The successful use of human induced pluripotent stem cells (iPSCs) for research or clinical applications requires the development of robust, efficient, and reproducible cryopreservation protocols. After cryopreservation, the survival rate of iPSCs is suboptimal and cell line-dependent. We assessed the use of ice recrystallization inhibitors (IRIs) for cryopreservation of human iPSCs.
View Article and Find Full Text PDFBackground: Bats are recognized as the natural reservoir of several zoonotic viruses that pose a threat to public health worldwide. In our recent reports we describe the identification of a novel poxvirus, IsrRAPXV, in Egyptian fruit bats. This poxvirus is associated with high morbidity and mortality in bats.
View Article and Find Full Text PDFThe retina is exquisitely patterned, with neuronal somata positioned at regular intervals to completely sample the visual field. Here, we show that phosphatase and tensin homolog (Pten) controls starburst amacrine cell spacing by modulating vesicular trafficking of cell adhesion molecules and Wnt proteins. Single-cell transcriptomics and double-mutant analyses revealed that Pten and Down syndrome cell adhesion molecule Dscam) are co-expressed and function additively to pattern starburst amacrine cell mosaics.
View Article and Find Full Text PDFAim: Abdominal breathing recently has demonstrated an important role in managing symptoms of Gastroesophageal Reflux Disease (GERD), improving quality of life, medication adherence, and sleep quality. This study aimed to evaluate the effectiveness of abdominal breathing on sleep and quality of life in patients with non-erosive gastroesophageal reflux.
Subject And Methods: A Quasi-experimental design was used.
A major goal of regenerative medicine is to generate tissue-specific mature and functional cells. However, current cell engineering protocols are still unable to systematically produce fully mature functional cells. While existing computational approaches aim at predicting transcription factors (TFs) for cell differentiation/reprogramming, no method currently exists that specifically considers functional cell maturation processes.
View Article and Find Full Text PDFCoronaviruses (CoVs) are enveloped viruses with a large RNA genome (26 to 32 kb) and are classified into four genera: , , and . CoV infections cause respiratory, enteric, and neurologic disorders in mammalian and avian species. In 2019, Oryx leucoryx animals suffered from severe hemorrhagic diarrhea and high morbidity rates.
View Article and Find Full Text PDFSingle-cell RNA-seq data contains a lot of dropouts hampering downstream analyses due to the low number and inefficient capture of mRNAs in individual cells. Here, we present Epi-Impute, a computational method for dropout imputation by reconciling expression and epigenomic data. Epi-Impute leverages single-cell ATAC-seq data as an additional source of information about gene activity to reduce the number of dropouts.
View Article and Find Full Text PDFAstrocytes arise from multipotent neural stem cells (NSCs) and represent the most abundant cell type of the central nervous system (CNS), playing key roles in the developing and adult brain. Since the differentiation of NSCs towards a gliogenic fate is a precisely timed and regulated process, its perturbation gives rise to dysfunctional astrocytic phenotypes. Inflammation, which often underlies neurological disorders, including neurodevelopmental disorders and brain tumors, disrupts the accurate developmental process of NSCs.
View Article and Find Full Text PDFThe quantification of the biological age of cells yields great promises for accelerating the discovery of novel rejuvenation strategies. Here, we present MultiTIMER, the first multi-tissue aging clock that measures the biological, rather than chronological, age of cells from their transcriptional profiles by evaluating key cellular processes. We applied MultiTIMER to more than 70,000 transcriptional profiles and demonstrate that it accurately responds to cellular stressors and known interventions while informing about dysregulated cellular functions.
View Article and Find Full Text PDFTissue regeneration requires coordination between resident stem cells and local niche cells. Here we identify that senescent cells are integral components of the skeletal muscle regenerative niche that repress regeneration at all stages of life. The technical limitation of senescent-cell scarcity was overcome by combining single-cell transcriptomics and a senescent-cell enrichment sorting protocol.
View Article and Find Full Text PDFCellular conversion can be induced by perturbing a handful of key transcription factors (TFs). Replacement of direct manipulation of key TFs with chemical compounds offers a less laborious and safer strategy to drive cellular conversion for regenerative medicine. Nevertheless, identifying optimal chemical compounds currently requires large-scale screening of chemical libraries, which is resource intensive.
View Article and Find Full Text PDFLegionella pneumophila grows within membrane-bound vacuoles in alveolar macrophages during human disease. Pathogen manipulation of the host cell is driven by bacterial proteins translocated through a type IV secretion system (T4SS). Although host protein synthesis during infection is arrested by the action of several of these translocated effectors, translation of a subset of host proteins predicted to restrict the pathogen is maintained.
View Article and Find Full Text PDFPrior knowledge of perturbation data can significantly assist in inferring the relationship between chemical perturbations and their specific transcriptional response. However, current databases mostly contain cancer cell lines, which are unsuitable for the aforementioned inference in non-cancer cells, such as cells related to non-cancer disease, immunology and aging. Here, we present ChemPert (https://chempert.
View Article and Find Full Text PDFGlioblastoma is believed to originate from nervous system cells; however, a putative origin from vessel-associated progenitor cells has not been considered. We deeply single-cell RNA-sequenced glioblastoma progenitor cells of 18 patients and integrated 710 bulk tumors and 73,495 glioma single cells of 100 patients to determine the relation of glioblastoma cells to normal brain cell types. A novel neural network-based projection of the developmental trajectory of normal brain cells uncovered two principal cell-lineage features of glioblastoma, neural crest perivascular and radial glia, carrying defining methylation patterns and survival differences.
View Article and Find Full Text PDFWhile immunopathology has been widely studied in patients with severe COVID-19, immune responses in non-hospitalized patients have remained largely elusive. We systematically analyze 484 peripheral cellular or soluble immune features in a longitudinal cohort of 63 mild and 15 hospitalized patients versus 14 asymptomatic and 26 household controls. We observe a transient increase of IP10/CXCL10 and interferon-β levels, coordinated responses of dominant SARS-CoV-2-specific CD4 and fewer CD8 T cells, and various antigen-presenting and antibody-secreting cells in mild patients within 3 days of PCR diagnosis.
View Article and Find Full Text PDFThe large-scale development of high-throughput sequencing technologies has not only allowed the generation of reliable omics data related to various regulatory layers but also the development of novel computational models in the field of stem cell research. These computational approaches have enabled the disentangling of a complex interplay between these interrelated layers of regulation by interpreting large quantities of biomedical data in a systematic way. In the context of stem cell research, network modeling of complex gene-gene interactions has been successfully used for understanding the mechanisms underlying stem cell differentiation and cellular conversion.
View Article and Find Full Text PDFIn the last two decades, studies of lymphoscintigraphy imaging in lymphatic mapping reported an extreme heterogeneity of skin lymphatic drainage of some skin area, in contrast with the previous scientific literature. The aim of this study was to investigate the presence of any correlations between the topographical location of cutaneous melanoma and the topographical location of sentinel lymph nodes. Data from 165 patients undergoing sentinel lymph node biopsy between January 2013 and May 2021 were analyzed, demonstrating that melanomas in the Lumbar region presented a significant more heterogeneous drainage by site than those in the Scapular region ( < 0.
View Article and Find Full Text PDFThe molecular underpinnings of the uncontrolled release of proinflammatory cytokines and chemokines ('cytokine storm'), which can cause organ damage and even mortality, are not completely understood. Furthermore, targeted therapeutic options to dampen such hyperinflammation are scarce. Here, we highlight the ways in which technological advances have set the stage for a new age of synergy between experimental and computational researchers to guide the discovery of novel therapeutic targets for modulating hyperinflammation.
View Article and Find Full Text PDFInfectious agents including viruses are important abortifacients and can cause fetal abnormalities in livestock animals. Here, samples that had been collected in Israel from aborted or malformed ruminant fetuses between 2015 and 2019 were investigated for the presence of the following viruses: the reoviruses bluetongue virus (BTV) and epizootic hemorrhagic disease virus (EHDV), the flaviviruses bovine viral diarrhea virus (BVDV) and border disease virus (BDV), the peribunyaviruses Shuni virus (SHUV) and Akabane virus (AKAV), bovine herpesvirus type 1 (BoHV-1) and bovine ephemeral fever virus (BEFV). Domestic (cattle, sheep, goat) and wild/zoo ruminants were included in the study.
View Article and Find Full Text PDFBackground: To define what type of injuries are more frequently related to medicolegal claims and civil action judgments.
Methods: We performed a scoping review on 14 studies and 2406 patients, analyzing medicolegal claims related to laparoscopic cholecystectomy injuries. We have focalized on three phases associated with claims: phase of care, location of injuries, type of injuries.
Diagnostic strategies for suspected pulmonary embolism (PE) have not been prospectively evaluated in COVID-19 patients. Prospective, multicenter, outcome study in 707 patients with both (suspected) COVID-19 and suspected PE in 14 hospitals. Patients on chronic anticoagulant therapy were excluded.
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