X-chromosome inactivation (XCI) in female lymphocytes is uniquely regulated, as the inactive X (Xi) chromosome lacks localized Xist RNA and heterochromatin modifications. Epigenetic profiling reveals that Xist RNA is lost from the Xi at the pro-B cell stage and that additional heterochromatic modifications are gradually lost during B cell development. Activation of mature B cells restores Xist RNA and heterochromatin to the Xi in a dynamic two-step process that differs in timing and pattern, depending on the method of B cell stimulation. Finally, we find that DNA binding domain of YY1 is necessary for XCI in activated B cells, as ex-vivo YY1 deletion results in loss of Xi heterochromatin marks and up-regulation of X-linked genes. Ectopic expression of the YY1 zinc finger domain is sufficient to restore Xist RNA localization during B cell activation. Together, our results indicate that Xist RNA localization is critical for maintaining XCI in female lymphocytes, and that chromatin changes on the Xi during B cell development and the dynamic nature of YY1-dependent XCI maintenance in mature B cells predisposes X-linked immunity genes to reactivation.

Background: Rotaviral nonstructural protein 4 (NSP4) disrupts Ca 2ϩ ion homeostasis by translocating to the endoplasmic reticulum. Results: In this study, we show translocation of NSP4 to mitochondria, dissipation of mitochondrial potential, and initiation of apoptosis, which NSP1 counteracts during early infection. Conclusion: NSP4 and NSP1 regulate apoptosis during infection. Significance: Study signifies modulation of cellular survival and apoptotic machinery by rotavirus for their own benefit.

Highlights d BCR signal strength is encoded as quantitatively distinct intracellular Ca 2+ signals d Ca 2+ dynamics are decoded by NF-kB, NFAT, and mTORC1 to drive cell fates d BCR-induced Ca 2+ signals are required for maximal B cell survival and proliferation d CD40 compensates for weak BCR/Ca 2+ signals to rescue NF-kBand mTORC1-dependent fates

Since the inception of SARS-CoV-2 in December 2019, many variants have emerged over time. Some of these variants have resulted in transmissibility changes of the virus and may also have impact on diagnosis, therapeutics and even vaccines, thereby raising particular concerns in the scientific community. The variants which have mutations in Spike glycoprotein are the primary focus as it is the main target for neutralising antibodies. SARS-CoV-2 is known to infect human through Spike glycoprotein and uses receptor-binding domain (RBD) to bind to the ACE2 receptor in human. Thus, it is of utmost importance to study these variants and their corresponding mutations. Such 12 different important variants identified so far are B.1.1.7 (Alpha), B.1.351 (Beta), B.1.525 (Eta), B.1.427/B.1.429 (Epsilon), B.1.526 (Iota), B.1.617.1 (Kappa), B.1.617.2 (Delta), C.37 (Lambda), P.1 (Gamma), P.2 (Zeta), P.3 (Theta) and the recently discovered B.1.1.529 (Omicron). These variants have 84 unique mutations in Spike glycoprotein. To analyse such mutations, multiple sequence alignment of 77681 SARS-CoV-2 genomes of 98 countries over the period from January 2020 to July 2021 is performed followed by phylogenetic analysis. Also, characteristics of new emerging variants are elaborately discussed. The individual evolution of these mutation points and the respective variants are visualised and their characteristics are also reported. Moreover, to judge the characteristics of the non-synonymous mutation points (substitutions), their biological functions are evaluated by PolyPhen-2 while protein structural stability is evaluated using I-Mutant 2.0.

MicroRNA (miRNA) expression is significantly influenced by viral infection, because of either host antiviral defences or proviral factors resulting in the modulation of viral propagation. This study was undertaken to identify and analyse the significance of cellular miRNAs during rotavirus (SA11 or KU) infection. Sixteen differentially regulated miRNAs were identified during rotavirus infection of which hsa-miR-142-5p was up-regulated and validated by quantitative polymerase chain reaction. Exogenous expression of miR-142-5p inhibitor resulted in a significant reduction of viral titer indicating proviral role of miR-142-5p. Functional studies of hsa-miR-142-5p identified its role in transforming growth factor beta (TGFβ) signalling as TGFβ receptor 2 and SMAD3 were degraded during both hsa-miR-142-5p overexpression and rotavirus infection. TGFβ is induced during rotavirus infection, which may promote apoptosis by activation of non-canonical pathways in HT29 cells. However, up-regulated miR-142-5p resulted in the inhibition of TGFβ-induced apoptosis suggesting its anti-apoptotic function. Rotavirus NSP5 was identified as a regulator of miR-142-5p expression. Concurrently, NSP5-HT29 cells showed inhibition of TGFβ-induced apoptosis and epithelial to mesenchymal transition by blocking non-canonical pathways. Overall, the study identified proviral function of hsa-miR-142-5p during rotavirus infection. In addition, modulation of TGFβ-induced non-canonical signalling in microsatellite stable colon cancer cells can be exploited for cancer therapeutics.