Spatio-temporal genetic variation in populations of wild emmer wheat, <Emphasis Type="Italic">Triticum turgidum</Emphasis> ssp. <Emphasis Type="Italic">dicoccoides</Emphasis>, as revealed by AFLP analysis

Genetic structure of natural populations of wild crop relatives has been the subject of many studies. Yet, most of them focused on the assessment of spatial genetic diversity, while information on long-term variation, affected by yearly changes, has been considered only in few cases. The present study aimed therefore, to estimate the spatio-temporal genetic variation in populations of wild emmer wheat, the progenitor of domesticated wheat, and to assess the contribution of spatial versus temporal factors to the maintenance of genetic variation in a population. Single spikes were collected in the years 1988 and 2002 from plants that grew in the same sampling points, from six different habitats in the Ammiad conservation site, Eastern Galilee, Israel. Seeds were planted in a nursery and DNA was extracted from each plant and analyzed by the AFLP method. Fourteen primer combinations yielded 1,545 bands of which 50.0 and 48.8% were polymorphic in the years 1988 and 2002, respectively. Genetic diversity was much larger within populations than between populations and the temporal genetic diversity was considerably smaller than the spatial one. Nevertheless, population genetic structure may vary to some degree in different years, mainly due to fluctuations in population size because of yearly rainfall variations. This may lead to predominance of different genotypes in different years. Clustering the plants by their genetic distances grouped them according to their habitats, indicating the existence of genotype-environment affinities. The significance of the results in relation to factors affecting the maintenance of polymorphism in natural populations is discussed. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

GluR2-free alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors intensify demyelination in experimental autoimmune encephalomyelitis

We adopted a genetic approach to test the importance of edited GluR2-free, Ca(2+)-permeable, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors in the pathophysiology of experimental autoimmune encephalomyelitis, an inflammatory demyelinative disorder resembling multiple sclerosis. Initial studies showed that oligodendroglial lineage cells from mice lacking functional copies of the gene encoding the GluR3 AMPA receptor subunit (Gria3) had a diminished capacity to assemble edited GluR2-free AMPA receptors, and were resistant to excitotoxicity in vitro. Neurological deficits and spinal cord demyelination elicited by immunization with myelin oligodendrocyte glycoprotein peptide were substantially milder in these Gria3 mutant mice than in their wild-type littermates. These results support the hypothesis that oligodendroglial excitotoxicity mediated by AMPA receptors that do not contain edited GluR2 subunits contributes to demyelination in experimental autoimmune encephalomyelitis, and suggest that inhibiting these Ca(2+)-permeable AMPA receptors would be therapeutic in multiple sclerosis.     

REST and Neural Gene Network Dysregulation in iPSC Models of Alzheimer’s Disease

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Analysis of the independent power of age-related,anthropometric and mechanical factors as determinants of the structure of radius and tibia in normal adults. A pQCT study

To compare the independent influence of mechanical and non-mechanical factors on bone features, multiple regression analyses were performed between pQCT indicators of radius and tibia bone mass, mineralization, design and strength as determined variables, and age or time since menopause (TMP), body mass, bone length and regional muscles’ areas as selected determinant factors, in Caucasian, physically active, untrained healthy men and pre- and post-menopausal women. In men and pre-menopausal women, the strongest influences were exerted by muscle area on radial features and by both muscle area and bone length on the tibia. Only for women, was body mass a significant factor for tibia traits. In men and pre-menopausal women, mass/design/strength indicators depended more strongly on the selected determinants than the cortical vBMD did (p<0.01-0.001 vs n.s.), regardless of age. However, TMP was an additional factor for both bones (p<0.01-0.001). The selected mechanical factors (muscle size, bone lengths) were more relevant than age/TMP or body weight to the development of allometrically-related bone properties (mass/design/strength), yet not to bone tissue “quality” (cortical vBMD), suggesting a determinant, rather than determined role for cortical stiffness. While the mechanical impacts of muscles and bone levers on bone structure were comparable in men and pre-menopausal women, TMP exerted a stronger impact than allometric or mechanical factors on bone properties, including cortical vBMD.     

Development and Validation of a Gene-Based Model for Outcome Prediction in Germ Cell Tumors Using a Combined Genomic and Expression Profiling Approach

Germ Cell Tumors (GCT) have a high cure rate, but we currently lack the ability to accurately identify the small subset of patients who will die from their disease. We used a combined genomic and expression profiling approach to identify genomic regions and underlying genes that are predictive of outcome in GCT patients. We performed array-based comparative genomic hybridization (CGH) on 53 non-seminomatous GCTs (NSGCTs) treated with cisplatin based chemotherapy and defined altered genomic regions using Circular Binary Segmentation. We identified 14 regions associated with two year disease-free survival (2yDFS) and 16 regions associated with five year disease-specific survival (5yDSS). From corresponding expression data, we identified 101 probe sets that showed significant changes in expression. We built several models based on these differentially expressed genes, then tested them in an independent validation set of 54 NSGCTs. These predictive models correctly classified outcome in 64–79.6% of patients in the validation set, depending on the endpoint utilized. Survival analysis demonstrated a significant separation of patients with good versus poor predicted outcome when using a combined gene set model. Multivariate analysis using clinical risk classification with the combined gene model indicated that they were independent prognostic markers. This novel set of predictive genes from altered genomic regions is almost entirely independent of our previously identified set of predictive genes for patients with NSGCTs. These genes may aid in the identification of the small subset of patients who are at high risk of poor outcome.     

Normal Values for Segmental Bioimpedance Spectroscopy in Pediatric Patients

Introduction

Localized limb edema is a clinically relevant sign in diseases such as post-thrombotic syndrome and lymphedema. Quantitative evaluation of localized edema in children is mainly done by measuring the absolute difference in limb circumference, which includes fat and fat-free mass. Bioimpedance spectroscopy (BIS) provides information on the fluid volume of a body segment. Our objective was to determine normal ranges for segmental (arm and leg) BIS measurements in healthy children. Additionally, we determined the normal ranges for the difference in arm and ankle circumference and explored the influence of handedness and the correlation between techniques.

Methods

Healthy children aged 1-18 years were recruited. The ratio of extracellular fluid content between contralateral limbs (estimated as the inter-arm and inter-leg extracellular impedance ratio), and the ratio of extracellular to intracellular fluid content for each limb (estimated as the intracellular to extracellular impedance ratio) were determined with a bioimpedance spectrometer. Arm and ankle circumference was determined with a Gulick II tape.

Results

We recruited 223 healthy children (48 infants, 54 preschoolers, 66 school-aged children, and 55 teenagers). Normal values for arm and leg BIS measurements, and for the difference in arm and ankle circumference were estimated for each age category. No influence of handedness was found. We found a statistically significant correlation between extracellular impedance ratio and circumference difference for arms among teenagers.

Conclusion

We determined normal BIS ranges for arms and legs and for the difference in circumference between arms and between ankles in children. There was no statistically significant correlation between extracellular impedance ratio and difference in circumference, except in the case of arms in adolescents. This may indicate that limb circumference measures quantities other than fluid, challenging the adequacy of this technique to determine the presence of localized edema in most age groups.     

Microbial carbon metabolism associated with electrogenic sulphur oxidation in coastal sediments

Recently, a novel electrogenic type of sulphur oxidation was documented in marine sediments, whereby filamentous cable bacteria (Desulfobulbaceae) are mediating electron transport over cm-scale distances. These cable bacteria are capable of developing an extensive network within days, implying a highly efficient carbon acquisition strategy. Presently, the carbon metabolism of cable bacteria is unknown, and hence we adopted a multidisciplinary approach to study the carbon substrate utilization of both cable bacteria and associated microbial community in sediment incubations. Fluorescence in situ hybridization showed rapid downward growth of cable bacteria, concomitant with high rates of electrogenic sulphur oxidation, as quantified by microelectrode profiling. We studied heterotrophy and autotrophy by following ¹³C-propionate and -bicarbonate incorporation into bacterial fatty acids. This biomarker analysis showed that propionate uptake was limited to fatty acid signatures typical for the genus Desulfobulbus. The nanoscale secondary ion mass spectrometry analysis confirmed heterotrophic rather than autotrophic growth of cable bacteria. Still, high bicarbonate uptake was observed in concert with the development of cable bacteria. Clone libraries of 16S complementary DNA showed numerous sequences associated to chemoautotrophic sulphur-oxidizing Epsilon- and Gammaproteobacteria, whereas ¹³C-bicarbonate biomarker labelling suggested that these sulphur-oxidizing bacteria were active far below the oxygen penetration. A targeted manipulation experiment demonstrated that chemoautotrophic carbon fixation was tightly linked to the heterotrophic activity of the cable bacteria down to cm depth. Overall, the results suggest that electrogenic sulphur oxidation is performed by a microbial consortium, consisting of chemoorganotrophic cable bacteria and chemolithoautotrophic Epsilon- and Gammaproteobacteria. The metabolic linkage between these two groups is presently unknown and needs further study.     

Association between Inflammation and Cardiac Geometry in Chronic Kidney Disease: Findings from the CRIC Study

Background

Left ventricular hypertrophy (LVH) and myocardial contractile dysfunction are independent predictors of mortality in patients with chronic kidney disease (CKD). The association between inflammatory biomarkers and cardiac geometry has not yet been studied in a large cohort of CKD patients with a wide range of kidney function.

Methods

Plasma levels of interleukin (IL)-1β, IL-1 receptor antagonist (IL-1RA), IL-6, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, high-sensitivity C-Reactive protein (hs-CRP), fibrinogen and serum albumin were measured in 3,939 Chronic Renal Insufficiency Cohort study participants. Echocardiography was performed according to the recommendations of the American Society of Echocardiography and interpreted at a centralized core laboratory.

Results

LVH, systolic dysfunction and diastolic dysfunction were present in 52.3%, 11.8% and 76.3% of the study subjects, respectively. In logistic regression analysis adjusted for age, sex, race/ethnicity, diabetic status, current smoking status, systolic blood pressure, urinary albumin- creatinine ratio and estimated glomerular filtration rate, hs-CRP (OR 1.26 [95% CI 1.16, 1.37], p<0.001), IL-1RA (1.23 [1.13, 1.34], p<0.0001), IL-6 (1.25 [1.14, 1.36], p<0.001) and TNF-α (1.14 [1.04, 1.25], p = 0.004) were associated with LVH. The odds for systolic dysfunction were greater for subjects with elevated levels of hs-CRP (1.32 [1.18, 1.48], p<0.001) and IL-6 (1.34 [1.21, 1.49], p<0.001). Only hs-CRP was associated with diastolic dysfunction (1.14 [1.04, 1.26], p = 0.005).

Conclusion

In patients with CKD, elevated plasma levels of hs-CRP and IL-6 are associated with LVH and systolic dysfunction.