NHR-49/PAARα and HLH-30/TFEB cooperate for C. elegans host defense via a flavin-containing monooxygenase

During bacterial infection, the host is confronted with multiple overlapping signals that are integrated at the organismal level to produce defensive host responses. How multiple signals are sensed by the host and how they elicit the transcription of specific host defense genes is much less understood at the whole-animal level than at the cellular level. The model organism Caenorhabditis elegans is known to mount transcriptional defense responses against intestinal bacterial infections that elicit overlapping starvation and infection responses, but the specific regulation of such responses is not well understood. By directly comparing C. elegans that were either starved or infected with Gram-positive bacterium Staphylococcus aureus revealed a large infection-specific transcriptional signature. This signature was almost completely abrogated by deletion of transcription factor hlh-30/TFEB, except for six genes including a flavin-containing monooxygenase (FMO) gene, fmo-2/FMO5. We found that the mechanism of fmo-2/FMO5 induction required the nuclear hormone receptor, NHR-49/PPARa, which induced fmo-2/FMO5 and host defense cell non-autonomously. Moreover, deletion of fmo-2/FMO5 severely compromised infection survival, thus identifying the first FMO important for innate immunity in animals. These findings for the first time reveal an infection-specific host response to S. aureus, identify HLH-30/TFEB as its main regulator, reveal that NHR-49/PPARa contributes to host defense, and demonstrate that FMOs are important innate immunity effectors in animals

Impact of Membrane Phospholipids and Exosomes on the Kinetics of Amyloid-β Fibril Assembly.

Alzheimer's disease (AD) is linked with the self-association of the amyloid-β peptide (Aβ) into oligomers and fibrils. The brain is a lipid rich environment for Aβ to assemble, while the brain membrane composition varies in an age dependent manner, we have therefore monitored the influence of lipid bilayer composition on the kinetics of Aβ40 fibril assembly. Using global-fitting models of fibril formation kinetics, we show that the microscopic rate constant for primary nucleation is influenced by variations in phospholipid composition. Anionic phospholipids and particularly those with smaller headgroups shorten fibril formation lag-times, while zwitterionic phospholipids tend to extend them. Using a physiological vesicle model, we show cellular derived exosomes accelerate Aβ40 and Aβ42 fibril formation. Two distinct effects are observed, the presence of even small amounts of any phospholipid will impact the slope of the fibril growth curve. While subsequent additions of phospholipids only affect primary nucleation with the associated change in lag-times. Heightened anionic phospholipids and cholesterol levels are associated with aging and AD respectively, both these membrane components strongly accelerate primary nucleation during Aβ assembly, making a link between disrupted lipid metabolism and Alzheimer's disease

Crisis of Agricultural in Uttar Pradesh: From Apprehension to Actuality

The Indian countryside where the large majority of its people reside is in the grip of a severe crisis relating to agriculture. The rural India is in acute distress- there is not enough work, not enough food to eat and not enough water to drink for the rural population.Dipankar Gupta (2005) seems brutally correct when he writes, “Agriculture (in India) today is an economic residue that generously accommodates non-achievers resigned to a life of sad satisfaction. The villager is as bloodless as the rural economy is lifeless. From rich to poor the trend is to leave the village…..”The situation looks extremely grim as we are in a situation where painkillers are adding to the pains and the medicines are aggravating the disease.  Government’s efforts of coming out of the quagmire are actually pushing agriculture further dipper and dipper into it.Manifestations of agrarian distress in contemporary India is not confined to the pockets of backwardness; even the regions having a high degree of commercial agriculture, using relatively better technology and having a relatively diversified cropping pattern have reported high indebtedness and distress of various kinds. While the perilous form of the crisis as reflected in form of farmer’s distress and suicide is visible at present mainly in states like Andhra Pradesh, Maharashtra (especially Vidarbha) and Kerala etc.; the preliminary signs of a brewing crisis is discernible also in the North Indian states of Punjab, Haryana and Uttar Pradesh. The crisis of agriculture in Uttar Pradesh has not reached an acute stage but it is a lingering crisis of low intensity reflected in stagnation in production, farmer’s indebtedness, poor returns to cultivation, and growing discontent of the farmers and alienation The literature on the nature and magnitude of crisis of agriculture of the type Uttar Pradesh is in, is rather sparse; while policy makers are not keen to even accept that something is wrong with agriculture in UP, the economists are too obsessed and occupied with the severe form of crisis existing elsewhere to pay any heed to it. The primary contention of the present write up is twofold- first, to conceptualise crisis of agriculture in order to see whether it is crisis of the agricultural sector or that of the agriculturists and second, to draw forth the point that the apprehension of a brewing crisis in UP is not false. If corrective measures are not taken at the earliest there is every likelihood that the apprehension of a major crisis of agriculture in the state would turn into actuality. The paper is organized in three sections. Section-I explicates the concept of the crisis taking help of relevant literature, Section-II briefly discusses the methodology of measurement of crisis of agriculture. Section-III presents a summary picture of UP agriculture and develops a composite index of crisis of agriculture for UP and some other states and the final section i.e. Section-IV suggests some interventions required to put the cart on track

Synthesis and characterization of silver nanoarticles from extract of Eucalyptus citriodora

The primary motivation for the study to develop simple eco-friendly green synthesis of silver nanoparticles using leaf extract of Eucalyptus citriodora as reducing and capping agent. The green synthesis process was quite fast and silver nanoparticles were formed within 0.5 h. The synthesis of the particles was observed by UV-visible spectroscopy by noting increase in absorbance. Characterization of the particles was carried out by X-ray diffraction, FTIR and electron microscopy. The developed nanoparticles demonstrated that E. citriodora is good source of reducing agents. UV-visible absorption spectra of the reaction medium containing silver nanoparticles showed maximum absorbance at 460 nm. FTIR analysis confirmed reduction of Ag+ to Ag0 atom in silver nanoparticles. The XRD pattern revealed the crystalline structure of silver nanoparticles. The SEM analysis showed the size and shape of the nanoparticles. The method being green, fast, easy and cost effective can be recommended for large scale production of AgNPs for their use in food, medicine and materials

The impact of nutritional counselling on serum lipids, dietary and physical activity patterns of school children

Eighty-eight school children and their parents who had been counselled regarding appropriate dietary and activity patterns aimed at reducing serum cholesterol were followed-up 21 months later to determine changes in dietary and activity patterns and in serum lipid levels. The decline in serum total cholesterol ranged from 8 to 14% in the different age and sex groups (P \u3c 0.05 to P \u3c 0.001). Serum triglycerides did not change significantly. Cholesterol intake decreased 36% and 54% in 10-14 year old boys and girls respectively (P \u3e 0.001). The activity level increased significantly in both the 5-9 year and 10-14 year olds (P \u3c 0.05 to P \u3c 0.005). These results show that nutrition education can bring about a change in dietary and activity patterns, resulting in a decline in serum cholesterol levels

Bioavailable constituents/metabolites of pomegranate (Punica granatum L) preferentially inhibit COX2 activity ex vivo and IL-1beta-induced PGE2 production in human chondrocytes in vitro

Several recent studies have documented that supplementation with pomegranate fruit extract inhibits inflammatory symptoms in vivo. However, the molecular basis of the observed effects has not been fully revealed. Although previous studies have documented the inhibition of nitric oxide and cyclooxygenase (COX) activity in vitro by plant and fruit extracts added directly into the culture medium but whether concentrations of bioactive compounds sufficient enough to exert such inhibitory effects in vivo can be achieved through oral consumption has not been reported. In the present study we determined the effect of rabbit plasma obtained after ingestion of a polyphenol rich extract of pomegranate fruit (PFE) on COX enzyme activity ex vivo and the IL-1β-induced production of NO and PGE2 in chondrocytes in vitro. Plasma samples collected before and 2 hr after supplementation with PFE were tested. Plasma samples collected after oral ingestion of PFE were found to inhibit the IL-1β-induced PGE2 and NO production in chondrocytes. These same plasma samples also inhibited both COX-1 and COX-2 enzyme activity ex vivo but the effect was more pronounced on the enzyme activity of COX-2 enzyme. Taken together these results provide additional evidence of the bioavailability and bioactivity of compounds present in pomegranate fruit after oral ingestion. Furthermore, these studies suggest that PFE-derived bioavailable compounds may exert an anti-inflammatory effect by inhibiting the inflammatory cytokine-induced production of PGE2 and NO in vivo