Association of cholesteryl ester transfer protein −629C > A polymorphism with high‐density lipoprotein cholesterol levels in coronary artery disease patients

In Turkish population, plasma HDL‐C levels were found to be lower than in any other country and it is suggested that this is associated with genetic origin. The cholesteryl ester transfer protein (CETP) ?629C > A polymorphism is associated with lower plasma CETP concentration, with increased HDL‐C level. In the present study, the frequency of ?629C > A polymorphism in patients with coronary artery disease (CAD) was investigated and the effect of genotype on HDL‐C was evaluated in a Turkish population. For this aim CETP ?629C > A polymorphism was studied in angiographically documented CAD patients and healthy controls. There was no statistical significance in the distribution of genotypes between patients and controls. Although A allele carriers with CAD had significantly lower HDL‐C levels than controls, plasma lipid levels showed no difference according to the genotypes. Adjustment by a logistic regression model predicting CAD status through HDL‐C and including some risk factors as covariate indicated that the HDL‐C doesn't have a significant association with CAD risk in CA and AA genotype carriers. Smoking, gender and hypertension were the common predictors for the HDL‐C levels in CA and AA carriers. Although HDL‐C appeared to be the only significant predictor of CAD in our study groups, the contribution of CETP ?629C > A polymorphism to the alterations in HDL‐C level appears to be weak to mention a protective effect of this polymorphism for CAD. In conclusion, the findings of the present study indicate that the CETP ?629C > A polymorphism is not among the determinants of the coronary artery disease in Turks. Copyright © 2009 John Wiley & Sons, Ltd.     

Traits associated with winter wheat grain yield in Central and West Asia

Improved adaptation of winter wheat(Triticum aestivum L.) to drought and heat may be influenced by days to heading, plant height, biomass, canopy temperature(CT) at grain filling, and rate of senescence. This study shows that,under supplemental irrigation or rainfed conditions, days to heading and plant height together explain up to 68% of grain yield(GY) variation, and these associations were further confirmed in several locations across West and Central Asia.Days to heading can be slightly reduced below that of check line Karahan to further improve GY while avoiding the effect of late frosts. Plant height has been decreased in recent germplasm, but further reductions below that of check line Karahan could still improve GY in a wide range of environments. However, in Iranian sites, taller genotypes showed better adaptation with higher biomass and increased reservesfor grain filling. Canopy temperature and rate senescence were not associated with GY. A normalized difference vegetation index, used to estimate biomass(Feekes stages 4–5), had intermediate heritability across environments and correlated positively with GY under low plant density and should be explored further as a tool for early selection.     

Association of PARP-1, NF-κB,NF-κBIA and IL-6, IL-1β and TNF-α with Graves Disease and Graves Ophthalmopathy

Background

Graves Disease (GD) is an autoimmune disorder affected by an interaction of multiple genes such as Nuclear Factor-κB (NF-κB), Nuclear Factor-κB Inhibitor (NF-κBIA), Poly (ADP-ribose) polymerase-1 (PARP-1) and cytokines like Interleukin-1β (IL-1β), Interleukin-6 (IL-6) and Tumor Necrosis Factor-α (TNF-α) and mostly accompanied by an ocular disorder, Graves Ophthalmopathy (GO). We hypothesize that there is a relationship between GD, GO, polymorphisms of inflammatory related genes and their association with cytokines, which may play important roles in autoimmune and inflammatory processes.

Subjects and methods

To confirm our hypothesis, we studied the polymorphisms and cytokine levels of 120 patients with GD and GO using PCR-RFLP and ELISA methods, respectively.

Results

We found that patients with GG genotype and carriers of G allele of PARP-1 G1672A polymorphism are at risk in the group having GD (p = 0.0007) while having GA genotype may be protective against the disease. PARP-1 C410T polymorphism was found to be associated with GO by increasing the risk by 1.7 times (p = 0.004). Another risk factor for development of GO was the polymorphism of del/ins of NFkB1 gene (p = 0.032) that increases the risk by 39%. Levels of cytokines were also elevated in patients with GD, but no association was found between levels of cytokines and the development of GO as there was no change in levels of cytokines.

Conclusions

We suggest that, PARP-1 and NFkB1 gene polymorphisms may be risk factors for developing Graves Disease and Ophthalmopathy.     

Daily rhythmicity and hibernation in the Anatolian ground squirrel under natural and laboratory conditions

We studied daily rhythmicity of body temperature (T _b) before and during hibernation in Anatolian ground squirrels (Spermophilus xanthoprymnus) under natural and laboratory conditions using surgically implanted temperature loggers. Under both conditions, robust daily T _b rhythmicity with parameters comparable to those of other ground squirrel species was observed before but not during hibernation. Euthermic animals had robust daily T _b rhythms with a mean of 37.0°C and a range of excursion of approximately 4°C. No T _b rhythm was detected during torpor bouts, either because T _b rhythmicity was absent or because the daily range of excursion was smaller than 0.2°C. The general patterns of hibernation that we observed in Anatolian ground squirrels were similar to those previously observed by other investigators in other species of ground squirrels.     

��-Catenin/T-cell Factor Signaling Is Activated during Lung Injury and Promotes the Survival and Migration of Alveolar Epithelial Cells

The Wnt/β-catenin signaling cascade activates genes that allow cells to adopt particular identities throughout development. In adult self-renewing tissues like intestine and blood, activation of the Wnt pathway maintains a progenitor phenotype, whereas forced inhibition of this pathway promotes differentiation. In the lung alveolus, type 2 epithelial cells (AT2) have been described as progenitors for the type 1 cell (AT1), but whether AT2 progenitors use the same signaling mechanisms to control differentiation as rapidly renewing tissues is not known. We show that adult AT2 cells do not exhibit constitutive β-catenin signaling in vivo, using the AXIN2^+/LacZ reporter mouse, or after fresh isolation of an enriched population of AT2 cells. Rather, this pathway is activated in lungs subjected to bleomycin-induced injury, as well as upon placement of AT2 cells in culture. Forced inhibition of β-catenin/T-cell factor signaling in AT2 cultures leads to increased cell death. Cells that survive show reduced migration after wounding and reduced expression of AT1 cell markers (T1α and RAGE). These results suggest that AT2 cells may function as facultative progenitors, where activation of Wnt/β-catenin signaling during lung injury promotes alveolar epithelial survival, migration, and differentiation toward an AT1-like phenotype.     

Evidence of fast serotonin transmission in frog slowly adapting type 1 responses

The Merkel cell-neurite (MCN) complex generates slowly adapting type 1 (SA1) response when mechanically stimulated. Both serotonin (5-HT) and glutamate have been implicated in the generation of normal SA1 responses, but previous studies have been inconclusive as to what their roles are or how synaptic transmission occurs. In this study, excised dorsal skin patches from common water frogs (Rana ridibunda) were stimulated by von Frey hairs during perfusion in a tissue bath, and single-unit spike activity was recorded from SA1 fibres. Serotonin had no significant effect on the SA1 response at low (10?μM) concentration, significantly increased activity in a force-independent manner at 100?μM, but decreased activity with reduced responsiveness to force at 1?mM. Glutamate showed no effect on the responsiveness to force at 100?μM. MDL 72222 (100?μM), an ionotropic 5-HT3 receptor antagonist, completely abolished the responsiveness to force, suggesting that serotonin is released from Merkel cells as a result of mechanical stimulation, and activated 5-HT3 receptors on the neurite. The metabotropic 5-HT2 receptor antagonist, ketanserin, greatly reduced the SA1 fibre's responsiveness to force, as did the non-specific glutamate receptor antagonist, kynurenic acid. This supports a role for serotonin and glutamate as neuromodulators in the MCN complex, possibly by activation and/or inhibition of signalling cascades in the Merkel cell associated with vesicle release. Additionally, it was observed that SA1 responses contained a force-independent component, similar to a dynamic response observed during mechanical vibrations.     

Evaluation of bioactivities of chlorokojic acid derivatives against dermatophytes couplet with cytotoxicity

In an attempt to find novel antifungal agents with improved activity, a series of compounds bearing 6-chloromethyl-3-hydroxy-2-substituted 4H-pyran-4-one moiety were synthesized and examined for their cytotoxic evaluation and antifungal activities against both standard and isolated dermatophytic fungal species Microsporum gypseum, Trichophyton mentagrophytes var. erinacei and Epidermophyton floccosum.