Cross-neutralization of SARS-CoV-2 by HIV-1 specific broadly neutralizing antibodies and polyclonal plasma

Cross-reactive epitopes (CREs) are similar epitopes on viruses that are recognized or neutralized by same antibodies. The S protein of SARS-CoV-2, similar to type I fusion proteins of viruses such as HIV-1 envelope (Env) and influenza hemagglutinin, is heavily glycosylated. Viral Env glycans, though host derived, are distinctly processed and thereby recognized or accommodated during antibody responses. In recent years, highly potent and/or broadly neutralizing human monoclonal antibodies (bnAbs) that are generated in chronic HIV-1 infections have been defined. These bnAbs exhibit atypical features such as extensive somatic hypermutations, long complementary determining region (CDR) lengths, tyrosine sulfation and presence of insertions/deletions, enabling them to effectively neutralize diverse HIV-1 viruses despite extensive variations within the core epitopes they recognize. As some of the HIV-1 bnAbs have evolved to recognize the dense viral glycans and cross-reactive epitopes (CREs), we assessed if these bnAbs cross-react with SARS-CoV-2. Several HIV-1 bnAbs showed cross-reactivity with SARS-CoV-2 while one HIV-1 CD4 binding site bnAb, N6, neutralized SARS-CoV-2. Furthermore, neutralizing plasma antibodies of chronically HIV-1 infected children showed cross neutralizing activity against SARS-CoV-2 pseudoviruses. Collectively, our observations suggest that human monoclonal antibodies tolerating extensive epitope variability can be leveraged to neutralize pathogens with related antigenic profile.     

Rationalisation of regimens of treatment of kala-azar with sodium stibogluconate in India: a randomised study

The efficacy and safety of six regimens of treatment for kala-azar (visceral leishmaniasis) with sodium stibogluconate were evaluated in a prospective randomised study to ascertain the optimal treatment for Indian patients. Altogether 371 patients with kala-azar were randomised to receive sodium stibogluconate intramuscularly at a dose of 10 mg/kg body weight/day for 20 or 40 days (groups A and A1, respectively), 15 mg/kg body weight/day for 20 or 40 days (groups B and B1, respectively), or 20 mg/kg body weight/day for 20 or 40 days (groups C and C1, respectively). Patients were examined blind before and at the end of treatment and every month for six months. The number of patients who were apparently cured—that is, those whose temperature had returned to normal at the end of their regimen of treatment—was 45 (78%) in group A, 53 (87%) in group A1, 50 (81%) in group B, 60 (95%) in group B1, 58 (92%) in group C, and 62 (97%) in group C1.At six months 62 patients (97%) in group C1, 51 (81%) in group C, 54 (86%) in group B1, 42 (68%) in group B, 45 (74%) in group A1, and 33 (57%) in group A had not relapsed and were cured as confirmed by a bone marrow aspirate free of parasites. The differences between groups C1 and C, B1 and B, and A1 and A were significant. Logistic regression of the proportion cured with the dose and length of treatment showed that both factors were significant in improving the rate of cure; the highest dose for the longer time (group C1) had the best rate of cure. One patient in group C1, 12 in group C, nine in group B1, 18 in group B, 15 in group A1, and 23 in group A were cured with extended courses of 20 mg sodium stibogluconate. One patient in each of groups C1, B, A1, and A became unresponsive to antimony and were cured with pentamidine. One patient in each of groups C1, B, and A became unresponsive to both antimony and pentamidine. The patients tolerated the longer duration of treatment safely, and side effects were minor.Sodium stibogluconate should be given intramuscularly in the dosage of 20 mg/kg for at least 40 days, when patients should be assessed for further treatment if necessary. Such a regimen should achieve the highest rate of cure with low toxicity and low rates of relapse and unresponsiveness.     

Campanian-Maastricthian (Late Cretaceous) veneroids (Bivalvia: Heterodonta) from the Ariyalur Group,South India

Eleven veneroid (Bivalvia) species are systematically described from the Campanian-Maastrichtian (Late Cretaceous) sediments of Ariyalur sub-basin of South India. Among these, only Crassatella (Crassatella) macrodonta (Sowerby) and Arctica lacianata (Stoliczka) were earlier recorded by Stoliczka. Protocardia (Pachycardium) madagascariensis (Colignon), Protocardia (Pachycardium) pauli (Cocquand), Epicyprina angulata (Sowerby), Venilicardia truncata (Sowerby), and Calva (Egelicalva) buttensis (Anderson) were previously unknown from the Late Cretaceous horizons of the Indian sub-continent. The present record also includes a new species Palaeomoera stoliczkai n. sp. erected on the basis of its unique hinge characters and surface features. Lucina (Lucina) cf. fallax Forbes, Nicaniella (Nicaniella) aff. trigonoides (Stoliczka), and Corbicula? sp. indet., are tentatively identified because of their imperfect preservation. The present record may add useful information to the understanding of the Late Cretaceous palaeobiology of the region.     

Distinct Molecular Strategies for Hox-Mediated Limb Suppression in Drosophila: From Cooperativity to Dispensability/Antagonism in TALE Partnership

The emergence following gene duplication of a large repertoire of Hox paralogue proteins underlies the importance taken by Hox proteins in controlling animal body plans in development and evolution. Sequence divergence of paralogous proteins accounts for functional specialization, promoting axial morphological diversification in bilaterian animals. Yet functionally specialized paralogous Hox proteins also continue performing ancient common functions. In this study, we investigate how highly divergent Hox proteins perform an identical function. This was achieved by comparing in Drosophila the mode of limb suppression by the central (Ultrabithorax and AbdominalA) and posterior class (AbdominalB) Hox proteins. Results highlight that Hox-mediated limb suppression relies on distinct modes of DNA binding and a distinct use of TALE cofactors. Control of common functions by divergent Hox proteins, at least in the case studied, relies on evolving novel molecular properties. Thus, changes in protein sequences not only provide the driving force for functional specialization of Hox paralogue proteins, but also provide means to perform common ancient functions in distinct ways.     

Role of curcumin and its nanoformulations in neurotherapeutics: A comprehensive review

Curcumin, a dietary polyphenol and major constituent of Curcuma longa (Zingiberaceae), is extensively used as a spice in Asian countries. For ages, turmeric has been used in traditional medicine systems to treat various diseases, which was possible because of its anti‐inflammatory, antioxidant, anticancerous, antiepileptic, antidepressant, immunomodulatory, neuroprotective, antiapoptotic, and antiproliferative effects. Curcumin has potent antioxidant, anti‐inflammatory, antiapoptotic, neurotrophic activities, which support its plausible neuroprotective effects in neurodegenerative disease. However, there is limited information available regarding the clinical efficacy of curcumin in neurodegenerative cases. The low oral bioavailability of curcumin may be speculated as a plausible factor that limits its effects in humans. Therefore, utilization of several approaches for the enhancement of bioavailability may improve clinical outcomes. Furthermore, the use of nanotechnology and a targeted drug delivery system may improve the bioavailability of curcumin. The present review is designed to summarize the molecular mechanisms pertaining to the neuroprotective effects of curcumin and its nanoformulations.