Since the outbreak of the novel coronavirus
disease COVID-19, caused by the SARS-CoV-2 virus, this disease has
spread rapidly around the globe. Considering the potential threat
of a pandemic, scientists and physicians have been racing to understand
this new virus and the pathophysiology of this disease to uncover
possible treatment regimens and discover effective therapeutic agents
and vaccines. To support the current research and development, CAS
has produced a special report to provide an overview of published
scientific information with an emphasis on patents in the CAS content
collection. It highlights antiviral strategies involving small molecules
and biologics targeting complex molecular interactions involved in
coronavirus infection and replication. The drug-repurposing effort
documented herein focuses primarily on agents known to be effective
against other RNA viruses including SARS-CoV and MERS-CoV. The patent
analysis of coronavirus-related biologics includes therapeutic antibodies,
cytokines, and nucleic acid-based therapies targeting virus gene expression
as well as various types of vaccines. More than 500 patents disclose
methodologies of these four biologics with the potential for treating
and preventing coronavirus infections, which may be applicable to
COVID-19. The information included in this report provides a strong
intellectual groundwork for the ongoing development of therapeutic
agents and vaccines.
An ongoing theme of the COVID-19 pandemic is the need for widespread availability of accurate and efficient diagnostic testing for detection of SARS-CoV-2 and antiviral antibodies in infected individuals. This report describes various assay techniques and tests for COVID-19 diagnosis. Most tests for early detection of SARS-CoV-2 RNA rely on the reverse transcription-polymerase chain reaction, but isothermal nucleic acid amplification assays, including transcription-mediated amplification and CRISPR-based methodologies, are promising alternatives. Identification of individuals who have developed antibodies to the SARS-CoV-2 virus requires serological tests, including enzyme-linked immunosorbent assay (ELISA) and lateral flow immunoassay. This report also provides an overview of current development in COVID-19 diagnostic techniques and products to facilitate future improvement and innovation.
This report examines various vaccine platforms including inactivated
vaccines, protein-based vaccines, viral vector vaccines, and nucleic
acid (DNA or mRNA) vaccines, and their ways of producing immunogens
in cells.
Hematopoietic cells isolated from patients with Bcr-Abl-positive leukemia exhibit multiple abnormalities of cytoskeletal and integrin function. These abnormalities are thought to play a role in the pathogenesis of leukemia; however, the molecular events leading to these abnormalities are not fully understood. We show here that the Abi1 pathway is required for Bcr-Abl to stimulate actin cytoskeleton remodeling, integrin clustering and cell adhesion. Expression of Bcr-Abl induces tyrosine phosphorylation of Abi1. This is accompanied by a subcellular translocation of Abi1/WAVE2 to a site adjacent to membrane, where an F-actin-enriched structure containing the adhesion molecules such as β1-integrin, paxillin and vinculin is assembled. Bcr-Abl-induced membrane translocation of Abi1/WAVE2 requires direct interaction between Abi1 and Bcr-Abl, but is independent of the phosphoinositide 3-kinase pathway. Formation of the F-actin-rich complex correlates with an increased cell adhesion to fibronectin. More importantly, disruption of the interaction between Bcr-Abl and Abi1 by mutations either in Bcr-Abl or Abi1 not only abolished tyrosine phosphorylation of Abi1 and membrane translocation of Abi1/WAVE2, but also inhibited Bcr-Abl-stimulated actin cytoskeleton remodeling, integrin clustering and cell adhesion to fibronectin. Together, these data define Abi1/WAVE2 as a downstream pathway that contributes to Bcr-Abl-induced abnormalities of cytoskeletal and integrin function.
ATM (ataxia telangiectasia mutated), the gene mutated in ataxia telangiectasia, is related to a family of large phosphatidylinositol 3-kinase domain-containing proteins involved in cell cycle control and DNA repair. We found that ATM 3a3 DT40 cells were more susceptible than wild-type cells to apoptosis induced not only by ionizing radiation and bleomycin but also by non-DNA-damaging apoptotic stimuli such as C 2 -ceramide. Furthermore, the apoptosis induced by C 2 -ceramide and H 2 O 2 was blocked by anti-oxidants, indicating that the ATM 3a3 DT40 cells had a heightened susceptibility to apoptosis induced by reactive oxygen intermediates (ROI), presumably due to defective ROI-detoxification activities. In support of this hypothesis, we found that more ROI were generated in ATM 3a3 DT40 cells than in wild-type cells, following treatment with the above apoptotic stimuli. These results indicate that ATM plays important roles in the maintenance of the cell homeostasis in response to oxidative damage.z 2000 Federation of European Biochemical Societies.
This study proposes to aggregately measure energy security performance with the principal component analysis. In its application of the methodology to four resource-poor yet economically advanced island economies in East Asia-Singapore, South Korea, Japan, and Taiwan, this study establishes a novel framework to conceptualize energy security. The framework incorporates three dimensions: vulnerability, efficiency, and sustainability, three indicators being allocated to each dimension. The study finds that all the three dimensions are critical for the resource-poor economies but have different weights in each of them. An urgent task for these four economies is to implement energy efficiency and conservation measures. Liberalization of electricity sector can be a helpful tool to reduce energy consumption and increase efficiency. All of them have been committed to promoting renewable energy development, which shall be further expanded in these economies.
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