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Biology subjects

R, G.

Publications and source records attributed to R, G..

5 recordsLinked to original sources

Host niche breadth differentially modulates the effects of anthropogenic disturbance across generalist and specialist parasites

Anthropogenic disturbances in natural habitats increase the risk of emerging infectious diseases in free-ranging host communities. Hence, understanding the processes driving such patterns is critical towards One Health. While anthropogenic disturbance is known to promote habitat-generalist host species through biotic homogenisation, generalist parasites (wider host breadth) also respond positively to the disturbed habitats. We hypothesise that generalist parasites are more likely to infect generalist hosts. We tested this hypothesis in a sky island system where generalist (Plasmodium) and specialist (Haemoproteus) haemosporidian parasites infect a range of bird hosts in disturbed and natural forest patches. We used a natural experiment framework to control for climatic differences (similar elevation) and habitat quality (same habitat type, but varying disturbance matrix). We collected 1106 samples from the field and examined the genus-level parasite prevalence and the host specificity of individual parasite lineages. Our results suggest that the generalist (Plasmodium) parasites are more prevalent in generalist birds, irrespective of disturbance. However, the specialist (Haemoproteus) parasites were more prevalent in specialist birds in natural forests than in disturbed forests. Among the individual parasite lineages, we found the host specificity to be associated with the degree of habitat specialisation of their host species. Our results provide evidence for the tendency of generalist parasites to infect generalist host species - a potential mechanism for a higher risk of emerging infectious diseases in human-dominated regions. We emphasise the role of host ecology in understanding the impact of anthropogenic disturbance on parasite prevalence in free-ranging host communities.

ecology↗

GPCR-targeted imaging and manipulation of homeostatic microglia in living systems

Microglia, the resident innate immune cells of the brain, are known to perform key roles such as synaptic pruning, apoptotic debris removal, and pathogen defense in the central nervous system. Microglial mutations are directly linked to many neurodevelopmental (e.g., schizophrenia) and neurodegenerative (e.g., Alzheimers disease) disorders, indicating the diagnostic and therapeutic potential of microglia for treating these conditions. Currently, we lack robust molecular tools to specifically image and manipulate microglia in vivo, which presents a major hurdle in our understanding of the brain-wide functions of these cells during the early onset of brain diseases. Here, we describe a molecular technology for imaging and manipulation of homeostatic microglia in live organisms (e.g., in zebrafish and mice) by covalently targeting the purinergic receptor, P2RY12. Using this technology, we imaged microglia-pathogen interactions in the larval zebrafish brain and revealed various morphological states of microglia in the adult mouse brain. We further expanded the microglia labelling approach to single-microglia tracking and microglial surfaceome mapping using photoactivatable fluorophores and photoproximity labelling, respectively. We anticipate the use of this universal tool for studying microglial biology across species to reveal the dynamics and polarization of resting microglia into a reactive state found in many neurodegenerative diseases.

immunology↗

Design, Synthesis, Molecular Docking and Biological Activity of Pyrazolopyridines as Promising Lead Candidates Against Mycobacterium tuberculosis

Pyrazolo[3,4-b]pyridine is a medicinally privileged structure. We have achieved a new and facile synthesis of a combinatorial library of its tetra- and persubstituted derivatives by trifluoracetic acid catalysed condensation of a group of 5-aminopyrazoles and a group of -oxoketene dithioacetals. Furthermore, we demonstrated structural modification of the products via reductive desulfurization, hydrolysis of the ester and Suzuki coupling of the bromo derivative with aryl bornoic acids. Some of the products were subjected to in vitro MABA assay against M. tuberclulosis H37Rv strain and in silico analysis by binding to pantothenate synthetase from M. tuberclulosis (MTBPS). The results indicated that the pyazolo[3,4-b]pyridine with N(1)CH3, C(3)C6H5, C(4) pCH3C6H5, C(5)CO2Et, C(6)SMe substitutions exhibits promising antituberculotic activity.

bioinformatics↗

Gene expression profiling of Tea (Camellia sinensis L.) in response to biotic stress using microarrays

The blister blight (BB) and grey blight (GB) diseases are the major biotic stresses, which affecting the plant health, yield and quality of tea. The study aims to understand the gene response of tea plants against destructing foliar diseases in terms of differential gene expression and their pathways through microarray analysis aid by MapMan(R) software. The results of expression profile analysis showed that 235 in BB and 258 for GB genes were differentially expressed (at P<0.05) which involving in gene regulatory function as biotic stress response. Similarly, 76 and 86 differentially expressed genes involving in cellular response during BB and GB diseases, respectively. However, 28 in BB and 9 in GB differentially expressed (P<0.01) genes were putatively involved in biotic stress response. The study also identified differentially expressed 75 transcription factors (TFs) belongs to 23 TFs superfamily act as either transcriptional activators or repressors. The study helps to understand the differential gene expression pattern and its cellular, molecular and biological mechanisms of tea plants of two different diseases based on microarray analysis. Further studies using biotechnological tools on the stress-responsive genes in the germplasm may enable us for development of disease resistance.

plant biology↗

Establishing wonder oil, Solanesol, as a novel inhibitor for Focal Adhesive Kinase by in silico strategies

Focal adhesion kinase (FAK) plays a primary role in regulating the activity of many signaling molecules. Increased FAK expression has been implicated in a series of cellular processes, including cell migration and survival. Inhibiting the activity of FAK for cancer therapy is currently under investigation. Hence, FAK and its inhibitors has been the subject of intensive research. To understand the structural factors affecting inhibitory potency, kinetic analysis, molecular docking and molecular dynamics simulation were studied in this project. Though, Solanesol was found have inhibitory activities towards FAK, no in silico tests were ever done on the same.\n\nDue to high flexibility of Solanesol (Rotatable bonds = 25), it is difficult to analyze using normal docking protocols. This paper introduces a novel method to dock and analyze molecules with high flexibility based on weighed contact based scoring method. This method uses blind docking technique, which was developed for protein peptide docking method, to generate conformations which were used to calculate contact based weights of residues. This method reveals the possible binding site for the small molecule. An exhaustive docking search on the acquired area reveals the docked confirmation of the compound. The final docked conformation was subjected to molecular dynamics to understand of binding stability. This study is in a good agreement with experimental results which shows Solanesol binds at ATP binding site and inhibit the phosphorylation of Focal Adhesion Kinase.

bioinformatics↗