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HRas is an important node that controls cellular signaling, proliferation, and differentiation. Mutants of HRas (e.g., the constitutively active HRas V12) can be oncogenic, and can also inhibit myoblast differentiation. The C-terminal cysteines of HRas (Cys181 and Cys184) serve as substrates for intra-cellular reversible palmitoylation and de-palmitoylation reactions, which control its subcellular distribution. The relationship between the C-terminal cysteines of HRas, its intracellular distribution, and its cellular activity has remained unclear. Understanding this relationship has important implications for targeting HRas in pathogenic states where it is activated. In this study, we show that a mutation in the C-terminal of HRas, C181S, is sufficient to cause increased levels of HRas V12 in the Golgi, decreased HRas V12-driven Akt and Erk signaling and reverse the ability of HRas V12 to inhibit myoblast differentiation. This demonstrates the importance of C-terminal cysteines in controlling HRas V12. It has been previously shown that Cys184 can also be irreversibly modified by an electrophilic prostaglandin lipid 15d-PGJ2. This lipid is released by senescent cells as a part of senescence-associated secretory phenotype (SASP). In this study, we show that 15d-PGJ2is secreted by senescent myoblasts formed by treatment with Doxorubicin. We also show that 15d-PGJ2causes decreased levels of HRas within Golgi, activates Erk signaling (but not Akt signaling), and inhibits differentiation of C2C12 myoblasts in an HRas Cys184-dependent fashion. Chemotherapeutics such as Doxorubicin drive senescence and loss of skeletal muscle homeostasis in cancer patients. This study suggests that targeting the senescence-derived synthesis of 15-PGJ2might be a target to promote muscle homeostasis after chemotherapy.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has triggered the COVID-19 pandemic. Several factors induce hypoxia in COVID-19. Despite being hypoxic, some SARS-CoV-2-infected individuals do not experience any respiratory distress, a phenomenon termed 'silent (or happy) hypoxia'. Prolonged undetected hypoxia could be dangerous, sometimes leading to death. A few studies attempted to unravel what causes silent hypoxia, however, the exact mechanisms are still elusive. Here, we aim to understand how SARS-CoV-2 causes silent hypoxia.

Background: Gastric cancer is one of the most prevalent cancers. As in many other solid tumors, hypoxia is a notable feature in gastric cancer as well. The hypoxic microenvironment promotes cancer by modulating expression of several master regulator oncoproteins. Carcinoembryonic antigen-related cell adhesion molecules or (CEACAMs) are adhesion proteins that have been associated with many epithelial tumors but their expression pattern in hypoxic gastric epithelial cells are not known. Since these membrane proteins have widespread roles in the intracellular and intercellular signaling, inflammation, angiogenesis and metastasis, we examined hypoxia-mediated regulation of CEACAM proteins. Methods: AGS, MKN45 and primary gastric epithelial cells were subjected to hypoxia of varying degrees and the changes in the CEACAM protein profile were evaluated by immunoblotting, FACS assay and immunofluorescence microscopy. In vitro DNA-binding assay and luciferase assays were performed to assess the transcriptional regulation of CEACAMs. Overexpression and suppression studies were also performed to elucidate upstream regulations of CEACAM proteins. Gastric cancer biopsy tissues were examined from consenting patients by performing fluorescence and confocal microscopy. Results: We found that varying degrees of hypoxia differentially modulate CEACAM expression in gastric cancer epithelial cells which in turn leads to altered proliferation and invasiveness of cancer cells. Interestingly, gastric adenocarcinoma and metastatic gastric cancer biopsies show distinct CEACAM signatures. These findings unfold further avenues highlighting the importance of CEACAM proteins as biomarkers of gastric cancer and as therapeutic targets to treat gastric cancer. Funding: Department of Atomic Energy (DAE). Citation Format: Indrajit Poirah, Debashish Chakraborty, Pragyesh Dixit, Supriya Samal, Pratyush Kumar Padhan, Alok Barik, Shivaram Prasad Singh, Bernhard B. Singer, Asima Bhattacharyya. Association between CEACAMs and hypoxia defines gastric cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1988.

In this paper, CoFe2O4/Cr2O3 nano-composites were prepared by sol gel auto-combustion route. The crystal structure of the as prepared composites was characterized by Rietveld refinement of X-ray diffraction pattern. The electrical behavior is investigated by the impedance spectroscopy in the temperature range of 300 to 400K on the frequency scale of 100Hz to 100k-Hz. The impedance spectrum reveals two types of relaxation in terms of two semicircles above 340K. The 1st semicircle is possibly due to the relaxation of grains whereas the 2nd semicircle corresponds to the grain boundary relaxation. The 1st relaxation shows non-Debye nature however the 2nd relaxation shows the Debye nature (extracted via Havriliak-Negami model). The change in capacitance with the application of magnetic field gives an indication of magnetoelectric coupling in the prepared nano-composites.