adita joshi | Delhi University 1 (original) (raw)

Papers by adita joshi

Long non-coding RNAs (lncRNA) represent an assorted class of transcripts having little or no prot... more Long non-coding RNAs (lncRNA) represent an assorted class of transcripts having little or no protein coding capacity and have recently gained importance for their function as regulators of gene expression. Molecular studies on lncRNA have uncovered multifaceted interactions with protein coding genes. It has been suggested that lncRNAs are an additional layer of regulatory switches involved in gene regulation during development and disease. LncRNAs expressing in specific tissues or cell types during adult stages can have potential roles in form, function, maintenance and repair of tissues and organs. We used RNA sequencing followed by computational analysis to identify tissue restricted lncRNA transcript signatures from five different tissues of adult zebrafish. The present study reports 442 predicted lncRNA transcripts from adult zebrafish tissues out of which 419 were novel lncRNA transcripts. Of these, 77 lncRNAs show predominant tissue restricted expression across the five major ...

We aimed to identify a prostate cancer DNA hypermethylationmicroarray signature (denoted as PHYMA... more We aimed to identify a prostate cancer DNA hypermethylationmicroarray signature (denoted as PHYMA) that differentiates prostate cancer from benign prostate hyperplasia (BPH), high from low-grade and lethal from non-lethal cancers. This is a non-randomized retrospective study in 111 local Asian men (87 prostate cancers and 24 BPH) treated from 1995 to 2009 in our institution. Archival prostate epithelia were laser-capture microdissected and genomic DNA extracted and bisulfite-converted. Samples were profiled using Illumina GoldenGate Methylation microarray, with raw data processed by GenomeStudio. A classification model was generated using support vector machine, consisting of a 55-probe DNA methylation signature of 46 genes. The model was independently validated on an internal testing dataset which yielded cancer detection sensitivity and specificity of 95.3 % and 100 % respectively, with overall accuracy of 96.4%. Second validation on another independent western cohort yielded 89.8...

Current Science, 2005

Current Research in Nutrition and Food Science, 2019

Erythrosine and tartrazine are common artificial food additives which have become a part of daily... more Erythrosine and tartrazine are common artificial food additives which have become a part of daily human consumption. Advised daily intake values for these agents are set strictly, however, the actual intake is much higher than the recommended ADI. A higher intake of erythrosine and tartrazine is shown to exhibit adverse effects in mammalian models, and is thus a matter of public health concern. In this study we have assessed and compared the dose-dependent effects of erythrosine and tartrazine on inducing oxidative stress in zebrafish embryos. We performed the superoxide dismutase (SOD) enzyme activity assay to test the effect of the two food colorants on reactive oxygen species (ROS) production. Erythrosine and tartrazine treated embryos showed significantly increased SOD activity in an enzyme assay. Additionally SOD mRNA transcripts in the treated embryos were found to be upregulated. Erythrosine and tartrazine treatment specifically altered SOD1 mRNA transcript levels while it ha...

Indian Journal of Genetics and Plant Breeding (The)

Wnt protein forms a multigenic family secreting signaling molecules important for various key dev... more Wnt protein forms a multigenic family secreting signaling molecules important for various key developmental events in animals. Wingless (wg) is the prototype member of Wnt gene family, while DWnt4 has been identified recently from a clonal library of proteins associated in vivo with Ubx protein. DWnt4 has been reported to function in embryo epidermis patterning, female gonade development, motor neuron axon guidance. In this study, validation was done for some reported functions of DWnt4 with ectopic expression and identified some novel functions using RNA interference. Knockdown of DWnt4 caused in ventral ectoderm reduced denticles with loss of one or two rows or entire denticle belt. Loss of DWnt4 also loss of polarity of wing hairs, loss of wing veins and notched wing phenotype. All the bristles from adult abdomen were lost when DWnt4 was driven with ubiquitous driver actineGal4. Tissue specific drivers enGal4 caused loss of polarity of dorsal tergite bristles and patches of tergites from adult abdomen. Thus, the DWnt4 seems to function in the cuticular differentiation of adult abdomen polarity of tergites bristles in Drosophila.

G3 (Bethesda, Md.), Apr 7, 2016

DNA transposons and retroviruses are important transgenic tools for genome engineering. An import... more DNA transposons and retroviruses are important transgenic tools for genome engineering. An important consideration affecting the choice of transgenic vector is their insertion site preferences. Previous large-scale analyses of Ds transposon integration sites in plants were done on the basis of reporter gene expression or germ-line transmission, making it difficult to discern vertebrate integration preferences. Here, we compare over 1300 Ds transposon integration sites in zebrafish with Tol2 transposon and retroviral integration sites. Genome-wide analysis shows that Ds integration sites in the presence or absence of marker selection are remarkably similar and distributed throughout the genome. No strict motif was found, but a preference for structural features in the target DNA associated with DNA flexibility (Twist, Tilt, Rise, Roll, Shift, and Slide) was observed. Remarkably, this feature is also found in transposon and retroviral integrations in maize and mouse cells. Our finding...

Indian Journal of Genetics and Plant Breeding (The), 2015

Evolutionarily conserved gene clusters serve as important genomic assets and are exploited to elu... more Evolutionarily conserved gene clusters serve as important genomic assets and are exploited to elucidate primal designs of genome evolution. The quest to understand contemporary functional significance of such clusters underlying their persistent evolutionary selection is reasonable. One such gene cluster in Drosophila is the ‘Wnt cluster’ comprising of DWnt4-wg-DWnt6-DWnt10 on the left arm of the second chromosome. Wnts are secreted glycoproteins that work as cell signaling molecules and are involved in myriad of cellular, developmental processes and diseases like cancer. Wingless (wg) is prototype of this family along with other 6 Wnt genes reported in Drosophila melanogaster. Wingless (wg) functions during ventral epidermis patterning in embryo, wing morphogenesis etc. DWnt4 semi- lethal mutants are known in the context of cell motility in ovarian morphogenesis. However, no lethal mutations for DWnt4 are reported so far. Similarly, the understanding of potential biological roles of DWnt6 and DWnt10 remains elusive as no classical genetic alleles are reported. To fill this lacuna we have tried to decipher the plausible role of DWnt6 and DWnt10 in ectoderm patterning of embryo. Here we report that though DWnt6 and DWnt10 are not expressed in ventral ectoderm of embryo, they are able to rescue the defects in cuticles in absence of DWnt4 or wg. Similarly knockdown of DWnt6 and DWnt10 transcripts in DWnt4 and wg epidermal/cuticular mutants resulted in increased defects in cuticles. These findings indicates that DWnt6 and DWnt10 can use canonical or non canonical Wnt pathway in absence of DWnt4 or wg and most probably they are using the same signaling mechanism in their natural function of domain which is yet to be known.

G3 (Bethesda, Md.), Jan 2, 2015

Since the sequencing of the human reference genome, many human disease-related genes have been di... more Since the sequencing of the human reference genome, many human disease-related genes have been discovered. However, understanding the functions of all the genes in the genome remains a challenge. The biological activities of these genes are usually investigated in model organisms, such as mice and zebrafish. Large-scale mutagenesis screens to generate disruptive mutations are useful for identifying and understanding the activities of genes. Here, we report a multifunctional mutagenesis system in zebrafish using the maize Ds transposon. Integration of the Ds transposable element containing an mCherry reporter for protein trap events, and an EGFP reporter for enhancer trap events, produced a collection of transgenic lines marking distinct cell and tissue types, and mutagenized genes in the zebrafish genome by trapping and prematurely terminating endogenous protein coding sequences. We obtained 642 zebrafish lines with dynamic reporter gene expression. The characterized fish lines with...

Zebrafish, 2014

The recent re-annotation of the transcriptome of human and other model organisms, using next-gene... more The recent re-annotation of the transcriptome of human and other model organisms, using next-generation sequencing approaches, has unravelled a hitherto unknown repertoire of transcripts that do not have a potential to code for proteins. These transcripts have been largely classified into an amorphous class popularly known as long noncoding RNAs (lncRNA). This discovery of lncRNAs in human and other model systems have added a new layer to the understanding of gene regulation at the transcriptional and post-transcriptional levels. In recent years, three independent studies have discovered a number of lncRNAs expressed in different stages of zebrafish development and adult tissues using a high-throughput RNA sequencing approach, significantly adding to the repertoire of genes known in zebrafish. A subset of these transcripts also shows distinct and specific spatiotemporal patterns of gene expression, pointing to a tight regulatory control and potential functional roles in development, organogenesis, and/ or homeostasis. This review provides an overview of the lncRNAs in zebrafish and discusses how their discovery could provide new insights into understanding biology, explaining mutant phenotypes, and helping in potentially modeling disease processes.

PLoS ONE, 2014

We aimed to identify a prostate cancer DNA hypermethylation microarray signature (denoted as PHYM... more We aimed to identify a prostate cancer DNA hypermethylation microarray signature (denoted as PHYMA) that differentiates prostate cancer from benign prostate hyperplasia (BPH), high from low-grade and lethal from non-lethal cancers. This is a non-randomized retrospective study in 111 local Asian men (87 prostate cancers and 24 BPH) treated from 1995 to 2009 in our institution. Archival prostate epithelia were laser-capture microdissected and genomic DNA extracted and bisulfiteconverted. Samples were profiled using Illumina GoldenGate Methylation microarray, with raw data processed by GenomeStudio. A classification model was generated using support vector machine, consisting of a 55-probe DNA methylation signature of 46 genes. The model was independently validated on an internal testing dataset which yielded cancer detection sensitivity and specificity of 95.3% and 100% respectively, with overall accuracy of 96.4%. Second validation on another independent western cohort yielded 89.8% sensitivity and 66.7% specificity, with overall accuracy of 88.7%. A PHYMA score was developed for each sample based on the state of methylation in the PHYMA signature. Increasing PHYMA score was significantly associated with higher Gleason score and Gleason primary grade. Men with higher PHYMA scores have poorer survival on univariate (p = 0.0038, HR = 3.89) and multivariate analyses when controlled for (i) clinical stage (p = 0.055, HR = 2.57), and (ii) clinical stage and Gleason score (p = 0.043, HR = 2.61). We further performed bisulfite genomic sequencing on 2 relatively unknown genes to demonstrate robustness of the assay results. PHYMA is thus a signature with high sensitivity and specificity for discriminating tumors from BPH, and has a potential role in early detection and in predicting survival.

Infection, Genetics and Evolution, 2012

Background: The date palm root borer Oryctes agamemnon (Coleoptera: Scarabaeidae) is one of the m... more Background: The date palm root borer Oryctes agamemnon (Coleoptera: Scarabaeidae) is one of the major pests of palms. In Saudi Arabia, both larvae and adults of Oryctes are particularly troublesome, especially during the establishment of young date palm orchards. Endosymbiotic bacteria are known to have a key role in food digestion and insecticide resistance mechanisms, and therefore are essential to their host insect. Identification of these bacteria in their insect host can lead to development of new insect pest control strategies. Results: Metagenomic DNA from larval midgut of the date palm root borer, O. agamemnon, was analyzed for endosymbiotic bacterial communities using denatured gradient gel electrophoresis (DGGE) utilizing 16S rRNA genes. The DGGE fingerprints with metagenomic DNA showed predominance of eleven major operational taxonomic units (OTUs) identified as members of Photobacterium, Vibrio, Allomonas, Shewanella, Cellulomonas, and Citrobacter, as well as uncultured bacteria, including some uncultured Vibrio members. DGGE profiles also showed shifts in the dominant bacterial populations of the original soil compared with those that existed in the larval midguts. The endosymbiotic bacterial community was dominated by members of the family Vibrionaceae (54.5%), followed by uncultured bacteria (18.2%), Enterobacteriaceae (9.1%), Shewanellaceae (9.1%), and Cellulomonadaceae (9.1%). Phylogenetic studies confirmed the affiliation of the dominant OTUs into specified families revealed by clustering of each phylotype to its corresponding clade. Relative frequency of each phylotype in larval midguts revealed predominance of Vibrio furnisii and Vibrio navarrensis, followed by uncultured bacterial spp., then Cellulomonas hominis, Shewanella algae, and Citrobacter freundii. Conclusion: Analysis of metagenomic DNA for endosymbiotic bacterial communities from the midgut of Oryctes larvae showed strong selection of specific bacterial populations that may have a key role in digestion, as well as other benefits to the larvae of O. agamemnon. Determination of the distinct endosymbiotic community structure and its possible biological functions within the insect could provide us with basic information for future pest control research.

We have traced in this paper the progress in Drosophila genetics research from the 1960s, at the ... more We have traced in this paper the progress in Drosophila genetics research from the 1960s, at the IARI, spearheaded by the visionary insight of M. S. Swaminathan. The work started with the study of indirect effect of radiation and the synergistic interaction of physical and chemical mutagens on chromosomal and genetic changes. This paved the way for the study of single gene mutants in dissecting developmental and behavioural processes. New genes discovered by us have been shown to encode conserved cell signalling molecules controlling developmental and behavioural pathways. With the complete sequencing of the Drosophila genome, in the year 2000, mounting evidence for the homology between Drosophila and human genes controlling genetic disorders became available. This has led to the fly becoming an indispensable tool for studying human diseases as well as a model to test for drugs and pharmaceuticals against human diseases and complex behavioural processes. For example wingless in Drosophila belongs to the conserved Wnt gene family and aberrant WNT signalling is linked to a range of human diseases, most notably cancer. Inhibition as well as activation of WNT signalling form the basis of an effective therapy for some cancers as well as several other clinical conditions. Recent experiments have shown that WNTs might also normally participate in self-renewal, proliferation or differentiation of stem cells and altering WNT signalling might be beneficial to the use of stem cells for therapeutic means. Likewise, the stambhA mutant of Drosophila which was discovered for its temperature-dependent paralytic behaviour is the fly homologue of Phospholipase Cβ β. Phospholipase C mediated G protein signalling plays a central role in vital processes controlling epilepsy, vision, taste, and olfaction in animals. Proteins of the G-signalling pathway are of intense research interest since many human diseases involve defects in G-protein signalling pathways. In fact, approximately 50% of the drugs used in clinical medicine target cellular pathways containing G-protein signalling elements. The detailed study of PLC-dependent G protein signalling in Drosophila is bound to throw light on the role of G protein-mediated biological functions and on similar genes and their functions in human diseases.