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To the Editor-The current outbreak of COVID-19 in India, which started in early March 2021, has created a new world record even beyond the outbreaks in the UK, the United States and Brazil. Prior to March 2021, less than 0.7% of the Indian population was infected with COVID-19. This current second wave took only 2 months to infect an additional ~0.36% of the population, and India is now recording over 0.4 million new cases per day (as of 23 April 2021). The true number is probably even higher, with some estimates putting the number of daily new cases at over 1 million, more than five times the officially recorded number 1 .The sudden surge in COVID-19 cases in India coincides with high prevalence of more-transmissible variants, associated with diagnostic test failures and antibody escape 2 . These coronavirus SARS-CoV-2 variants of concern-B.1.1.7 (501Y.V1), B.1.351 (501Y.V2) and B.1.1.28.1 (501Y.V3; also known as P.1)-were observed during the sudden surge in COVID-19 cases in the UK, South Africa and Brazil, respectively, with subsequent local transmission across the world 2,3 (Fig. 1a).In India, the frequency of 501Y.V1 is higher than that of 501Y.V2 and 501Y.V.3 (Fig. 1b). The recently designated variant of concern B.1.617 and variant of interest B.1.618 have also been gaining attention in India 3 (Fig. 1a-c). Variant B.1.617.1 shows co-occurrence of three key mutations in sequence encoding the viral spike protein: L452R, E484Q and P681R. L452R raised concerns in the United States as part of the California variants B.1.427 and B.1.429 and conferred resistance to the neutralizing monoclonal antibodies X593 and P2B-2F6 4 . E484Q shares antibody-escape features similar to those of mutation E484K, seen in variants 501Y.V2, 501Y.V3 and B.1.618 2 . P681R may enhance processing by host proteases by extending the polybasic 'RRAR' motif, which results in a greater viral load and the potential for increased transmission. Another similar variant of concern, B.1.617.2, with mutations L452R, T478K and P681R, is highly prevalent in the state of Gujrat in India 3 . There was enrichment for the mutation T478K or T478R when SARS-CoV-2 was subjected to weak neutralizing antibodies, which indicates this mutation may lead to antibody escape.

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SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus 2) has accumulated multiple mutations during its global circulation. Recently, three SARS-CoV-2 lineages, B.1.1.7 (501Y.V1), B.1.351 (501Y.V2) and B.1.1.28.1 (P.1), have emerged in the United Kingdom, South Africa and Brazil, respectively. Here, we have presented global viewpoint on implications of emerging SARS-CoV-2 variants based on structural–function impact of crucial mutations occurring in its spike (S), ORF8 and nucleocapsid (N) proteins. While the N501Y mutation was observed in all three lineages, the 501Y.V1 and P.1 accumulated a different set of mutations in the S protein. The missense mutational effects were predicted through a COVID-19 dedicated resource followed by atomistic molecular dynamics simulations. Current findings indicate that some mutations in the S protein might lead to higher affinity with host receptors and resistance against antibodies, but not all are due to different antibody binding (epitope) regions. Mutations may, however, result in diagnostic tests failures and possible interference with binding of newly identified anti-viral candidates against SARS-CoV-2, likely necessitating roll out of recurring “flu-like shots” annually for tackling COVID-19. The functional relevance of these mutations has been described in terms of modulation of host tropism, antibody resistance, diagnostic sensitivity and therapeutic candidates. Besides global economic losses, post-vaccine reinfections with emerging variants can have significant clinical, therapeutic and public health impacts.

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Resistin is a small secretory protein that has a pleiotropic role in rodents and humans. Both rodent resistin and human resistin have an extremely stable and high-order multimeric structure. Moreover, there is significant variation in the source of secretion and the diversity of functions of resistin. Mouse resistin resists insulin action and contributes to type 2 diabetes mellitus, while human resistin plays a role in inflammation and also functions as a small accessory chaperone. Currently, active research in the area identified a significant role for resistin in stress biology and as a biomarker in diagnostics to evaluate disease status and treatment outcome. This review summarizes recent developments within resistin biology including their association with obesity, inflammation, stress response mechanisms, and its role in clinical diagnostics.

The genome of Mycobacterium tuberculosis, the causal organism of tuberculosis (TB), encodes a unique protein family known as the PE/PPE/PGRS family, present exclusively in the genus Mycobacterium and nowhere else in the living kingdom, with largely unexplored functions. We describe the functional significance of the PGRS domain of Rv0297, a member of this family. In silico analyses revealed the presence of intrinsically disordered stretches and putative endoplasmic reticulum (ER) localization signals in the PGRS domain of Rv0297 (Rv0297PGRS). The PGRS domain aids in ER localization, which was shown by infecting macrophage cells with M. tuberculosis and by overexpressing the protein by transfection in macrophage cells followed by activation of the unfolded protein response, as evident from increased expression of GRP78/GRP94 and CHOP/ATF4, leading to disruption of intracellular Ca2+ homeostasis and increased nitric oxide (NO) and reactive oxygen species (ROS) production. The consequent activation of the effector caspase-8 resulted in apoptosis of macrophages, which was Toll-like receptor 4 (TLR4) dependent. Administration of recombinant Rv0297PGRS (rRv0297PGRS) also exhibited similar effects. These results implicate a hitherto-unknown role of the PGRS domain of the PE_PGRS protein family in ER stress-mediated cell death through TLR4. Since this protein is already known to be present at later stages of infection in human granulomas it points to the possibility of it being employed by M. tuberculosis for its dissemination via an apoptotic mechanism.

Objective: Trans-fatty acids (TFAs) are formed during partial hydrogenation of vegetable oils and are shown to be more atherogenic than saturated fatty acids (SFAs). Our previous study showed that dietary TFAs decrease adipose tissue insulin sensitivity to a greater extent than SFAs in rats. We hypothesized that the effects of these fatty acids on insulin sensitivity could be mediated through an alteration in gene expression. In the current study we have investigated the effects of dietary TFAs or SFAs on expression of genes associated with insulin sensitivity in rat adipose tissue. Design and methods: Male weanling Wistar/NIN rats were divided into four groups and fed one of the following diets containing 10% fat (g/100 g diet) differing only in the fatty acid composition for 3 months: control diet (3.7% linoleic acid (LA)), SFA diet (5% SFA), TFA diet 1 (1.5% TFA þ 1% LA) and TFA diet 2 (1.5% TFA þ 2% LA). The mRNA expression of peroxisome proliferator-activated receptor g (PPARg), lipoprotein lipase (LPL), glucose transporter-4 (GLUT4), resistin and adiponectin was analyzed in epididymal fat using RT-PCR. The effects of TFA were studied at two levels of LA to understand the beneficial effects of LA over the effects of TFA. Results: Both dietary SFA and TFA upregulated the mRNA levels of resistin. Dietary SFA downregulated adiponectin and GLUT4 and upregulated LPL, while TFA downregulated PPARg and LPL. The effects of dietary TFA on PPARg and resistin were not counteracted by increased LA (TFA diet 2). Conclusion: The effects of SFAs on the aforementioned genes except PPARg could be extrapolated towards decreased insulin sensitivity, while only the alteration in the mRNA levels of PPARg and resistin could be associated with insulin resistance in TFA-fed rats. These findings suggest that dietary SFAs and TFAs alter the expression of different genes associated with insulin sensitivity in adipose tissue. European Journal of Endocrinology 153 159-165