Neuron-specific ablation of eIF5A or deoxyhypusine synthase leads to impairments in growth,viability, neurodevelopment,and cognitive functions in mice

Eukaryotic initiation factor 5A (eIF5A)^†, ^‡ is an essential protein that requires a unique amino acid, hypusine, for its activity. Hypusine is formed exclusively in eIF5A post-translationally via two enzymes, deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase. Each of the genes encoding these proteins, Eif5a, Dhps, and Dohh, is required for mouse embryonic development. Variants in EIF5A or DHPS were recently identified as the genetic basis underlying certain rare neurodevelopmental disorders in humans. To investigate the roles of eIF5A and DHPS in brain development, we generated four conditional KO mouse strains using the Emx1-Cre or Camk2a-Cre strains and examined the effects of temporal- and region-specific deletion of Eif5a or Dhps. The conditional deletion of Dhps or Eif5a by Emx1 promotor–driven Cre expression (E9.5, in the cortex and hippocampus) led to gross defects in forebrain development, reduced growth, and premature death. On the other hand, the conditional deletion of Dhps or Eif5a by Camk2a promoter–driven Cre expression (postnatal, mainly in the CA1 region of the hippocampus) did not lead to global developmental defects; rather, these KO animals exhibited severe impairment in spatial learning, contextual learning, and memory when subjected to the Morris water maze and a contextual learning test. In both models, the Dhps-KO mice displayed more severe impairment than their Eif5a-KO counterparts. The observed defects in the brain, global development, or cognitive functions most likely result from translation errors due to a deficiency in active, hypusinated eIF5A. Our study underscores the important roles of eIF5A and DHPS in neurodevelopment.     

Some studies on UASB bioreactors for the stabilization of low strength industrial effluents

The suitability of two stage biomethanation process using upflow anaerobic sludge blanket (UASB) bioreactors was studied for the treatment of low strength industrial effluents like rice mill wastewater. Maximum VFA yield was 0.75 mg (as acetic acid) per mg of COD consumed at a flow rate of 25 ml/min. Hydraulic retention time (HRT) of 1 hr was found suitable for acidification process. In the methanogenic reactor, the overall BOD and COD reductions were 89% and 78% respectively at loading rate of 3 kg COD m^х d^у, and HRT of 30 hrs. Gas yield in methanogenic reactor was 0.56 lits. per kg COD consumed which contains 62% v/v methane.     

Adsorption and bio-degradation of phenol by chitosan-immobilized Pseudomonas putida (NICM 2174)

Biodegradation of phenol by Pseudomonas putida (NICM 2174), a potential biodegradent of phenol has been investigated for its degrading potential under different conditions. Pseudomonas putida (NICM 2174) cells immobilized in chitosan were used to degrade phenol. Adsorption of phenol by the chitosan immobilized matrix played an important role in reducing the toxicity of phenol. In the present work, results of the batch equilibrium adsorption of phenol on chitosan from its aqueous solution at different particle sizes (0.177 mm, 0.384 mm, 1.651 mm) and initial concentration of phenol (20, 40, 60, 80, 100, 120, 140, 160, 180, 200 mg/l) have been reported. The adsorption isotherms are described by Langmuir, Freundlich and Redlich-Peterson types of equations. These indicate favourable adsorption with chitosan. From the adsorption isotherms, the adsorption capacity, energy of adsorption, number of layers and the rate constants were evaluated. In batch kinetic studies the factors affecting the rate of biodegradation of phenol, were initial phenol concentration (0.100 g/l, 0.200 g/l, 0.300 g/l), temperature (30v°C, 34v°C, 38v°C) and pH (7.0, 8.0, 9.0). Biodegradation kinetic data indicated the applicability of Lagergren equation. The process followed first order rate kinetics. The biodegradation data generally fit the Lagergren equation and the intraparticle diffusion rate equation from which adsorption rate constants, diffusion rate constants and diffusion coefficients were determined. Intraparticle diffusion was found to be the rate-limiting step. Cell growth contributed significantly to phenol removal rates especially when the degradation medium was supplemented with a utilizable carbon source.     

Cholinesterase inhibition and its association with hematological,biochemical and oxidative stress markers in chronic pesticide exposed agriculture workers

The present study investigated the pesticide induced adverse health effects, hematological and biochemical alterations among agriculture workers. A cross sectional study of 51 agriculture workers and 54 unexposed subjects was carried out to evaluate hematological and biochemical alterations in blood. Pesticide exposed individuals were reported adverse clinical outcomes, including tingling, muscle pain, headache, skin disease, etc. A significant alterations in the level of hematological parameters, liver and renal dysfunctions markers and lipid profile suggested hematological, hepatic and renal dysfunctions. A significant decrease in the activity of acetylcholinesterase, reduced glutathione, superoxide dismutase, catalase and increased level of lipid peroxidation was also observed in these agriculture workers. Correlation coefficient analysis showed a positive correlation of chronic exposure with most of the hematological and biochemical parameters. The results demonstrate that the chronic exposure of pesticides cause reduction in the acetylcholinesterase activity and enhanced the risk of adverse clinical outcomes in agriculture workers.     

The cyanotoxin-microcystins: current overview

The monocyclic heptapeptides microcystins (MCs), are a group of hepatotoxins, produced worldwide by some bloom-forming cyanobacterial species/strains both in marine and freshwater ecosystems. MCs are synthesized non-ribosomally by large multi-enzyme complexes consisting of different modules including polyketide synthases and non-ribosomal peptide synthetases, as well as several tailoring enzymes. More than 85 different variants of MCs have been reported to exist in nature. These are chemically stable, but undergo bio-degradation in natural water reservoirs. Direct or indirect intake of MCs through the food web is assumed to be a highly exposed route in risk assessment of cyanotoxins. MCs are the most commonly found cyanobacterial toxins that cause a major challenge for the production of safe drinking water and pose a serious threat to global public health as well as fundamental ecological processes due to their potential carcinogenicity. Here, we emphasize recent updates on different modes of action of their possible carcinogenicity. Besides the harmful effects on human and animals, MC producing cyanobacteria can also present a harmful effect on growth and development of agriculturally important plants. Overall, this review emphasizes the current understanding of MCs with their occurrence, geographical distribution, accumulation in the aquatic as well as terrestrial ecosystems, biosynthesis, climate-driven changes in their synthesis, stability and current aspects on its degradation, analysis, mode of action and their ecotoxicological effects.     

Molecular analysis of prokaryotic diversity in the deep subsurface of the former Homestake gold mine,South Dakota,USA

A culture-independent molecular phylogenetic analysis was carried out to study the prokaryotic diversity in two soil samples collected from the subsurface (1.34 km depth) of the former Homestake gold mine, Lead, South Dakota, USA at two sites, the Ross shaft and number 6 Winze. Microbial community analyses were performed by cloning and sequencing of 16S rRNA genes retrieved directly from soil samples. Geochemical characterization of soils revealed high amount of toxic metals such as As, Cd, Co, Cr, Cu, Ni, Pb, Zn, and U at both the sites. Phylogenetic analyses showed that soil samples were predominantly composed of phylotypes related to phylum Proteobacteria. Other phyla detected in libraries were Acidobacteria, Actinobacteria, Bacteroidetes, Chloroflexi, Chlorobi, Firmicutes, Gemmatimonadetes, Nitrospirae, Planctomycetes, Verrucomicrobia, and candidate divisions OP10 and TM7. The majority (>95%) of the phylotypes retrieved in the libraries were most closely related to environmental sequences from yet-uncultured bacteria representing a hitherto unidentified diversity. The archaeal communities at both the sites exhibited lower diversity and were most closely affiliated to uncultivated species within the Crenarchaeota. Results showed the existence of diverse microbial populations in deep subsurface environment of the Homestake gold mine. Statistical analyses demonstrated that each site harbored phylogenetically distinct microbial populations that were more diverse at Ross site compare to winze site.     

Activation of c-MET induces a stem-like phenotype in human prostate cancer

Prostate cancer consists of secretory cells and a population of immature cells. The function of immature cells and their mutual relation with secretory cells are still poorly understood. Immature cells either have a hierarchical relation to secretory cells (stem cell model) or represent an inducible population emerging upon appropriate stimulation of differentiated cells. Hepatocyte Growth Factor (HGF) receptor c-MET is specifically expressed in immature prostate cells. Our objective is to determine the role of immature cells in prostate cancer by analysis of the HGF/c-MET pathway.Gene-expression profiling of DU145 prostate cancer cells stimulated with HGF revealed induction of a molecular signature associated with stem cells, characterized by up-regulation of CD49b, CD49f, CD44 and SOX9, and down-regulation of CD24 ('stem-like signature'). We confirmed the acquisition of a stem-like phenotype by quantitative PCR, FACS analysis and Western blotting. Further, HGF led to activation of the stem cell related Notch pathway by up-regulation of its ligands Jagged-1 and Delta-like 4. Small molecules SU11274 and PHA665752 targeting c-MET activity were both able to block the molecular and biologic effects of HGF. Knock-down of c-MET by shRNA infection resulted in significant reduction and delay of orthotopic tumour-formation in male NMRI mice. Immunohistochemical analysis in prostatectomies revealed significant enrichment of c-MET positive cells at the invasive front, and demonstrated co-expression of c-MET with stem-like markers CD49b and CD49f.In conclusion, activation of c-MET in prostate cancer cells induced a stem-like phenotype, indicating a dynamic relation between differentiated and stem-like cells in this malignancy. Its mediation of efficient tumour-formation in vivo and predominant receptor expression at the invasive front implicate that c-MET regulates tumour infiltration in surrounding tissues putatively by acquisition of a stem-like phenotype.     

Biochemical changes and adaptive strategies of plants under heavy metal stress

Heavy metal contamination of soil, aqueous waste stream and ground water causes major environmental and human health problems. Heavy metals are major environmental pollutants when they are present in high concentration in soil and show potential toxic effects on growth and development in plants. Due to unabated, indiscriminate and uncontrolled discharge of hazardous chemicals including heavy metals into the environment, plant continuously have to face various environmental constraints. In plants, seed germination is the first exchange interface with the surrounding medium and has been considered as highly sensitive to environmental changes. One of the crucial events during seed germination entails mobilization of seed reserves which is indispensable for the growth of embryonic axis. But, metabolic alterations by heavy metal exposure are known to depress the mobilization and utilization of reserve food by affecting the activity of hydrolytic enzymes. Some plants possess a range of potential mechanisms that may be involved in the detoxification of heavy metals by which they manage to survive under metal stress. High tolerance to heavy metal toxicity could rely either on reduced uptake or increase planned internal sequestration which is manifested by an interaction between a genotype and its environment. Such mechanism involves the binding of heavy metals to cell wall, immobilization, exclusion of the plasma membrane, efflux of these toxic metal ions, reduction of heavy metal transport, compartmentalization and metal chelation by tonoplast located transporters and expression of more general stress response mechanisms such as stress proteins. It is important to understand the toxicity response of plant to heavy metals so that we can utilize appropriate plant species in the rehabilitation of contaminated areas. Therefore, in the present review attempts have been made to evaluate the effects of increasing level of heavy metal in soils on the key behavior of hydrolytic and nitrogen assimilation enzymes. Additionally, it also provides a broad overview of the strategies adopted by plants against heavy metal stress.     

Chemical diversity in the essential oil of Indian valerian (Valeriana jatamansi Jones)

To explore the diversity in the essential oil yield and composition of Valeriana jatamansi Jones (syn. V. wallichii DC) growing wild in Uttarakhand (Western Himalaya), 17 populations were collected from different locations and grown under similar conditions. Comparative results showed considerable variations in the essential oil yield and composition. The essential oil yield varied from 0.21 to 0.46% in the fresh roots and rhizomes of different populations of V. jatamansi. Analysis of the essential oils by GC (RI) and GC/MS and the subsequent classification by principal component analysis (PCA) resulted in six clusters with significant variations in their terpenoid composition. Major components in the essential oils of the different populations were patchouli alcohol (1; 13.4-66.7%), α-bulnesene (3; <0.05-23.5%), α-guaiene (4; 0.2-13.3%), guaiol (5; <0.05-12.2%), seychellene (6; 0.2-9.9%) viridiflorol (<0.05-7.3%), and β-gurjunene (7; 0.0-7.1%). V. jatamansi populations with contents of 1 higher than 60% may be utilized commercially in perfumery.