Animal Biology - Publications

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Browsing Animal Biology - Publications by Author "Ahmed, Niyaz"
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    Diagnostic potential of an iron-regulated hemin-binding protein HbpA that is widely conserved in Leptospira interrogans
    ( 2008-12-01) Sridhar, Velineni ; Manjulata Devi, Sundru ; Ahmed, Niyaz ; Sritharan, Manjula
    Like most bacteria, Leptospira spp. requires iron for growth. However, they face conditions of iron limitation due to the low solubility of the ferric iron and additionally due to the observation that most of the available iron is held as protein-bound iron by the mammalian host. Our experimental observations with pathogenic Leptospira showed that they do not elaborate siderophores upon iron limitation. In Leptospira interrogans serovar Lai, we demonstrated direct acquisition of iron via an iron-regulated hemin-binding protein HbpA. PCR analysis and Southern hybridization studies revealed that the hbpA gene was conserved in the serovars belonging to L. interrogans species and was absent in the non-pathogenic Leptospira biflexa serovar Patoc and Leptospira meyeri serovar Ranarum. Here, we extended the PCR-based detection of the hbpA gene to clinical isolates and demonstrated the hbpA amplicon in all the serovars belonging to L. interrogans species from a total collection of 91 clinical isolates obtained from different geographical regions. In addition, we detected anti-HbpA antibodies in the serum of patients with leptospirosis. PCR-based detection of hbpA in clinical isolates of serovars and the in vivo expression of HbpA reflects the diagnostic potential of this antigen. © 2008.
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    Disease-causing mutations in proteins: Structural analysis of the CYP1b1 mutations causing primary congenital glaucoma in humans
    ( 2006-01-01) Achary, Malkaram S. ; Reddy, Aramati B.M. ; Chakrabarti, Subhabrata ; Panicker, Shirly G. ; Mandal, Anil K. ; Ahmed, Niyaz ; Balasubramanian, Dorairajan ; Hasnain, Seyed E. ; Nagarajaram, Hampapathalu A.
    In this communication, we report an in-depth structure-based analysis of the human CYP1b1 protein carrying disease-causing mutations that are discovered in patients suffering from primary congenital glaucoma (PCG). The "wild-type" and the PCG mutant structures of the human CYP1b1 protein obtained from comparative modeling were subjected to long molecular dynamics simulations with an intention of studying the possible impact of these mutations on the protein structure and hence its function. Analysis of time evolution as well as time averaged values of various structural properties - especially of those of the functionally important regions: the heme binding region, substrate binding region, and substrate access channel - gave some insights into the possible structural characteristics of the disease mutant and the wild-type forms of the protein. In a nutshell, compared to the wild-type the core regions in the mutant structures are associated with subtle but significant changes, and the functionally important regions seem to adopt such structures that are not conducive for the wild-type-like functionality. © 2006 by the Biophysical Society.
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    Genome of a novel isolate of Paracoccus denitrificans capable of degrading N,N-Dimethylformamide
    ( 2011-10-01) Siddavattam, Dayananda ; Karegoudar, Timmanagouda B. ; Mudde, Santosh Kumar ; Kumar, Narender ; Baddam, Ramani ; Avasthi, Tiruvayipati Suma ; Ahmed, Niyaz
    The bacterial genus Paracoccus is comprised of metabolically versatile organisms having diverse degradative capabilities and potential industrial and environmental applications for bioremediation in particular. We report a de novo-assembled sequence and annotation of the genome of a novel isolate of Paracoccus denitrificans originally sourced from coal mine tailings in India. The isolate was capable of utilizing N,N-dimethylformamide (DMF) as a source of carbon and nitrogen and therefore holds potential for bioremediation and mineralization of industrial pollutants. The genome sequence and biological circuitry revealed thereupon will be invaluable in understanding the metabolic capabilities, functioning, and evolution of this important bacterial organism. © 2011, American Society for Microbiology.
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    Helicobacter pylori cell translocating kinase (CtkA/JHP0940) is pro-apoptotic in mouse macrophages and acts as auto-phosphorylating tyrosine kinase
    ( 2014-11-01) Tenguria, Shivendra ; Ansari, Suhail A. ; Khan, Nooruddin ; Ranjan, Amit ; Devi, Savita ; Tegtmeyer, Nicole ; Lind, Judith ; Backert, Steffen ; Ahmed, Niyaz
    The Helicobacter pylori gene JHP0940 has been shown to encode a serine/threonine kinase which can induce cytokines in gastric epithelial cells relevant to chronic gastric inflammation. Here we demonstrate that JHP0940 can be secreted by the bacteria, triggers apoptosis in cultured mouse macrophages and acts as an auto-phosphorylating tyrosine kinase. Recombinant JHP0940 protein was found to decrease the viability of RAW264.7 cells (a mouse macrophage cell line) up to 55% within 24. h of co-incubation. The decreased cellular viability was due to apoptosis, which was confirmed by TUNEL assay and Fas expression analysis by flow-cytometry. Further, we found that caspase-1 and IL-1beta were activated upon treatment with JHP0940. These results point towards possible action through the host inflammasome. Our in vitro studies using tyrosine kinase assays further demonstrated that JHP0940 acts as auto-phosphorylating tyrosine kinase and induces pro-inflammatory cytokines in RAW264.7 cells. Upon exposure with JHP0940, these cells secreted IL-1beta, TNF-alpha and IL-6, in a dose- and time-dependent manner, as detected by ELISA and transcript profiling by q-RT-PCR. The pro-inflammatory, pro-apoptotic and other regulatory responses triggered by JHP0940 lead to the assumption of its possible role in inducing chronic inflammation for enhanced bacterial persistence and escape from host innate immune responses by apoptosis of macrophages.
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    Identification of novel mutations causing familial primary congenital glaucoma in Indian pedigrees
    ( 2002-05-13) Panicker, Shirly G. ; Reddy, Aramati B.M. ; Mandal, Anil K. ; Ahmed, Niyaz ; Nagarajaram, Hampapathalu A. ; Hasnain, Seyed E. ; Balasubramanian, Dorairajan
    PURPOSE. To determine the possible molecular genetic defect underlying primary congenital glaucoma (PCG) in India and to identify the pathogenic mutations causing this childhood blindness. METHODS. Twenty-two members of five clinically well-characterized consanguineous families were studied. The primary candidate gene CYP1B1 was amplified from genomic DNA, sequenced, and analyzed in control subjects and patients to identify the disease-causing mutations. RESULTS. Five distinct mutations were identified in the coding region of CYP1B1 in eight patients of five PCG-affected families, of which three mutations are novel. These include a novel homozygous frameshift, compound heterozygous missense, and other known mutations. One family showed pseudodominance, whereas others were autosomal recessive with full penetrance. In contrast to all known CYP1B1 mutations, the newly identified frameshift is of special significance, because all functional motifs are missing. This, therefore, represents a rare example of a natural functional CYP1B1 knockout, resulting in a null allele (both patients are blind). CONCLUSIONS. The molecular mechanism leading to the development of PCG is unknown. Because CYP1B1 knockout mice did not show a glaucoma phenotype, the functional knockout identified in this study has important implications in elucidating the pathogenesis of PCG. Further understanding of how this molecular defect leads to PCG could influence the development of specific therapies. This is the first study to describe the molecular basis of PCG from the Indian subcontinent and has profound and multiple clinical implications in diagnosis, genetic counseling, genotype-phenotype correlations and prognosis. Hence, it is a step forward in preventing this devastating childhood blindness.
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    Novel mutation in FOXC1 wing region causing Axenfeld-Rieger anomaly
    ( 2002-12-01) Panicker, Shirly G. ; Sampath, Srirangan ; Mandal, Anil K. ; Reddy, Aramati B.M. ; Ahmed, Niyaz ; Hasnain, Seyed E.
    PURPOSE. To determine the possible molecular genetic defect underlying Axenfeld-Rieger anomaly (ARA) and to identify the pathogenic mutation causing this anterior segment dysgenesis in an Indian pedigree. METHODS. The FOXC1 gene was amplified from genomic DNA of members of an ARA-affected family and control subjects using four novel sets of primers. The amplicons were directly sequenced, and the sequences were analyzed to identify the disease-causing mutation. RESULTS. A heterozygous novel missense mutation was identified in the coding region of the FOXC1 gene in all three patients in this family. Consistent with the autosomal dominant inheritance pattern, the mutation segregated with the disease phenotype and was fully penetrant. The mutation was found in the wing region of the highly conserved forkhead domain of the FOXC1 gene and resulted in a very severe phenotype leading to blindness. CONCLUSIONS. This is the first study to demonstrate that a mutation in the FOXC1 wing region can cause an anterior segment dysgenesis of the eye. This mutation resulted in blindness in the ARA-affected family, and the findings-suggest that the FOXC1 wing region has a functional role in the normal development of the eye. Moreover, this is the first study from India to report the genetic etiology of Axenfeld-Rieger anomaly. Genotype-phenotype correlations of FOXC1 may help in establishing the disease prognosis and also in understanding the clinical and genetic heterogeneity associated with various anterior segment dysgenesis caused by this gene.