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Biology subjects

Dhillon, M. S.

Publications and source records attributed to Dhillon, M. S..

3 recordsLinked to original sources

Oxygen deprivation implicated in rapid coral mortality -- an emerging perilous threat to coral reefs

Tropical coral reefs are undergoing unprecedented degradation1, primarily due to the increasing intensity and frequency of marine heatwaves with climate change2-4. Coral bleaching is a well-known ramification of marine heatwaves, but rapid coral mortality is an emerging paradigm that visually manifests as the sloughing of tissue from the coral skeleton. Unlike coral bleaching, coral tissue sloughing precludes any prospect of holobiont recovery beyond the initial onset1,5,6, indicating a life-or-death tipping point. Here, we experimentally confirm this phenomenon occurs when temperatures increase within temporal windows of hours to days, consistent with field observations7,8. Through microscale measurements of dissolved oxygen in the diffusive boundary layers of two abundant, keystone reef-building corals, we demonstrate that rapid temperature increases coincide with intrinsic oxygen deprivation, occurring before gross tissue disintegration or coral tissue sloughing. We propose that this distinct phenomenon arises from rapid heating, rendering the coral holobiont incapable of engaging in reactive processes to counteract the combined effects of heightened aerobic demands and impaired photosynthetic function. The passive diffusion of O2 from the surrounding bulk water is likely insufficient to meet the holobionts requirements, as explained by the Einstein-Smoluchowski kinetic theory of gases and Brownian motion9,10. These insights into coral tissue sloughing underscore the complexity of holobiont responses to stress and biophysical consequences of heatwaves. A granular understanding of these mechanisms is urgently needed, particularly regarding how heating rates may change under future climate scenarios, to re-evaluate the potentially under-recognised threats facing coral reefs.

ecology↗

Synovial fluid transcriptome dynamics in osteoarthritis progression: Implications in pathogenesis

BackgroundOsteoarthritis, a degenerative joint disease associated with various pathological manifestations in the joint including cartilage loss, alterations in subchondral bone and synovial inflammation. ObjectiveThis study aimed to elucidate the transcriptional and molecular changes in synovial fluid associated with OA progression, focusing on differential gene expression and pathway enrichment across OA grades. MethodologyPatients with different OA grades were recruited from PGIMER, Chandigarh, following the KL classification. Microarray analysis was conducted to study the transcriptional profiles in different OA grades using a fold-change (FC) cutoff of 2 and a p-value cutoff of 0.05, followed by pathway analysis performed using GSEA and STRING database. Selected genes from microarray and pathway analysis were validated using qRT-PCR. ResultsMicroarray analysis reveals distinct gene expression patterns corresponding to different OA stages (KL grade 2 to KL grade 4). Notably, the upregulation of AMTN and DKK2, alongside the downregulation of MSLN, highlighted their roles in pathological mineralization and disrupted bone remodeling in OA. Pathway enrichment analysis revealed significant changes in immune response, inflammation related pathways and cellular processes such as autophagy and programmed cell death, indicating their involvement in disease progression. Furthermore, mitochondrial dysfunction and impaired autophagy were linked to increased inflammation in advanced OA. ConclusionThese findings suggest that targeting mineralization and inflammatory pathways could offer novel therapeutic avenues for OA management.

pathology↗

Metabolic switching and cell wall remodelling of Mycobacterium tuberculosis during bone tuberculosis

Bone tuberculosis is widely characterized by irreversible bone destruction caused by Mycobacterium tuberculosis. Mycobacterium has the ability to adapt to various environmental stresses by altering its transcriptome in order to establish infection in the host. Thus, it is of critical importance to understand the transcriptional profile of M. tuberculosis during infection in the bone environment compared to axenic cultures of exponentially growing M.tb. In the current study, we characterized the in vivo transcriptome of M. tuberculosis within abscesses or necrotic specimens obtained from patients with bone TB using whole genome microarrays in order to gain insight into the M. tuberculosis adaptive response within this host microenvironment. A total of 914 mycobacterial genes were found to be significantly over-expressed and 1688 were repressed (fold change>2; p-value [≤]0.05) in human bone TB specimens. Overall, the mycobacteria displayed a hypo-metabolic state with significant (p[≤]0.05) downregulation of major pathways involved in translational machinery, cellular and protein metabolism and response to hypoxia. However, significant enrichment (p [≤]0.05) of amino-sugar metabolic processes, membrane glycolipid biosynthesis, amino acid biosynthesis (serine, glycine, arginine and cysteine) and accumulation of mycolyl-arabinogalactan-peptidoglycan complex suggests possible mycobacterial survival strategies within the bone lesions by strengthening its cell wall and cellular integrity. Data were also screened for M.tb virulence proteins using Virulent Pred and VICM Pred tools, which revealed five genes (Rv1046c, Rv1230c, DppD, PE_PGRS26 and PE_PGRS43) with a possible role in the pathogenesis of bone TB. Next, an osteoblast cell line model for bone TB was developed allowing for significant intracellular multiplication of M.tb. Interestingly, three virulence genes (Rv1046c, DppD and PE_PGRS26) identified from human bone TB microarray data were also found to be overexpressed by intracellular M. tuberculosis in osteoblast cell lines. Overall, these data demonstrate that M. tuberculosis alters its transcriptome as an adaptive strategy to survive in the host and establish infection in bone. Additionally, the in vitro osteoblast model we describe may facilitate our understanding of the pathogenesis of bone TB. Author SummaryMusculoskeletal tuberculosis is the third most common manifestation of extra-pulmonary tuberculosis and massive bone destruction along with vertebral discs are one of the hallmarks of this disease. Mycobacterium tuberculosis, the causative agent, has the tremendous potential to adapt itself to different host environments due to its ability to alter the expression of genes/proteins belonging to different pathways. This study shows that the mycobacterial infection in bone is driven by the increased expression of genes belonging to cell wall remodelling and DNA damage repair pathways important for its survival. Further data analysis showed that some of these genes are coding for proteins possessing virulence potential that may be essential for survival of M. tuberculosis under such hostile environment of bone. We also developed an in vitro model of bone tuberculosis using an osteoblast cell line and validated the expression of these virulence factors. Identification of such virulence factors in the bone environment by M. tuberculosis may aid to identify new therapeutic targets for bone TB. Further, development of cell line model for bone TB is important to understand some unknown facets of this disease.

microbiology↗