ADAM10 and ADAM17 promote SARS-CoV-2 cell entry and spike protein-mediated lung cell fusion.

The severe-acute-respiratory-syndrome-coronavirus-2 (SARS-CoV-2) is the causative agent of COVID-19, but host cell factors contributing to COVID-19 pathogenesis remain only partly understood. We identify the host metalloprotease ADAM17 as a facilitator of SARS-CoV-2 cell entry and the metalloprotease ADAM10 as a host factor required for lung cell syncytia formation, a hallmark of COVID-19 pathology. ADAM10 and ADAM17, which are broadly expressed in the human lung, cleave the SARS-CoV-2 spike protein (S) in vitro, indicating that ADAM10 and ADAM17 contribute to the priming of S, an essential step for viral entry and cell fusion. ADAM protease-targeted inhibitors severely impair lung cell infection by the SARS-CoV-2 variants of concern alpha, beta, delta, and omicron and also reduce SARS-CoV-2 infection of primary human lung cells in a TMPRSS2 protease-independent manner. Our study establishes ADAM10 and ADAM17 as host cell factors for viral entry and syncytia formation and defines both proteases as potential targets for antiviral drug development.

The changes in the effects of social media use of Cypriots due to COVID-19 pandemic.

Social media is the leading medium which is used for communication during the COVID-19 pandemic. The research conducted aims to fill the gap of literature related to social media use during the COVID-19 pandemic. This research aims at uncovering the influences of social media use in several dimensions during lockdown(s). The study aims to answer the research question of: Are the influences of social media use different from normal times? The online questionnaire has been completed by six hundred and sixty-eight users within the period of lockdown. The author prepared the questionnaire, which is composed of 22 positive statements in order to evaluate the effects of social media use during the COVID-19 pandemic. A 5 point Likert scale was used, where reliability and validity were calculated by the Cronbach's alpha value, which was 0.751. Findings highlight that users have more information about COVID-19, and they follow recent information via social media, which shows the shift towards digital medium. Findings also indicate that users are aware of fake news, and they follow official sources. Social media is powerful to affect decision-makers, and respondents' social media use did not create any panic or anxiety amongst them. This research indicates that respondents' social media use during COVID-19 is different from normal times as a common purpose triggers this, survival. Before the COVID-19 pandemic, most of social media shares were like a dream or a strong desire that may cause anxiety in others. During the pandemic, people are in lockdown and share similar feelings and follow similar behavioural patterns. As there is a common purpose and struggle via users, psychological well-being is not affected negatively.

CD8+ T cells induce interferon-responsive oligodendrocytes and microglia in white matter aging.

A hallmark of nervous system aging is a decline of white matter volume and function, but the underlying mechanisms leading to white matter pathology are unknown. In the present study, we found age-related alterations of oligodendrocyte cell state with a reduction in total oligodendrocyte density in aging murine white matter. Using single-cell RNA-sequencing, we identified interferon (IFN)-responsive oligodendrocytes, which localize in proximity to CD8+ T cells in aging white matter. Absence of functional lymphocytes decreased the number of IFN-responsive oligodendrocytes and rescued oligodendrocyte loss, whereas T-cell checkpoint inhibition worsened the aging response. In addition, we identified a subpopulation of lymphocyte-dependent, IFN-responsive microglia in the vicinity of the CD8+ T cells in aging white matter. In summary, we provide evidence that CD8+ T-cell-induced, IFN-responsive oligodendrocytes and microglia are important modifiers of white matter aging.

Dissociation of microdissected mouse brain tissue for artifact free single-cell RNA sequencing.

Single-cell RNA sequencing (scRNA-seq) provides the transcriptome of individual cells and addresses previously intractable problems including the central nervous system's transcriptional responses during health and disease. However, dissociating brain cells is challenging and induces artificial transcriptional responses. Here, we describe an enzymatic dissociation method for mouse brain that prevents dissociation artifacts and lowers technical variations with standardized steps. We tested this protocol on microdissected brain tissue of 3-week- to 24-month-old mice and obtained high-quality scRNA-seq results. For complete details on the use and execution of this protocol, please refer to Safaiyan et al. (2021).

White matter aging drives microglial diversity.

Aging results in gray and white matter degeneration, but the specific microglial responses are unknown. Using single-cell RNA sequencing from white and gray matter separately, we identified white matter-associated microglia (WAMs), which share parts of the disease-associated microglia (DAM) gene signature and are characterized by activation of genes implicated in phagocytic activity and lipid metabolism. WAMs depend on triggering receptor expressed on myeloid cells 2 (TREM2) signaling and are aging dependent. In the aged brain, WAMs form independent of apolipoprotein E (APOE), in contrast to mouse models of Alzheimer's disease, in which microglia with the WAM gene signature are generated prematurely and in an APOE-dependent pathway similar to DAMs. Within the white matter, microglia frequently cluster in nodules, where they are engaged in clearing degenerated myelin. Thus, WAMs may represent a potentially protective response required to clear degenerated myelin accumulating during white matter aging and disease.

ZenoFishDb v1.1: A Database for Xenotransplantation Studies in Zebrafish.

Rapidly accumulating literature has proven feasibility of the zebrafish xenograft models in cancer research. Nevertheless, online databases for searching the current zebrafish xenograft literature are in great demand. Herein, we have developed a manually curated database, called ZenoFishDb v1.1 (https://konulab.shinyapps.io/zenofishdb), based on R Shiny platform aiming to provide searchable information on ever increasing collection of zebrafish studies for cancer cell line transplantation and patient-derived xenografts (PDXs). ZenoFishDb v1.1 user interface contains four modules: DataTable, Visualization, PDX Details, and PDX Charts. The DataTable and Visualization pages represent xenograft study details, including injected cell lines, PDX injections, molecular modifications of cell lines, zebrafish strains, as well as technical aspects of the xenotransplantation procedures in table, bar, and/or pie chart formats. The PDX Details module provides comprehensive information on the patient details in table format and can be searched and visualized. Overall, ZenoFishDb v1.1 enables researchers to effectively search, list, and visualize different technical and biological attributes of zebrafish xenotransplantation studies particularly focusing on the new trends that make use of reporters, RNA interference, overexpression, or mutant gene constructs of transplanted cancer cells, stem cells, and PDXs, as well as distinguished host modifications.

Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity.

The causative agent of coronavirus disease 2019 (COVID-19) is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For many viruses, tissue tropism is determined by the availability of virus receptors and entry cofactors on the surface of host cells. In this study, we found that neuropilin-1 (NRP1), known to bind furin-cleaved substrates, significantly potentiates SARS-CoV-2 infectivity, an effect blocked by a monoclonal blocking antibody against NRP1. A SARS-CoV-2 mutant with an altered furin cleavage site did not depend on NRP1 for infectivity. Pathological analysis of olfactory epithelium obtained from human COVID-19 autopsies revealed that SARS-CoV-2 infected NRP1-positive cells facing the nasal cavity. Our data provide insight into SARS-CoV-2 cell infectivity and define a potential target for antiviral intervention.