• Arun Kumar

      Articles written in Journal of Biosciences

    • Estrogenic and antiestrogenic properties of clomiphene citrate in laboratory mice

      Arun Kumar Pranab L Pakrasi

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      The estrogen agonistic and antagonistic properties of clomiphene citrate were investigated in the mice. Clomiphene citrate was tested at various doses of 0.1, 1.0, 10 and 100 μg for three consecutive days in immature and mature bilaterally ovariectomized mice. Clomiphene citrate showed uterotrophic activity in both immature and ovariectomized conditions. The lower doses of 0.1 and 1.0 μg were ineffective to show any uterotrophic stimulation. Clomiphene citrate at 10 μg dose produced 305.56% increase in uterine weight i.e., 27.70 ± 0.24 vs 6.83 ± 0.06 in immature and 182.27% i.e., 42.68 ± 1.12 vs 15.12 ± 0.57 in ovariectomized mice. Clomiphene citrate at 100 μg dose showed significant uterotrophic effect e.g., 435.57% i.e., 36.58 ±0.34 vs 6.83 ± 0.06 in immature and 586% i.e., 103.80 ± 0.60 in ovariectomized mice. When clomiphene citrate was administered in combination with 0.32 μg of estradiol 17-β it caused significant antagonistic effect (decrease in uterine weight) at 10 and 100 μg respectively. Clomiphene citrate at 10 μg dose produced 32% i.e., 28.93 ± 0.43 vs 38.04 ± 2.68 in immature and 35% i.e., 59.64±1.44 vs 83.34 ±0.25 in ovariectomized mice respectively. Histological observation clearly showed that clomiphene citrate at 10 and 100 μg doses did not cause any differential hypertrophy of the epithelial layer. Similar doses in combination with estradiol produced significant antagonistic effect on uterine weight and luminal epithelial cell height.

    • Genomic imprinting: mom and dad (epi)genetics

      Arun Kumar

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    • Insect drift over the northern Arabian sea in early summer

      S C Pathak Vandana Kulshrestha Arun Kumar Choubey A H Parulekar

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      Air borne insects, mostly carried by wind currents, were trapped over the northern Arabian sea (16‡ to 20‡ N; 68‡ to 72‡ E), in the course of cruise No. 111, ORVSAGAR KANYA (March 14 to April 7, 1996). A total of 2,301 insects belonging to 8 different orders, 47 families and 173 species were trapped. Of these, Hymenoptera was represented by the largest number (1082), which was followed by Hemiptera (586), Diptera (552), Coleoptera (51), Neuroptera (10), Trichoptera (03), Lepidoptera (03) and Orthoptera (01). The trapped insects were mostly between 0.6 mm to over 11 mm long. The data was examined for α-diversity as well as for possible correlations between various parameters like the diversity index, size and number of insects trapped on one hand and the distance of the nearest land mass in wind direction, on the other.

    • Rett and ICF syndromes: methylation moves into medicine

      Arun Kumar

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    • Alzheimer’s disease: amyloidβ-peptide antibody vaccine as plaque remover

      Arun Kumar

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    • Retinitis pigmentosa: mutations in a receptor tyrosine kinase gene,MERTK

      Arun Kumar

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    • Tuberous sclerosis complex: ADrosophila connection

      Arun Kumar S C Girimaji

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    • Primary microcephaly:microcephalin andASPM determine the size of the human brain

      Arun Kumar M Markandaya S C Girimaji

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    • AtMBD6, a methyl CpG binding domain protein, maintains gene silencing in Arabidopsis by interacting with RNA binding proteins

      ADWAITA PRASAD PARIDA AMRAPALI SHARMA ARUN KUMAR SHARMA

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      DNA methylation, mediated by double-stranded RNA, is a conserved epigenetic phenomenon that protects a genome fromtransposons, silences unwanted genes and has a paramount function in plant or animal development. Methyl CpG bindingdomain proteins are members of a class of proteins that bind tomethylated DNA. The Arabidopsis thaliana genome encodes13 methyl CpG binding domain (MBD) proteins, but themolecular/biological functions of most of these proteins are still notclear. In the present study, we identified four proteins that interact with AtMBD6. Interestingly, three of them contain RNAbinding domains and are co-localized with AtMBD6 in the nucleus. The interacting partners includes AtRPS2C (a 40Sribosomal protein), AtNTF2 (nuclear transport factor 2) and AtAGO4 (Argonoute 4). The fourth protein that physicallyinteracts with AtMBD6 is a histone-modifying enzyme, histone deacetylase 6 (AtHDA6), which is a known component ofthe RNA-mediated gene silencing system. Analysis of genomic DNA methylation in the atmbd6, atrps2c and atntf2mutants, using methylation-sensitive PCR detected decreased DNA methylation at miRNA/siRNA producing loci,pseudogenes and other targets of RNA-directed DNA methylation. Our results indicate that AtMBD6 is involved inRNA-mediated gene silencing and it binds to RNA binding proteins like AtRPS2C, AtAGO4 and AtNTF2. AtMBD6 alsointeracts with histone deacetylase AtHDA6 that might have a role in chromatin condensation at the targets of RdDM.

    • AtMBD4: A methylated DNA binding protein negatively regulates a subset of phosphate starvation genes

      ADWAITA PRASAD PARIDA AMRAPALI SHARMA ARUN KUMAR SHARMA

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      DNA methylation is an important epigenetic modification that governs transcriptional regulation. The methylation mark isread by a special class of proteins called methyl-CpG-binding domain proteins. The role of DNA methylation has beenfound in X-chromosome inactivation, genomic imprinting, transposon silencing, and self-incompatibility. Recently,remodeling of global DNA methylation was demonstrated in Arabidopsis during low phosphate availability. The presentstudy reports that AtMBD4 gene of Arabidopsis negatively regulates phosphate starvation. The T-DNA insertion mutation atthe AtMBD4 locus exhibited altered root architecture as compared to wild-type plants. Using microarray hybridization andanalysis, an increased transcript accumulation of 242 genes was observed in the mutant. Many of these genes were relatedto phosphate transporters and transcription factors, involved in phosphate starvation response. Comparison of data ofatmbd4 mutant with publicly available microarray data of phosphate starvation response indicated the role of AtMBD4protein in phosphate starvation response. Further, promoter analysis of up-regulated genes suggested that cis-regulatoryelements like MBS, W-box, and B1BS are more prominent in the promoters of up-regulated genes. Upon performing amethylation-specific PCR, a decreased DNA methylation in the promoter regions of up-regulated genes was observed. Theaccumulation of anthocyanin and inorganic phosphate in the atmbd4 mutant was found to be higher than the wild-typeplant. Altered root morphology, up-regulation of phosphate starvation-induced genes in atmbd4 mutant suggests thatAtMBD4 negatively regulates the phosphate starvation response.

    • Haploinsufficient tumor suppressor Tip60 negatively regulates oncogenic Aurora B kinase

      ARNAB BOSE SURABHI SUDEVAN VINAY J RAO HIROKI SHIMA ARUN KUMAR TRIVEDI KAZUHIKO IGARASHI TAPAS K KUNDU

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      The Aurora kinases represent a group of serine/threonine kinases which are crucial regulators of mitosis. DysregulatedAurora kinase B (AurkB) expression, stemming from genomic amplification, increased gene transcription or overexpressionof its allosteric activators, is capable of initiating and sustaining malignant phenotypes. Although AurkB level in cells iswell-orchestrated, studies that relate to its stability or activity, independent of mitosis, are lacking. We report that AurkBundergoes acetylation in vitro by lysine acetyltransferases (KATs) belonging to different families, namely by p300 andTip60. The haploinsufficient tumor suppressor Tip60 acetylates two highly conserved lysine residues within the kinasedomain of AurkB which not only impinges the protein stability but also its kinase activity. These results signify a probableoutcome on the increase in ‘‘overall activity’’ of AurkB upon Tip60 downregulation, as observed under cancerous conditions.The present work, therefore, uncovers an important functional interplay between AurkB and Tip60, frailty of whichmay be an initial event in carcinogenesis.

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