S. K. Gakhar
Maharshi Dayanand University
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Featured researches published by S. K. Gakhar.
Acta Tropica | 2015
Rini Dhawan; Kuldeep Gupta; Mithilesh Kajla; Sanjeev Kumar; S. K. Gakhar; Parik Kakani; Tania Pal Choudhury; Lalita Gupta
Anopheles culicifacies mosquitoes are able to transmit both falciparum and vivax malaria in India. More than 65% of malaria cases reported annually spread through this vector. Despite the fact that it poses major vectorial burden in India, the molecular basis of its immune role against Plasmodium development has not been explored intensively. Here, we characterized An. culicifacies SOCS (suppressor of cytokine signaling) gene, a regulator of STAT pathway and its expression analysis upon Plasmodium infection. Our analysis has demonstrated that An. culicifacies SOCS gene shares strikingly high level of sequence similarity in SH2 domain and SOCS box region with other mosquito species. However, its N-terminal identity is limited to Anophelines mosquito only, suggesting its genus specific role. SOCS mRNA is expressed in all developmental stages of mosquito and its expression is higher in male than female adults. SOCS mRNA is significantly induced after Plasmodium infection in midgut tissue indicating its involvement in the immune defense responses. This is the first evidence of involvement of SOCS as an immune gene in Indian malaria vector An. culicifacies.
Insect Science | 2010
Vipin; Madhulika Dube; S. K. Gakhar
Abstract Anopheles stephensi is the main vector of urban malaria in South Asia. Three ecological variants (‘type’, ‘mysorensis’and‘intermediate’) of An. stephensi have been reported on the basis of ecology and egg morphology. However, it is unclear if there is any genetic isolation between the three variants. We analyzed the three variants of An. stephensi using eight microsatellite loci and found that large and significant genetic differentiation exists between them (mean FST= 0.393 and mean RST= 0.422). Pairwise estimates of genetic differentiation between the variants were ‘type’ versus ‘mysorensis’ (mean FST= 0.411 and mean RST= 0.308), ‘type’ versus ‘intermediate’ (mean FST= 0.388 and mean RST= 0.518) and ‘intermediate’ versus ‘mysorensis’ (mean FST= 0.387 and mean RST= 0.398) and all were statistically significant (P < 0.05). The greater sensitivity of RST in differentiation indicated that mutations and not genetic drift had generated the differences between three variants of An. stephensi. The present study indicated large genetic differentiation and presence of non‐significant low level of gene flow between the three variants (‘type’, ‘mysorensis’and‘intermediate’) of An. stephensi.
Journal of Phylogenetics & Evolutionary Biology | 2015
Mithilesh Kajla; Kuldeep Gupta; Parik Kakani; Rini Dhawan; Tania Pal Choudhury; Lalita Gupta; S. K. Gakhar; Sanjeev Kumar
Background: Human malaria parasite Plasmodium falciparum is transmitted by several species of Anopheles mosquito. The advancement of drug-resistant parasites and insecticide resistance in mosquito vectors are major hurdles in the malaria control. Alternatively, the manipulation of mosquito immunity is also an ideal way to block Plasmodium development inside the insect host. This approach demands the identification of key mosquito molecules that regulate anti-plasmodial immunity. Our previous findings revealed that the silencing of Anopheles gambiae heme peroxidase 15 (AgHPX15, AGAP013327) induced mosquito innate immunity and drastically suppressed the development of human and rodent malaria parasites. Further, we aim to characterize HPX15 orthologs in Indian malaria vectors and other worldwide-distributed anophelines to understand the novelty of this molecule as a plausible target to block Plasmodium development. Method: AgHPX15 orthologs were cloned from major Indian malaria vectors A. stephensi and A. culicifacies and their conserve domains were determined by CDD search tool. The sequence homology and phylogenetic relationship of these clones with other heme peroxidases was analysed using Mega5.2 software. Results and conclusion: We found that A. stephensi AsHPX15 and A. culicifacies AcHPX15 clones are close orthologs of A. gambiae AgHPX15. The phylogenetic relationship of these anopheline HPX15 with other animal and plant heme peroxidases revealed that they form a separate lineage-specific cluster and their orthologs are not found in human, nematodes or other related arthropods such as, Drosophila, Aedes and Culex mosquitoes. However, their putative orthologs are present in 16 other globally distributed anophelines and exhibit a highly conserved amino acids identity in the range of 70-99%. Based on these findings we propose that the anopheline-specific and evolutionary conserved heme peroxidase HPX15 may serve as a unique target for designing transmission-blocking strategies to block Plasmodium-mosquito cycle. These findings will generate new frontiers in the field of malaria research and disease control.
Drug Metabolism Reviews | 2015
Renu Chaudhary; Bharat Singh; Manish Kumar; S. K. Gakhar; Adesh K. Saini; Virinder S. Parmar; Anil Kumar Chhillar
Abstract Global statistical data shed light on an alarming trend that every year thousands of people die due to adverse drug reactions as each individual responds in a different way to the same drug. Pharmacogenomics has come up as a promising field in drug development and clinical medication in the past few decades. It has emerged as a ray of hope in preventing patients from developing potentially fatal complications due to adverse drug reactions. Pharmacogenomics also minimizes the exposure to drugs that are less/non-effective and sometimes even found toxic for patients. It is well reported that drugs elicit different responses in different individuals due to variations in the nucleotide sequences of genes encoding for biologically important molecules (drug-metabolizing enzymes, drug targets and drug transporters). Single nucleotide polymorphisms (SNPs), the most common type of polymorphism found in the human genome is believed to be the main reason behind 90% of all types of genetic variations among the individuals. Therefore, pharmacogenomics may be helpful in answering the question as to how inherited differences in a single gene have a profound effect on the mobilization and biological action of a drug. In the present review, we have discussed clinically relevant examples of SNP in associated diseases that can be utilized as markers for “better management of complex diseases” and attempted to correlate the drug response with genetic variations. Attention is also given towards the therapeutic consequences of inherited differences at the chromosomal level and how associated drug disposition and/or drug targets differ in various diseases as well as among the individuals.
Entomological Research | 2010
Vipin; Madhulika Dube; S. K. Gakhar
The population structure of An. stephensi in North‐west India was studied to assess the impact of the Aravalli Hills, as a barrier to gene flow using microsatellite markers. Large and significant genetic differentiation was found along the sides of, as well as across, the Aravalli Hills as the mean FST and RST on west vs. east of the Aravalli Hills were 0.213, 0.112 and 0.179, 0.056, respectively. Similarly, across the hills, mean values of FST and RST were 0.100 and 0.094, respectively. Genetic diversity on both sides did not vary significantly. The FST values were more sensitive than RST values, indicating that genetic drift might have caused genetic differentiation between populations. A positive correlation (r = 0.0149 and 0.157, respective to FST and RST) was found between genetic differentiations and geographic distances irrespective of the hills. Low level of gene flow was found along both sides (Nm = 0.92 and 0.14; west vs. east of Aravalli Hills, respectively) as compared to across the Aravalli Hills (Nm = 2.25). It was found that the Aravalli Hills are not working as an effective barrier to gene flow for An. Stephensi, maybe because of the low average height and discontinuous hills, however, the distance is playing a major role for differentiation between populations due to active mode of dispersal of An. stephensi mosquitoes which have a short flight range. All this information should help draw the strategies for genetic control of mosquitoes using transgenic mosquitoes.
PLOS ONE | 2015
Priyanka Chahar; M. Kaushik; Sarvajeet Singh Gill; S. K. Gakhar; Natrajan Gopalan; Manish Datt; Amit Sharma; Ritu Gill
Despite a significant drop in malaria deaths during the past decade, malaria continues to be one of the biggest health problems around the globe. WD40 repeats (WDRs) containing proteins comprise one of the largest and functionally diverse protein superfamily in eukaryotes, acting as scaffolds for assembling large protein complexes. In the present study, we report an extensive in silico analysis of the WDR gene family in human malaria parasite Plasmodium falciparum. Our genome-wide identification has revealed 80 putative WDR genes in P. falciparum (PfWDRs). Five distinct domain compositions were discovered in Plasmodium as compared to the human host. Notably, 31 PfWDRs were annotated/re-annotated on the basis of their orthologs in other species. Interestingly, most PfWDRs were larger as compared to their human homologs highlighting the presence of parasite-specific insertions. Fifteen PfWDRs appeared specific to the Plasmodium with no assigned orthologs. Expression profiling of PfWDRs revealed a mixture of linear and nonlinear relationships between transcriptome and proteome, and only nine PfWDRs were found to be stage-specific. Homology modeling identified conservation of major binding sites in PfCAF-1 and PfRACK. Protein-protein interaction network analyses suggested that PfWDRs are highly connected proteins with ~1928 potential interactions, supporting their role as hubs in cellular networks. The present study highlights the roles and relevance of the WDR family in P. falciparum, and identifies unique features that lay a foundation for further experimental dissection of PfWDRs.
Malaria Journal | 2014
Mithilesh Kajla; Parik Kakani; Tania Pal Choudhary; Kuldeep Gupta; Rini Dhawan; S. K. Gakhar; Lalita Gupta; Sanjeev Kumar
Background Malaria is major health problem in tropical and subtropical countries of the world. The WHO reported, 207 million malaria cases and 627,000 deaths in 2013 [1]. Malaria is caused by Plasmodium, which completes its asexual cycle in human host and sexual cycle in the female Anopheline mosquito. In order to combat malaria several strategies are in progress, blocking Plasmodium development inside mosquitos is one of them. For this transmission blocking approach we need to understand mosquito immune system and its interaction with Plasmodium at molecular levels. In the African malaria vector, Anopheles gambiae, a peroxidase HPX15 (IMPer) is reported to modulate mosquito immunity against Plasmodium [2]. Furthermore we are interested in understanding the regulation of Plasmodium development by its orthologous peroxidase-mediated immune responses in major Indian malaria vectors An. stephensi and An. culicifacies.
Insect Science | 2007
Rajnikant Dixit; Sarita Dixit; Upal Roy; Yogesh S. Shouche; S. K. Gakhar
In this study, we describe the partial genomic organization of ribosomal protein S7 gene isolated from the mosquito Anopheles stephensi. Initially a 558 bp partial cDNA sequence was amplified as precursor mRNA sequence containing 223 bp long intron. 5′ and 3′ end sequences were recovered using end specific rapid amplification of cDNA ends (RACE) polymerase chain reaction. The full‐length cDNA sequence was 914 nucleotide long with an open reading frame capable of encoding 192 amino acid long protein with calculated molecular mass of 22 174 Da and a pI point of 9.94. Protein homology search revealed > 75% identity to other insects S7 ribosomal proteins. Analysis of sequence alignment revealed several highly conserved domains, one of which is related to nuclear localization signal (NLS) region of human rpS7. Interestingly, intron nucleotide sequence comparison with A. gambiae showed a lesser degree of conservation as compared to coding and untranslated regions. Like this, early studies on the genomic organization and cDNA/ Expressed sequence tag analysis (EST) could help in genome annotation of A. stephensi, and would be likely to be sequenced in the future.
Infection, Genetics and Evolution | 2016
Richa Sharma; Arvind Sharma; Ashwani Kumar; Madhulika Dube; S. K. Gakhar
Malaria is a major public health problem in India because climatic condition and geography of India provide an ideal environment for development of malaria vector. Anopheles stephensi is a major urban malaria vector in India and its control has been hampered by insecticide resistance. In present study population genetic structure of A. stephensi is analyzed at macro geographic level using 13 microsatellite markers. Significantly high genetic differentiation was found in all studied populations with differentiation values (FST) ranging from 0.0398 to 0.1808. The geographic distance was found to be playing a major role in genetic differentiation between different populations. Overall three genetic pools were observed and population of central India was found to be coexisting in two genetic pools. High effective population size (Ne) was found in all the studied populations.
American Journal of Tropical Medicine and Hygiene | 2006
Geeta Goswami; O. P. Singh; Nutan Nanda; K. Raghavendra; S. K. Gakhar; Sarala K. Subbarao