Biology subjects

Srivastava, S. K.

Publications and source records attributed to Srivastava, S. K..

6 recordsLinked to original sources

bioRxiv2025

Distribution and environmental drivers of multi-functional community traits in the Sundarbans mangrove forest

Mangrove forests are vital blue-carbon ecosystems, playing a crucial role in global carbon storage, climate regulation, and biodiversity conservation. However, escalating environmental threats, particularly salinity intrusion, necessitate a deeper understanding of their functional dynamics to inform effective conservation and restoration strategies. This study examines the distribution of multi-functional community traits (MFCT) and their environmental drivers across mangrove functional groups (pioneer, mid-successional, climax) along salinity gradients in the Sundarbans, the worlds largest mangrove forest. Using data from 62 plots, nine functional traits from 17 mangrove species were analysed to evaluate MFCT diversity and its environmental determinants. Results revealed distinct variations in MFCT diversity, with mid-successional species exhibiting the highest trait diversity (64.0 {+/-} 1.58), followed by climax (51.3 {+/-} 2.09) and pioneer groups (50.2 {+/-} 2.26). Climax species demonstrated resilience to salinity increases (R{superscript 2} = 0.29, p < 0.001), whereas mid-successional and pioneer groups were negatively affected (R{superscript 2} = 0.22, p < 0.001 and R{superscript 2} = 0.17, p < 0.001). Annual precipitation exerted contrasting effects, reducing diversity in climax species (R{superscript 2} = 0.25, p < 0.001) but enhancing it in mid-successional (R{superscript 2} = 0.22, p < 0.001) and pioneer groups (R{superscript 2} = 0.06, p = 0.05). Notably, MFCT values remained stable across salinity gradients, underscoring the ecosystems functional resilience. These findings highlight mid-successional species as keystones in sustaining mangrove multifunctionality and resilience under environmental stressors. Prioritizing these species in conservation and restoration efforts can mitigate the impacts of salinity intrusion and climate variability. By integrating the MFCT framework, resource managers can develop targeted restoration strategies to enhance ecosystem functionality and long-term stability. These insights provide a critical foundation for policymakers to align global mangrove conservation with adaptive management strategies, reinforcing coastal resilience, biodiversity conservation, and climate change mitigation.

ecology↗

bioRxiv2024

Tumor-induced endothelial RhoA activation mediates tumor cell transendothelial migration and metastasis

Abstract/SummaryThe endothelial barrier plays an active role in transendothelial tumor cell migration during metastasis, however, the endothelial regulatory elements of this step remain obscure. Here we show that endothelial RhoA activation is a determining factor during this process. Breast tumor cell-induced endothelial RhoA activation is the combined outcome of paracrine IL-8-dependent and cell-to-cell contact {beta}1 integrin-mediated mechanisms, with elements of this pathway correlating with clinical data. Endothelial-specific RhoA blockade or in vivo deficiency inhibited the transendothelial migration and metastatic potential of human breast tumor and three murine syngeneic tumor cell lines, similar to the pharmacological blockade of the downstream RhoA pathway. These findings highlight endothelial RhoA as a potent, universal target in the tumor microenvironment for anti-metastatic treatment of solid tumors.

physiology↗

bioRxiv2023

A new efficacious Mcl-1 inhibitor maximizes bortezomib and venetoclax responsiveness in resistant multiple myeloma cells

Despite a record number of clinical studies investigating various anti-cancer drugs, the 5-year survival rate for multiple myeloma (MM) patients in the United States is only 55%, and nearly all patients relapse. Poor patient outcomes demonstrate that myeloma cells are "born to survive," which means they can adapt and evolve following treatment. As a result, new therapeutic approaches to combat this survival mechanism and target treatment-resistant malignant cells are required. Mcl-1, an anti-apoptotic protein, is required for the development of MM and resistance to therapy. This study looks at the possibility of KS18, a Mcl-1 inhibitor derived from pyoluteorin, to treat resistant MM. We show that KS18 inhibits Mcl-1 selectively and promotes post-translational modifications, resulting in UPS-dependent Mcl-1 degradation. Our findings show that KS18-induced Mcl-1 degradation results in caspase-dependent apoptosis. Importantly, KS18 triggered apoptosis in MM patient samples and bortezomib-resistant cells, synergizing with venetoclax to boost apoptosis. Furthermore, KS18 inhibits colony formation in bortezomib-resistant cells. KS18 treated NSG mice displayed significant tumor shrinkage without significant toxicity after four weeks of therapy with a single acceptable dose each week, indicating its powerful anti-neoplastic and anti-resistance characteristics. This study strongly implies that KS18 may treat MM and provide new hope to patients who are experiencing recurrence or resistance. Key pointsO_LIGiven that KS18 is a robust Mcl-1 inhibitor that targets Mcl-1 efficiently, it has the potential to be a novel treatment for multiple myeloma. C_LIO_LIKS18 has shown promise in re-sensitizing myeloma cells to chemotherapy as well as in overcoming resistance to bortezomib, venetoclax, and ABT-737. C_LI

pharmacology and toxicology↗

bioRxiv2023

A soybean pattern recognition receptor conferring broad-spectrum pathogen and pest resistance regulates expression of several NLR receptor proteins

Overexpressors of Glycine max disease resistant 1 (GmDR1) exhibits broad-spectrum resistance against Fusarium virguliforme, soybean cyst nematode (SCN), spider mites, and soybean aphids in soybean. To understand the mechanisms of broad-spectrum immunity mediated by GmDR1, we investigated the transcriptomes of a strong and a weak GmDR1-overexpressors following treatment with chitin, a pathogen- and pest-associated molecular pattern (PAMP) found in these organisms. The strong and weak GmDR1-overexpressors exhibited altered expression of 6,098 and 992 genes, respectively, as compared to the nontransgenic control following chitin treatment. However, only 192 of these genes exhibited over two-fold changes in expression levels in both strong and weak GmDR1-overexpressors as compared to the control. MapMan analysis of the 192 genes revealed 64 biotic stress-related genes, of which 53 were induced and 11 repressed as compared to the control. The 53 chitin-induced genes include nine that encode receptor kinases, 13 encode nucleotide-binding leucine-rich repeat (NLR) receptor proteins, seven encoding WRKY transcription factors, four ethylene response factors, and three MYB-like transcription factors. Investigation of a subset of these genes revealed three receptor protein kinases, seven NLR proteins, and one WRKY transcription factor genes that are induced following F. virguliforme and SCN infection. The integral plasma membrane GmDR1 protein most likely recognizes PAMPs including chitin and activates transcription of genes encoding receptor kinases and NLR proteins. GmDR1 could be a pattern recognition receptor that regulates the expression of several NLRs for expression of PAMP-triggered immunity and/or priming the effector triggered immunity.

plant biology↗

bioRxiv2022

Genomic analysis unveils the role of genome degradation events and gene flux in the emergence and persistence of S. Paratyphi A lineages

Paratyphoid fever caused by S. Paratyphi A is endemic in parts of Asia and Sub-Saharan Africa. The proportion of enteric fever cases caused by S. Paratyphi A has substantially increased, yet only limited data is available on the population structure and genetic diversity of this serovar. We examined the phylogenetic distribution and evolutionary trajectory of S. Paratyphi A isolates collected as part of the Indian enteric fever surveillance study "Surveillance of Enteric Fever in India (SEFI)." In the study period (2017-2020), S. Paratyphi A comprised 17.6% (441/2503) of total enteric fever cases in India, with the isolates highly susceptible to all the major antibiotics used for treatment except fluoroquinolones. Phylogenetic analysis clustered the global S. Paratyphi A collection into seven lineages (A-G), and the present study isolates were distributed in lineages A, C and F. Our analysis documented that the genome degradation events and gene acquisitions or losses play a major role in the evolution of new S. Paratyphi A lineages/sub-lineages. A total of 10 pseudogene-forming mutations possibly associated with the emergence of lineages were identified. Pan-genome analysis identified the insertion of P2/PSP3 phage and acquisition of IncX1 plasmid during the selection in 2.3.2/2.3.3 and 1.2.2 genotypes, respectively. We also identified that the six characteristic missense mutations associated with the lipopolysaccharide (LPS) biosynthesis genes of S. Paratyphi A confer only a low structural impact and would therefore have minimal impact on vaccine effectiveness. Since S. Paratyphi A is human restricted, high levels of genetic drift are not expected unless these bacteria transmit to naive hosts. However, public-health investigation and intervention by means of genomic surveillance would be continually needed to avoid S. Paratyphi A serovar becoming a public health threat similar to the S. Typhi of today.

genomics↗

bioRxiv2022

Development of a Novel Bruton's Tyrosine Kinase Inhibitor that exerts Anti-Cancer Activities Potentiates Response of Chemotherapeutic Agents In Multiple Myeloma Stem Cell-Like Cells

Despite recent improvements in multiple myeloma (MM) treatment, MM remains an incurable disease and most patients experience a relapse. The major reason for myeloma recurrence is the persistent stem cell-like population. It has been demonstrated that overexpression of Brutons tyrosine kinase (BTK) in MM stem cell-like cells is correlated with drug resistance and poor prognosis. We have developed a novel small BTK inhibitor, KS151, which is unique compared to other BTK inhibitors. Unlike ibrutinib, and the other BTK inhibitors such as acalabrutinib, orelabrutinib, and zanubrutinib that covalently bind to the C481 residue in the BTK kinase domain, KS151 can inhibit BTK activities without binding to C481. This feature of KS151 is important because C481 becomes mutated in many patients and causes drug resistance. We demonstrated that KS151 inhibits in vitro BTK kinase activities and is more potent than ibrutinib. Furthermore, by performing a semi-quantitative, sandwich-based array for 71-tyrosine kinase phosphorylation, we found that KS151 specifically inhibits BTK. Our western blotting data showed that KS151 inhibits BTK signaling pathways and is effective against bortezomib-resistant cells as well as MM stem cell-like cells. Moreover, KS151 potentiates the apoptotic response of bortezomib, lenalidomide, and panobinostat in both MM and stem cell-like cells. Interestingly, KS151 inhibits stemness markers and is efficient in inhibiting Nanog and Gli1 stemness markers even when MM cells were co-cultured with bone marrow stromal cells (BMSCs). Overall, our results show that we have developed a novel BTK inhibitor effective against the stem cell-like population, and potentiates the response of chemotherapeutic agents.

molecular biology↗