Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily infects the respiratory tract, but pulmonary and cardiac complications occur in severe coronavirus disease 2019 (COVID-19). To elucidate molecular mechanisms in the lung and heart, we conducted paired experiments in human stem cell-derived lung alveolar type II (AT2) epithelial cell and cardiac cultures infected with SARS-CoV-2. With CRISPR-Cas9-mediated knockout of ACE2, we demonstrated that angiotensin-converting enzyme 2 (ACE2) was essential for SARS-CoV-2 infection of both cell types but that further processing in lung cells required TMPRSS2, while cardiac cells required the endosomal pathway.
View Article and Find Full Text PDFSarcopenia, the age-related decline in muscle function, places a considerable burden on health-care systems. While the stereotypic hallmarks of sarcopenia are well characterized, their contribution to muscle wasting remains elusive, which is partly due to the limited availability of animal models. Here, we have performed cellular and molecular characterization of skeletal muscle from the African killifish-an extremely short-lived vertebrate-revealing that while many characteristics deteriorate with increasing age, supporting the use of killifish as a model for sarcopenia research, some features surprisingly reverse to an "early-life" state in the extremely old stages.
View Article and Find Full Text PDFClonal selection and drift drive both normal tissue and cancer development. However, the biological mechanisms and environmental conditions underpinning these processes remain to be elucidated. Clonal selection models are centered in Darwinian evolutionary theory, where some clones with the fittest features are selected and populate the tissue or tumor.
View Article and Find Full Text PDFAcute myeloid leukemia (AML) is one of the most prevalent and acute blood cancers with a poor prognosis and low overall survival rate, especially in the elderly. Although several new AML markers and drug targets have been recently identified, the rate of long-term cancer eradication has not improved significantly due to the presence and drug resistance of AML cancer stem cells (CSCs). Here we develop a novel computational pipeline to analyze the transcriptomic profiles of AML cancer (stem) cells and identify novel candidate AML CSC markers and drug targets.
View Article and Find Full Text PDFBiological systems are composed of highly complex networks, and decoding the functional significance of individual network components is critical for understanding healthy and diseased states. Several algorithms have been designed to identify the most influential regulatory points within a network. However, current methods do not address all the topological dimensions of a network or correct for inherent positional biases, which limits their applicability.
View Article and Find Full Text PDFBioinform Biol Insights
December 2017
Background: Circadian rhythms are physiological and behavioral cycles with a period of approximately 24 hours that control various functions including gene expression. Circadian disruption is associated with a variety of diseases, especially cancer. Although some of the oncogenes and tumor suppressor genes (TSGs) are known as clock-controlled genes (CCGs), the analysis and annotation of circadian expression of most human oncogenes and TSGs are still lacking.
View Article and Find Full Text PDFEpigenetic complexes control various pathways within the cells. Their abnormalities can be involved in the initiation and the progression of different types of cancer. Nucleosome remodeling and deacetylase (NuRD) is an epigenetic complex that comprises several subunits such as PHF6.
View Article and Find Full Text PDFCircadian rhythms refer to the endogenous rhythms that are generated to synchronize physiology and behavior with 24-h environmental cues. These rhythms are regulated by both external cues and molecular clock mechanisms in almost all cells. Disruption of circadian rhythms, which is called circadian disruption, affects many biological processes within the body and results in different long-term diseases, including cancer.
View Article and Find Full Text PDFLong non-coding RNAs (lncRNAs) refer to a group of RNAs that are usually more than 200 nucleotides and are not involved in protein generation. Instead, lncRNAs are involved in different regulatory processes, such as regulation of gene expression. Different lncRNAs exist throughout the genome.
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