Association between high dietary intake of the n-3 polyunsaturated fatty acid docosahexaenoic acid and reduced risk of Crohn's disease

Background: There are plausible mechanisms for how dietary docosahexaenoic acid (DHA), an n−3 polyunsaturated fatty acid, could prevent Crohn's disease (CD). Aim: To conduct a prospective study to investigate the association between increased intake of DHA and risk of CD. Methods: Overall, 229 702 participants were recruited from nine European centres between 1991 and 1998. At recruitment, dietary intakes of DHA and fatty acids were measured using validated food frequency questionnaires. The cohort was monitored through to June 2004 to identify participants who developed incident CD. In a nested case–control analysis, each case was matched with four controls; odds ratios (ORs) were calculated for quintiles of DHA intake, adjusted for total energy intake, smoking, other dietary fatty acids, dietary vitamin D and body mass index. Results: Seventy-three participants developed incident CD. All higher quintiles of DHA intake were inversely associated with development of CD; the highest quintile had the greatest effect size (OR = 0.07; 95% CI = 0.02–0.81). The OR trend across quintiles of DHA was 0.54 (95% CI = 0.30–0.99, Ptrend = 0.04). Including BMI in the multivariate analysis, due to its correlation with dietary fat showed similar associations. There were no associations with the other dietary fatty acids studied. Conclusion: There were inverse associations, with a biological gradient between increasing dietary docosahexaenoic acid intakes and incident Crohn's disease. Further studies in other populations should measure docosahexaenoic acid to determine if the association is consistent and the hypothesis tested in randomised controlled trials of purely docosahexaenoic acid supplementation

P-type ATPases in Mycobacterium tuberculosis

Tuberculosis is a deadly disease caused by bacteria of the genus Mycobacterium. One-third of the world’s population is infected with Mycobacterium tuberculosis. Two million these deaths occur each year in immunocompromised AIDS patients. M. tuberculosis has co-evolved with humans for many thousands of years. The bacillus has developed tactics to overcome the immune defense system and multiply in the macrophage. At the interface of the host and pathogen interactions, there is an interchange of metals and electrolytes. The host on one hand reduces the availability of metals essential for pathogen survival, like manganese and iron, in the macrophage and increases potassium ions which reduces pH in the phagolysosome. The host also generates Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS), to create toxic affects through interactions with metals and metalloproteins. M. tuberculosis copes with the hostile environment in the macrophage by preventing the acidification of the phagolysosome, secreting antioxidant enzymes such as alkylhydroperoxidase (AhpF) and peroxiredoxin (AhpC), superoxide dismutase, SodA and SodC, and catalase KatG through the SecA system. M. tuberculosis contains 28 metal transporters, among them there are 12 unique P-type ATPases. This is an unusually high number of P-type ATPases in an organism. These ATPases transport several monovalent and divalent metals (Cu+, Cu2+, Ag+, Zn2+, Na+, K+, Ca2+, Cd2+, Pb2+, Mn2+, Mg2+, and Co2+) across biological membranes, using energy from ATP hydrolysis. Our analysis has revealed that these P-type ATPases have homologs in other intracellular symbiotic/pathogenic bacteria and certain chemolithotrophic archaea and bacteria. A corelation can hence be drawn among these pumps and the capability of surviving in noxious environments and coping with adverse redox conditions. Possible substrates were identified by determining the consensus sequences in different helices of these ATPases. However, out of the 12 P-type ATPases confirmed, transported substrate could be postulated for four of these proteins; CtpA, CtpB, CtpV and KdpB. Using bioinformatic approaches we have characterized the possible genetic environment of these genes. The transmembrane regions were analyzed for consensus sequences and the N-terminals and C-terminals were scrutinized for metal binding domains, and we were able to categorize these ATPases into P1 type and P2 type ATPases. In an attempt to determine the substrate specificity, two of these ATPases (CtpC and ctpG) were cloned and transformed into Escherichia coli cells. Cells expressing CtpC were grown in different concentrations of metals and pHs. In these experiments CtpC was found to show an interaction with copper and cadmium. Pure protein was obtained by His-tag purification and para-Nitro Phenol Phosphatase (pNPPase) assay was performed with different metals, it was found that copper and zinc activated the phosphatase activity of the enzyme; and cobalt and manganese were inhibitory. Inhibition of the pNPP assay could mean that there would be activation in the ATPase assay, meaning that cobalt and manganese could be possible substrates to this enzyme

On the structural response of eukaryotic cells

textThe actin, microtubule and intermediate filament cytoskeletal polymer assemblies, along with their accessory proteins, govern the mechanical or structural response of an eukaryotic cell to an external stress. Using statistical mechanics tools, this dissertation investigates the molecular properties, such as mesh size, persistence length and filament length, that determine the structural strength of the in vivo polymer networks, with an emphasis on the actin network or the cortex of cells. Our study of actin shows how the wide range of shear moduli from 1 Pa to 1 kPa that spans the viscous sol-like state to the elastic gel-like state witnessed in eukaryotic cells can be achieved through transient crosslinking and the spatial distribution of actin and actin crosslinking proteins alone. Thus, this gel-sol transition is achieved without the action of any severing or capping proteins that depolymerize the actin network. In order to understand how the microscopic quantities controlling the structural properties of these in vivo polymers are related to the deformation of a cell observed experimentally, a cell model is created by us. It starts with modeling the actin cortex as a thick shell and increases in complexity to include microtubules and the nucleus. Our cell model predicts that the structural response of the cell amplifies changes in molecular properties such as the in vivo actin concentration. Hence, the sensitivity of the structural response to cytoskeletal changes can be used to distinguish between different cells such as normal and cancer cells and can serve as an indicator of disease.Physic

Concentration in Knowledge Output: A case of Economics Journals

This paper assesses the degree of author concentration in seven economics journals, which were published in India during 1990-2002. To measure the degree of author concentration, Lotka's Law was used. Moreover, we also make an exploratory analysis of the geographic, economics subfield and institutional concentration in 704 economics journals. An important finding of this paper is that specialized journals in the sample report the highest degree of author concentration. This result is quite similar to the findings by Cox and Chung (1991). Furthermore, there are several instances showing that the journals lean towards certain norms; this may affect the flow of innovative ideas into economics. We conclude that a knowledge activity, involving the high degree of concentration and a biased publication process, may affect the flow of new ideas into the discipline.Concentration, Lotka's Law