Two novel CTNS mutations in cystinosis patients in Thailand

Cystinosis is an autosomal recessive disorder characterized by defective transport of cystine across the lysosomal membrane and resulting in renal, ophthalmic, and other organ abnormalities. Mutations in the CTNS gene cause a deficiency of the transport protein, cystinosin. We performed mutation analysis of CTNS in six cystinosis patients from four families in Thailand. Using PCR sequencing of the entire coding regions, we identified all eight mutant alleles, including two mutations, p.G309D and p.Q284X, that have not been previously reported. This study expands the mutational and population spectrum of nephropathic cystinosis.     

Phytoremediation potential of paragrass--an in situ approach for chromium contaminated soil

The present in situ phytoextraction approach uses paragrass (Brachiaria mutica (Forssk) Stapf) as a hyper accumulator for attenuation of chromium level in soil and mine waste water at South Kaliapani chromite mine area of Orissa. The bioconcentration factor (BCF) for Cr was maximum (0.334) in 100 days grown paragrass weeds. Transportation index (Ti) i.e. 6.16 and total accumulation rate (TAR) i.e. 8.2 mg kg(-1)day(-1) was maximum in 125 days old paragrass grown in Cr contaminated experimental cultivated plots. Cr bioaccumulation in roots was nearly 1000 times more than shoots. Paragrass showed luxuriant growth with massive fibrous roots when grown over Cr contaminated soils (11,170 mg/ kg dry soil). Cr bioaccumulation varies significantly with plant age, biomass and level of Cr contamination in irrigated mine waste water and soil. Paragrass could be used as hyperaccumulators as it showed rapid massive growth with a high tolerance to Cr.     

Influence of Lime and Organic Matter on the Mobility of Cadmium in Cadmium-Contaminated Soil in Relation to Nutrition of Spinach

Cadmium and cadmium compounds are water soluble, mobile in most soils, bio-available, and tend to bio-accumulate. A pot culture experiment was conducted on contaminated soil to study the influence of lime and organic matter on the mobility of cadmium in spinach and its rhizosphere soil. Application of lime (50% and 100% lime requirement) and organic matter (0.5 and 1% by weight of soil) to soil decreased the availability of Cd to the soil and plant throughout the crop growth. The highest diethylene triamine penta-acetic acid (DTPA) extractable Cd was 10.84 mg kg^?1 in the treatment OM₀ L₀ (No application of organic matter and lime) at 20 days after sowing of spinach. Likewise, the highest Cd concentration in spinach roots and shoots were 19.80 and 17.0 mg kg^?1 in the treatment OM₀ L₀ at 20 days after sowing. The Cd concentration in spinach roots and shoots were decreased by 63.23 and 71.88%, respectively, in the treatment OM₁ L₁₀₀ (application of FYM at 1.0% by weight of soil and lime at 100% lime requirement) after 60 days of growth. The lowest concentrations of Cd in the soil and plant after the harvest of the crop were 2.88 and 4.27 mg kg^?1, respectively, in the treatment OM₁ L₁₀₀ and resulted in 65.75 and 71.55% decrease over control (OM₀ L₀). The highest total chlorophyll content of leaves was 2.19 mg kg^?1 of fresh weight in the treatment OM₁ L₁₀₀ at 40 days of crop growth.     

IL-4 Haplotype -590T, -34T and Intron-3 VNTR R2 Is Associated with Reduced Malaria Risk among Ancestral Indian Tribal Populations

Background

Interleukin 4 (IL-4) is an anti-inflammatory cytokine, which regulates balance between T_H1 and T_H2 immune response, immunoglobulin class switching and humoral immunity. Polymorphisms in this gene have been reported to affect the risk of infectious and autoimmune diseases.

Methods

We have analyzed three regulatory IL-4 polymorphisms; -590C>T, -34C>T and 70 bp intron-3 VNTR, in 4216 individuals; including: (1) 430 ethnically matched case-control groups (173 severe malaria, 101 mild malaria and 156 asymptomatic); (2) 3452 individuals from 76 linguistically and geographically distinct endogamous populations of India, and (3) 334 individuals with different ancestry from outside India (84 Brazilian, 104 Syrian, and 146 Vietnamese).

Results

The -590T, -34T and intron-3 VNTR R2 alleles were found to be associated with reduced malaria risk (P<0.001 for -590C>T and -34C>T, and P = 0.003 for VNTR). These three alleles were in strong LD (r²>0.75) and the TTR2 (-590T, -34T and intron-3 VNTR R2) haplotype appeared to be a susceptibility factor for malaria (P = 0.009, OR = 0.552, 95% CI = 0.356 –0.854). Allele and genotype frequencies differ significantly between caste, nomadic, tribe and ancestral tribal populations (ATP). The distribution of protective haplotype TTR2 was found to be significant (χ² ₃ = 182.95, p-value <0.001), which is highest in ATP (40.5%); intermediate in tribes (33%); and lowest in caste (17.8%) and nomadic (21.6%).

Conclusions

Our study suggests that the IL-4 polymorphisms regulate host susceptibility to malaria and disease progression. TTR2 haplotype, which gives protection against malaria, is high among ATPs. Since they inhabited in isolation and mainly practice hunter-gatherer lifestyles and exposed to various parasites, IL-4 TTR2 haplotype might be under positive selection.     

Structure and Binding Interface of the Cytosolic Tails of αXβ2 Integrin

Background

Integrins are signal transducer proteins involved in a number of vital physiological processes including cell adhesion, proliferation and migration. Integrin molecules are hetero-dimers composed of two distinct subunits, α and β. In humans, 18 α and 8 β subunits are combined into 24 different integrin molecules. Each of the subunit comprises a large extracellular domain, a single pass transmembrane segment and a cytosolic tail (CT). The CTs of integrins are vital for bidirectional signal transduction and in maintaining the resting state of the receptors. A large number of intracellular proteins have been found to interact with the CTs of integrins linking integrins to the cytoskeleton.

Methodology/Principal Findings

In this work, we have investigated structure and interactions of CTs of the leukocyte specific integrin αXβ2. We determined the atomic resolution structure of a myristoylated CT of αX in perdeuterated dodecylphosphocholine (DPC) by NMR spectroscopy. Our results reveal that the 35-residue long CT of αX adopts an α-helical conformation for residues F4-N17 at the N-terminal region. The remaining residues located at the C-terminal segment of αX delineate a long loop of irregular conformations. A segment of the loop maintains packing interactions with the helical structure by an extended non-polar surface of the αX CT. Interactions between αX and β2 CTs are demonstrated by ¹⁵N-¹H HSQC NMR experiments. We find that residues constituting the polar face of the helical conformation of αX are involved in interactions with the N-terminal residues of β2 CT. A docked structure of the CT complex indicates that a network of polar and/or salt-bridge interactions may sustain the heteromeric interactions.

Conclusions/Significance

The current study provides important insights into the conservation of interactions and structures among different CTs of integrins.