Attitude toward genetic testing for cancer risk in Istanbul

To identify attitudes toward genetic testing, and the effects of this information on decisions regarding issues such as pregnancy, abortion, and prophylactic surgery, several subsets of the Turkish population were surveyed in hospital settings. Individuals (n = 179) chosen arbitrarily from four different subsets of a Turkish population were asked to participate in a confidential 23-question survey. Survey participants were familiar with the concept of cancer being a familial disease (85.5%), and 84.7% of them expressed interest in genetic testing to determine cancer risk, 83.9% would have their fetuses tested for such cancer risk, 65.1% would terminate their pregnancies, 92.2% would have their children tested if they were determined to have an increased cancer risk, 71.9% would agree to undergo prophylactic oophorectomy or orchiectomy and 67.6% would have mastectomy/prostatectomy should there be an increased cancer risk to these organs. It appears that at least the sampled segment of a Turkish population is willing to undergo genetic testing to determine if they are at increased risk for cancer. The feasibility and acceptance of genetic testing and the influence of education and genetic counseling in the Turkish people should further be evaluated with a larger stratified sample of the population.     

Seasonal changes in respiration of halophytes in salt playas in the Great Basin,U.S.A.

Many desert playas are covered with water in the early spring. As theweather becomes warmer and drier, water evaporates, increasing saltcontent of the soil from 7,000 to almost 16,000 mmol NaCl Kg^-1. Changes in respiratory metabolism during the growing season of fourhalophytes characteristic of cold desert playas was followed usingcalorimetry. In order of decreasing salt tolerance, the species examinedwere: the forbs Salicornia rubra, S. utahensis; the grass Distichlisspicata; and the shrub Allenrolfea occidentalis. Tissue collected in thefield from sites of low and high salinity in a single playa during May, June,and August of 1997 was put in isothermal calorimeters and the metabolicheat rate (q) and respiration rate (R_CO2) measured. Efficiency ofsubstrate carbon conversion (q/R_CO2) and predicted specific growthrate (H_BR_SG) were calculated. These species are allwell-adapted to the environment in which they are found. Highestmetabolism, respiration, efficiency and growth are found during May andJune and are lowest during the hot, dry month of August. Differencesbetween the species are also noted.     

Alleviation of Cadmium Toxicity in Brassica juncea L. (Czern. & Coss.) by Calcium Application Involves Various Physiological and Biochemical Strategies

Calcium (Ca) plays important role in plant development and response to various environmental stresses. However, its involvement in mitigation of heavy metal stress in plants remains elusive. In this study, we examined the effect of Ca (50 mM) in controlling cadmium (Cd) uptake in mustard (Brassica juncea L.) plants exposed to toxic levels of Cd (200 mg L⁻¹ and 300 mg L⁻¹). The Cd treatment showed substantial decrease in plant height, root length, dry weight, pigments and protein content. Application of Ca improved the growth and biomass yield of the Cd-stressed mustard seedlings. More importantly, the oil content of mustard seeds of Cd-stressed plants was also enhanced with Ca treatment. Proline was significantly increased in mustard plants under Cd stress, and exogenously sprayed Ca was found to have a positive impact on proline content in Cd-stressed plants. Different concentrations of Cd increased lipid peroxidation but the application of Ca minimized it to appreciable level in Cd-treated plants. Excessive Cd treatment enhanced the activities of antioxidant enzymes superoxide dismutase, ascorbate peroxidase and glutathione reductase, which were further enhanced by the addition of Ca. Additionally, Cd stress caused reduced uptake of essential elements and increased Cd accumulation in roots and shoots. However, application of Ca enhanced the concentration of essential elements and decreased Cd accumulation in Cd-stressed plants. Our results indicated that application of Ca enables mustard plant to withstand the deleterious effect of Cd, resulting in improved growth and seed quality of mustard plants.     

Differential Patterns and Determinants of Cardiac Autonomic Nerve Dysfunction during Endotoxemia and Oral Fat Load in Humans

The autonomic nervous system (ANS) plays an important role in regulating the metabolic homeostasis and controlling immune function. ANS alterations can be detected by reduced heart rate variability (HRV) in conditions like diabetes and sepsis. We determined the effects of experimental conditions mimicking inflammation and hyperlipidemia on HRV and heart rate (HR) in relation to the immune, metabolic, and hormonal responses resulting from these interventions. Sixteen lean healthy subjects received intravenous (i.v.) low-dose endotoxin (lipopolysaccharide [LPS]), i.v. fat, oral fat, and i.v. glycerol (control) for 6 hours, during which immune, metabolic, hormonal, and five HRV parameters (pNN50, RMSSD, low-frequency (LF) and high-frequency (HF) power, and LF/HF ratio) were monitored and energy metabolism and insulin sensitivity (M-value) were assessed. LPS infusion induced an increase (AUC) in HR and LF/HF ratio and decline in pNN50 and RMSSD, while oral fat resulted in elevated HR and a transient (hours 1-2) decrease in pNN50, RMSSD, and HF power. During LPS infusion, ΔIL-1ra levels and ΔIL-1ra and ΔIL-1ß gene expression correlated positively with ΔLF/HF ratio and inversely with ΔRMSSD. During oral fat intake, ΔGLP-1 tended to correlate positively with ΔHR and inversely with ΔpNN50 and ΔRMSSD. Following LPS infusion, lipid oxidation correlated positively with HR and inversely with pNN50 and RMSSD, whereas HRV was not related to M-value. In conclusion, suppression of vagal tone and sympathetic predominance during endotoxemia are linked to anti-inflammatory processes and lipid oxidation but not to insulin resistance, while weaker HRV changes in relation to the GLP-1 response are noted during oral fat load.

Trial Registration

ClinicalTrials.gov NCT01054989     

BMI as a Mediator of the Relationship between Muscular Fitness and Cardiometabolic Risk in Children: A Mediation Analysis

Objective

Muscular fitness levels have been associated with cardiometabolic risk in children, although whether body weight acts as a confounder or as an intermediate variable in this relationship remains controversial. The aim of this study was to examine whether the association between muscular fitness and cardiometabolic risk factors is mediated by body mass index (BMI).

Design and Methods

Cross-sectional study using a sample of 1158 schoolchildren aged 8-11 years from the province of Cuenca, Spain. We measured anthropometrics and biochemical variables and we calculated a muscular fitness index as the sum of z-scores of handgrip dynamometry/weight and standing long jump, and we estimated a previously validated cardiometabolic risk index (CMRI). Linear regression models were fitted for mediation analysis to assess whether the association between muscular fitness and cardiometabolic risk was mediated by BMI.

Results

Children with normal weight (NW) had a better cardiometabolic risk profile than their overweight (OW) or obese (OB) peers after controlling for muscular fitness. Marginal estimated mean±SE values for NW, OW and OB categories of CMRI were -0.75±0.06<0.84±0.10<2.18±0.16 in boys and -0.73±0.06<0.96±0.10<2.71±0.17 in girls, both p<0.001. Children with higher levels of muscular fitness had a better cardiometabolic risk profile (CMRI marginal estimated mean±SE 1.04±0.13>0.05±0.09>-1.16±0.13 for lower, middle and upper quartiles of muscular fitness in boys and 1.01±0.16>0.10±0.09>-1.02±0.15 in girls, both p<0.001), but differences disappeared when controlling for BMI. BMI acted as a full mediator between muscular fitness and most cardiometabolic risk factors (Sobel test z=-11.44 for boys; z=-11.83 for girls; p<0.001 in CMRI mediation model) and as a partial mediator in the case of waist circumference (Sobel test z=-14.86 for boys; z=-14.51 for girls; p<0.001).

Conclusions

BMI mediates the association between muscular fitness and cardiometabolic risk in schoolchildren. Overall, good muscular fitness is associated with lower cardiometabolic risk, but particularly when accompanied by normal weight.     

Diversity of the cell-wall associated genomic island of the archaeon Haloquadratum walsbyi

Background

Haloquadratum walsbyi represents up to 80 % of cells in NaCl-saturated brines worldwide, but is notoriously difficult to maintain under laboratory conditions. In order to establish the extent of genetic diversity in a natural population of this microbe, we screened a H. walsbyi enriched metagenomic fosmid library and recovered seven novel version of its cell-wall associated genomic island. The fosmid inserts were sequenced and analysed.

Results

The novel cell-wall associated islands delineated two major clades within H. walsbyi. The islands predominantly contained genes putatively involved in biosynthesis of surface layer, genes encoding cell surface glycoproteins and genes involved in envelope formation. We further found that these genes are maintained in the population and that the diversity of this region arises through homologous recombination but also through the action of mobile genetic elements, including viruses.

Conclusions

The population of H. walsbyi in the studied saltern brine is composed of numerous clonal lineages that differ in surface structures including the cell wall. This type of variation probably reflects a number of mechanisms that minimize the infection rate of predating viruses.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1794-8) contains supplementary material, which is available to authorized users.     

Effects of nicotine and vitamin E on 6-phosphogluconate dehydrogenase activity in some rat tissues in vivo and in vitro

The aim of this study was to investigate whether nicotine affects 6-phosphogluconate dehydrogenase (6PGD) enzyme activity in some rat tissues, and to see the modulatory effects of vitamin E on this effect in vivo. In addition, the effects of nicotine and vitamin E on 6PGD activity were also tested in vitro. The groups were: nicotine [0.5 mg/kg/day, intraperitoneal (i.p.)]; nicotine + vitamin E [75 mg/kg/day, intragastric (i.g.)]; and control group (receiving only vehicles). There were eight rats per group and supplementation period was 3 weeks. The results of in vivo study showed that nicotine activated the muscle, lungs, and testicular 6PGD enzyme activity but had no effect on heart and liver 6PGD activity. Also, nicotine + vitamin E activated the muscle, testicle, and liver 6PGD enzyme activity, while this combination had no effect on heart, and lungs in vivo. When nicotine is administered with vitamin E the increase in 6PGD enzyme activity in muscle and testicles were lower. On the other hand the increase in 6PGD enzyme activity was eliminated by vitamin E in lungs, while 6PGD enzyme activity was increased by vitamin E, which was not affected by nicotine only. In vitro results correlated well with in vivo experimental results. Our results suggest that vitamin E may favourably increase 6PGD enzyme activity in liver in nicotine treated rats, while it has negligible effects on this enzyme activity in other tissues.     

Protective role of TIRAP functional variant against development of coronary artery disease

Coronary artery disease (CAD) is the leading cause of sudden death worldwide. Inflammation is proved to be an important player in development of the CAD. Inflammation is directly regulated by the Toll like receptors (TLRs). Susceptibility of CAD is influenced by genetic variations within TLRs and the proteins involved in its signaling cascade. The TIRAP/MAL {TIR domain containing adaptor protein / MyD88 (myeloid differentiation primary response gene 88) adaptor-like} exhibits maximum genetic variations of all adaptor proteins involved in TLR signaling cascade. Susceptibility to a number of diseases can be influenced due to presence of S180L single nucleotide polymorphism (SNP) of TIRAP/MAL. This study was conducted to investigate the functional role of this well characterized S180L polymorphism on susceptibility to CAD among Pakistani patients. A total of 146 Pakistani CAD patients and 147 controls were genotyped by Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR) and the data was analyzed by using 2-tailed Chi square (x²) test. The p value ≤ 0.05 was considered to be significant.Significantly high frequency of homozygous L180L genotype was observed among healthy subjects as compared to the CAD patients [24 (16%) vs 7 (5%); x² 11.85; p = 0.003]. Moreover, the allele frequency of the minor allele; 180L was observed to be significantly higher among controls than the CAD patients, having same direction of association [156 (53%) vs 131 (45%); OR (95% CI) = 0.7198 (0.520–0.996); p < 0.05).Our results indicate that protective effect of L180L; a coding variant of TIRAP/MAL against CAD is discernible.     

A bioluminogenic HDAC activity assay: validation and screening

Histone deacetylase (HDAC) enzymes modify the acetylation state of histones and other important proteins. Aberrant HDAC enzyme function has been implicated in many diseases, and the discovery and development of drugs targeting these enzymes is becoming increasingly important. In this article, the authors report the evaluation of homogeneous, single-addition, bioluminogenic HDAC enzyme activity assays that offer less assay interference by compounds in comparison to fluorescence-based formats. The authors assessed the key operational assay properties including sensitivity, scalability, reproducibility, signal stability, robustness (Z'), DMSO tolerance, and pharmacological response to standard inhibitors against HDAC-1, HDAC-3/NcoR2, HDAC-6, and SIRT-1 enzymes. These assays were successfully miniaturized to a 10 μL assay volume, and their suitability for high-throughput screening was tested in validation experiments using 640 drugs approved by the Food and Drug Administration and the Hypha Discovery MycoDiverse natural products library, which is a collection of 10 049 extracts and fractions from fermentations of higher fungi and contains compounds that are of low molecular weight and wide chemical diversity. Both of these screening campaigns confirmed that the bioluminogenic assay was high-throughput screening compatible and yielded acceptable performance in confirmation, counter, and compound/extract and fraction concentration-response assays.