排序方式: 共有75条查询结果,搜索用时 15 毫秒
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M Kohli C Vaishnavi S Jaswal S Kaur N K Ganguly 《Journal of hygiene, epidemiology, microbiology, and immunology》1992,36(2):201-206
Peritoneal macrophages from uninfected controls and Mycobacterium leprae infected Swiss albino mice were studied for their respiratory burst (RB) activity at different time intervals. The RB metabolic activity of macrophages declined significantly after 3 month infection using latex (p less than 0.001) and M. leprae (p less than 0.01) as stimuli. However, significant rise (p less than 0.001) in the oxidative metabolic activity was seen at 6 and 9 months postinfection period on stimulation with both the stimuli. The sharp rise in the oxidative metabolic status at peak period of infection in the experimental animals suggests that the macrophages are functionally normal though M. leprae is unable to trigger the respiratory burst sufficiently. 相似文献
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Akinwunmi Oni-Orisan Mayank Kaushal Wenjun Li Jack Leschke B. Douglas Ward Aditya Vedantam Benjamin Kalinosky Matthew D. Budde Brian D. Schmit Shi-Jiang Li Vaishnavi Muqeet Shekar N. Kurpad 《PloS one》2016,11(3)
Functional magnetic resonance imaging (fMRI) studies have demonstrated alterations during task-induced brain activation in spinal cord injury (SCI) patients. The interruption to structural integrity of the spinal cord and the resultant disrupted flow of bidirectional communication between the brain and the spinal cord might contribute to the observed dynamic reorganization (neural plasticity). However, the effect of SCI on brain resting-state connectivity patterns remains unclear. We undertook a prospective resting-state fMRI (rs-fMRI) study to explore changes to cortical activation patterns following SCI. With institutional review board approval, rs-fMRI data was obtained in eleven patients with complete cervical SCI (>2 years post injury) and nine age-matched controls. The data was processed using the Analysis of Functional Neuroimages software. Region of interest (ROI) based analysis was performed to study changes in the sensorimotor network using pre- and post-central gyri as seed regions. Two-sampled t-test was carried out to check for significant differences between the two groups. SCI patients showed decreased functional connectivity in motor and sensory cortical regions when compared to controls. The decrease was noted in ipsilateral, contralateral, and interhemispheric regions for left and right precentral ROIs. Additionally, the left postcentral ROI demonstrated increased connectivity with the thalamus bilaterally in SCI patients. Our results suggest that cortical activation patterns in the sensorimotor network undergo dynamic reorganization following SCI. The presence of these changes in chronic spinal cord injury patients is suggestive of the inherent neural plasticity within the central nervous system. 相似文献
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Germline variants in oculocutaneous albinism genes and predisposition to familial cutaneous melanoma
Vaishnavi Nathan Peter A. Johansson Jane M. Palmer Madeleine Howlie Hayley R. Hamilton Karin Wadt Gran Jnsson Kelly M. Brooks Antonia L. Pritchard Nicholas K. Hayward 《Pigment cell & melanoma research》2019,32(6):854-863
Approximately 1%–2% of cutaneous melanoma (CM) is classified as strongly familial. We sought to investigate unexplained CM predisposition in families negative for the known susceptibility genes using next‐generation sequencing of affected individuals. Segregation of germline variants of interest within families was assessed by Sanger sequencing. Several heterozygous variants in oculocutaneous albinism (OCA) genes: TYR, OCA2, TYRP1 and SLC45A2, were present in our CM cohort. OCA is a group of autosomal recessive genetic disorders, resulting in pigmentation defects of the eyes, hair and skin. Missense variants classified as pathogenic for OCA were present in multiple families and some fully segregated with CM. The functionally compromised TYR p.T373K variant was present in three unrelated families. In OCA2, known pathogenic variants: p.V443I and p.N489D, were present in three families and one family, respectively. We identified a likely pathogenic SLC45A2 frameshift variant that fully segregated with CM in a family of four cases. Another four‐case family harboured cosegregating variants (p.A24T and p.R153C) of uncertain functional significance in TYRP1. We conclude that rare, heterozygous variants in OCA genes confer moderate risk for CM. 相似文献
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Mythreyi Narasimhan Vaishnavi Khamkar Sarika Tilwani Sorab N. Dalal Dhanlaxmi Shetty P.G. Subramanian Sanjay Gupta Rukmini Govekar 《Journal of cell communication and signaling》2022,16(2):207
Chronic myeloid leukemia (CML) epitomises successful targeted therapy, where inhibition of tyrosine kinase activity of oncoprotein Bcr-Abl1 by imatinib, induces remission in 86% patients in initial chronic phase (CP). However, in acute phase of blast crisis, 80% patients show resistance, 40% among them despite inhibition of Bcr-Abl1 activity. This implies activation of either Bcr-Abl1- independent signalling pathways or restoration of signalling downstream of inactive Bcr-Abl1. In the present study, mass spectrometry and subsequent in silico pathway analysis of differentiators in resistant CML-CP cells identified key differentiators, 14–3-3ε and p38 MAPK, which belong to Bcr-Abl1 pathway. Their levels and activity respectively, indicated active Bcr-Abl1 pathway in CML-BC resistant cells, though Bcr-Abl1 is inhibited by imatinib. Further, contribution of these components to resistance was demonstrated by inhibition of Bcr-Abl1 down-stream signalling by knocking-out of 14–3-3ε and inhibition of p38 MAPK activity. The observations merit clinical validation to explore their translational potential.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12079-021-00647-x. 相似文献
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Hong-Duc Phan Andrew S Norris Chen Du Kye Stachowski Bela
H Khairunisa Vaishnavi Sidharthan Biswarup Mukhopadhyay Mark
P Foster Vicki
H Wysocki Venkat Gopalan 《Nucleic acids research》2022,50(14):8154
RNase P is a ribonucleoprotein (RNP) that catalyzes removal of the 5′ leader from precursor tRNAs in all domains of life. A recent cryo-EM study of Methanocaldococcus jannaschii (Mja) RNase P produced a model at 4.6-Å resolution in a dimeric configuration, with each holoenzyme monomer containing one RNase P RNA (RPR) and one copy each of five RNase P proteins (RPPs; POP5, RPP30, RPP21, RPP29, L7Ae). Here, we used native mass spectrometry (MS), mass photometry (MP), and biochemical experiments that (i) validate the oligomeric state of the Mja RNase P holoenzyme in vitro, (ii) find a different stoichiometry for each holoenzyme monomer with up to two copies of L7Ae, and (iii) assess whether both L7Ae copies are necessary for optimal cleavage activity. By mutating all kink-turns in the RPR, we made the discovery that abolishing the canonical L7Ae–RPR interactions was not detrimental for RNase P assembly and function due to the redundancy provided by protein–protein interactions between L7Ae and other RPPs. Our results provide new insights into the architecture and evolution of RNase P, and highlight the utility of native MS and MP in integrated structural biology approaches that seek to augment the information obtained from low/medium-resolution cryo-EM models. 相似文献
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K Vaishnavi N Saxena N Shah R Singh K Manjunath M Uthayakumar SP Kanaujia SC Kaul K Sekar R Wadhwa 《PloS one》2012,7(9):e44419
BACKGROUND AND PURPOSE: Withanolides are naturally occurring chemical compounds. They are secondary metabolites produced via oxidation of steroids and structurally consist of a steroid-backbone bound to a lactone or its derivatives. They are known to protect plants against herbivores and have medicinal value including anti-inflammation, anti-cancer, adaptogenic and anti-oxidant effects. Withaferin A (Wi-A) and Withanone (Wi-N) are two structurally similar withanolides isolated from Withania somnifera, also known as Ashwagandha in Indian Ayurvedic medicine. Ashwagandha alcoholic leaf extract (i-Extract), rich in Wi-N, was shown to kill cancer cells selectively. Furthermore, the two closely related purified phytochemicals, Wi-A and Wi-N, showed differential activity in normal and cancer human cells in vitro and in vivo. We had earlier identified several genes involved in cytotoxicity of i-Extract in human cancer cells by loss-of-function assays using either siRNA or randomized ribozyme library. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we have employed bioinformatics tools on four genes, i.e., mortalin, p53, p21 and Nrf2, identified by loss-of-function screenings. We examined the docking efficacy of Wi-N and Wi-A to each of the four targets and found that the two closely related phytochemicals have differential binding properties to the selected cellular targets that can potentially instigate differential molecular effects. We validated these findings by undertaking parallel experiments on specific gene responses to either Wi-N or Wi-A in human normal and cancer cells. We demonstrate that Wi-A that binds strongly to the selected targets acts as a strong cytotoxic agent both for normal and cancer cells. Wi-N, on the other hand, has a weak binding to the targets; it showed milder cytotoxicity towards cancer cells and was safe for normal cells. The present molecular docking analyses and experimental evidence revealed important insights to the use of Wi-A and Wi-N for cancer treatment and development of new anti-cancer phytochemical cocktails. 相似文献
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Vanika Gupta Saudamini Venkatesan Martik Chatterjee Zeeshan A. Syed Vaishnavi Nivsarkar Nagaraj G. Prasad 《Evolution; international journal of organic evolution》2016,70(4):934-943
Maintenance and deployment of the immune system are costly and are hence predicted to trade‐off with other resource‐demanding traits, such as reproduction. We subjected this longstanding idea to test using laboratory experimental evolution approach. In the present study, replicate populations of Drosophila melanogaster were subjected to three selection regimes—I (Infection with Pseudomonas entomophila), S (Sham‐infection with MgSO4), and U (Unhandled Control). After 30 generations of selection flies from the I regime had evolved better survivorship upon infection with P. entomophila compared to flies from U and S regimes. However, contrary to expectations and previous reports, we did not find any evidence of trade‐offs between immunity and other life history related traits, such as longevity, fecundity, egg hatchability, or development time. After 45 generations of selection, the selection was relaxed for a set of populations. Even after 15 generations, the postinfection survivorship of populations under relaxed selection regime did not decline. We speculate that either there is a negligible cost to the evolved immune response or that trade‐offs occur on traits such as reproductive behavior or other immune mechanisms that we have not investigated in this study. Our research suggests that at least under certain conditions, life‐history trade‐offs might play little role in maintaining variation in immunity. 相似文献