Molecular characterization of an aquaporin-2 mutation causing a severe form of nephrogenic diabetes insipidus.

The water channel aquaporin 2 (AQP2) is responsible for water reabsorption by kidney collecting duct cells. A substitution of amino acid leucine 137 to proline in AQP2 (AQP2-L137P) causes Nephrogenic Diabetes Insipidus (NDI). This study aimed to determine the cell biological consequences of this mutation on AQP2 function. Studies were performed in HEK293 and MDCK type I cells, transfected with wildtype (WT) AQP2 or an AQP2-L137P mutant. AQP2-L137P was predominantly detected as a high-mannose form of AQP2, whereas AQP2-WT was observed in both non-glycosylated and complex glycosylated forms. In contrast to AQP2-WT, the AQP2-L137P mutant did not accumulate on the apical plasma membrane following stimulation with forskolin. Ubiquitylation of AQP2-L137P was different from AQP2-WT, with predominance of non-distinct protein bands at various molecular weights. The AQP2-L137P mutant displayed reduced half-life compared to AQP2-WT. Treatment of cells with chloroquine increased abundance of AQP2-WT, but not AQP2-L137P. In contrast, treatment with MG132 increased abundance of AQP2-L137P but not AQP2-WT. Xenopus oocytes injected with AQP2-WT had increased osmotic water permeability when compared to AQP2-L137P, which correlated with lack of the mutant form in the plasma membrane. From the localization of the mutation and nature of the substitution it is likely that AQP2-L137P causes protein misfolding, which may be responsible for the observed functional defects. The data suggest that the L137P mutation results in altered AQP2 protein maturation, increased AQP2 degradation via the proteasomal pathway and limited plasma membrane expression. These combined mechanisms are likely responsible for the phenotype observed in this class of NDI patients.

Evaluation of pharmacochaperone-mediated rescue of mutant V2 receptor proteins.

Nephrogenic Diabetes Insipidus is a rare disorder which is characterized by severe water imbalance in the body. The disease can be acquired or inherited. AVPR2 (arginine vasopressin type 2 receptor) mutations are responsible for genetical type of the disorder. Mutations in the AVPR2 gene may cause loss-of-function due to conformational defects. According to the mutation type, the three-dimensional structure of AVPR2 may be affected even if it is functional and therefore it may not reach the plasma membrane where it is functional. Consequently, it is generally trapped in the Endoplasmic reticulum or Golgi apparatus, which are the quality control systems of the cell. Pharmacological chaperones have been used to retrieve these mutant AVPR2s from these quality control systems of the cell and take them to the plasma membrane for therapeutic purposes. In this study, in order to analyze the effects of two pharmacological chaperones, SR121463B and SR49059, we performed total ELISA and surface ELISA studies and cAMP accumulation assays on mutant receptors (G12E, R68W, V88M, ΔR67_G69/G107W, R106C, V162A and T273M). We observed that pharmacological chaperones may act differently on mutated AVPR2s. Cell surface expression of the mutant receptors and cAMP accumulation response, after stimulation with AVP, were mostly improved by these pharmacological chaperones. We believe that, this study presents important results with respect to the process of the variable type of mutated proteins in the cell and may help in developing a process of new types of chaperones.

Optimizing Winter Wheat Resilience to Climate Change in Rain Fed Crop Systems of Turkey and Iran.

Erratic weather patterns associated with increased temperatures and decreasing rainfall pose unique challenges for wheat breeders playing a key part in the fight to ensure global food security. Within rain fed winter wheat areas of Turkey and Iran, unusual weather patterns may prevent attaining maximum potential increases in winter wheat genetic gains. This is primarily related to the fact that the yield ranking of tested genotypes may change from one year to the next. Changing weather patterns may interfere with the decisions breeders make about the ideotype(s) they should aim for during selection. To inform breeding decisions, this study aimed to optimize major traits by modeling different combinations of environments (locations and years) and by defining a probabilistic range of trait variations [phenology and plant height (PH)] that maximized grain yields (GYs; one wheat line with optimal heading and height is suggested for use as a testing line to aid selection calibration decisions). Research revealed that optimal phenology was highly related to the temperature and to rainfall at which winter wheat genotypes were exposed around heading time (20 days before and after heading). Specifically, later winter wheat genotypes were exposed to higher temperatures both before and after heading, increased rainfall at the vegetative stage, and reduced rainfall during grain filling compared to early genotypes. These variations in exposure to weather conditions resulted in shorter grain filling duration and lower GYs in long-duration genotypes. This research tested if diversity within species may increase resilience to erratic weather patterns. For the study, calculated production of a selection of five high yielding genotypes (if grown in five plots) was tested against monoculture (if only a single genotype grown in the same area) and revealed that a set of diverse genotypes with different phenologies and PHs was not beneficial. New strategies of progeny selection are discussed: narrow range of variation for phenology in families may facilitate the discovery and selection of new drought-resistant and avoidant wheat lines targeting specific locations.

Mining Centuries Old In situ Conserved Turkish Wheat Landraces for Grain Yield and Stripe Rust Resistance Genes.

Wheat landraces in Turkey are an important genetic resource for wheat improvement. An exhaustive 5-year (2009-2014) effort made by the International Winter Wheat Improvement Programme (IWWIP), a cooperative program between the Ministry of Food, Agriculture and Livestock of Turkey, the International Center for Maize and Wheat Improvement (CIMMYT) and the International Center for Agricultural Research in the Dry Areas (ICARDA), led to the collection and documentation of around 2000 landrace populations from 55 provinces throughout Turkey. This study reports the genetic characterization of a subset of bread wheat landraces collected in 2010 from 11 diverse provinces using genotyping-by-sequencing (GBS) technology. The potential of this collection to identify loci determining grain yield and stripe rust resistance via genome-wide association (GWA) analysis was explored. A high genetic diversity (diversity index = 0.260) and a moderate population structure based on highly inherited spike traits was revealed in the panel. The linkage disequilibrium decayed at 10 cM across the whole genome and was slower as compared to other landrace collections. In addition to previously reported QTL, GWA analysis also identified new candidate genomic regions for stripe rust resistance, grain yield, and spike productivity components. New candidate genomic regions reflect the potential of this landrace collection to further increase genetic diversity in elite germplasm.

Exploiting genetic diversity from landraces in wheat breeding for adaptation to climate change.

Climate change has generated unpredictability in the timing and amount of rain, as well as extreme heat and cold spells that have affected grain yields worldwide and threaten food security. Sources of specific adaptation related to drought and heat, as well as associated breeding of genetic traits, will contribute to maintaining grain yields in dry and warm years. Increased crop photosynthesis and biomass have been achieved particularly through disease resistance and healthy leaves. Similarly, sources of drought and heat adaptation through extended photosynthesis and increased biomass would also greatly benefit crop improvement. Wheat landraces have been cultivated for thousands of years under the most extreme environmental conditions. They have also been cultivated in lower input farming systems for which adaptation traits, particularly those that increase the duration of photosynthesis, have been conserved. Landraces are a valuable source of genetic diversity and specific adaptation to local environmental conditions according to their place of origin. Evidence supports the hypothesis that landraces can provide sources of increased biomass and thousand kernel weight, both important traits for adaptation to tolerate drought and heat. Evaluation of wheat landraces stored in gene banks with highly beneficial untapped diversity and sources of stress adaptation, once characterized, should also be used for wheat improvement. Unified development of databases and promotion of data sharing among physiologists, pathologists, wheat quality scientists, national programmes, and breeders will greatly benefit wheat improvement for adaptation to climate change worldwide.

Evaluating dietary quality in diabetes by the Healthy Eating Index.

Diabetes and diabetes-induced complications is a rising health concern in Northern Cyprus. Of the adult population in Northern Cyprus, 12.2% has diabetes and 90% of all individuals suffering from cardiovascular disease are people with diabetes. The aim of this study was to evaluate nutritional habits of people with diabetes in Northern Cyprus in order to make the necessary recommendations to improve their eating habits to prevent diabetes-induced complications. We used the Healthy Eating Index (HEI) to evaluate dietary quality of people with diabetes in Northern Cyprus based on their 24-hour food intake. A total of 200 participants with diabetes were selected randomly from the out-patient clinic of Dr. Burhan Nalbantoglu central hospital in Nicosia. Individuals were asked to complete a questionnaire to determine their 24-hour food intake and frequency of intake of various food substances. The mean HEI score for the subjects with diabetes was 58.8. The HEI component scores for saturated fat, vegetables, dairy products and meat consumption were less than 5, whereas average scores for fat, cholesterol, fruits, grains, and sodium consumption were more than 5. The meat component of the HEI had the lowest mean score (3.3). There was statistical significance between male and female subjects regarding the HEI scores for meat and nutrient variety intake. In conclusion, the results of the present study suggest that subjects with diabetes in Northern Cyprus should improve their diet by decreasing their intake of saturated fat and by increasing their intake of vegetables, meat and milk.

Lessons learnt from influences of the Marmara earthquake on glycemic control and quality of life in people with type 1 diabetes.

To examine the short- and long-term influences of the Marmara earthquake, which occurred on August 17, 1999 in Turkey, on glycemic control and quality of life (QOL), HbA1c, insulin requirement and QOL of 88 people with type 1 diabetes living in the quake zone were evaluated one year before (PreE), 3 months after (PostE) and one year after (FE) the earthquake. HbA1c levels and daily insulin requirements increased significantly at PostE (HbA1c from 7.4 +/- 1.3% to 8.5 +/- 1.8%, p<0.05; insulin from 0.58 +/- 0.2 IU/kg/day to 0.77 +/- 0.2 IU/kg/day, p<0.05). Mean total QOL scores at PostE were significantly lower than the scores obtained at PreE (62.7 +/- 17.3 vs 74.2 +/- 13.4, p<0.001). There were no significant differences between HbA1c levels and total QOL scores at PreE and FE. People with type 1 diabetes living in the same house after the earthquake and not having enough food supply were reported to have lower QOL than people moving to another house and having enough food supply after the earthquake (p = 0.014, p<0.0001, respectively). The Marmara Earthquake had a negative impact on the glycemic control and QOL of the subjects with type 1 diabetes for the short term but prequake scores might be achieved after a long period.

Diabetes education: a chance to improve well-being of Turkish people with type 2 diabetes.

To examine the influence of diabetes education on well-being, 255 patients with type 2 diabetes were recruited according to whether they attended a diabetes education program (n=126) or not (n=129). In patients who had participated in the program, the mean anxiety score was significantly lower, whereas positive well-being and general well-being scores were significantly higher than for patients who had not participated. Factors related to lower well-being included: being female, taking insulin, not attending a diabetes education program and having HbA(1c) level greater than 8%. The odds of having better well-being were two-fold higher in patients participating the diabetes education program compared with those who had not. Diabetes education has a crucial role in improving the well-being of patients with type 2 diabetes. All patients with diabetes should be encouraged to attend a diabetes education program.