bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sequential functional differentiation of luminal epithelial cells regulated by maternal and embryonic signaling in the mouse endometrium
Authors: Wang Hai-Quan , Li Dong , Liu Jingyu , Jiang Yue , Zhou Ji-Dong , Wang Zhi-Long , Tang Xin-Yi , Zhang Yang , Zhen Xin , Cao Zhi-Wen , Sheng Xiao-Qiang , Yang Chao-Fan , Yue Qiu-ling , Ding Li-jun , Hu Ya-li , Hu Zhi-Bin , Li Chao-Jun , Yan Gui-Jun , Sun Hai-Xiang 
Published: May 2022

SummaryEmbryo implantation requires temporospatial maternal-embryo dialog to regulate the interactions between an activated blastocyst and a receptive endometrium; however, the details of the related cell-specific coordination is largely unknown because of the cellular complexity and dynamic developmental processes of both the embryo and endometrium during peri-implantation. By comparing single-cell RNA (scRNA) data obtained from entire uteri of pregnant and pseudo-pregnant mice with embryos that were in the oviduct (dpc2.5 days post-coitum [dpc]) or had entered the uterus (after 3.5 dpc), we found a maternal estrogen and progesterone signaling-dependent functional differentiation process in which progesterone induced estrogen-responsive luminal epithelial cells to differentiate into two new types of epithelial cells: adhesion epithelial cells (AECs) and supporting epithelial cells (SECs) on 2.5 dpc. In addition to maternal signaling data, the uterine scRNA and corresponding embryo bulk sequencing data were obtained, and analyses revealed that embryonic Pdgfa and Efna3/4 signaling activated AECs and SECs, enhancing the attachment of embryos to the endometrium after implantation. Specifically, embryonic signaling induced additional transformation of AECs by preventing adjacent AECs, but not AECs away from the embryo in the implantation chamber, from undergoing apoptosis. Furthermore, we demonstrated that epithelial cell differentiation and related regulatory signaling were largely conserved in humans and mice. In the human endometrium, developmental defects of SOX9-positive epithelial cells similar to luminal epithelial cells were related to thin endometrium. Our work provides comprehensive and systematic information on endometrial luminal epithelial cell development directed by maternal and embryonic signaling, which is important for endometrial receptivity and embryo implantation.
A deep learning framework for structural variant discovery and genotyping
Authors: Popic Victoria , Rohlicek Chris , Cunial Fabio , Garimella Kiran , Meleshko Dmitry , Hajirasouliha Iman 
Published: May 2022

AbstractStructural variants (SV) are a major driver of genetic diversity and disease in the human genome and their discovery is imperative to advances in precision medicine and our understanding of human genetics. Existing SV callers rely on hand-engineered features and heuristics to model SVs, which cannot easily scale to the vast diversity of SV types nor fully harness all the information available in sequencing datasets. Since deep neural networks can learn complex abstractions directly from the data, they offer a promising approach for general SV discovery. Here we propose an extensible deep learning framework, Cue, to call and genotype SVs. At a high level, Cue converts sequence alignments to multi-channel images that capture multiple SV-informative signals and uses a stacked hourglass convolutional neural network to predict the type, genotype, and genomic locus of the SVs captured in each image. We show that Cue outperforms the state of the art in the detection of five classes of SVs (including two types of complex SVs and subclonal SVs) on synthetic and real short-read data and that it can be easily extended to other sequencing platforms, such as long and linked read sequencing technologies, while achieving competitive performance. By design, Cue can also be automatically extended to support new SV classes: this versatility is crucial as novel SV types are discovered in ongoing population-scale sequencing initiatives.
Gene expression signatures underlying inbreeding depression as revealed by whole-transcriptome analysis of selectively bred strains of the Pacific Oyster (Crassostrea gigas)
Authors: Shi Chenyu , Zhang Fuqiang , Li Qi , Liu Shikai 
Published: May 2022

AbstractExploring molecular mechanisms of inbreeding depression is significant for the conservation and sustainable use of the rare breed with a specific trait of high production value. In this work, we conducted whole-transcriptome analysis of two selectively bred Pacific oyster strains with one inbred strain showing significant growth depression. A total of 7980, 2677, and 28 differentially expressed protein-coding genes (DEGs), lncRNAs (DELs), and miRNAs (DEMs) were identified, respectively. The majority of DEGs and predicted target genes of DELs and DEMs were significantly enriched in biological process including immune response, cell proliferation, and apoptosis pathways. A set of genes with specific expression patterns as revealed by cluster profiling and enrichment analysis were identified, which may underlie inbreeding depression of the inbred strain. Furthermore, a competing endogenous RNA (ceRNA) network was constructed by integrative analysis of DEGs, DELs, and DEMs, supporting that ncRNAs, as regulators of gene expression, could be critical modulators in multiple subsystems involved in inbreeding depression.
Beneficial effects of cellular coinfection resolve inefficiency in influenza A virus transcription
Authors: Shartouny Jessica R. , Lee Chung-Young , Lowen Anice C. 
Published: May 2022

SummaryFor diverse viruses, cellular infection with single vs. multiple virions can yield distinct biological outcomes. We previously found that influenza A/guinea fowl/Hong Kong/WF10/99 (H9N2) virus (GFHK99) displays a particularly high reliance on multiple infection in mammalian cells. Here, we sought to uncover the viral processes underlying this phenotype. We found that the need for multiple infection maps amino acid 26K of the viral PA protein. PA 26K suppresses endonuclease activity and viral transcription, specifically within cells infected at low multiplicity. In the context of the higher functioning PA 26E, inhibition of PA using baloxavir acid augments reliance on multiple infection. Together, these data suggest a model in which sub-optimal activity of the GFHK99 endonuclease results in inefficient priming of viral transcription, an insufficiency which can be overcome with the introduction of additional viral templates to the cell. These findings offer rare mechanistic insight into the benefits of viral collective dispersal.Graphical Abstract
Differential regulation of GUV mechanics via actin network architectures
Authors: Wubshet Nadab H. , Wu Bowei , Veerapaneni Shravan , Liu Allen P. 
Published: May 2022

AbstractActin networks polymerize and depolymerize to construct highly organized structures, thereby, endowing the mechanical phenotypes found in a cell. It is generally believed that the amount of filamentous actin and actin network architecture determine cytoplasmic viscosity and elasticity of the whole cell. However, the intrinsic complexity of a cell and numerous other endogenous cellular components make it difficult to study the differential role of distinct actin networks in regulating cell mechanics. Here, we model a cell by using giant unilamellar vesicles (GUVs) encapsulating actin filaments and networks assembled by various actin crosslinker proteins. Perturbation of these cytoskeletal vesicles using AC electric fields revealed that deformability depends on lumenal viscosity and actin network architecture. While actin-free vesicles exhibited large electromechanical deformations, deformations of GUVs encapsulating actin filaments were significantly dampened. The suppression of electrodeformation of actin-GUVs can be similarly recapitulated by using aqueous PEG 8000 solutions at different concentrations to modulate viscosity. Furthermore, alpha actinin-crosslinked actin networks resulted in decreased GUV deformability in comparison to actin filament-encapsulating GUVs, and membrane-associated actin networks through the formation of dendritic actin cortex greatly dampened electrodeformation of GUVs. These results highlight the organization of actin networks regulates the mechanics of GUVs and shed insights into the origin of differential deformability of cells.
Clinical implementation of routine whole-genome sequencing for hospital infection control of multi-drug resistant pathogens
Authors: Forde Brian M , Bergh Haakon , Cuddihy Thom , Hajkowicz Krispin , Hurst Trish , Playford E. Geoffrey , Henderson Belinda C. , Runnegar Naomi , Clark Julia , Jennison Amy V , Moss Susan , Hume Anna , Leroux Hugo , Beatson Scott A , Paterson David L , Harris Patrick NA 
Published: May 2022

ABSTRACTBackgroundProspective whole-genome sequencing (WGS)-based surveillance may be the optimal approach to rapidly identify transmission of multi-drug resistant (MDR) bacteria in the healthcare setting.Materials/methodsWe prospectively collected methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), carbapenem-resistant Acinetobacter baumannii (CRAB), extended-spectrum beta-lactamase (ESBL-E) and carbapenemase-producing Enterobacterales (CPE) isolated from blood cultures, sterile sites or screening specimens across three large tertiary referral hospitals (2 adult, 1 paediatric) in Brisbane, Australia. WGS was used to determine in silico multi-locus sequence typing (MSLT) and resistance gene profiling via a bespoke genomic analysis pipeline. Putative transmission events were identified by comparison of core genome single nucleotide polymorphisms (SNPs). Relevant clinical meta-data were combined with genomic analyses via customised automation, collated into hospital-specific reports regularly distributed to infection control teams.ResultsOver four years (April 2017 to July 2021) 2,660 isolates were sequenced. This included MDR gram-negative bacilli (n=293 CPE, n=1309 ESBL), MRSA (n=620) and VRE (n=433). A total of 379 clinical reports were issued. Core genome SNP data identified that 33% of isolates formed 76 distinct clusters. Of the 76 clusters, 43 were contained to the three target hospitals, suggesting ongoing transmission within the clinical environment. The remaining 33 clusters represented possible inter-hospital transmission events or strains circulating in the community. In one hospital, proven negligible transmission of non-multi-resistant MRSA enabled changes to infection control policy.ConclusionsImplementation of routine WGS for MDR pathogens in clinical laboratories is feasible and can enable targeted infection prevention and control interventions.SummaryWe initiated a program of routine sequencing of multi-drug resistant organisms. A custom analysis pipeline was used to automate reporting by incorporating clinical meta-data with genomics to define clusters and support infection control interventions.
Automated and combined HIV, HBV, HCV, and syphilis testing among illegal gold miners in French Guiana using a standardized dried blood device
Authors: Pisoni Amandine , Reynaud Elisa , Douine Maylis , Hureau Louise , Cordellat Carmen Alcocer , Schaub Roxane , Poland Dennis , Monkel Richard , Lommen Joan , Yenkoyan Konstantin , Vreden Stephen , Nacher Mathieu , Tuaillon Edouard 
Published: May 2022

AbstractBlood spotted onto filter paper can be easily collected outside healthcare facilities and shipped to a central laboratory for serological testing. However, dried blood testing generally requires manual processing for pre-analytical steps. In this study, we used a standardized blood collection device combined with an automated elution system to test illegal gold miners living in French Guiana for HIV, HBV, HCV and syphilis. We included 378 participants, 102 females and 266 males, in three illegal gold mining resting sites. Blood collected on the Ser-Col device (Labonovum) was eluted using an automated system (SCAUT Ser-Col automation, Blok System Supply) and an automated analyzer (Alinity i, Abbott). Ser-Col results were compared to both plasma results, considered the gold standard, and to DBS results, considered the reference sampling method using dried blood. In plasma samples, two participants (0.5%) tested positive for HIV, six (1.5%) tested positive for hepatitis B surface antigen (HBsAg), eight were weakly positive for anti-HCV antibodies but negative for HCV RNA, and 47 tested positive for treponemal antibodies (12.4%), including 20 females (19.6%) and 27 males (9.8%, p= 0.010179). We observed a full concordance of Ser-Col and DBS results for HIV diagnosis compared to plasma results. Ser-Col and DBS samples tested positive in five HBsAg carriers and negative for one participant with a low HBsAg level in plasma (0.5 IU/mL). All participants tested negative for HCV in Ser-Col and DBS samples, including the eight participants who tested low positive for HCV antibodies and HCV RNA negative in plasma. Among syphilis seropositive participants, 41 (87.2%) and 40 (85.1%) tested positive for treponemal antibodies in Ser-Col and DBS samples, respectively. The Ser-Col method allows automated dried blood testing of HIV, HBV, HCV and syphilis with performances comparable to DBS. Automated approaches to test capillary blood transported on dried blood devices may facilitate large-scale surveys and improve testing of populations living in remote areas.Graphical abstract
Dauer quiescence as well as continuity of the life cycle after dauer-exit in Caenorhabditis elegans are dependent on the endoribonuclease activity of XRN-2
Authors: Chowdhury Tamoghna , Samajdar Aniruddha , Sardar Moumita , Chatterjee Saibal 
Published: May 2022

AbstractCaenorhabditis elegans embarks on a quiescent dauer state upon exposure to unfavourable conditions and can sustain for a very long period without food, but it returns to continuous life cycle upon arrival of suitable conditions. Thus, dauer state plays a critical role in its adaptive fitness and survival. ATP-independent endoribonuclease activity of XRN-2 has been implicated in dauer microRNA metabolism, perturbation of which causes their collapse within a very short span of time. Here, we present a detailed comparative analyses of dauer transcriptomes from a conditional mutant strain for the endoribonuclease activity of XRN-2, maintained under control and experimental conditions. We observed that even a limited disruption of microRNA homeostasis in experimental dauers results in deregulation of a large number of mRNA targets. Our bioinformatic analyses, supported by morphological, physiological, and behavioral evidence further demonstrate critical changes in metabolism leading to a state unsupportive of dauer maintenance, alongside potential defects in multiple neuronal activities, which might have caused an overall disruption of dauer plasticity. We explore a possible role of this endoribonuclease activity towards the maintenance of chromatin architecture and transposon expression that in turn might affect the transcriptional program critically required for the maintenance of non-aging, long-lived dauers. Finally, we also demonstrate that perturbation of the endoribonuclease activity during the dauer state exerts drastic adverse effects on the continuity of life cycle after dauer-exit. They not only fail to recapitulate the wild type events of germline development and embryogenesis, but also present traits of very old worms and formation of ‘tumor-like’ structures in the proximal gonad.
The transcription factor RUNX2 drives the generation of human NK cells and promotes tissue residency
Authors: Wahlen Sigrid , Matthijssens Filip , Van Loocke Wouter , Taveirne Sylvie , Kiekens Laura , Persyn Eva , van Ammel Els , De Vos Zenzi , De Munter Stijn , Matthys Patrick , Van Nieuwerburgh Filip , Taghon Tom , Vandekerckhove Bart , Van Vlierberghe Pieter , Leclercq Georges 
Published: May 2022

ABSTRACTNK cells are innate lymphocytes that eliminate virus-infected and cancer cells by cytotoxicity and cytokine secretion. In addition to circulating NK cells, distinct tissue-resident NK subsets have been identified in various organs. Although transcription factors regulating NK cell development and function have been extensively studied in mice, the role of RUNX2 in these processes has not been investigated, neither in mice nor in human. Here, by manipulating RUNX2 expression with either knockdown or overexpression in human hematopoietic stem cell-based NK cell differentiation cultures, combined with transcriptomic and ChIP-sequencing analyses, we established that RUNX2 drives the generation of NK cells, possibly through induction of IL-2Rβ expression in NK progenitor cells. Importantly, RUNX2 promotes tissue residency in human NK cells. Our findings have the potential to improve existing NK cell-based cancer therapies and can impact research fields beyond NK cell biology, since tissue-resident subsets have also been described in other lymphocyte subpopulations.
Relationships of Worldwide Onobrychis species: from seed & pod morphology and molecular perspective
Authors: Zarrabian Mohammad , Dehkordi Azam Nikbakht , Ehtemam Mohammad Hossein , Majidi Mohammad Mahdi 
Published: May 2022

AbstractThe present study aimed to investigate the phylogeny of 31 Onobrychis species with the help of seed and fruit macro & micro-morphological traits and ISSR molecular markers. The species were found to be highly variable in their seed and fruit morphological traits. Also, a new type of fruit (O. crista galli type), in addition to the three predefined types of fruit, was introduced. From molecular perspective, a set of 22 ISSR primers were shown to have a good efficiency for genetic discrimination among the species. Bayesian model based STRUCTURE analysis grouped the genotypes into 4 genetic clusters, and the high value of Fst calculated for these clusters indicated a high level of genetic differentiation among them. On the other hand, based on the Maximum Likelihood phylogenetic tree, our results are in agreement with the subgenus classification (Onobrychis and Sisyrosema), while contrary to Sisyrosema, the Onobrychis subgenus (the Lophobrychis and Onobrychis sections) appears not to be monophyletic. Furthermore, in contrast to the traditional taxonomic classification, species belonging to the Lophobrychis section do not form a coherent group, indicating that this section could be considered as a heterogeneous unit and perhaps could be merge into the Onobrychis section.HighlightThis paper discusses a worldwide phylogenic analysis and population structures of Onobrychis genus. The results of this paper provide a comprehensive answer to complexity of subgenus and section discrimination.
Visualizing the Coordination of APE1 and DNA Polymerase β During Base Excision Repair
Authors: Fairlamb Max S. , Washington Todd M. , Freudenthal Bret D. 
Published: May 2022

ABSTRACTBase Excision Repair (BER) is carried out by a series of DNA repair proteins that function in a step-by-step process to identify, remove, and replace DNA damage. As DNA damage is processed during BER, the DNA transitions through various intermediate states, called BER intermediates, which if left exposed can develop into double-strand DNA breaks and trigger programmed cell death signaling. Previous studies have proposed that in order to minimize exposure of the BER intermediates, each protein may remain bound to its product prior to the next protein binding. Thus, a short-lived complex consisting of the BER intermediate, the incoming enzyme, and the outgoing enzyme may form between each step of the BER pathway. The transfer of BER intermediates between enzymes, known as BER coordination, has yet to be directly visualized and the mechanistic details of the process remain unclear. Here, we utilize single-molecule total internal reflection fluorescence (TIRF) microscopy to investigate the mechanism of BER coordination between apurinic/apyrimidinic endonuclease 1 (APE1) and DNA polymerase β (Pol β). When preformed complexes comprised of APE1 and the incised AP-site product were subsequently bound by Pol β, the Pol β enzyme dissociated shortly after binding in a majority of the observations. In the events where Pol β binding was followed by APE1 dissociation (i.e., DNA hand-off), Pol β had remained bound for a longer period of time to allow disassociation of APE1. Our results indicate that, in the absence of other BER factors, transfer of the BER intermediate from APE1 to Pol β during BER is dependent on the dissociation kinetics of APE1 and the duration that Pol β remains bound near the APE1-5’ nick complex. These findings provide insight into how APE1 and Pol β coordinate the transfer of DNA within the BER pathway.
Context-dependent effects explain divergent prognostic roles of Tregs in cancer
Authors: Amblard Elise , Soumelis Vassili 
Published: May 2022

AbstractAssessing cancer prognosis is a challenging task, given the heterogeneity of the disease. Multiple features (clinical, environmental, genetic) have been used for such assessments. The tumor immune microenvironment (TIME) is a key feature, and describing the impact of its many components on cancer prognosis is an active field of research. The complexity of the tumor microenvironment context makes it difficult to use the human TIME to assess prognosis, as demonstrated by the example of regulatory T cells (Tregs). The effect of Tregs on prognosis is ambiguous, with different studies considering them to be negative, positive or neutral. We focused on five different cancer types (breast, colorectal, gastric, lung and ovarian). We clarified the definition of Tregs and their utility for assessing cancer prognosis by taking the context into account via the following parameters: the Treg subset, the anatomical location of these cells, and the neighboring cells. With a meta-analysis on these three parameters, we were able to clarify the prognostic role of Tregs. We found that CD45RO+ Tregs had a reproducible negative effect on prognosis across cancer types, and we gained insight into the contributions of the anatomical location of Tregs and of their neighboring cells on their prognostic value. Our results suggest that Tregs play a similar prognostic role in all cancer types. We also established guidelines for improving the design of future studies addressing the pathophysiological role of Tregs in cancer.
Syntaxin Habc is required to open Unc18 to template SNARE assembly
Authors: Parra-Rivas Leonardo A. , Palfreyman Mark T. , Vu Thien N. , Jorgensen Erik M. 
Published: May 2022

AbstractSNARE and Unc18 proteins form the core of the membrane fusion complex at synapses. The fusion machinery is evolutionarily ancient and mediates constitutive fusion in yeast. We demonstrate that the SNARE and Unc18 machinery in the nematode C. elegans can be replaced by yeast proteins and still carry out synaptic transmission. However, substitutions of individual components from yeast disrupts fusion. To understand the functional interactions within the core machinery we adopted an ‘interspecies complementation’ approach using yeast. Synaptic transmission could be restored in chimeras when two key interfaces were present: a novel Habc-Unc18 contact site and an Unc18-SNARE motif contact site. An open form of Unc18 could bypass the requirement for the Habc-Unc18 interface. Together, these data suggest that the Habc domain of syntaxin is required for Unc18 to adopt an open conformation; open Unc18 then templates SNARE complex formation.