bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discovery of new deregulated miRNAs in gingivo buccal carcinoma using Group Benjamini Hochberg method: a commentary on “A quest for miRNA bio-marker: a track back approach from gingivo buccal cancer to two different types of precancers”
Authors: Koner Salil , De Sarkar Navonil , Laha Nilanjana 
Published: February 2023

AbstractThis formal comment is in response to “A quest for miRNA bio-marker: a track back approach from gingivo buccal cancer to two different types of precancers” written by De Sarkar and colleagues in 2014. The above-mentioned paper found seven miRNAs to be significantly deregulated in 18 gingivo-buccal cancer samples. However, they suspected more miRNAs to be deregulated based on their exploratory statistical analysis. To control the false discovery rate (FDR), the authors used the Benjamini Hochberg (BH) method, which does not leverage any available biological information on the miRNAs. In this work, we show that some specialized versions of the BH method, which can exploit positional information on the miRNAs, can lead to seven more discoveries with this data. Specifically, we group the closely located miRNAs, and use the group Benjamini Hochberg (GBH) methods (Hu et al., 2010), which reportedly have more statistical power than the BH method (Liu et al., 2019). The whole transcriptome analysis of Sing et al. (2017) and previous literature on the miRNAs suggest that most of the newly discovered miRNAs play a role in oncogenesis. In particular, the newly discovered miRNAs include hsa-miR-1 and hsa-miR-21-5p, whose cancer-related activities are well-established. Our findings indicate that incorporating the GBH method into suitable microarray studies may potentially enhance scientific discoveries via the exploitation of additional biological information.
Three-Dimensional Bioconjugated Liquid-Like Solid (LLS) Enhance Characterization of Solid Tumor - Chimeric Antigen Receptor T cell interactions
Authors: Nguyen Duy T. , Liu Ruixuan , Ogando-Rivas Elizabeth , Pepe Alfonso , Pedro Diego , Qdasait Sadeem , Nguyen Nhi Tran Yen , Lavrador Julia M. , Golde Griffin R. , Smolchek Ryan A. , Ligon John , Jin Linchun , Tao Haipeng , Webber Alex , Phillpot Simon , Mitchell Duane A. , Sayour Elias J , Huang Jianping , Castillo Paul , Sawyer W. Gregory 
Published: February 2023

AbstractCancer immunotherapy offers lifesaving treatments for cancers, but the lack of reliable preclinical models that could enable the mechanistic studies of tumor-immune interactions hampers the identification of new therapeutic strategies. We hypothesized 3D confined microchannels, formed by interstitial space between bio-conjugated liquid-like solids (LLS), enable CAR T dynamic locomotion within an immunosuppressive TME to carry out anti-tumor function. Murine CD70-specific CAR T cells cocultured with the CD70-expressing glioblastoma and osteosarcoma demonstrated efficient trafficking, infiltration, and killing of cancer cells. The anti-tumor activity was clearly captured via longterm in situ imaging and supported by upregulation of cytokines and chemokines including IFNg, CXCL9, CXCL10, CCL2, CCL3, and CCL4. Interestingly, target cancer cells, upon an immune attack, initiated an “immune escape” response by frantically invading the surrounding microenvironment. This phenomenon however was not observed for the wild-type tumor samples which remained intact and produced no relevant cytokine response. Single cells collection and transcriptomic profiling of CAR T cells at regions of interest revealed feasibility of identifying differential gene expression amongst the immune subpopulations. Complimentary 3D in vitro platforms are necessary to uncover cancer immune biology mechanisms, as emphasized by the significant roles of the TME and its heterogeneity.
Tenacibaculosis in wild-caught, captive Chinook salmon (Oncorhynchus tshawytscha) in British Columbia, Canada
Authors: Cicco Emiliano Di , Zinn Kaitlyn R. , Johnston Stephen D. , Kaukinen Karia H. , Li Shaorong , Archambault Jonathan F. , Mantha-Rensi Kaleb N. R. , Zielke Kayla A. J. , Bugg William S. , Mordecai Gideon J. , Bass Arthur L. , Deeg Christoph M. , Bateman Andrew W. , Hinch Scott G. , Miller Kristina M. 
Published: February 2023

AbstractSubstantial, acute mortality was observed in wild-caught Chinook salmon (Oncorhynchus tshawytscha) of various ages and sizes, from sub-adults to returning adults, held in tanks during two holding studies carried out in August and September 2022 at the Bamfield Marine Sciences Centre (BMSC), in Bamfield, British Columbia, Canada. Within days of capture, a substantial number of fish began presenting lethargy, loss of balance, abnormal swimming behavior, and skin ulcers involving the caudal peduncle, fins, belly, trunk and mouth. Molecular testing revealed high levels ofTenacibaculum dicentrarchiin skin swabs and gills, without appreciable consistent detections of other infectious agents.T. dicentrarchiwas also isolated from the skin ulcers. Histological analysis confirmed the presence of ulcerative dermatitis and myositis, associated with mats of filamentous, rod-shaped bacteria. In two individuals, the infection became systemic, with a bacterial colony (identified asT. dicentrarchi) observed in the liver of one individual. In-situ hybridization againstT. dicentrarchiandT. maritimumconfirmed the presence of only the former agent in the gills and skin ulcers of the affected fish. This clinical report represents the first diagnosed case of tenacibaculosis in wild-caught (captive) Chinook salmon in British Columbia.CONFLICT OF INTERESTThe authors have no conflicts of interest to report.DATA AVAILABILITY STATEMENTThe data that support the findings of this study are available from the corresponding author upon reasonable request.
Postfire recovery of western US conifer forests (1984-2017) using space-borne lidar data
Authors: Ilangakoon Nayani , Balch Jennifer K. , Nagy R. Chelsea , Iglesias Virginia 
Published: February 2023

AbstractConiferous forests account for 78% of the western US forests and store a substantial amount of carbon. Wildfires significantly alter vegetation structure, and hence the forest carbon stock. This study evaluates post-fire vegetation recovery trajectories and rates across the western US using recently launched Global Ecosystem Dynamic Investigations (GEDI) mission lidar data. Three ecoregions studied here, the Pacific Northwest, Southern Rockies, and Northern Rockies, show fire severity and ecoregion specific recovery trajectories for canopy height (CH), plant area index (PAI), and the foliage height diversity (FHD). The recovery trajectories are characterized by an initial decline in vegetation structure (CH, PAI, and FHD) during the first 9-25 years postfire followed by a gain of the structure. Regions of low burn severity can fully recover to the unburned background state within the first three decades while the high burn severity regions may recover in the first century, but only in the absence of fires within this period. The PNW exhibits the slowest recovery rate. According to our results, all three ecoregions feature a loss of growing stock volume (GSV) (−1% - - 48%). Time since fire, fire severity, and altitude were identified as the most significant drivers of postfire vegetation recovery, likely because they integrate the distance to seed source, vegetation composition, and the local climate. Our study suggests that, if fire return intervals become shorter than 50 years, these three ecoregions will have significantly reduced their woody vegetation, hence the carbon stocks. In addition, all the ecoregions studied here exhibit extensive impacts from other disturbances such as beetle invasion. It is therefore important to consider the effects of compound disturbances on vegetation recovery trajectories to infer the future carbon potential in these ecosystems.
The N terminus-only (trans) function of the Adhesion GPCR Latrophilin-1 controls multiple processes in reproduction ofC. elegans
Authors: Matúš Daniel , Groß Victoria Elisabeth , Fiedler Franziska , Post Wilbert Berend , Knierim Alexander Bernd , Schön Johanna Lena , Schöneberg Torsten , Prömel Simone 
Published: February 2023

ABSTRACTAdhesion G protein-coupled receptors (aGPCR) are unique molecules. They are able to transmit classical signals via G-protein activation (7TM-dependent/cissignaling) as well as to mediate functions solely through their extracellular N termini, completely independent of the seven transmembrane helices domain (7TM) and the C terminus (7TM-independent/N terminus-only/transfunction). This dual mode of action is highly unusual for GPCRs and allows for a plethora of possible cellular consequences. However, the physiological implications and molecular details of this N terminus-mediated signaling are not well understood. Here, we identify three distinct 7TM-independent/transfunctions of the aGPCR Latrophilin homolog LAT-1 in the nematodeCaenorhabditis eleganstogether regulating reproduction: sperm guidance, germline apoptosis and proliferative activity of germ cells in the gonadal stem cell niche. In these contexts, the receptor elicits its functions in a non-cell autonomous manner from adjacent somatic cells. These functions might be realized through alternative splicing of the receptor specifically generating N terminus-only variants. Thus, our findings shed light on the versatility of 7TM-independent/N terminus-only/transfunctions of aGPCR and discusses possible molecular details.
UNRAVELing the synergistic effects of psilocybin and environment on brain-wide immediate early gene expression in mice
Authors: Rijsketic Daniel Ryskamp , Casey Austen B. , Barbosa Daniel A.N. , Zhang Xue , Hietamies Tuuli M. , Ramirez-Ovalle Grecia , Pomrenze Matthew , Halpern Casey H. , Williams Leanne M. , Malenka Robert C. , Heifets Boris D. 
Published: February 2023

AbstractThe effects of context on the subjective experience of serotonergic psychedelics have not been fully examined in human neuroimaging studies, partly due to limitations of the imaging environment. Here, we administered saline or psilocybin to mice in their home cage or an enriched environment, immunofluorescently-labeled brain-wide c-Fos, and imaged cleared tissue with light sheet microscopy to examine the impact of context on psilocybin-elicited neural activity at cellular resolution. Voxel-wise analysis of c-Fos-immunofluorescence revealed differential neural activity, which we validated with c-Fos+cell density measurements. Psilocybin increased c-Fos expression in the neocortex, caudoputamen, central amygdala, and parasubthalamic nucleus and decreased c-Fos in the hypothalamus, cortical amygdala, striatum, and pallidum. Main effects of context and psilocybin-treatment were robust, widespread, and spatially distinct, whereas interactions were surprisingly sparse.
Mechanism of outer membrane destabilization by global reduction of protein content
Authors: Mikheyeva Irina V. , Sun Jiawei , Huang Kerwyn Casey , Silhavy Thomas J. 
Published: February 2023

AbstractThe outer membrane (OM) of Gram-negative bacteria such asEscherichia coliis an asymmetric bilayer with the glycolipid lipopolysaccharide (LPS) in the outer leaflet and glycerophospholipids in the inner. Nearly all integral OM proteins (OMPs) have a characteristic β-barrel fold and are assembled in the OM by the BAM complex, which contains one essential β-barrel protein (BamA), one essential lipoprotein (BamD), and three non-essential lipoproteins (BamBCE). A gain-of-function mutation inbamAenables survival in the absence of BamD, showing that the essential function of this protein is regulatory. We demonstrate that the global reduction in OMPs caused by BamD loss weakens the OM, altering cell shape and causing OM rupture in spent medium. To fill the void created by OMP loss, PLs flip into the outer leaflet. Under these conditions, mechanisms that remove PLs from the outer leaflet create tension between the OM leaflets, which contributes to membrane rupture. Rupture is prevented by suppressor mutations that release the tension by halting PL removal from the outer leaflet. However, these suppressors do not restore OM stiffness or normal cell shape, revealing a possible connection between OM stiffness and cell shape.Significance StatementThe outer membrane (OM) is a selective permeability barrier that contributes to the intrinsic antibiotic resistance of Gram-negative bacteria. Biophysical characterization of the roles of the component proteins, lipopolysaccharides, and phospholipids is limited by both the essentiality of the OM and its asymmetrical organization. In this study, we dramatically change OM physiology by limiting the protein content, which requires phospholipid localization to the outer leaflet and thus disrupts OM asymmetry. By characterizing the perturbed OM of various mutants, we provide novel insight into the links among OM composition, OM stiffness, and cell shape regulation. These findings deepen our understanding of bacterial cell envelope biology and provide a platform for further interrogation of OM properties.
Community composition and the environment modulate the population dynamics of type VI secretion in human gut bacteria
Authors: Robitaille Sophie , Simmons Emilia L. , Verster Adrian J. , McClure Emily Ann , Royce Darlene B. , Trus Evan , Swartz Kerry , Schultz Daniel , Nadell Carey D. , Ross Benjamin D. 
Published: February 2023

ABSTRACTUnderstanding the relationship between the composition of the human gut microbiota and the ecological forces shaping it is of high importance as progress towards therapeutic modulation of the microbiota advances. However, given the inaccessibility of the gastrointestinal tract, our knowledge of the biogeographical and ecological relationships between physically interacting taxa has been limited to date. It has been suggested that interbacterial antagonism plays an important role in gut community dynamics, but in practice the conditions under which antagonistic behavior is favored or disfavored by selection in the gut environment are not well known. Here, using phylogenomics of bacterial isolate genomes and analysis of infant and adult fecal metagenomes, we show that the contact-dependent type VI secretion system (T6SS) is repeatedly lost from the genomes ofBacteroides fragilisin adults compare to infants. Although this result implies a significant fitness cost to the T6SS, but we could not identifyin vitroconditions under which such a cost manifests. Strikingly, however, experiments in mice illustrated that theB. fragilisT6SS can be favored or disfavored in the gut environment, depending on the strains and species in the surrounding community and their susceptibility to T6SS antagonism. We use a variety of ecological modeling techniques to explore the possible local community structuring conditions that could underlie the results of our larger scale phylogenomic and mouse gut experimental approaches. The models illustrate robustly that the pattern of local community structuring in space can modulate the extent of interactions between T6SS-producing, sensitive, and resistant bacteria, which in turn control the balance of fitness costs and benefits of performing contact-dependent antagonistic behavior. Taken together, our genomic analyses,in vivostudies, and ecological theory point toward new integrative models for interrogating the evolutionary dynamics of type VI secretion and other predominant modes of antagonistic interaction in diverse microbiomes.
LISTER: Semi-automatic metadata extraction from annotated experiment documentation in eLabFTW
Authors: Musyaffa Fathoni A. , Rapp Kirsten , Gohlke Holger 
Published: February 2023

ABSTRACTThe availability of scientific methods, code, and data is key for reproducing an experiment. Research data should be made available following the FAIR principle (findable,accessible,interoperable, andreusable). For that, the annotation of research data with metadata is central. However, existing research data management workflows often require that metadata should be created by the corresponding researchers, which takes effort and time. Here, we developed LISTER as a methodological and algorithmic solution to disentangle the creation of metadata from ontology alignment and extract metadata from annotated template-based experiment documentation using minimum effort. We focused on tailoring the integration between existing platforms by using eLabFTW as the electronic lab notebook and adopting the ISA (investigation,study,assay) model as the abstract data model framework; DSpace is used as a data cataloging platform. LISTER consists of three components: customized eLabFTW entries using specific hierarchies, templates, and tags; a ‘container’ concept in eLabFTW, making metadata of a particular container content extractable along with its underlying, related containers; a Python-based app to enable easy-to-use, semi-automated metadata extraction from eLabFTW entries. LISTER outputs metadata as machine-readable .json and human-readable .csv formats, and MM descriptions in .docx format that could be used in a thesis or manuscript. The metadata can be used as a basis to create or extend ontologies, which, when applied to the published research data, will significantly enhance its value due to a more complete and holistic understanding of the data, but might also enable scientists to identify new connections and insights in their field. We applied LISTER to the fields of computational biophysical chemistry as well as protein biochemistry and molecular biology, and our concept should be extendable to other life science areas.
The Conserved C-terminal End Segment of Troponin T Is A New Tropomyosin-Binding Site Modulating the Kinetics of Cardiac Muscle
Authors: Cao Tianxin , Feng Han-Zhong , Jin J.-P. 
Published: February 2023

ABSTRACTEvolved from duplication of a troponin I (TnI)-like ancestor gene, troponin T (TnT) and TnI are two subunits of the troponin complex that regulates the contraction and relaxation of striated muscles. Proteolytic deletion of the evolutionarily added N-terminal variable region of TnT in adaptation to acute myocardial stress restores a conformation like that of the C-terminal end segment of TnI, a tropomyosin (Tm)-binding and inhibitory structure, with an effect on reducing the contractile velocity of cardiac muscle to prolong ejection time and sustain the stroke volume. To investigate the underlying mechanism of this adaptive conditional function of TnT that is known to have two Tm-binding sites, our study localized a conformationally modulated new Tm-binding site in the highly conserved 14 amino acid C-terminal end segment of TnT. Localized surface plasmon resonance data showed that a hypertrophic cardiomyopathy mutation R278C within the C-terminal end segment of TnT alters the tropomyosin binding with direct responses to physiological concentrations of Ca2+. The functions are retained in the form of free peptide with an inhibitory regulatory effect on the contractile and relaxation kinetics of skinned cardiac muscle. In addition to revealing the underlying mechanisms of cTnT-ND adaptation and cardiac TnT C-terminal myopathic mutations, the new findings provide novel insights into the structure-function relationship of TnT in the kinetics of striated muscle contraction and relaxation with broad physiological and pathophysiological implications.
Numerical Modeling of Natural Fracture Distributions in Shale
Authors: LI Yaping , CHEN Xiaowei , SHAO Yongbo 
Published: February 2023

AbstractThe production efficiency of shale gas is affected by the interaction between hydraulic and natural fractures. This study presents a simulation of natural fractures in shale reservoirs, based on a discrete fracture network (DFN) method for hydraulic fracturing engineering. Fracture properties of the model are calculated from core fracture data, according to statistical mathematical analysis. The calculation results make full use of the quantitative information of core fracture orientation, density, opening and length, which constitute the direct and extensive data of mining engineering. The reliability and applicability of the model are analyzed with regard to model size and density, a calculation method for dominant size and density being proposed. Then, finite element analysis is applied to a hydraulic fracturing numerical simulation of a shale fractured reservoir in southeastern Chongqing. The hydraulic pressure distribution, fracture propagation, acoustic emission information and in situ stress changes during fracturing are analyzed. The results show the application of fracture statistics in fracture modeling and the influence of fracture distribution on hydraulic fracturing engineering. The present analysis may provide a reference for shale gas exploitation.
Three Indeterminate Forms of Scalidophoran Worms from the Cambrian Fortunian of South China
Authors: QIN Jiachen , LIU Yunhuan , SHAO Tiequan , WANG Qi , ZHANG Yanan , ZHOU Xingyu , LIU Mingjin 
Published: February 2023

AbstractA wide variety of scalidophoran worms have been found in the Cambrian Fortunian in recent years, suggesting that scalidophorans diversified during this age. Here, we report new scalidophoran material obtained from the 2nd member of the Kuanchuanpu Formation (Fortunian Stage) in Zhangjiagou Lagerstätte, Xixiang County, Shaanxi Province, South China. Three indeterminate forms of scalidophoran worms are described in detail. The morphology of these worms differs from that of any coeval worms and may represent new taxa. However, because these fossils are fragmented and lack detailed information on the arrangement pattern of introvert scalids, they are named here in open nomenclature. This study enriches the diversity of the earliest scalidophorans to 7 genera and species and 10 indeterminate forms. Based on the new fossils, Fortunian scalidophoran worms can be divided into three categories: (1) worms with microannuli; (2) worms with macroannuli; and (3) worms without annuli.
Highlighting the immunohistochemical differences of malignant mesothelioma subtypes via case presentations
Authors: Sejben Anita , Pancsa Tamás , Tiszlavicz László , Furák József , Paróczai Dóra , Zombori Tamás 
Published: February 2023

AbstractMalignant mesothelioma (MM) is a rare tumor of mesothelial cells, with an increasing incidence both in developed and developing countries. MM has three major histological subtypes, in order of frequency, according to the World Health Organization (WHO) Classification of 2021: epithelioid, biphasic, and sarcomatoid MM. Distinction may be a challenging task for the pathologist, due to the unspecific morphology.Here, we present two cases of diffuse MM subtypes to emphasize the immunohistochemical (IHC) differences, and to facilitate diagnostic difficulties. In our first case of epithelioid mesothelioma, the neoplastic cells showed cytokeratin 5/6 (CK5/6), calretinin, and Wilms‐tumor‐1 (WT1) expression, while remaining negative with thyroid transcription factor‐1 (TTF‐1). BRCA1 associated protein‐1 (BAP1) negativity was seen in the neoplastic cells' nucleus, reflecting loss of the tumor suppressor gene. In the second case of biphasic mesothelioma, expression of epithelial membrane antigen (EMA), CKAE1/AE3, and mesothelin was observed, while WT1, BerEP4, CD141, TTF1, p63, CD31, calretinin, and BAP1 expressions were not detected.Due to the absence of specific histological features, the differentiation between MM subtypes could be a challenging task. In routine diagnostic work, IHC may be the proper method in distinction. According to our results and literature data, CK5/6, mesothelin, calretinin, and Ki‐67 should be applied in subclassification.