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Akshay Anand Neel Kamal Sharma Amod Gupta Sudesh Prabhakar Suresh Kumar Sharma Ramandeep Singh Pawan Kumar Gupta 《PloS one》2012,7(11)
Background
Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly population. We have shown previously that mice deficient in monocyte chemoattractant protein-1 (MCP1/CCL2) or its receptor (CCR2) develop the features of AMD in senescent mice, however, the human genetic evidence so far is contradictory. We hypothesized that any dysfunction in the CCL2 and its receptor result could be the contributing factor in pathogenesis of AMD.Methods and Findings
133 AMD patients and 80 healthy controls were enrolled for this study. Single neucleotid Polymorphism for CCL2 and CCR2 was analyzed by real time PCR. CCL2 levels were determined by enzyme-linked immunosorbent assay (ELISA) after normalization to total serum protein and percentage (%) of CCR2 expressing peripheral blood mononuclear cells (PBMCs) was evaluated using Flow Cytometry. The genotype and allele frequency for both CCL2 and CCR2 was found to be significantly different between AMD and normal controls. The CCL2 ELISA levels were significantly higher in AMD patients and flow Cytometry analysis revealed significantly reduced CCR2 expressing PBMCs in AMD patients as compared to normal controls.Conclusions
We analyzed the association between single neucleotide polymorphisms (SNPs) of CCL2 (rs4586) and CCR2 (rs1799865) with their respective protein levels. Our results revealed that individuals possessing both SNPs are at a higher risk of development of AMD. 相似文献32.
Neel Kamal Sharma Amod Gupta Sudesh Prabhakar Ramandeep Singh Suresh Kumar Sharma Wei Chen Akshay Anand 《PloS one》2013,8(7)
The purpose of the study was to determine serum complement factor H (CFH) levels in patients of age related macular degeneration (AMD) and examine its association with CFH Y402H polymorphism. 115 AMD patients and 61 normal controls were recruited in this study. The single nucleotide polymorphism was assayed by real time PCR and serum CFH levels were measured by ELISA and standardized to total serum protein. Chi-square test was applied to polymorphism analysis while Mann Whitney U-statistic for CFH-levels. Mendelian randomization approach was used for determining causal relationship. The genotype frequency differed between the AMD patients (TT- 18.3%, TC-41.3% and CC-40.4%) and controls (TT-76.3%, TC-13.6%, and CC-10.1%) (p = 0001). The frequency of alleles was also significantly different when AMD (T-39% and C-61%) was compared to controls (T-83% and C-17%) (p = 0.0001). Level of serum CFH was significantly lower in AMD patients as compared to normal controls (p = 0.001). Our data showed that the CFH Y402H polymorphism is a risk factor for AMD in the North Indian population. Mendelian randomization approach revealed that CFH Y402H polymorphism affects AMD risk through the modification of CFH serum levels. 相似文献
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STIM1- and Orai1-mediated Ca2+ oscillation orchestrates invadopodium formation and melanoma invasion
Jianwei Sun Fujian Lu Huifang He Junling Shen Jane Messina Rahel Mathew Dapeng Wang Amod A. Sarnaik Wei-Chiao Chang Minjung Kim Heping Cheng Shengyu Yang 《The Journal of cell biology》2014,207(4):535-548
Ca2+ signaling has been increasingly implicated in cancer invasion and metastasis, and yet, the underlying mechanisms remained largely unknown. In this paper, we report that STIM1- and Orai1-mediated Ca2+ oscillations promote melanoma invasion by orchestrating invadopodium assembly and extracellular matrix (ECM) degradation. Ca2+ oscillation signals facilitate invadopodial precursor assembly by activating Src. Disruption of Ca2+ oscillations inhibited invadopodium assembly. Furthermore, STIM1 and Orai1 regulate the proteolysis activity of individual invadopodia. Mechanistically, Orai1 blockade inhibited the recycling of MT1–matrix metalloproteinase (MMP) to the plasma membrane and entrapped MT1-MMP in the endocytic compartment to inhibit ECM degradation. STIM1 knockdown significantly inhibited melanoma lung metastasis in a xenograft mouse model, implicating the importance of this pathway in metastatic dissemination. Our findings provide a novel mechanism for Ca2+-mediated cancer cell invasion and shed new light on the spatiotemporal organization of store-operated Ca2+ signals during melanoma invasion and metastasis. 相似文献
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Anamika Mishra Muhasin Asaf Amod Kumar Diwakar Dattatreya Kulkarni Richa Sood Sandeep Bhatia Bharat Bhushan Ashwin Ashok Raut 《中国病毒学》2022,37(3):465-468
Highlights
· Highthrouput sequencing of small RNA of H5N1 infected and mock infected chicken lungs.
· 297 miRNAs identified in mock-infected and 201 miRNAs identified in AIV infected chicken lungs.
· 36 miRNAs were upregulated and 90 were downregulated during H5N1 infection.
· Functional analysis and gene ontology of predicted target genes of expressed miRNAs.
· MAPK pathway, NF-κB, IGF and gga-let-7b might play important role during H5N1 pathogenesis. 相似文献
· Highthrouput sequencing of small RNA of H5N1 infected and mock infected chicken lungs.
· 297 miRNAs identified in mock-infected and 201 miRNAs identified in AIV infected chicken lungs.
· 36 miRNAs were upregulated and 90 were downregulated during H5N1 infection.
· Functional analysis and gene ontology of predicted target genes of expressed miRNAs.
· MAPK pathway, NF-κB, IGF and gga-let-7b might play important role during H5N1 pathogenesis. 相似文献
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Piyanard Boonnate Sakda Waraasawapati Wiphawi Hipkaeo Supattra Pethlert Amod Sharma Carlo Selmi Vitoon Prasongwattana Ubon Cha’on 《PloS one》2015,10(6)
Background
The amount of dietary monosodium glutamate (MSG) is increasing worldwide, in parallel with the epidemics of metabolic syndrome. Parenteral administration of MSG to rodents induces obesity, hyperglycemia, hyperlipidemia, insulin resistance, and type 2 diabetes. However, the impact of dietary MSG is still being debated. We investigated the morphological and functional effects of prolonged MSG consumption on rat glucose metabolism and on pancreatic islet histology.Methods
Eighty adult male Wistar rats were randomly subdivided into 4 groups, and test rats in each group were supplemented with MSG for a different duration (1, 3, 6, or 9 months, n=20 for each group). All rats were fed ad libitum with a standard rat chow and water. Ten test rats in each group were provided MSG 2 mg/g body weight/day in drinking water and the 10 remaining rats in each group served as non-MSG treated controls. Oral glucose tolerance tests (OGTT) were performed and serum insulin measured at 9 months. Animals were sacrificed at 1, 3, 6, or 9 months to examine the histopathology of pancreatic islets.Results
MSG-treated rats had significantly lower pancreatic β-cell mass at 1, 6 and 9 months of study. Islet hemorrhages increased with age in all groups and fibrosis was significantly more frequent in MSG-treated rats at 1 and 3 months. Serum insulin levels and glucose tolerance in MSG-treated and untreated rats were similar at all time points we investigated.Conclusion
Daily MSG dietary consumption was associated with reduced pancreatic β-cell mass and enhanced hemorrhages and fibrosis, but did not affect glucose homeostasis. We speculate that high dietary MSG intake may exert a negative effect on the pancreas and such effect might become functionally significant in the presence or susceptibility to diabetes or NaCl; future experiments will take these crucial cofactors into account. 相似文献36.
Shahin Lockman Michael Hughes Fred Sawe Yu Zheng James McIntyre Tsungai Chipato Aida Asmelash Mohammed Rassool Sylvester Kimaiyo Douglas Shaffer Mina Hosseinipour Lerato Mohapi Francis Ssali Margret Chibowa Farida Amod Elias Halvas Evelyn Hogg Beverly Alston-Smith Laura Smith Robert Schooley John Mellors Judith Currier the OCTANE ACTG A/OCTANE Study Team 《PLoS medicine》2012,9(6)
Background
Nevirapine (NVP) is widely used in antiretroviral treatment (ART) of HIV-1 globally. The primary objective of the AA5208/OCTANE trial was to compare the efficacy of NVP-based versus lopinavir/ritonavir (LPV/r)-based initial ART.Methods and Findings
In seven African countries (Botswana, Kenya, Malawi, South Africa, Uganda, Zambia, and Zimbabwe), 500 antiretroviral-naïve HIV-infected women with CD4<200 cells/mm3 were enrolled into a two-arm randomized trial to initiate open-label ART with tenofovir (TDF)/emtricitabine (FTC) once/day plus either NVP (n = 249) or LPV/r (n = 251) twice/day, and followed for ≥48 weeks. The primary endpoint was time from randomization to death or confirmed virologic failure ([VF]) (plasma HIV RNA<1 log10 below baseline 12 weeks after treatment initiation, or ≥400 copies/ml at or after 24 weeks), with comparison between treatments based on hazard ratios (HRs) in intention-to-treat analysis. Equivalence of randomized treatments was defined as finding the 95% CI for HR for virological failure or death in the range 0.5 to 2.0. Baseline characteristics were (median): age = 34 years, CD4 = 121 cells/mm3, HIV RNA = 5.2 log10copies/ml. Median follow-up = 118 weeks; 29 (6%) women were lost to follow-up. 42 women (37 VFs, five deaths; 17%) in the NVP and 50 (43 VFs, seven deaths; 20%) in the LPV/r arm reached the primary endpoint (HR 0.85, 95% CI 0.56–1.29). During initial assigned treatment, 14% and 16% of women receiving NVP and LPV/r experienced grade 3/4 signs/symptoms and 26% and 22% experienced grade 3/4 laboratory abnormalities. However, 35 (14%) women discontinued NVP because of adverse events, most in the first 8 weeks, versus none for LPV/r (p<0.001). VF, death, or permanent treatment discontinuation occurred in 80 (32%) of NVP and 54 (22%) of LPV/r arms (HR = 1.7, 95% CI 1.2–2.4), with the difference primarily due to more treatment discontinuation in the NVP arm. 13 (45%) of 29 women tested in the NVP versus six (15%) of 40 in the LPV/r arm had any drug resistance mutation at time of VF.Conclusions
Initial ART with NVP+TDF/FTC demonstrated equivalent virologic efficacy but higher rates of treatment discontinuation and new drug resistance compared with LPV/r+TDF/FTC in antiretroviral-naïve women with CD4<200 cells/mm3.Trial registration
ClinicalTrials.gov Please see later in the article for the Editors'' Summary NCT00089505相似文献37.
Palazzo Fabiana Moi Dieison André Mantovano Tatiane Lansac-Tôha Fábio Amodêo Bonecker Claudia Costa 《Limnology》2023,24(2):137-149
Limnology - Understanding how the occurrence and abundance of invasive species vary over time and the environmental factors that cause such variation is important for managing and controlling... 相似文献
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Environmental factors exert predominant effects on testate amoeba metacommunities during droughts in floodplains 下载免费PDF全文
Rodrigo Leite Arrieira Leilane Talita Fatoreto Schwind Claudia Costa Bonecker Fábio Amodêo Lansac‐Tôha 《Austral ecology》2017,42(2):210-217
Metacommunities have been evaluated as models for the relative importance of environmental and spatial processes in assembling ecological communities. Here, we tested the hypothesis that different hydrological periods (drought and flooding) influence the environmental associations of planktonic testate amoeba metacommunities. We predicted that environmental factors would exert the strongest effects on species dispersal under drought, but that they would be less significant during flooding. Testate amoebae were sampled during drought and flooding, from 72 lakes in four Brazilian floodplains (Amazonian, Araguaia, Pantanal and Paraná). Partial redundancy analysis indicated that only environmental factors were significant; they were significant in all floodplain lakes during the drought. Only the Paraná floodplain had significant results for environmental factors during both hydrological periods. Spatial factors did not contribute significantly to any of the metacommunities. The depth, pH and variables related to environmental productivity were identified as major predictors in the assembly of testate amoeba communities. Our results highlight that different hydrological periods vary in their relative importance in environmental and spatial processes. The species‐sorting model was predominant during drought, while stochastic processes prevailed during flooding in all but the Paraná floodplain. In the Paraná floodplain, the construction of dams could potentially alter the effects of environmental and spatial factors on the dispersal of planktonic testate amoebae. The pH and the environmental productivity factors were largely responsible for species selection and the structuring of the planktonic testate amoebae metacommunities in Brazilian floodplains. 相似文献
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