Biology subjects

Ray, R.

Publications and source records attributed to Ray, R..

26 records · Page 2Linked to original sources

bioRxiv2022

Mapping the risks of China's global coastal development to marine socio-ecological systems

Rapid coastal development continues to jeopardize the integrity of marine socio-ecological systems. China is now the largest bilateral creditor in the world, committing nearly half a trillion US dollars to overseas development finance since 2008. Meanwhile, there are growing concerns over the impacts of this boom in Chinese development finance on marine systems. Here, we quantify the risks of coastal development projects financed by China to marine biodiversity and coastal Indigenous communities. Ports present the greatest impact risks to marine systems, in terms of both magnitude and area at risk, with power plants, roads, and other facilities presenting relatively high localized risks. Risks are most prominent in Africa and the Caribbean, with coastal Indigenous communities in Western and Central Africa particularly vulnerable to the potential negative impacts of development. All projects present some risk to threatened marine species and potential critical habitats, but few present high risks to nearby marine protected areas. Most projects present additional risks to ecosystems that are already under increasing human pressures, but some are likely to introduce new risks to relatively intact ecosystems. "Bluing" future coastal development projects in Chinas overseas development finance portfolio will require more social and environmental safeguards, higher standards for host-country impact assessments, and greater integration of land-sea risk mitigation and management approaches.

ecology↗

bioRxiv2022

Modified E2 glycoprotein of hepatitis C virus enhances pro-inflammatory cytokines and protective immune response in mice

Hepatitis C virus (HCV) is characterized by a high number of chronic cases owing to an impairment of innate and adaptive immune responses. CD81 on the cell surface facilitates HCV entry by interacting with the E2 envelope glycoprotein. On the other hand, CD81/E2 binding on immune related cells may also influence host response outcome to HCV infection. Here, we performed site-specific amino acid substitution in the front layer of E2 sequence to reduce CD81 binding and evaluate HCV candidate vaccine potential. The altered sE2 protein (F442NYT), unlike sE2, displayed a significant reduction in CD81 binding, induced pro-inflammatory cytokines, and repressed anti-inflammatory response in primary monocyte-derived macrophages as antigen presenting cells. Further, sE2F442NYT stimulated CD4+T cell proliferation. Immunization of Balb/c mice with an E1/sE2F442NYT RNA-lipid nanoparticle (LNP) displayed improved IgG1 to IgG2a isotype switching, an increase in HCV pseudotype virus neutralizing antibodies, and resistance to challenge infection with a surrogate recombinant vaccinia virus expressing HCV E1-E2-NS2(aa134-966), unlike parental E1/sE2 immunization. Further investigation on modified E2 antigen for selection as antigen may provide helpful information for HCV vaccine development. One Sentence SummaryReduced HCV E2-CD81 binding and immune response

microbiology↗

bioRxiv2022

Circulatory exosomes from COVID-19 patients trigger NLRP3 inflammasome in endothelial cells

SARS-CoV-2 infection induces inflammatory response, cytokine storm, venous thromboembolism, coagulopathy, and multiple organ damage. Resting endothelial cells prevent coagulation, control blood flow and inhibit inflammation. However, it remains unknown how SARS-CoV-2 induces strong molecular signals in distant cells for immunopathogenesis. In this study, we examined the consequence of human endothelial cells (microvascular endothelial cells (HMEC-1) and liver endothelial cells (TMNK-1)) to exosomes from plasma of severe COVID-19 patients. We observed a significant induction of NLRP3, caspase-1 and IL-1{beta} mRNA expression in the endothelial cells following exposure to exosomes from plasma of COVID-19 patients as compared to that of healthy donors. Activation of caspase-1 was noted in the endothelial cell culture medium following exposure to the COVID-19 exosomes. Further, COVID-19 exosomes significantly induced mature IL-1{beta} secretion in the endothelial cell culture medium. Thus, our results demonstrated for the first time that exosomes from COVID-19 plasma trigger NLRP3 inflammasome in endothelial cells of distant organs.

immunology↗

bioRxiv2021

A SARS-CoV-2 targeted siRNA-nanoparticle therapy for COVID-19

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in humans. Despite several emerging vaccines, there remains no verifiable therapeutic targeted specifically to the virus. Here we present a highly effective siRNA therapeutic against SARS-CoV-2 infection using a novel lipid nanoparticle delivery system. Multiple small-interfering RNAs (siRNAs) targeting highly conserved regions of the SARS-CoV-2 virus were screened and three candidate siRNAs emerged that effectively inhibit virus by greater than 90% either alone or in combination with one another. We simultaneously developed and screened two novel lipid nanoparticle formulations for the delivery of these candidate siRNA therapeutics to the lungs, an organ that incurs immense damage during SARS-CoV-2 infection. Encapsulation of siRNAs in these LNPs followed by in vivo injection demonstrated robust repression of virus in the lungs and a pronounced survival advantage to the treated mice. Our LNP-siRNA approaches are scalable and can be administered upon the first sign of SARS-CoV-2 infection in humans. We suggest that an siRNA-LNP therapeutic approach could prove highly useful in treating COVID-19 disease as an adjunctive therapy to current vaccine strategies.

synthetic biology↗

bioRxiv2021

SARS-CoV-2 spike protein expressing epithelial cells promotes senescence associated secretory phenotype in endothelial cells and increased inflammatory response

Increased mortality in COVID-19 often associates with thrombotic and microvascular complications. We have recently shown that SARS-CoV-2 spike protein promotes inflammatory cytokine IL-6/IL-6R induced trans-signaling responses which modulate MCP-1 expression in human endothelial cells. MCP-1 is secreted as a major component of the senescence associated secretory phenotype (SASP). Virus infected or Spike transfected human pulmonary epithelial cells (A549) exhibited an increase in senescence related marker proteins. TMNK; as a representative human endothelial cell line, when exposed to cell culture supernatant derived from A549 cells expressing SARS-CoV-2 spike protein (Spike CM) exhibited a senescence phenotype with enhanced p16, p21, and SA-{beta}-galactosidase expression. Inhibition of IL-6 trans-signaling by Tocilizumab, prior to exposure of supernatant to endothelial cells, inhibited p16 and p21 induction. Likewise, inhibition of receptor signaling by Zanabrutinib or Brd4 function by AZD5153 also led to limited induction of p16 expression. Senescence lead to an enhanced level of adhesion molecule, ICAM-1 and VCAM-1 in human endothelial cells, and TPH1 attachment by in vitro assay. Inhibition of senescence or SASP function prevented ICAM/VCAM expression and leukocyte attachment. We also observed an increase in oxidative stress in A549 spike transfected and endothelial cells exposed to Spike CM. ROS generation in TMNK was reduced after treatment with the IL-6 specific inhibitor Tociliximab, and with the specific inhibitors Zanabrutinib and AZD5153. Taken together, we identified that the exposure of human endothelial cells to cell culture supernatant derived from SARS-CoV-2 spike protein expression displayed cellular senescence markers leading to enhanced leukocyte adhesion with coronary blockade potential.

immunology↗

bioRxiv2021

Exosomes from COVID-19 patients carry tenascin-C and fibrinogen-β in triggering inflammatory signals in distant organ cells

SARS-CoV-2 infection causes cytokine storm and overshoot immunity in humans; however, it remains to be determined whether genetic material of SARS-CoV-2 and/or virus induced soluble mediators from lung epithelial cells as natural host are carried out by macrophages or other vehicles at distant organs causing tissue damage. We speculated that exosomes as extracellular vesicles are secreted from SARS-CoV-2 infected cells may transport messages to other cells of distant organs leading to pathogenic consequences. For this, we took an unbiased proteomic approach for analyses of exosomes isolated from plasma of healthy volunteers and SARS-CoV-2 infected patients. Our results revealed that tenascin-C (TNC) and fibrinogen-{beta} (FGB) are highly abundant in exosomes from SARS-CoV-2 infected patients plasma as compared to that of healthy normal controls. Since TNC and FGB stimulate pro-inflammatory cytokines via NF-{kappa}B pathway, we examined the status of TNF-, IL-6 and CCL5 expression upon exposure of hepatocytes to exosomes from COVID-19 patients and observed significant increase when compared with that from healthy subjects. Together, our results demonstrated that soluble mediators, like TNC and FGB, are transported through plasma exosomes in SARS-CoV-2 infected patients and trigger pro-inflammatory cytokine expression in cells of distant organs in COVID-19 patients. ImportanceExosomes play an important role in intercellular communication by inducing physiological changes in recipient cells by transferring bioactive proteins. Little is known about exosomes from SARS-CoV-2 infected cells and their role in pathogenesis. Here, we have carefully examined and analyzed this aspect of SARS-CoV-2 infection. Our results uncovered the potential mechanisms by which SARS-CoV-2 communicates with other cells of distant organs and promotes pathogenesis. We expect to detect whether other factors are modulated in the presence of COVID-19 exosomes. Our exosomes related proteomic experiments prioritize after initial verification to further examine their role in SARS-CoV-2 associated other pathogenic mechanisms to target for therapeutic modalities.

physiology↗

bioRxiv2020

Western Ghats Myrtaceae are not Gondwana elements but likely dispersed from south-east Asia

Gondwana break-up is one of the key sculptors of the global biogeographic pattern including Indian subcontinent. Myrtaceae, a Gondwana family, demonstrates a high diversity across Indian Western Ghats. A rich paleo-records in Deccan Intertrappean bed in India strive to reconcile two contending hypothesis of origin and diversification of Myrtaceae in India, namely Gondwana elements floated on peninsular India or lineages invading from south-east Asia. In this study, we have reconstructed the biogeographic history of Myrtaceae of Western Ghats of India combining fossil-calibrated phylogeny, ancestral area reconstruction, and comparing various dispersal models. Phylogenetic reconstructions divided lineages into multiple clades at the tribal level that mostly is in agreement with previous descriptions. Dated tree indicated a presumable Gondwanan origin of Myrtaceae (95.7 Ma). The Western Ghats taxa are relatively younger and seem to have arrived either through long-distance oceanic dispersal in middle Eocene (Rhodomyrtus tomentosa), and Miocene (Eugenia) or through major overland dispersals throughout Miocene (Syzygium). However, late Cretaceous fossilsin India lends support to the existence of proto-Myrtaceae on floating peninsular India. Taken together, we conclude that Myrtaceae lineages on the biotic ferry were perhaps extirpated by Deccan volcanism leaving a little or no trace of living Gondwanan link, while the Western Ghats was likely enriched by dispersed elements either from south-east Asia or from South America.

genomics↗

bioRxiv2019

Nitric oxide acts as a cotransmitter in a subset of dopaminergic neurons to diversify memory dynamics

Animals employ multiple and distributed neuronal networks with diverse learning rules and synaptic plasticity dynamics to record distinct temporal and statistical information about the world. However, the molecular mechanisms underlying this diversity are poorly understood. The anatomically defined compartments of the insect mushroom body function as parallel units of associative learning, with different learning rates, memory decay dynamics and flexibility (Aso & Rubin 2016). Here we show that nitric oxide (NO) acts as a neurotransmitter in a subset of dopaminergic neurons in Drosophila. NOs effects develop more slowly than those of dopamine and depend on soluble guanylate cyclase in postsynaptic Kenyon cells. NO acts antagonistically to dopamine; it shortens memory retention and facilitates the rapid updating of memories. The interplay of NO and dopamine enables memories stored in local domains along Kenyon cell axons to be specialized for predicting the value of odors based only on recent events. Our results provide key mechanistic insights into how diverse memory dynamics are established in parallel memory systems.

neuroscience↗