heightened IL-17A production by skin T cells, which was particularly sustained among CD4+T cells into adulthood and sufficient to exacerbate inflammatory skin pathologies. Neonatal skin monocytes were enriched in expression of negative regulators of the IL-1 pathway. Functional in vivo experiments confirmed a key role for excessive IL-1R1 signaling in T cells as contributing to the dysregulated type 17 response in neonatal monocyte-depleted mice. Thus, a commensal-driven wave of monocytes into neonatal skin critically facilitates long-term immune homeostasis in this prominent barrier tissue.
Translation fidelity and respiration deficits in CLPP-deficient tissues: Mechanistic insights from mitochondrial complexome
Authors: Key Jana , Gispert Suzana , Koepf Gabriele , Steinhoff-Wagner Julia , Reichlmeir Marina , Auburger Georg 
Published: September 2023

AbstractMitochondrial matrix peptidase CLPP is crucial during cell stress. Its loss causes Perrault syndrome type 3 (PRLTS3) with infertility, neurodegeneration and growth deficit. Its target proteins are disaggregated by CLPX, which also regulates heme biosynthesis via unfolding ALAS enzyme, providing access of pyridoxal-5’-phosphate (PLP). Despite efforts in diverse organisms with multiple techniques, CLPXP substrates remain controversial. Here, avoiding recombinant overexpression, we employed complexomics in mitochondria from three mouse tissues to identify endogenous targets. CLPP absence caused accumulation and dispersion of CLPX-VWA8 as AAA+ unfoldases, and of PLPBP. Similar changes and CLPX-VWA8 comigration were evident for mitoribosomal central protuberance clusters, translation factors like GFM1-HARS2, RNA granule components LRPPRC-SLIRP, and enzymes OAT-ALDH18A1. Mitochondrially translated proteins in testis showed reductions to <30% for MTCO1-3, misassembly of complex-IV supercomplex, and accumulated metal-binding assembly factors COX15-SFXN4. Indeed, heavy metal levels were increased for iron, molybdenum, cobalt and manganese. RT-qPCR showed compensatory downregulation only forClpxmRNA, most accumulated proteins appeared transcriptionally upregulated. Immunoblots validated VWA8, MRPL38, MRPL18, GFM1 and OAT accumulation. Coimmunoprecipitation confirmed CLPX binding to MRPL38, GFM1 and OAT, so excess CLPX and PLP may affect their activity. Our data elucidate mechanistically the mitochondrial translation fidelity deficits, which underlie progressive hearing impairment in PRLTS3.
Repeated FRAP of the actin-binding protein CapG in the cell nucleus - a functional assay for EGF signaling in the single live breast cancer cell
Authors: Fernandez MK , Sinha M , Renz M 
Published: October 2023

AbstractCompartmentalization and differential distribution of proteins within a cell maintain cellular function and viability. CapG is the only gelsolin-related actin-binding protein that distributes in steady state diffusively throughout cytoplasm and cell nucleus. To detect changes in CapG’s nuclear shuttling in response to external stimuli on the single cell level, we established repeated FRAP experiments of one and the same breast cancer cell. With this experimental set up, we found that ATP-depletion reversibly decreased CapG’s shuttling into the cell nucleus. The addition of epidermal growth factor (EGF) increased CapG’s nuclear shuttling within minutes. Serum-starvation doubled the number of breast cancer cells from 40% to 80% displaying increased CapG shuttling in response to EGF. Testing five different potential CapG phosphorylation sites, we found that serine 70 mediates the increase in CapG’s nuclear shuttling triggered by EGF. Thus, repeated FRAP of CapG in the cell nucleus can be used as functional readout of signaling cascades in the same single live breast cancer cell.
Resident Synovial Macrophages in Synovial Fluid: Implications for Immunoregulation in Infectious and Inflammatory Arthritis
Authors: Cyndari Karen I. , Scorza Breanna M. , Zacharias Zeb R. , Strand Leela , Mahachi Kurayi , Oviedo Juan Marcos , Gibbs Lisa , Pessoa-Pereira Danielle , Ausdal Graham , Hendricks Dylan , Yahashiri Rika , Elkins Jacob M. , Gulbrandsen Trevor , Peterson Andrew R. , Willey Michael C. , Fairfax Keke C. , Petersen Christine A. 
Published: October 2023

AbstractObjectivesResident synovial macrophages (RSM) provide immune sequestration of the joint space and are likely involved in initiation and perpetuation of the joint-specific immune response. We sought to identify RSM in synovial fluid (SF) and demonstrate migratory ability, in additional to functional changes that may perpetuate a chronic inflammatory response within joint spaces.MethodsWe recruited human patients presenting with undifferentiated arthritis in multiple clinical settings. We used flow cytometry to identify mononuclear cells in peripheral blood and SF. We used a novel transwell migration assay with humanex-vivosynovium obtained intra-operatively to validate flow cytometry findings. We used single cell RNA-sequencing (scRNA-seq) to further identify macrophage/monocyte subsets. ELISA was used to evaluate the bone-resorption potential of SF.ResultsWe were able to identify a rare population of CD14dim, OPG+, ZO-1+cells consistent with RSM in SF via flow cytometry. These cells were relatively enriched in the SF during infectious processes, but absolutely decreased compared to healthy controls. Similar putative RSM were identified usingex vivomigration assays when MCP-1 and LPS were used as migratory stimulus. scRNA-seq revealed a population consistent with RSM transcriptionally related to CD56+cytotoxic dendritic cells and IDO+M2 macrophages.ConclusionWe identified a rare cell population consistent with RSM, indicating these cells are likely migratory and able to initiate or coordinate both acute (septic) or chronic (autoimmune or inflammatory) arthritis. RSM analysis via scRNA-seq indicated these cells are M2 skewed, capable of antigen presentation, and have consistent functions in both septic and inflammatory arthritis.
Introducing Molecular Hypernetworks for Discovery in Multidimensional Metabolomics Data
Authors: Colby Sean M , Shapiro Madelyn R , Lin Andy , Bilbao Aivett , Broeckling Corey D , Purvine Emilie , Joslyn Cliff A 
Published: October 2023

AbstractOrthogonal separations of data from high-resolution mass spectrometry can provide insight into sample composition and help address the challenge of complete annotation of molecules in untargeted metabolomics. “Molecular networks” (MNs), as used, for example, in the Global Natural Products Social Molecular Networking platform, are an increasingly popular computational strategy for exploring and visualizing molecular relationships and improving annotation. MNs use graph representations to show the re-lationships between measured multidimensional data features. MNs also show promise for using network science algorithms to automatically identify targets for annotation candidates and to dereplicate features associated to a single molecular identity. How-ever, more advanced methods may better represent the complexity present in samples. Our work aims to increase confidence in annotation propagation by extending molecular network methods to include “molecular hypernetworks” (MHNs), able to natively repre-sent multiway relationships among observations supporting both human and analytical processing. In this paper we first introduce MHNs illustrated with simple examples, and demonstrate how to build them from liquid chromatography-and ion mobility spectrometry-separated MS data. We then describe a method to construct MHNs di-rectly from existing MNs as their “clique reconstructions”, demonstrating their utility by comparing examples of previously published graph-based MNs to their respective MHNs.
Nuanced patterns of biological collecting trends revealed by informatic investigation of zoological natural history collection records
Authors: Card Daren C. 
Published: October 2023

AbstractNatural history museums comprise a unique and important component of biological infrastructure worldwide, and underlie diverse research, education, and outreach in the natural sciences. Each museum is built around one or more biological collections that serve as a repository of important materials for study, which have contributed to scientific research in increasingly important areas ranging from understanding global climate change to developing new biotechnological applications. However, despite centuries of existence, global collections sizes have only been recently estimated, and aside from analyses of certain institutions or well-studied clades, little is known about how patterns of collecting activity across institutions, geographic regions, or taxonomic clades, or how these patterns vary across time. To address this important gap in our understanding of critical life sciences infrastructure, I gathered and analyzed zoological records associated with preserved specimens collected between 1900 and 2015 and housed in worldwide natural history collections using data from the Global Biodiversity Information Facility. My analysis indicated that global, museum-associated collecting activity focused on animals has varied greatly over time, peaking around 2000 and declining significantly since. By stratifying data by institution, nation, and taxonomic phylum and class, I also illuminated how individual data series contribute to these global patterns. Institutions and nations had either concentrated or dispersed periods of relatively high collecting activity that occurred over different time periods, although most growth occurred in the second half of the 20th century for both many individual institutions and globally. Certain taxonomic clades comprise the largest proportions of collections records over this time period, namely arthropods (especially insects) and chordates (especially vertebrates), underscoring the taxonomically biased collecting histories of many institutions. Altogether, my analyses provide a critical, early view of historical zoological collecting activity and, to help other museum stakeholders to explore the data and results in more depth, I also describe and release NHMinformatics, an interactive dashboard built using R Shiny. These resources, when combined with recommendations I have made for sustainable collections growth, will be helpful for establishing policy goals, provisioning museum infrastructure, and training curatorial personnel.