Biology subjects

Deshpande, G.

Publications and source records attributed to Deshpande, G..

23 records · Page 2Linked to original sources

bioRxiv2021

Comparison of the pathogenicity and virus shedding of SARS CoV-2 VOC 202012/01 and D614G variant in hamster model

The emergence of SARS-CoV-2 variants has posed a serious challenge to public health system and vaccination programs across the globe. We have studied the pathogenicity and virus shedding pattern of the SARS-CoV-2 VOC 202012/01 and compared with D614G variant in Syrian hamsters. VOC 202012/01 could produce disease in hamsters characterized by body weight loss and respiratory tract tropism but mild lung pathology. Further, we also documented that neutralizing antibodies developed against VOC 202012/01 could equally neutralize D614G variant. Higher load of VOC 202012/01 in the nasal wash specimens was observed during the first week of infection outcompeting the D614G variant. The findings suggest increased fitness of VOC 202012/01 to the upper respiratory tract which could lead to higher transmission. Further investigations are needed to understand the transmissibility of new variants. One-Sentence SummarySARS-CoV-2 VOC 202012/01 infected hamsters demonstrated high viral RNA shedding through the nasal secretions and significant body weight loss with mild lung pathology compared to the D614G variant.

microbiology↗

bioRxiv2021

Assessment of immunogenicity and protective efficacy of ZyCoV-D DNA vaccine candidates in Rhesus macaques against SARS-CoV-2 infection

Vaccines remain the key protective measure to achieve herd immunity to control the disease burden and stop COVID-19 pandemic. We have developed and assessed the immunogenicity and protective efficacy of two formulations (1mg and 2mg) of ZyCoV-D (a plasmid DNA based vaccine candidates) administered through Needle Free Injection System (NFIS) and syringe-needle (intradermal) in rhesus macaques with three dose vaccine regimens. The vaccine candidate 2mg dose administered using Needle Free Injection System (NFIS) elicited a significant immune response with development of SARS-CoV-2 S1 spike region specific IgG and neutralizing antibody (NAb) titers during the immunization phase and significant enhancement in the levels after the virus challenge. In 2 mg NFIS group the IgG and NAb titers were maintained and showed gradual rise during the immunization period (15 weeks) and till 2 weeks after the virus challenge. It also conferred better protection to macaques evident by the viral clearance from nasal swab, throat swab and bronchoalveolar lavage fluid specimens in comparison with macaques from other immunized groups. In contrast, the animals from placebo group developed high levels of viremia and lung disease following the virus challenge. Besides this, the vaccine candidate also induced increase lymphocyte proliferation and cytokines response (IL-6, IL-5).The administration of the vaccine candidate with NFIS generated a better immunogenicity response in comparison to syringe-needle (intradermal route). The study demonstrated immunogenicity and protective efficacy of the vaccine candidate, ZyCoV-D in rhesus macaques.

microbiology↗

bioRxiv2021

Neutralization of UK-variant VUI-202012/01 with COVAXIN vaccinated human serum

We performed the plaque reduction neutralization test (PRNT50) using sera collected from the 26 recipients of BBV152/COVAXIN against hCoV-19/India/20203522 (UK-variant) and hCoV27 19/India/2020Q111 (heterologous strain). A comparable neutralization activity of the vaccinated individuals sera showed against UK-variant and the heterologous strain with similar efficiency, dispel the uncertainty of possible neutralization escape.

molecular biology↗

bioRxiv2020

Satb2 acts as a gatekeeper for major developmental transitions during early vertebrate embryogenesis

Zygotic genome activation (ZGA) initiates regionalized transcription responsible for the acquisition of distinct cellular identities. ZGA is dependent upon dynamic chromatin architecture sculpted by conserved DNA-binding proteins. However, whether the tissue-specific transcription is mechanistically linked with the onset of ZGA is unknown. Here, we have addressed the involvement of chromatin organizer SATB2 in orchestrating these processes during vertebrate embryogenesis. Integrative analysis of transcriptome, genome-wide occupancy and chromatin accessibility revealed contrasting molecular functions of maternal and zygotic pools of Satb2. Maternal Satb2 represses zygotic genes by influencing the interplay between the pluripotency factors. By contrast, zygotic Satb2 activates transcription of the same group of genes during neural crest development and organogenesis. Comparative analysis of maternal versus zygotic function of Satb2 underscores how these antithetical activities are temporally coordinated and functionally implemented. We discuss the evolutionary implications of the biphasic and bimodal regulation of landmark developmental transitions by a single determinant.

developmental biology↗

bioRxiv2018

Rab converter DMon1 constitutes a novel node in the brain-gonad axis essential for female germline maturation

Monensin-sensitive 1 (Mon1) is an endocytic regulator that participates in the conversion of Rab5 positive early endosomes to Rab7 positive late endosomes. In Drosophila, loss of mon1 (Dmon1) leads to sterility. The Dmon1 mutant females have extremely small ovaries with complete absence of late stage egg chambers-a phenotype reminiscent of mutations in the insulin pathway genes. Consistently, we find that expression of many Drosophila insulin-like peptides (Dilps) is down regulated in Dmon1 mutants. Conversely, feeding an insulin-rich diet can rescue the ovarian defects induced by the loss of Dmon1.\n\nSurprisingly however, Dmon1 is required in the tyramine/octopaminergic neurons (OPNs) and not in the ovaries or the insulin producing cells (IPCs). Thus, knockdown of Dmon1 in just the OPNs is sufficient to mimic the ovarian phenotype while expression of Dmon1 in the OPNs alone, is sufficient to rescue the mutant defect.\n\nLastly, we have identified dilp5 as a critical target of Dmon1. Both, protein and mRNA levels of Dilp5 levels are reduced in Dmon1 mutants and IPC-specific dilp5 over expression can ameliorate the Dmon1 dependent sterility defect. The study thus identifies Dmon1 as a novel molecular player in the brain-gonad axis and underscores the significance of inter-organ systemic communication during development.\n\nSignificance Statement Functional significance of the long-distance systemic communication during organogenesis has emerged as a major area of enquiry. We have focused our attention on an endocytic regulator DMon1, that appears to participate in a remote control type of mechanism. We report a novel tripartite circuitry that involves Dmon1 activity in Octopaminergic neurons, its influence on insulin production in the insulin producing cells (IPCs) which, in turn, is required for the progression of oogenesis. Our results document a spatially remote non-autonomous control mechanism involving neuronal cross-talk that orchestrates developmental regulation of oogenesis. Importantly our data provide a unique example of how distinct neuronal hubs can engineer metabolic pathways underlying growth/differentiation and highlight the importance of systemic regulation of organogenesis.

developmental biology↗