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41.
Exposure of rats to 1-15 Gy gamma radiation (60Co) induced hyperthermia, whereas 20-200 Gy induced hypothermia. Exposure either to the head or to the whole body to 10 Gy induced hyperthermia, while body-only exposure produced hypothermia. This observation indicates that radiation-induced fever is a result of a direct effect on the brain. The hyperthermia due to 10 Gy was significantly attenuated by the pre- or post-treatment with a cyclooxygenase inhibitor, indomethacin. Hyperthermia was also altered by the central administration of a mu-receptor antagonist naloxone but only at low doses of radiation. These findings suggest that radiation-induced hyperthermia may be mediated through the synthesis and release of prostaglandins in the brain and to a lesser extent to the release of endogenous opioid peptides. The release of histamine acting on H1 and H2 receptors may be involved in radiation-induced hypothermia, since both the H1 receptor antagonist, mepyramine, and H2 receptor antagonist, cimetidine, antagonized the hypothermia. The results of these studies suggest that the release of neurohumoral substances induced by exposure to ionizing radiation is dose dependent and has different consequences on physiological processes such as the regulation of body temperature. Furthermore, the antagonism of radiation-induced hyperthermia by indomethacin may have potential therapeutic implications in the treatment of fever resulting from accidental irradiations. 相似文献
42.
Kandasamy Saravanan Magudeeswaran Sivanandam Govindasamy Hunday Lakshmanan Mathiyalagan 《Journal of biomolecular structure & dynamics》2019,37(9):2339-2354
Alzheimer disease (AD) is a cruel neurodegenerative disorder caused by the deposition of amyloid β (Aβ) peptide inside the brain. The β-secretase (beta amyloid precursor protein (APP) cleaving enzyme 1, BACE1) is one of the enzymes involved in the cleavage of APP that leads to the Aβ formation and it is the primary target for the treatment of AD. Recent report outlines that verubecestat molecule strongly inhibits BACE1; however, its structure, binding mechanism and the stability in the active site of BACE1 are not yet known. The present study aims to determine the structure, binding affinity and the stability of verubecestat molecule in the active site of BACE1 from the molecular docking, quantum mechanics/molecular mechanics (QM/MM)-based charge density analysis and molecular dynamics simulation. Verubecestat molecule was docked at BACE1; it shows high binding affinity towards BACE1. Further, the conformational geometry and the intermolecular interactions of verubecestat in the active site of BACE1 were determined. The molecule forms strong interaction with the neighboring amino acids in the active site of BACE1. The onsite QM/MM-based charge density analysis reveals the nature of charge density distribution and the topological properties of intermolecular interactions of verubecestat molecule in the active site of BACE1. The calculated electrostatic potential (ESP) of verubecestat in the active site of BACE1 displays high negative and positive ESP regions of the molecule. This onsite QM/MM analysis is more relevant to the physiological situation. The molecular dynamics simulation has been performed, which confirms the high stability and compactness of verubecestat in the active site of BACE1. The MM-generalized Born surface area and MM-Poisson Boltzmann surface area free energy calculations of verubecestat–BACE1 also confirm the high binding affinity of verubecestat.
Communicated by Ramaswamy H. Sarma 相似文献
43.
Viraj Bhat Manish Parashar Hua Liu Nagarajan Kandasamy Mohit Khandekar Scott Klasky Sherif Abdelwahed 《Cluster computing》2007,10(4):365-383
Efficient and robust data streaming services are a critical requirement of emerging Grid applications, which are based on
seamless interactions and coupling between geographically distributed application components. Furthermore the dynamism of
Grid environments and applications requires that these services be able to continually manage and optimize their operation
based on system state and application requirements. This paper presents a design and implementation of such a self-managing
data-streaming service based on online control strategies. A Grid-based fusion workflow scenario is used to evaluate the service
and demonstrate its feasibility and performance.
相似文献
Sherif AbdelwahedEmail: |
44.
Genome‐wide analyses of rice root development QTLs and development of an online resource, Rootbrowse
Pala Suryapriya Allada Snehalatha Ulaganathan Kayalvili Radha Krishna Sukpal singh Kandasamy Ulaganathan 《Bioinformation》2009,3(6):279-281
Genetic control of root development in rice is complex and the underlying mechanisms (constitutive and adaptive) are poorly understood. Lowland and upland varieties of indica and japonica rice with contrasting root development characteristics have been crossed, mapping populations developed and a number of QTLs in different chromosomes were identified. As these studies have used different sets of markers and many of the QTLs identified are long, it is difficult to exploit the varietal difference for improved root traits by marker assisted selection and for identification of concerned alleles. Intensive data mining of literature resulted in the identification 861 root development QTLs and associated microsatellite markers located on different chromosomes. The QTL and marker data generated and the genome sequence of rice were used for construction of a relational database, Rootbrowse, using MySQL relational database management system and Bio::DB::GFF schema. The data is viewed using GBrowse visualization tool. It graphically displays a section of the genome and all features annotated on it including the QTLs. The QTLs can be displayed along with SSR markers, protein coding genes and/or known root development genes for prediction of probable candidate genes. 相似文献
45.
Adam Doern Xianjun Cao Arlene Sereno Christopher L. Reyes Angelina Altshuler Flora Huang Cathy Hession Albert Flavier Michael Favis Hon Tran Eric Ailor Melissa Levesque Tracey Murphy Lisa Berquist Susan Tamraz Tracey Snipas Ellen Garber William S. Shestowsky Rachel Rennard Christilyn P. Graff Xiufeng Wu William Snyder Lindsay Cole David Gregson Michael Shields Steffan N. Ho Mitchell E. Reff Scott M. Glaser Jianying Dong Stephen J. Demarest Kandasamy Hariharan 《The Journal of biological chemistry》2009,284(15):10254-10267
46.
Adrian C. Nicolescu Arulmozhi D. Kandasamy Richard Schulz 《Biochemical and biophysical research communications》2009,387(4):646-1013
Matrix metalloproteinase-2 (MMP-2), a ubiquitously expressed zinc-dependent endopeptidase, and poly(ADP-ribosyl) polymerase (PARP), a nuclear enzyme regulating DNA repair, are activated by nitroxidative stress associated with various pathologies. As MMP-2 plays a detrimental role in heart injuries resulting from enhanced nitroxidative stress, where PARP and MMP inhibitors are beneficial, we hypothesized that PARP inhibitors may affect MMP-2 activity. Using substrate degradation assays to determine MMP-2 activity we found that four PARP inhibitors (3-AB, PJ-34, 5-AIQ, and EB-47) inhibited 64 kDa MMP-2 in a concentration-dependent manner. The IC50 values of PJ-34 and 5-AIQ were in the high micromolar range and comparable to those of known MMP-2 inhibitors doxycycline, minocycline or o-phenanthroline, whereas those for 3-AB and EB-47 were in the millimolar range. Co-incubation of PARP inhibitors with doxycycline showed an additive inhibition of MMP-2 that was significant for 3-AB alone. These data demonstrate that the protective effects of some PARP inhibitors may include inhibition of MMP-2 activity. 相似文献
47.
Ramani Kandasamy Lourdusamy John Kennedy Chandran Vidya Ramasamy Boopathy Ganesan Sekaran 《Journal of Molecular Catalysis .B, Enzymatic》2010,62(1):58-65
Mesoporous activated carbon (MAC) derived from rice husk is used for the immobilization of acidic lipase (ALIP) produced from Pseudomonas gessardii. The purified acidic lipase had the specific activity and molecular weight of 1473 U/mg and 94 kDa respectively. To determine the optimum conditions for the immobilization of lipase onto MAC, the experiments were carried out by varying the time (10–180 min), pH (2–8), temperature (10–50 °C) and the initial lipase activity (49 × 103, 98 × 103, 147 × 103 and 196 × 103 U/l in acetate buffer). The optimum conditions for immobilization of acidic lipase were found to be: time—120 min; pH 3.5; temperature—30 °C, which resulted in achieving a maximum immobilization of 1834 U/g. The thermal stability of the immobilized lipase was comparatively higher than that in its free form. The free and immobilized enzyme kinetic parameters (Km and Vmax) were found using Michaelis–Menten enzyme kinetics. The Km values for free enzyme and immobilized one were 0.655 and 0.243 mM respectively. The immobilization of acidic lipase onto MAC was confirmed using Fourier Transform-Infrared Spectroscopy, X-ray diffraction analysis and scanning electron microscopy. 相似文献
48.
Zidovudine (AZT) is commonly used to treat patients with AIDS, but it is limited by toxicity and high dosing needs. Alternative formulations have been proposed to overcome these drawbacks. The objective of this study was to evaluate process-related variables like hydration and sonication time, rotation speed of evaporation flask, and the effects of charge-inducing agent and centrifugation on zidovudine entrapment and release from niosomes. Formulation of zidovudine niosomes was optimized by altering the proportions of Tween, Span and cholesterol. The effect of process–related variables like hydration time, sonication time, charge-inducing agent, centrifugation and rotational speed of evaporation flask on zidovudine entrapment and release from niosomes was evaluated. The effect of changes in osmotic shock and viscosity were also evaluated. Non-sonicated niosomes were in the size range of 2-3.5 μm and sonicated niosomes formulated with Tween 80 and dicetylphosphate (DCP) had a mean diameter of 801 nm. Zidovudine niosomes formulated with Tween 80 entrapped high amounts of drug and the addition of DCP enhanced drug release for a longer time (88.72% over 12 h). The mechanism of release from Tween 80 formulation was the Fickian type and obeyed first-order release kinetics. Niosomes can be formulated by proper adjustment of process parameters to enhance zidovudine entrapment and sustainability of release. These improvements in zidovudine formulation may be useful in developing a more effective AIDS therapy. 相似文献
49.
Thottethodi Subrahmanya Keshava Prasad Shivakumar Keerthikumar Raghothama Chaerkady Kumaran Kandasamy Santosh Renuse Arivusudar Marimuthu Abhilash Karavattu Venugopal Joji Kurian Thomas Harrys K. C. Jacob Renu Goel Harsh Pawar Nandini A. Sahasrabuddhe Venkatarangaiah Krishna Bipin G. Nair Marjan Gucek Robert N. Cole Raju Ravikumar H. C. Harsha Akhilesh Pandey 《Clinical proteomics》2010,6(4):163-173