FREE RADICAL LOAD IN LYMPHOID ORGANS (SPLEEN AND THYMUS) OF INDIAN GOAT CAPRA HIRCUS: ROLE OF SEX, SEASON AND MELATONIN

Objective: Lymphoid organs (i.e. spleen and thymus) are important due to functional dynamicity. As a result, the generated free radicals may limit their function. Thus, present study was aimed to note seasonal and sex dependent variation in free radical status in Indian goat Capra hircus under the aegis of melatonin which is a well-known antioxidant.Methods: Markers of oxidative stress (i.e. Super Oxide Dismutase; SOD, Catalase; CAT, Glutathione Peroxidases; GPx) were measured by standardized protocols. Total Antioxidant Status (TAS) was measured by 2, 2′-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid; ABTS) radical cation method and Lipid Per Oxidation (LPO) was measured by Thiobarbituric acid reactive substances (TBARS) level. Glucocorticoid Receptor (GR) expression in lymphoid organs was noted by Western Blot analysis. The circulatory level of cortisol and melatonin were estimated by commercial ELISA kits.Results: We noted significantly high levels of SOD, Catalase, GPx activities and ABTS level in lymphoid organs during monsoon and low during winter. Malonaldehyde; MDA a marker for lipid peroxidation was significantly high during summer and was significantly low during monsoon and winter. Cortisol level was significantly high during monsoon whereas melatonin level was significantly high during winter. GR expression was significantly high in males during monsoon and winter, but the level was significantly high only during monsoon in females.Conclusion: All the results suggest that monsoon and winter are the seasons of stress and to buffer the elevated stress level, melatonin coupled both the roles of free radical scavenger (as a free molecule) and elevation of antioxidant enzymes.Â

Atomistic studies of thin film growth

We present here a summary of some recent techniques used for atomistic studies of thin film growth and morphological evolution. Specific attention is given to a new kinetic Monte Carlo technique in which the usage of unique labeling schemes of the environment of the diffusing entity allows the development of a closed data base of 49 single atom diffusion processes for periphery motion. The activation energy barriers and diffusion paths are calculated using reliable manybody interatomic potentials. The application of the technique to the diffusion of 2-dimensional Cu clusters on Cu(111) shows interesting trends in the diffusion rate and in the frequencies of the microscopic mechanisms which are responsible for the motion of the clusters, as a function of cluster size and temperature. The results are compared with those obtained from yet another novel kinetic Monte Carlo technique in which an open data base of the energetics and diffusion paths of microscopic processes is continuously updated as needed. Comparisons are made with experimental data where available

Theoretical aspects of vertical and lateral manipulation of atoms

Using total energy calculations, based on interaction potentials from the embedded atom method, we show that the presence of the tip not only lowers the barrier for lateral diffusion of the adatom towards it, but also shifts the corresponding saddle point. For a Cu adatom at a (100) microfacetted step on Cu(111) this shift is 0.6 A. The effect of the tip geometry and shape on the energetics of lateral manipulation was found to be subtle. In the case of vertical manipulation of a Cu adatom on flat, stepped, and kinked Cu surfaces we find an unusual but interesting result. It is found that as the tip approaches the surface, it becomes easier to extract the adatom from the stepped and kinked surfaces, as compared to the flat surface. This counter intuitive result can be explained in terms of tip induced changes in the bonding of the adatom to its low coordinated surroundings.Comment: 8figures, to appear in Surf. Sci., VAS10 proceeding

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Atomistic studies of manipulation, growth and diffusion on fcc metal surfaces

Doctor of PhilosophyDepartment of PhysicsIn this dissertation I present an extensive study of several issues related to manipulation, growth and diffusion of atoms and nanoclusters on fcc metal surfaces. One of the important aspects in understanding the effect of adatoms or clusters or even the effect of a tip is to examine the energy landscape of the surface in the presence of these objects. In our study of lateral manipulation using a tip, the use of the Grid method to obtain the energy landscape, has revealed useful information about the shift in the saddle point. Calculations on homogeneous as well as heterogeneous fcc(111) metal systems have been performed. Vertical manipulation on flat, stepped and kinked surfaces have given interesting results about the ease of manipulation on these surfaces. During growth, atoms at the edges of stepped surfaces experience an effect called the Kink Ehrlich Schwoebel Effect (KESE). Fluctuations that occur along the step edges play an important role in island decay for islands in the vicinity of a step edge, as observed in many experiments. Our standard Kinetic Monte Carlo (KMC) study on the vicinals of Cu(001) systems has shown that the KES barrier is in fact responsible for the ledge morphology that we see in our systems. To investigate cluster diffusion on fcc(111) systems which are more complex due to the occurrence of two types of step edge microfacets ((100) and (111)) in them, a KMC technique involving a unique pattern recognition scheme was developed to classify the environment of an atom. The energy barriers for different mechanisms were calculated extensively for Cu/Cu(111) as well as Ag/Ag(111) systems, using the NEB. The intriguing results obtained for these two-dimensional clusters, show magic cluster sizes having much lower diffusivity at 300 K as compared to the general clusters. The dependence of the diffusion coefficient on temperature as well as size of cluster has also been explored. Diffusion prefactors play an important role in the diffusion mechanisms. Most of the KMC studies assume a fixed prefactor. However, realistically this is not true. To get an understanding of the prefactors and their ratios for the important mechanisms, a study on the Ag/Ag(111) system shows that the ratio of the prefactors for step edge to terrace diffusion > 1, at low temperatures, which is in agreement with experimental observations. A molecular dynamics (MD) study was also performed to get an understanding of the initial evolution of certain clusters and the important mechanisms involved. All these investigations have given us a deep insight into several intriguing surface phenomena, observed in experiments and theoretical simulations

Crystallization and preliminary X-ray diffraction studies of NP24-I, an isoform of a thaumatin-like protein from ripe tomato fruits

A thaumatin-like antifungal protein, NP24-I, has been isolated from ripe tomato fruits. It was crystallized by the vapour-diffusion method and data were collected to 2.45 Å. The structure was solved by molecular replacement