Histone lysine acetylation is central to epigenetic control of gene transcription. The bromodomain, found in chromatin-associated proteins and histone acetyltranferases, functions as the sole protein module known to bind acetyl-lysine... more
Histone lysine acetylation is central to epigenetic control of gene transcription. The bromodomain, found in chromatin-associated proteins and histone acetyltranferases, functions as the sole protein module known to bind acetyl-lysine motifs. Recent structural and functional analyses of bromodomains' recognition of lysine-acetylated peptides derived from major acetylation sites in histones and cellular proteins provide new insights into differences in ligand binding selectivity as well as unifying features of histone recognition by the bromodomains. These new findings highlight the functional importance of bromodomain/acetyl-lysine binding as a pivotal mechanism for regulating protein-protein interactions in histone-directed chromatin remodeling and gene transcription. These new studies also support the notion that functional diversity of a conserved bromodomain structural fold is achieved by evolutionary changes of structurally flexible amino-acid sequences in the ligand binding site such as the ZA and BC loops.
Research Interests: Transcription Regulation, Transcription Factors, Protein Structure and Function, Protein-Protein Interaction, Humans, and 13 moreAnimals, Histone Modification, Oncogene, Ligand Binding, Chromatin remodeling, Functional diversity, Clinical Sciences, Histone acetyltransferases, Lysine, Protein Conformation, Amino Acid Sequence, Cell Cycle Proteins, and Ligands
Research Interests: Biochemistry, Genetics, Biophysics, Molecular Biology, Stem Cells, and 28 moreMigration, MicroRNA, Cancer, Cell Cycle, Cell Biology, DNA damage, Apoptosis, Adhesion, Gene Silencing, Nature, Cytoskeleton, Signal Transduction, Transcription, Biological Sciences, Methylation, Signalling, Chromatin, Histones, Cell nucleus, Chlorella, Viral Infection, Polarity, Zebrafish, Amino Acid Sequence, Protein Transport, Nuclear localization signal, Gene Expression Regulation, and Molecular Sequence Data
Research Interests: Thermodynamics, Kinetics, Membrane Proteins, Biological Chemistry, Magnetic Resonance Spectroscopy, and 14 moreSignal Transduction, Biological Sciences, Humans, Biological, Peptides, Phosphorylation, CHEMICAL SCIENCES, Protein Conformation, Calorimetry, Amino Acid Sequence, Protein Binding, Hydrogen-Ion Concentration, Ligands, and Molecular Sequence Data
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Acquired immunodeficiency syndrome (AIDS) has emerged as a serious health problem in India. Although tuberculosis appears to be the commonest opportunistic infection, studies pertaining to opportunistic viruses are scant In the present... more
Acquired immunodeficiency syndrome (AIDS) has emerged as a serious health problem in India. Although tuberculosis appears to be the commonest opportunistic infection, studies pertaining to opportunistic viruses are scant In the present study co infection with EBV was evaluated in patients with AIDS using a highly sensitive polymerase chain reaction besides anti Zebra antibody assays for diagnosis of an active EBV infection in 37 patients of full-blown AIDS and 32 healthy seropositives. Thirty healthy laboratory workers were used as controls. Out of 37 patients with AIDS, 12 were positive for anti Zebra antibodies and 23 were positive for EBV by the PCR reaction. Out of the 32 seropositives, 3 were positive for anti Zebra antibodies and 4 were positive by PCR assay. The difference between seropositives and AIDS was significant (p < .05). None of the controls were positive for an active EBV infection. It is concluded that active EBV infection is an important co infection in patient...
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Cytomegalovirus (CMV) is a frequent opportunistic infection in immunocompromised individuals particularly those receiving organ transplants and harbouring HIV infection. The classical CMV syndrome may be seen in only a small percentage of... more
Cytomegalovirus (CMV) is a frequent opportunistic infection in immunocompromised individuals particularly those receiving organ transplants and harbouring HIV infection. The classical CMV syndrome may be seen in only a small percentage of patients and tissue diagnosis is cumbersome, costly and requires hospitalization. Hence there is an urgent need to establish accurate and early diagnosis for proper institution of therapy. An attempt was made to detect active CMV co-infection in patients with HIV/AIDS using three assays and the positivity rates in the 2 groups compared. In the present study, we used a highly sensitive polymerase chain reaction (PCR) for immediate early gene of CMV, pp65 antigenaemia assay and IgM ELISA assay to detect the presence of CMV co-infection in 37 patients with AIDS and 32 healthy HIV seropositives. Thirty healthy laboratory workers served as normal controls. Of the 37 patients with AIDS, 12 (32.4%) showed a positive reaction by PCR and only 4 patients wer...
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The classic investigations of the malaria epidemics in the Punjab led to the conclusion that in this most populous and most malarious province of the present-day Pakistan, epidemics occurred regularly at intervals of approximately eight... more
The classic investigations of the malaria epidemics in the Punjab led to the conclusion that in this most populous and most malarious province of the present-day Pakistan, epidemics occurred regularly at intervals of approximately eight years. Against this background, the results of a Malaria Control Programme launched in 1975 are examined. The Programme, supported by USAID and WHO, represents in economic terms the greatest effort made against malaria in the country. Malathion, the main attack weapon of the Programme, was used on an unprecedented scale. This created logistic and--unexpectedly--toxicity problems among the spraying workers. Despite these difficulties, an over-all reduction of 76% in the slide positivity rate was observed in the first two years of operations of the Programme. The authors warn against measures which may curtail the activities of the Programme when, according to the cyclical periodicity of malaria in the Punjab, an epidemic wave can be expected in 1980-8...
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A field study was conducted at NIA experimental farm, Tandojam to observe the growth and nutrients (macro and micro) content of some salt tolerant multipurpose tree species (Acacia ampliceps, Acacia stenophylla, Acacia nilotica,... more
A field study was conducted at NIA experimental farm, Tandojam to observe the growth and nutrients (macro and micro) content of some salt tolerant multipurpose tree species (Acacia ampliceps, Acacia stenophylla, Acacia nilotica, Eucalyptus camaldulensis, and Conocarpus lancifolius) under saline environment. The salinity of the soil was varying from medium saline to very highly saline. The growth performances recorded at 3, 6 and 9 months after transplantation showed that overall survival of all the species tested, was good (70 %). The species Acacia ampliceps had maximum survival percentage (98.09%) followed by Conocarpus lancifolius (96.82%), Acacia nilotica (96.19 %), Acacia stenophylla (89.52 %), and Eucalyptus camaldulensis (70.47 %). The plant height at 9 months after transplantation was maximum in Acacia nilotica (200cm), followed by Eucalyptus camaldulensis (190 cm), Acacia ampliceps (127.2 cm), Acacia stenophylla (125.4 cm), and Conocarpus lancifolius (125.1 cm).The leaves s...
There has been an exponential rise of HIV positive patients as observed at the surveillance center of Nehru Hospital. Most patients are poor and cannot afford repeated viral load assays. Therefore, there is a need to identify cost... more
There has been an exponential rise of HIV positive patients as observed at the surveillance center of Nehru Hospital. Most patients are poor and cannot afford repeated viral load assays. Therefore, there is a need to identify cost effective and reliable surrogate markers of disease activity. In the present study absolute number of CD4 cells, beta2 micro-globulin, circulating nucleosomes were studied in 30 patients of AIDS, 30 seropositives and 30 healthy controls. In addition viral load, P-24 assay, and TNFR-II assays were done in seropositive and AIDS patients. The mean CD4 cells in patients with AIDS were 69.66 +/- 68.25 mm3 while in seropositives values was 370 +/- 201.29 mm3. The mean CD4 cells in healthy controls were however 690 +/- 198 mm3. The differences in all the groups were highly significant (p&amp;amp;amp;amp;lt;0.001). The mean CD4 values in Indians are significantly lower than reported from the west. The lower number of CD4 cells in healthy population is interpreted to be due to immune activation. The CD8 cell number in controls was 650 +/- 207 mm3 this figure is also higher than that observed in the west. P-24 assay failed to delineate between seropositives and patients with AIDS. Although, beta2 microglobulin levels were significantly higher in AIDS than in seropositives and higher in seropositives than in controls yet with the best possible cut off, it had a sensitivity of only 70% in delineating the two conditions. The correlation between CD4 cells and viral load was more significant when the CD4 cells were below 200 mm3. Five out of 30 patients with a CD4 of 300-600 mm3 had a viral load of over 1 x 10(5) cop/ml. The difference in TNF R-II levels between seropositives and AIDS was however more impressive. With a cut off of 550 pg/ml it had a sensitivity of 95% in delineating HIV from AIDS. It is concluded that a combination of absolute number of CD4 cells and TNF R-II assay along with clinical evaluation may be used to monitor therapy in resource poor countries where frequent viral load assay is unaffordable.
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Research Interests: Engineering, Physics, Chemistry, Biology, Cell Cycle, and 18 moreMitochondria, Medicine, Multidisciplinary, Protein Stability, Molecular chaperones, Quality Assurance, Humans, Phenotype, PLoS one, Acetylation, Cell Proliferation, Cell Cycle Arrest, NAD, Subcellular Fractions, Protein Binding, Sirtuin, Protein Transport, and Cell Growth
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MAP kinases (MAPKs), which control mitogenic signal transduction in all eukaryotic organisms, are inactivated by dual specificity MAPK phosphatases (MKPs). MKP-3, a prototypical MKP, achieves substrate specificity through its N-terminal... more
MAP kinases (MAPKs), which control mitogenic signal transduction in all eukaryotic organisms, are inactivated by dual specificity MAPK phosphatases (MKPs). MKP-3, a prototypical MKP, achieves substrate specificity through its N-terminal domain binding to the MAPK ERK2, resulting in the activation of its C-terminal phosphatase domain. The solution structure and biochemical analysis of the ERK2 binding (EB) domain of MKP-3 show that regions that are essential for ERK2 binding partly overlap with its sites that interact with the C-terminal catalytic domain, and that these interactions are functionally coupled to the active site residues of MKP-3. Our findings suggest a novel mechanism by which the EB domain binding to ERK2 is transduced to cause a conformational change of the C-terminal catalytic domain, resulting in the enzymatic activation of MKP-3.
Research Interests: Western blotting, Signal Transduction, Cell and Molecular Biology, Biological Sciences, Humans, and 16 moreMutagenesis, Sequence alignment, Molecular Cell Biology, Mitogen Activated Protein Kinase, Active site, Protein Secondary Structure Prediction, Substrate Specificity, Amino Acid Sequence, MAP Kinase, Protein Binding, Enzymatic Activity, Protein Tyrosine Phosphatases, Conformational Change, Solution Structure, Static Electricity, and Molecular Sequence Data
Research Interests: Magnetic Resonance Spectroscopy, HIV, Cell and Molecular Biology, Biological Sciences, Molecular Recognition, and 12 moreHumans, Sequence alignment, Molecular Cell Biology, Human immunodeficiency virus, Lysine, Acetylation, Three Dimensional, Amino Acid Sequence, Protein Binding, Solution Structure, Molecular Structure, and Molecular Sequence Data
Research Interests: Membrane Proteins, Signal Transduction, Biological Sciences, Humans, Sequence alignment, and 11 moreAnimals, Molecular Cell Biology, Phosphotyrosine, Neuronal Differentiation, Protein Secondary Structure Prediction, Amino Acid Profile, Amino Acid Sequence, Recombinant Proteins, Site-directed Mutagenesis, Conformational Change, and Molecular Sequence Data
Research Interests: Nuclear Magnetic Resonance, Cell Cycle, Magnetic Resonance Spectroscopy, DNA damage, Western blotting, and 20 moreBiological Sciences, Molecular Recognition, Cell line, Humans, Mice, Animals, Kinase inhibitor, Plasmids, Molecular Cell Biology, Transcription Factor, Protein Secondary Structure Prediction, Lysine, Three Dimensional, Protein Conformation, Cell Cycle Arrest, Amino Acid Sequence, Protein Binding, Molecular Sequence Data, DNA mutational analysis, and fibroblasts
Research Interests: Organic Chemistry, Water, Medicinal Chemistry, Modeling, Transcription Factors, and 17 moreHIV, Optimization, Humans, Virus, Life Cycle, Free Energy, Human immunodeficiency virus, Canonical Ensemble, Histone acetyltransferases, Small Molecule, Medicinal, Molecular Model, Cell Cycle Proteins, Ligands, Monte Carlo Method, Chemical Modification, and Molecular Interactions
Columnar cell lesions are known as a link between normal breast and low grade neoplastic lesions in female, but have not been established in the male breast. This study evaluated the presence of ducts showing columnar cell-like features... more
Columnar cell lesions are known as a link between normal breast and low grade neoplastic lesions in female, but have not been established in the male breast. This study evaluated the presence of ducts showing columnar cell-like features in the male breast. Seventy-one consecutive surgical resections from men (6 invasive breast carcinoma of grade 3, 1 atypical ductal hyperplasia and 64 other lesions) were reviewed to identify foci of dilated ducts with columnar epithelial cells, and their morphological features including apical snouts, intraluminal secretions and calcifications were assessed. The expression of CK5/6 and estrogen receptor (ER) was evaluated immunohistochemically. Clinicopathological features including patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; age, histological diagnosis and gynaecomastoid hyperplasia were documented. Ducts showing columnar cell-like features were identified in 39 cases, morphologically as distended ducts with round or undulating outline. There was an outer layer of myoepithelial cells and an inner layer of columnar luminal cells showing apical snouts, but without intraluminal secretions or calcifications. Immunohistochemically, these columnar epithelial cells were negative for CK5/6 in 38/39 cases and all were ER heterogeneously positive. These changes were associated with older age, but their incidence did not differ whether they were associated with invasive breast carcinoma, atypical ductal hyperplasia and other lesions. In the male breast, there is an entity sharing morphological features and immunohistochemical profile of columnar cell lesions.
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Epstein Barr virus (EBV) has a unique association with several human malignancies, especially lymphoproliferative disorders, mainly lymphomas in adults. There is paucity of data pertaining to EBV association with various cancers in India... more
Epstein Barr virus (EBV) has a unique association with several human malignancies, especially lymphoproliferative disorders, mainly lymphomas in adults. There is paucity of data pertaining to EBV association with various cancers in India . The study aims to investigate the association of EBV in childhood leukemia. Patients attending pediatric oncology services of the referral center have been included in the study. Twenty-five consecutive pediatric patients with acute lymphocytic lukemia (ALL) were subjected to EBV studies employing sensitive polymerase chain reaction followed by hybridization for presence of Bam H1-W region of EBV genome and detection of anti Z EBV replication activator (ZEBRA) antibodies using Western blot. Positive control included a case of Burkitt&amp;amp;amp;amp;amp;amp;amp;amp;#39;s lymphoma and infectious mononucleosis each. Raji cells were used as positive control with each test. The PCR for EBV was positive in 8/25 patients of ALL. Western blot test using anti ZEBRA antibodies was positive in 5/25(20%) cases of ALL. Considering PCR as the gold standard, 32% of the children with ALL had evidence of active EBV replication. The positive controls were consistently positive. None of the 30 healthy laboratory controls, 22 age matched disease controls, 12 cases of AML and 15 cases of multiple myeloma were positive either by PCR or Western blots assays (P &amp;amp;amp;amp;amp;amp;amp;amp;lt; 0. 01). There was no statistically significant correlation between duration of therapy and EBV positivity (P &amp;amp;amp;amp;amp;amp;amp;amp;gt; 0.05). These studies indicate that a significant number of patients with ALL show evidence of active EBV replication.
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Research Interests: Microbiology, Flow Cytometry, Western blotting, DNA, Spleen, and 17 moreVirulence, Experimental parasitology, Cell line, Humans, Liver, Female, Animals, Male, Visceral Leishmaniasis, cDNA, Veterinary Sciences, Recombinant Protein, Human Subjects, Recombinant Proteins, Enzyme Linked Immunosorbent Assay, cDNA library, and Interferon gamma
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Indiais experiencing rapid and extensive spread of HIV. There are an estimated 2 to 5 million Indians infected with HIV today, and 50,000 to 100,000 cases of AIDS may have al-ready occurred in the country.1 The most rapid and... more
Indiais experiencing rapid and extensive spread of HIV. There are an estimated 2 to 5 million Indians infected with HIV today, and 50,000 to 100,000 cases of AIDS may have al-ready occurred in the country.1 The most rapid and well-docu-mented spread of HIV has occurred in ...
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Aqueous leaf extract of common lambsquarters (Chenopodium album L.) was evaluated alone or in combination with NaCl salinity for its influence on germination, seedling growth and contents of Na, K, and Ca by shoots and roots of wheat. The... more
Aqueous leaf extract of common lambsquarters (Chenopodium album L.) was evaluated alone or in combination with NaCl salinity for its influence on germination, seedling growth and contents of Na, K, and Ca by shoots and roots of wheat. The leaf extract and NaCl alone or in combination did not have any significant effect on germination, but the shoot and root
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A water culture experiment was conducted, to study the re-sponse of three wheat genotypes (Sarsabz, Kiran-95 and Pasban-90) to low and high potassium levels, (0.01 and 10 mM KC1) grown under two salinity concentrations (50 mM and 150 AM,... more
A water culture experiment was conducted, to study the re-sponse of three wheat genotypes (Sarsabz, Kiran-95 and Pasban-90) to low and high potassium levels, (0.01 and 10 mM KC1) grown under two salinity concentrations (50 mM and 150 AM, NaCI). The results ...