Normalization of Illumina Infinium whole-genome SNP data improves copy number estimates and allelic intensity ratios

Background  

Illumina Infinium whole genome genotyping (WGG) arrays are increasingly being applied in cancer genomics to study gene copy number alterations and allele-specific aberrations such as loss-of-heterozygosity (LOH). Methods developed for normalization of WGG arrays have mostly focused on diploid, normal samples. However, for cancer samples genomic aberrations may confound normalization and data interpretation. Therefore, we examined the effects of the conventionally used normalization method for Illumina Infinium arrays when applied to cancer samples.     

Microsatellite Variation in Populations of Atlantic Salmon from North Europe

Our aim was to investigate the level of genetic differentiation in northern European populations of Atlantic salmon, to establish the genetic relationship among major salmon populations in Russia and North Norway, and to compare these to populations from the western Atlantic lineage. Samples were collected along an east—west axis, from Pechora River in Russia to Restigouche River in Quebec, Canada. A total of 439 individual salmon were collected from seven rivers (sample sizes from 50 to 84 individuals). The samples were analysed for variation at four microsatellite loci; Ssa13.37, Ssa14, Ssa171 and Ssa171. Significant differences were found between most of the European populations, and the populations from the Tana and Pechora Rivers were most distinct. The samples from the Rivers Mezenskaya Pizhma and Emtsa in Arkhangelsk oblast in Russia were not significantly different from each other in an exact test of population differences. All other river pairs were significantly different. These results confirmed the deep genetic divergence between American and European salmon populations demonstrated in earlier studies, with alleles specific to continent found in three of the microsatellites.     

Environmental cadmium exposure and forearm bone density

Environmental exposure to cadmium may give rise to osteomalacia combined with renal dysfunction, so called 'Itai-Itai disease', which was endemic in the heavily polluted area in Japan. The main focus of this study was to investigate whether environmental exposure to cadmium is associated with low bone mass in a population living near a smelter. A total of 790 persons (302 males and 488 females), who were all over 35 years old and resided in areas near a lead, zinc and cadmium smelter and in a control area in southeast China, completed a questionnaire, and bone mineral density was measured by SPA-4 single photon absorptiometry at the radius and ulna. Cadmium content of urine was determined by graphite-furnace atomic absorption spectrophotometry as a measure of dose. The present study shows that forearm bone densities were negatively correlated with urinary cadmium excretion (p < 0.001) and forearm bone density decreased linearly with age (p < 0.001) and urinary cadmium (p < 0.01), suggesting a dose-effect relationship between cadmium dose and bone mineral density. Based on the World Health Organization criteria, (bone mineral density < -2.5 SDs below the normal young adult), the prevalence of osteoporosis in women increased from 34.0% in the control area to 51.9% in the heavily polluted area (p < 0.01) among subjects over 50 years old, and the odds ratio value was 2.09 (95% CI: 1.08-4.03) for the highly polluted area compared with the control area. A striking observation in the study was a marked increase of the prevalence of fracture in the cadmium-polluted area in both sexes. It was concluded that environmental exposure to cadmium is associated with an increased loss of bone mineral density in both gender, leading to osteoporosis and increased risk of fractures, especially in the elderly and in females.     

Nutritional interactions in intestinal cadmium uptake - Possibilities for risk reduction

Effects of dietary composition and trace element status on fractional intestinal cadmium uptake is reviewed below. Fractional cadmium uptake is of fundamental importance for internal dose, related individual susceptibility to cadmium, induced renal damage and eventually bone disease. Diet composition with regard to macronutrients has some effects on cadmium bioavailability. Major determinants of intestinal cadmium uptake are however diet composition with regard to crude fibres and trace elements, especially iron. Deficiencies may increase intestinal cadmium uptake 5-8 times. Ultimate risk management would be not to raise crops on cadmium polluted soil. Provisionally, assurance of optimal trace element statusin persons exposed to cadmium is essential for risk reduction.     

A cell-penetrating peptidic GRP78 ligand for tumor cell-specific prodrug therapy

Tumor targeting peptides are promising vehicles for site-directed cancer therapy. Pep42, a cyclic 13-mer oligopeptide that specifically binds to glucose-regulated protein 78 (GRP78) and internalized into cancer cells, represents an excellent vehicle for tumor cell-specific chemotherapy. Here, we report the synthesis and evaluation of Pep42-prodrug conjugates that contain a cathepsin B-cleavable linker, resulting in the traceless release of drug inside the cancer cells.     

Micellar electrokinetic chromatography separation and laser-induced fluorescence detection of the lipid peroxidation product 4-hydroxynonenal

4-Hydroxnonenal (HNE) is a product of lipid peroxidation in biological systems that causes a variety of harmful biological effects. A method for identifying HNE based on derivatization with the fluorescent reagent dansylhydrazine (5-(dimethylamino)naphthalene-1-sulphonehydrazine (DNSH) followed by micellar electrokinetic chromatography separation laser-induced fluorescence detection has been developed. The derivatization reaction has also been investigated for significant experimental parameters and rat brain homogenates with induced lipid peroxidation have been analysed for HNE contents. The limit of detection (3 S/N) was 30 nM or 0.3 fmol in the injected sample.     

Longevity Determined by Paternal Ancestors' Nutrition during Their Slow Growth Period

Social circumstances often impinge on later generations in a socio-economic manner, giving children an uneven start in life. Overfeeding and overeating might not be an exception. The pathways might be complex but one direct mechanism could be genomic imprinting and loss of imprinting. An intergenerational "feedforward" control loop has been proposed, that links grandparental nutrition with the grandchild's growth. The mechanism has been speculated to be a specific response, e.g. to their nutritional state, directly modifying the setting of the gametic imprint on one or more genes. This study raises the question: Can overnutrition during a child's slow growth period trigger such direct mechanisms and partly determine mortality? Data were collected by following-up a cohort born in 1905 in Överkalix parish, northernmost Sweden. The probands were characterised by their parents' or grandparents' access to food during their own slow growth period. Availability of food in the area was defined by referring to historical data on harvests and food prices, records of local community meetings and general historical facts. If there was a surfeit of food in the environment when the paternal grandfather was a 9–12 year old boy a shortening of the proband survival could be demonstrated. The influence of parents', maternal grandparents' and paternal grandmothers' access to food during their slow growth period was discounted in a multivariable analysis. The results are indicative of very early programming mechanisms in human adaptation to the social environment.