SNP array-based homozygosity mapping reveals MCPH1 deletion in family with autosomal recessive mental retardation and mild microcephaly

Very little is known about the molecular basis of autosomal recessive MR (ARMR) because in developed countries, small family sizes preclude mapping and identification of the relevant gene defects. We therefore chose to investigate genetic causes of ARMR in large consanguineous Iranian families. This study reports on a family with six mentally retarded members. Array-based homozygosity mapping and high-resolution microarray-based comparative genomic hybridization (array CGH) revealed a deletion of approximately 150–200 kb, encompassing the promoter and the first six exons of the MCPH1 gene, one out of four genes that have been previously implicated in ARMR with microcephaly. Reexamination of affected individuals revealed a high proportion of prematurely condensed chromosomes, which is a hallmark of this condition, but in spite of the severity of the mutation, all patients showed only borderline to mild microcephaly. Therefore the phenotypic spectrum of MCPH1 mutations may be wider than previously assumed, with ARMR being the only consistent clinical finding.     

Effects of ascorbic acid on cadmium-induced oxidative stress and performance of broilers

The effects of cadmium on performance, antioxidant defense system, liver and kidney functions, and cadmium accumulation in selected tissues of broiler chickens were studied. Whether the possible adverse effects of cadmium would reverse with the antioxidant ascorbic acid was also investigated. Hence, 4 treatment groups (3 replicates of 10 chicks each) were designed in the study: control, ascorbic acid, cadmium, and cadmium plus ascorbic acid. Cadmium was given via the drinking water at a concentration of 25 mg/L for 6 wk. Ascorbic acid was added to the basal diet at 200 mg/kg either alone or with cadmium. Cadmium decreased the body weight (BW), body weight gain (BWG), and feed efficiency (FE) significantly at the end of the experiment, wheras its effect on feed consumption (FC) was not significant. Cadmium increased the plasma malondialdehyde (MDA) level as an indicator of lipid peroxidation and lowered the activity of blood superoxide dismutase (SOD). Liver function enzymes, aspartate amino transferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and gamma glutamyl transferase (GGT) activities were not changed by cadmium. Cadmium ingestion did not alter serum creatinine levels. Although the serum cadmium level was not elevated, cadmium mainly accumulated in the kidneys, liver, pancreas, and muscle. Ascorbic acid supplementation resulted in a reduction of MDA level previously increased by cadmium and a restoration in SOD activity. However, ascorbic acid did not ameliorate the growth inhibitory effect of cadmium nor did it prevent accumulation of cadmium in analyzed tissues. These data indicate that oxidative stress, induced by cadmium, plays a role in decreasing the performance of broilers and that dietary supplementation by ascorbic acid might be useful in reversing the lipid peroxidation induced by cadmium and partly alleviating the adverse effect of cadmium on performance of broilers.     

Seasonal and locational effects on serum, milk, liver and kidney chromium, manganese, copper, zinc, and iron concentrations of dairy cows

Chromium (Cr), manganese (Mn), copper (Cu), zinc (Zn), and iron (Fe) concentrations were quantified in serum (n=112), milk (n=112), liver (n=70), and kidney samples (n=67) of dairy cows from an iron-steel processing region (Payas-Iskenderun) and from an area free of industrial pollution (Antakya) in Hatay, located in Southern Turkey. Samples were collected in the summer and winter and element determinations were carried out by inductively coupled plasma-atomic emission spectrometry. The mean concentrations of selected elements in serum were found to be similar in both regions. Milk samples collected from the nonindustrial region in the summer had higher Cr, Mn, and Zn concentrations than the polluted region. The liver Cu and kidney Mn levels of samples taken from the industrial region in winter were higher than samples of the unpolluted region. Copper and Fe concentrations in milk, Cr, Mn, Zn, and Fe levels in the liver, and Cr, Cu, Zn, and Fe levels in kidney samples were not found to be different among the regions in both seasons. Copper concentrations were below the critical level in the 25% of serum and 32% of liver samples analyzed in this study. Fifteen percent of serum samples and most of the liver samples had lower amounts of Zn than other reported studies. Although slight differences were observed between the industrial and nonindustrial regions, industrial activities and seasonal changes had no significant effect on selected element concentrations on cows and their milk.     

Transmission electron microscopy study of the effects of cadmium and copper on fetal rat liver tissue

During the entire period of their pregnancies, three groups of adult pregnant Wistar albino rats were provided with tap water (control; group I) or with tap water containing 10 mg/kg CdCl₂ (group II) or 10 mg/kg CdCl₂ plus 10 mg/kg CuSO₄ (group III). At term, the animals were sacrificed and the fetal livers were removed and examined under electron microscopy. The liver tissue of the fetuses in maternal groups II and III showed degenerative changes to their hepatocytes. In group II, the smooth endoplasmic reticulum tubules showed dilatation, and the mitochondria showed a dense matrix. In group III, some mitochondrial degeneration was also seen, with a diluted matrix and mitochondrial dilatation. There were also more heterochromatic nuclei and an increased number of ribosomes. None of these histopathological changes were present in the fetal liver samples from the maternal group I control animals.