Common SNPs in FTO Gene Are Associated with Obesity Related Anthropometric Traits in an Island Population from the Eastern Adriatic Coast of Croatia

Background

Multiple studies have provided compelling evidence that the FTO gene variants are associated with obesity measures. The objective of the study was to investigate whether FTO variants are associated with a broad range of obesity related anthropometric traits in an island population.

Methodology/Principal Findings

We examined genetic association between 29 FTO SNPs and a comprehensive set of anthropometric traits in 843 unrelated individuals from an island population in the eastern Adriatic coast of Croatia. The traits include 11 anthropometrics (height, weight, waist circumference, hip circumference, bicondilar upper arm width, upper arm circumference, and biceps, triceps, subscapular, suprailiac and abdominal skin-fold thicknesses) and two derived measures (BMI and WHR). Using single locus score tests, 15 common SNPs were found to be significantly associated with “body fatness” measures such as weight, BMI, hip and waist circumferences with P-values ranging from 0.0004 to 0.01. Similar but less significant associations were also observed between these markers and bicondilar upper arm width and upper arm circumference. Most of these significant findings could be explained by a mediating effect of “body fatness”. However, one unique association signal between upper arm width and rs16952517 (P-value = 0.00156) could not be explained by this mediating effect. In addition, using a principle component analysis and conditional association tests adjusted for “body fatness”, two novel association signals were identified between upper arm circumference and rs11075986 (P-value = 0.00211) and rs16945088 (P-value = 0.00203).

Conclusions/Significance

The current study confirmed the association of common variants of FTO gene with “body fatness” measures in an isolated island population. We also observed evidence of pleiotropic effects of FTO gene on fat-free mass, such as frame size and muscle mass assessed by bicondilar upper arm width and upper arm circumference respectively and these pleiotropic effects might be influenced by variants that are different from the ones associated with “body fatness”.     

Decoding RNA motional codes

When proteins and small molecules bind to RNA, they often alter its conformation. These structural changes are an essential aspect of the ability of RNA to sense signaling molecules and modulate gene expression. Thus far, few studies have been dedicated to understanding how RNA moves at a residue level and how these motions change upon complex formation. A recent report highlights how intrinsic motions in RNA correlate with its ability to bind to cognate ligands.     

In vitro cytoprotective activity of cyanidin 3-glucoside extracts from Haematocarpus validus pomace on streptozotocin induced oxidative damage in pancreatic β-cells

Cyanidin-3-glucoside (C3Ghv) compounds were purified and isolated from the anthocyanins extract of Haematocarpus validus. C3Ghv were studied for antioxidant and cytoprotective properties on pancreatic β-cells of rat insulinoma cells (RINm5F) against the oxidative stress induced by streptozotocin (STZ). The exposure of RINm5F cells to C3Ghv at concentration of 100 and 200 μg/mL for 24 h reduced 10% and 23% cell viability, respectively, as compared to control cells. The pre-treatment of RINm5F cells with C3Ghv (50 µg/mL) increased the cell viability by 29% as compared to control, on being treated with STZ (10 mM) for 24 h. The pre-treatment of RINm5F cells with C3Ghv (50 µg/mL) for 24 h followed by exposure to STZ (10 mM) for 1 h decreased the generation of reactive oxygen species (ROS) by 57%, generation of nitric oxide by 22.8%, generation of malondialdehyde (MDA) by 32%, the production of p-ERK ½ by 83%, p-JNK by 82.6%, p-MEK by 57%, and p-p38 MAPK by 64%. The C3Ghv treatment also decreased the ratio of apoptotic proteins Bax to Bcl-2 by 61%, and improved the M2 phase of cell cycle by 75% as compared to STZ treated cells. The overall results suggest that C3Ghv protects pancreatic β-cells against oxidative stress-induced apoptosis, thereby implicating the significant role of C3Ghv as an antidiabetic agent.     

Applying novel genome-wide linkage strategies to search for loci influencing type 2 diabetes and adult height in American Samoa

Type 2 diabetes mellitus (T2DM) is a common complex phenotype that by the year 2010 is predicted to affect 221 million people globally. In the present study we performed a genome-wide linkage scan using the allele-sharing statistic Sall implemented in Allegro and a novel two-dimensional genome-wide strategy implemented in Merloc that searches for pairwise interaction between genetic markers located on different chromosomes linked to T2DM. In addition, we used a robust score statistic from the newly developed QTL-ALL software to search for linkage to variation in adult height. The strategies were applied to a study sample consisting of 238 sib-pairs affected with T2DM from American Samoa. We did not detect any genome-wide significant susceptibility loci for T2DM. However, our two-dimensional linkage investigation detected several loci pairs of interest, including 11q22 and 21q21, 9q21 and 11q22, 1p22-p21 and 4p15, and 4p15 and 15q11-q14, with a two-loci maximum LOD score (MLS) greater than 2.00. Most detected individual loci have previously been identified as susceptibility loci for diabetes-related traits. Our two-dimensional linkage results may facilitate the selection of potential candidate genes and molecular pathways for further diabetes studies because these results, besides providing candidate loci, also demonstrate that polygenic effects may play an important role in T2DM. Linkage was detected (p value of 0.005) for variation in adult height on chromosome 9q31, which was reported previously in other populations. Our finding suggests that the 9q31 region may be a strong quantitative trait locus for adult height, which is likely to be of importance across populations.     

Body Condition,Energy Balance and Immune Status of Periparturient Murrah Buffaloes (Bubalus bubalis) Supplemented with Inorganic Chromium

Periparturient Murrah buffaloes were used to determine whether body condition, energy balance and immune status are affected by inorganic Cr supplementation. Twenty-four Murrah buffaloes were blocked into four groups having six animals in each group and fed for 60 days pre-partum to 150 days post-partum. Feeding regimen was same in all the groups except that these were supplemented with 0.0, 0.5, 1.0 and 1.5 of Cr per kilogram of dry matter (DM) in the four respective groups. Buffaloes were weighed at fortnightly intervals. Blood samples were collected from the jugular vein at days ?60, ?30, ?15, ?7, 0, 7, 15, 30, 60, 90, 120 and 150 of experimental feeding for the estimation of non-esterified fatty acid (NEFA), beta-hydroxybutyric acid (BHBA), Cr level, lymphocyte proliferation, neutrophil phagocytic activity, plasma total immunoglobulin (TIg), immunoglobulin G (IgG) and cortisol levels. Results revealed that with approaching parturition, dry matter intake (DMI), immune response and plasma Cr level decreased (P?NEFA and BHBA concentrations showed increasing (P?P?NEFA and BHBA concentrations. The results of present findings indicated that dietary inorganic Cr supplementation reduced lipid mobilization and improved immune response in periparturient buffaloes.     

Sequence,biophysical, and structural analyses of the PstS lipoprotein (BB0215) from Borrelia burgdorferi reveal a likely binding component of an ABC‐type phosphate transporter

The Lyme disease agent Borrelia burgdorferi, which is transmitted via a tick vector, is dependent on its tick and mammalian hosts for a number of essential nutrients. Like other bacterial diderms, it must transport these biochemicals from the extracellular milieu across two membranes, ultimately to the B. burgdorferi cytoplasm. In the current study, we established that a gene cluster comprising genes bb0215 through bb0218 is cotranscribed and is therefore an operon. Sequence analysis of these proteins suggested that they are the components of an ABC‐type transporter responsible for translocating phosphate anions from the B. burgdorferi periplasm to the cytoplasm. Biophysical experiments established that the putative ligand‐binding protein of this system, BbPstS (BB0215), binds to phosphate in solution. We determined the high‐resolution (1.3 Å) crystal structure of the protein in the absence of phosphate, revealing that the protein's fold is similar to other phosphate‐binding proteins, and residues that are implicated in phosphate binding in other such proteins are conserved in BbPstS. Taken together, the gene products of bb0215‐0218 function as a phosphate transporter for B. burgdorferi.     

The arginine and serine‐rich domains of Acinus modulate splicing

Apoptotic chromatin condensation inducer in the nucleus (Acinus) is an RNA‐binding protein that has a functional role in inducing apoptotic chromatin condensation and regulating messenger RNA (mRNA) processing. Acinus interacts with the spliceosomal machinery and is a member of the ASAP (apoptosis and splicing‐associated protein complex) as well as the EJC (exon junction complex), which gets deposited onto mRNA during splicing. In this study, we have used in vivo splicing assays to characterize the function of Acinus in pre‐mRNA splicing more closely. We show that full‐length Acinus‐S′, an isoform of Acinus, does not have a role in modulating splice site selection in human immunodeficiency virus 1 minigene reporter system. In contrast, we observed that the tethering of arginine/serine (RS) and RNPS1‐SAP18‐binding (RSB) domains of Acinus could regulate the selection of alternative splice sites, thereby revealing the potential of Acinus in stimulating alternative splicing. Altogether, our data suggest that the RS and RSB domains play a critical role in regulating splicing activity via selection of distinct splice sites during pre‐mRNA splicing.     

Vermicomposting of distillation waste of citronella plant (Cymbopogon winterianus Jowitt.) employing Eudrilus eugeniae

Laboratory experiment on vermicomposting of distillation waste of java citronella (Cymbopogon winterianus Jowitt.) was carried out employing Eudrilus eugeniae, in two seasonal trials, covering summer and winter periods. Two vermicomposting treatments were conducted in earthen pots, one with citronella plant waste only (CW) and the other, a mixture of citronella waste and cowdung in the proportion 5:1 (CW + CD). Vermicomposting of citronella waste resulted reduction in C/N ratio (83.5-87.7%), enhancement of ash content and a number of macro and micronutrients. The FT-IR spectroscopy of the vermicompost revealed the reduction in aliphatic and aromatic compound as well as increase in amide group after the 105 days stabilization process. The vermicompost output was significantly enhanced in CW + CD treatment than CW treatment. Even, nutrient content of the vermicompost was also higher in CW + CD treatment than CW alone indicating the positive role of cowdung in improvement of quantity and quality.