Association of vitamin D binding protein polymorphism with long-term kidney allograft survival in Hispanic kidney transplant recipients

Polymorphism of genes encoding components of the vitamin D pathway including vitamin D receptor (VDR) and vitamin D binding protein (VDBP), have been widely explored due to the complex role played by vitamin D in renal transplant outcomes. In this study, we investigated whether polymorphisms of genes encoding VDR and VDBP were associated with allograft survival or acute rejection (AR) among a Hispanic kidney transplant population. A total of 502 Hispanic renal allograft recipients at the St. Vincent Medical Center between 2001 and 2010 were genotyped for four different single nucleotide polymorphisms of VDR: FokI C>T (rs2228570), BsmI G>A (rs1544410), ApaI T>G (rs7975232), and TaqI T>C (rs731236). We also performed genotyping for one common polymorphism in the VDBP gene (rs4588). Survival was significantly improved for patients who were homozygous GG for the rs4588 G>T allele in the VDBP gene (GG vs. GT + TT, OR = 0.63, p = 0.02) while GT genotype was associated with a higher risk of graft loss (GT vs. GG + TT, OR = 1.67, p = 0.01). We found no association for polymorphic markers in VDR with allograft survival and AR. The frequency of the haplotype GTCG (in the order of VDR FokI C>T, BsmI G>A, ApaI T>G, and TaqI T>C), was significantly different in the patients with graft rejection compared to the control (p = 0.007) while ACCA haplotype was found to be associated with graft loss (p = 0.02). Hence, the VDBP G>T polymorphism (rs4588) and two haplotypes (GTCG and ACCA) of VDR appear to be associated with renal allograft outcomes among Hispanic allograft recipients.     

Rotenone-induced oxidative stress and apoptosis in human liver HepG2 cells

Rotenone, a commonly used pesticide, is well documented to induce selective degeneration in dopaminergic neurons and motor dysfunction. Such rotenone-induced neurodegenration has been primarily suggested through mitochondria-mediated apoptosis and reactive oxygen species (ROS) generation. But the status of rotenone induced changes in liver, the major metabolic site is poorly investigated. Thus, the present investigation was aimed to study the oxidative stress-induced cytotoxicity and apoptotic cell death in human liver cells-HepG2 receiving experimental exposure of rotenone (12.5–250 μM) for 24 h. Rotenone depicted a dose-dependent cytotoxic response in HepG2 cells. These cytotoxic responses were in concurrence with the markers associated with oxidative stress such as an increase in ROS generation and lipid peroxidation as well as a decrease in the glutathione, catalase, and superoxide dismutase levels. The decrease in mitochondrial membrane potential also confirms the impaired mitochondrial activity. The events of cytotoxicity and oxidative stress were found to be associated with up-regulation in the expressions (mRNA and protein) of pro-apoptotic markers viz., p53, Bax, and caspase-3, and down-regulation of anti-apoptotic marker Bcl-2. The data obtain in this study indicate that rotenone-induced cytotoxicity in HepG2 cells via ROS-induced oxidative stress and mitochondria-mediated apoptosis involving p53, Bax/Bcl-2, and caspase-3.     

Genetic diversity of commercially grown Moringa oleifera Lam. cultivars from India by RAPD, ISSR and cytochrome P450-based markers

Moringa oleifera is a less used, drought-tolerant tropical plant, rich in nutritionally and nutraceutically important bioactive compounds. It is native to India and now under cultivation in many countries, but no data is available on genetic variability. Three DNA marker techniques, i.e., random amplified polymorphic DNA (RAPD), inter simple sequence repeat (ISSR) and cytochrome P₄₅₀ gene-based markers were used for the detection of genetic variability in eight Indian cultivars of M. oleifera, collected from various states of India. A total of 17 RAPD, 6 ISSR and 7 pairs of cytochrome P₄₅₀-based markers generated 48.68, 48.57 and 40.00 % polymorphisms, respectively. The marker index (MI) for each of these marker systems (3.25 for RAPD, 4.73 ISSR and 2.95 for Cyt P₄₅₀-based markers) suggest that ISSR markers are the most effective for assessment of genetic diversity. Based on the three types of marker data, the eight cultivars of M. oleifera were grouped into four sub-clusters in a dendrogram, but without any distinct geographical pattern. This suggests spread of planting material and high rates of gene flow through cross pollination. High bootstrap values (94.4 and 82.3) were obtained at major nodes of the dendrogram using the winboot software. The dendrogram and PCA plots generated from the binary data matrices of the three marker systems were found highly concordant to each other. This study reveals a huge genetic diversity among the cultivars and this can be utilised for conservation and cultivar development in breeding programmes to produce high yielding, nutritionally superior cultivars.     

Bacillus cereus adhesion: Real time investigation of the effect on the chemistry of industrial stainless steel

The initial microorganism adhesion on substrate is an important step for the biofilm formation. The surface properties of the stainless steel and B. cereus were characterized by the sessile drop technique. Moreover, the physicochemical properties of surface adhesion and the impact of bio adhesion to the stainless steel were determined at different time of contact (2, 4, 7, 9 and 24 h). The results showed that the strain was hydrophilic (Giwi = 3.37 mJ/m²), whereas the substratum has hydrophobic character (Giwi = ?57.6 mJ/m²). Stainless steel surface presents a weak electron-donor character (γ^? = 4.1 mJ/m²) conversely to B. cereus that presents an important parameter (γ^? = 31.6 mJ/m²). The bio adhesion was investigated at different time of contact. The data analysis after 2 h, confirmed the adhesion of B. cereus with an amount of 10 cfu/cm² which increased to 1.210⁴ cfu/cm² after 24 h. Interestingly, despite the difference of hydropohbicity, the interaction between B. cereus and substratum was favored by the thermodynamic aspect of adhesion (ΔG_adhesion < 0). Interestingly, the study of the effect of B. cereus adhesion on the stainless steel has revealed that, the substratum becomes hydrophilic (θ° = 41.3, ΔGiwi = 39.6 mJ/m²) and highly electron donor (Γ^? = 52.9 mJ/m²) after 2 h of bio adhesion.     

Economic activity in the South-Asian population in Britain: the impact of ethnicity,religion, and class

This paper expands the existing literature on ethnicity and economic activity in Britain by studying the impact of religion and class. It argues that while the class location of the different South-Asian groups is important in determining their labour market outcomes, it does not operate independently from ethnicity; rather it is highly influenced by ethnicity in the process of determining the labour market participation of these groups. We use data obtained from the 2001 UK Census on Indian, Pakistani, and Bangladeshi men and women aged between twenty and twenty nine. Our findings confirm that class structure of the South-Asian groups is highly ethnicized, in that the ethno-religious background and class are interwoven to the extent that the separation between them is not easy, if not impossible.     

Land use impacts on freshwater regulation, erosion regulation, and water purification: a spatial approach for a global scale level

Purpose

Rarely considered in environmental assessment methods, potential land use impacts on a series of ecosystem services must be accounted for in widely used decision-making tools such as life cycle assessment (LCA). The main goal of this study is to provide an operational life cycle impact assessment characterization method that addresses land use impacts at a global scale by developing spatially differentiated characterization factors (CFs) and assessing the extent of their spatial variability using different regionalization levels.

Methods

The proposed method follows the recommendations of previous work and falls within the framework and principles for land use impact assessment established by the United Nations Environment Programme/Society of Environmental Toxicology and Chemistry Life Cycle Initiative. Based on the spatial approach suggested by Saad et al. (Int J Life Cycle Assess 16: 198–211, 2011), the intended impact pathways that are modeled pertain to impacts on ecosystem services damage potential and focus on three major ecosystem services: (1) erosion regulation potential, (2) freshwater regulation potential, and (3) water purification potential. Spatially-differentiated CFs were calculated for each biogeographic region of all three regionalization scale (Holdridge life regions, Holdridge life zones, and terrestrial biomes) along with a nonspatial world average level. In addition, seven land use types were assessed considering both land occupation and land transformation interventions.

Results and discussion

A comprehensive analysis of the results indicates that, when compared to all resolution schemes, the world generic averaged CF can deviate for various ecosystem types. In the case of groundwater recharge potential impacts, this range varied up to factors of 7, 4.7, and 3 when using the Holdridge life zones, the Holdridge regions, and the terrestrial biomes regionalization levels, respectively. This validates the importance of introducing a regionalized assessment and highlights how a finer scale increases the level of detail and consequently the discriminating power across several biogeographic regions, which could not have been captured using a coarser scale. In practice, the implementation of such regionalized CFs suggests that an LCA practitioner must identify the ecosystem in which land occupation or transformation activities occur in addition to the traditional inventory data required—namely, the land use activity and the inventory flow.

Conclusions

The variability of CFs across all three regionalization levels provides an indication of the uncertainty linked to nonspatial CFs. Among other assumptions and value choices made throughout the study, the use of ecological borders over political boundaries was deemed more relevant to the interpretation of environmental issues related to specific functional ecosystem behaviors.     

Leprosy Reactions Show Increased Th17 Cell Activity and Reduced FOXP3+ Tregs with Concomitant Decrease in TGF-β and Increase in IL-6

Background

50% of leprosy patients suffer from episodes of Type 1/ reversal reactions (RR) and Type 2/ Erythema Nodosum Leprosum (ENL) reactions which lead to morbidity and nerve damage. CD4⁺ subsets of Th17 cells and CD25⁺FOXP3⁺ regulatory T cells (Tregs) have been shown to play a major role in disease associated immunopathology and in stable leprosy as reported by us and others. The aim of our study was to analyze their role in leprosy reactions.

Methodology and Principle Findings

Quantitative reverse transcribed PCR (qPCR), flowcytometry and ELISA were used to respectively investigate gene expression, cell phenotypes and supernatant levels of cytokines in antigen stimulated PBMC cultures in patients with stable disease and those undergoing leprosy reactions. Both types of reactions are associated with significant increase of Th17 cells and associated cytokines IL-17A, IL-17F, IL-21, IL-23 and chemokines CCL20, CCL22 as compared to matching stable forms of leprosy. Concurrently patients in reactions show reduction in FOXP3⁺ Treg cells as well as reduction in TGF-β and increase in IL-6. Moreover, expression of many T cell markers, cytokines, chemokines and signaling factors were observed to be increased in RR as compared to ENL reaction patients.

Conclusions

Patients with leprosy reactions show an imbalance in Th17 and Treg populations. The reduction in Treg suppressor activity is associated withhigherTh17cell activity. The combined effect of reduced TGF-β and enhanced IL-6, IL-21 cytokines influence the balance between Th17 or Treg cells in leprosy reactions as reported in the murine models and autoimmune diseases. The increase in Th17 cell associated cytokines may contribute to lesional inflammation.