SUMMARY null null Previous studies showed that the high mortality caused by viruses such as SARS-CoV-2 and influenza virus, primarily results from the complications of a cytokine storm. Therefore, it is critical to identify the key factors participating in the cytokine storm. Here, we demonstrate that the interferon-induced protein 35 (IFP35), plays an important role in the cytokine storm induced by SARS-CoV-2 and influenza virus infection. We find that the levels of serum IFP35 in SARS-CoV-2 pa...
#1Kenta Niimi(UHSA: University of Health Sciences Antigua)H-Index: 1
#2Jun Nakae(IUHW: International University of Health and Welfare)H-Index: 31
Last. Tatsuo Furuyama(UHSA: University of Health Sciences Antigua)H-Index: 17
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Summary null null Intraluminal lymphatic valves (LVs) contribute to the prevention of lymph backflow and maintain circulatory homeostasis. Several reports have investigated the molecular mechanisms which promote LV formation; however, the way in which they are suppressed is not completely clear. We show that the forkhead transcription factor FOXO1 is a suppressor of LV formation and maintenance in lymphatic endothelial cells. Oscillatory shear stress by bidirectional flow inactivates FOXO1 via A...
#1Jennifer E. Klomp(UNC: University of North Carolina at Chapel Hill)H-Index: 8
#2Ye S. Lee(UNC: University of North Carolina at Chapel Hill)H-Index: 1
Last. Channing J. Der(UNC: University of North Carolina at Chapel Hill)H-Index: 109
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We apply genetic screens to delineate modulators of KRAS mutant pancreatic ductal adenocarcinoma (PDAC) sensitivity to ERK inhibitor treatment, and we identify components of the ATR-CHK1 DNA damage repair (DDR) pathway. Pharmacologic inhibition of CHK1 alone causes apoptotic growth suppression of both PDAC cell lines and organoids, which correlates with loss of MYC expression. CHK1 inhibition also activates ERK and AMPK and increases autophagy, providing a mechanistic basis for increased efficac...
Last. Guokai Chen(UM: University of Macau)H-Index: 18
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Pluripotent stem cells (PSCs) can be maintained in a continuum of cellular states with distinct features. Exogenous lipid supplements can relieve the dependence on de novo lipogenesis and shift global metabolism. However, it is largely unexplored how specific lipid components regulate metabolism and subsequently the pluripotency state. In this study, we report that the metabolic landscape of human PSCs (hPSCs) is shifted by signaling lipid lysophosphatidic acid (LPA), which naturally exists. LPA...
Summary null null A core network of widely expressed proteins within the glutamatergic post-synapse mediates activity-dependent synaptic plasticity throughout the brain, but the specific proteomic composition of synapses differs between brain regions. Here, we address the question, how does proteomic composition affect activity-dependent protein-protein interaction networks (PINs) downstream of synaptic activity? Using quantitative multiplex co-immunoprecipitation, we compare the PIN response of...
Summary null CD4+ T cells have a remarkable potential to differentiate into diverse effector lineages following activation. Here, we probe the heterogeneity present among naive CD4+ T cells before encountering their cognate antigen to ask whether their effector potential is modulated by pre-existing transcriptional and chromatin landscape differences. Single-cell RNA sequencing shows that key drivers of variability are genes involved in T cell receptor (TCR) signaling. Using CD5 expression as a ...
Last. Charan Ranganath(UCD: University of California, Davis)H-Index: 66
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Summary null null The hippocampus, well known for its role in episodic memory, might also be an important brain region for extracting structure from our experiences in order to guide future decisions. Recent evidence in rodents suggests that the hippocampus supports decision making by representing task structure in cooperation with the orbitofrontal cortex (OFC). Here, we examine how the human hippocampus and OFC represent task structure during an associative learning task that required learning...
Last. Yuquan Wei(SCU: Sichuan University)H-Index: 71
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Summary null Cancer cells utilize rapidly elevated cellular antioxidant programs to accommodate chemotherapy-induced oxidative stress; however, the underlying mechanism remains largely unexplored. Here we screen redox-sensitive effectors as potential therapeutic targets for colorectal cancer (CRC) treatment and find that cyclophilin A (CypA) is a compelling candidate. Our results show that CypA forms an intramolecular disulfide bond between Cys115 and Cys161 upon oxidative stress and the oxidize...
Summary null The persistence of anti-viral immunity is essential for protection and exhibits profound heterogeneity across individuals. Here, we elucidate the factors that shape maintenance and function of anti-viral T cell immunity in the body by comprehensive profiling of virus-specific T cells across blood, lymphoid organs, and mucosal tissues of organ donors. We use flow cytometry, T cell receptor sequencing, single-cell transcriptomics, and cytokine analysis to profile virus-specific CD8+ T...
Summary null Mechanoelectrical transduction is mediated by the opening of different types of force-sensitive ion channels, including Piezo1/2 and the TREK/TRAAK K2P channels. Piezo1 curves the membrane locally into an inverted dome that reversibly flattens in response to force application. Moreover, Piezo1 forms numerous preferential interactions with various membrane lipids, including cholesterol. Whether this structural architecture influences the functionality of neighboring membrane proteins...
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