Genetic Control of Obesity and Gut Microbiota Composition in Response to High-Fat,High-Sucrose Diet in Mice

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Highlights? Detailed analysis of diet-induced obesity in more than 100 inbred mouse strains ? Identification of 11 genetic loci associated with obesity and dietary responsiveness ? Significant overlap between mouse loci with human GWAS loci for obesity ? Strain-specific shifts in gut microbiota composition in response to dietary intervention     

Vagus nerve stimulation inhibits seizure activity and protects blood–brain barrier integrity in kindled rats with cortical dysplasia

AimsThis study investigates the effects of vagus nerve stimulation (VNS) on seizure severity and blood–brain barrier (BBB) integrity in kindled rats with cortical dysplasia (CD).Main methodsPregnant rats were exposed to 145 cGy of gamma-irradiation on day 17 of pregnancy. In offsprings, kindling was induced by giving subconvulsive doses of pentylenetetrazole. Left VNS was performed for 48 h at output currents of 0.5 or 1 mA. Horseradish peroxidase (HRP) was used to study the BBB permeability. Immunohistochemistry for occludin and P-glycoprotein (P-gp) was also performed.Key findingsKindled rats with CD exhibited seizures with mean Racine's scores of 3.57 ± 1.2 during video EEG recording. Kindled animals with CD receiving VNS at 0.5 and 1.0 mA did not exhibit either clinical or electrophysiological signs of seizure. Immunostaining for occludin, a tight junction protein, in hippocampus remained relatively intact in all groups. VNS-treated and -untreated kindled animals with CD revealed intense immunostaining for P-gp in hippocampal formation (P < 0.01). Electron microscopic observations revealed frequent transport vesicles containing electron-dense HRP reaction products in the cytoplasm of brain capillary endothelial cells in both cerebral cortex and hippocampus of kindled animals with CD. Those which were exposed to 1 mA VNS were observed to have brain capillary endothelial cells largely devoid of HRP reaction products in both cerebral cortex and hippocampus.SignificanceThe results of this study suggest that VNS therapy at 1 mA inhibits seizure activity and protects BBB integrity by limiting the enhancement of transcellular pathway in kindled animals with CD.     

Effects of Different Medical Treatments on Serum Copper,Selenium and Zinc Levels in Patients with Rheumatoid Arthritis

The aim of the present study was to measure the changes in serum selenium, zinc, and copper in patients being treated for rheumatoid arthritis. Thirty-two patients and 52 healthy controls were included in the study. The copper level was higher and those of selenium and zinc were lower in the patients relative to controls. Treatment with methotrexate elevated the zinc levels, but not zinc and selenium. Treatments with salazopyrin, corticosteroids, chloroquine, and non-steroidal anti-inflammatory drugs did not change the levels of any of the elements studied. The decrease in zinc and selenium levels and elevation in copper levels observed in the patients probably resulted from the defense response of organism and are mediated by inflammatory-like substances.     

Variation of bioactive secondary metabolites in <Emphasis Type="Italic">Hypericum origanifolium</Emphasis> during its phenological cycle

The genus Hypericum has received considerable interest from scientists, as it contains the variety of structurally diverse natural products which possess a wide array of biological properties. The present study was conducted to determine ontogenetic and morphogenetic variation of hypericin, chlorogenic acid and flavonoids, as rutin, hyperoside, apigenin-7-O-glucoside, quercitrin and quercetin content in Hypericum origanifolium growing in Turkey. Wild growing plants were harvested at vegetative, floral budding, full flowering, fresh fruiting and mature fruiting stages and dissected into stem, leaf and reproductive tissues and assayed for bioactive compounds by HPLC method. Hypericin, quercetin and quercitrin content in whole plant increased during course of ontogenesis and the highest level was reached in blooming stage. On the contrary, hyperoside content of whole plant decreased linearly with advancing of development stages and the highest level was observed at vegetative stage. Plants produced similar amount of chlorogenic acid at all stages of plant phenology except for mature fruiting at which the amount of this compound was decreased sharply. Among different tissues, reproductive parts accumulated the highest level of hypericin, quercetin and quercitrin, however, leaves produced substantially higher amount of chlorogenic acid and hyperoside. Rutin and apigenin-7-O-glucoside were detectable in all tissues only during fruit maturation. The presence and variation of these bioactive substances in H. origanifolium were reported for the first time.     

Venlafaxine Modulates Depression-Induced Oxidative Stress in Brain and Medulla of Rat

Venlafaxine is an approved antidepressant that is an inhibitor of both serotonin and norepinephrine transporters. Medical treatment with oral venlafaxine can be beneficial to depression due to reducing free radical production in the brain and medulla of depression- induced rats because oxidative stress may a play role in some depression. We investigated the effect of venlafaxine administration and experimental depression on lipid peroxidation and antioxidant levels in cortex brain, medulla and erythrocytes of rats. Thirty male wistar rats were used and were randomly divided into three groups. Venlafaxine (20 mg/kg) was orally supplemented to depression-induced rats constituting the first group for four week. Second group was depression-induced group although third group was used as control. Depressions in the first and second groups were induced on day zero of the study by chronic mild stress. Brain, medulla and erythrocytes samples were taken from all animals on day 28. Depression resulted in significant decrease in the glutathione peroxidase (GSH-Px) activity and vitamin C concentrations of cortex brain, glutathione (GSH) value of medulla although their levels were increased by venlafaxine administration to the animals of depression group. The lipid peroxidation levels in the three tissues and nitric oxide value in cortex brain elevated although their levels were decreased by venlafaxine administration. There were no significant changes in cortex brain vitamin A, erythrocytes vitamin C, GSH-Px and GSH, medulla vitamin A, GSH and GSH-Px values. In conclusion, cortex brain within the three tissues was most affected by oxidative stress although there was the beneficial effect of venlafaxine in the brain of depression-induced rats on investigated antioxidant defenses in the rat model. The treatment of depression by venlafaxine may also play a role in preventing oxidative stress. Abstract of the paper was submitted in 1st Ion Channels and Oxidative Stress Congress, 14–16 September 2006, Isparta, Turkey.     

Characterization of humic materials extracted from hazelnut husk and hazelnut husk amended soils

This study was carried out to determine effects of composted hazelnut husk (CHH) on some chemical properties of soil and soil humic acid (HA). Compost application increases organic matter (OM) content of the soil considerably, OM value of 3.18% became 3.89% in 3 years time interval. Before application of compost, the soil pH was found to be 5.37, while after compost application it became 5.61. FTIR characteristics of humic acid/humic acid-like materials extracted from the original hazelnut husk, composted hazelnut husk and composted hazelnut husk amended soil have been investigated. C and O content of humic acid-like/humic acid materials were in the range of 41.4–50.8% and 37.8–50.5%, respectively. The N content of the humic acid/humic acid-like materials are in the expected range for humic materials which is 2–6%. Comparison of FTIR spectra of hazelnut husk and composted hazelnut husk humic acid-like fractions shows that both exhibit similar but not identical series of IR bands indicating the presence of the same functional groups in both samples. The only difference in the spectra seemed to be a decrement in the peak intensities of composted sample compared to uncomposted one. The similar differentiation of the intensities of IR bands of compost applied soil sample has also been observed. The FTIR spectral results show that the characteristics of composted material tend to become similar to that of soil humic acids characteristics in time.     

Population estimate and body size of European pond turtles (<Emphasis Type="Italic">Emys orbicularis</Emphasis>) from Pazarağaç (Afyonkarahisar/Turkey)

Data on population size, adult sex ratio, body size and mass are provided for a population of the turtle Emys orbicularis near Pazara?aç (Afyonkarahisar/Turkey). Using the mark-recapture method (triple catch), a population size of 664 turtles was estimated (95% confidence interval, range 332–996), corresponding to a density of 83 turtles per hectare (range 41.5–124.5). The adult sex-ratio was significantly skewed in favor of males (2.02 males: 1 female; P < 0.001). Almost all recorded specimens were adult (98.1%). Mean straight carapace length (SCL) and body mass (BM) of adult turtles were: SCL = 128.65 mm, BM = 345 g for males (n = 168) and SCL = 135.37 mm, BM = 463 g for females (n = 83).     

Mutations in CKAP2L,the Human Homolog of the Mouse Radmis Gene,Cause Filippi Syndrome

Filippi syndrome is a rare, presumably autosomal-recessive disorder characterized by microcephaly, pre- and postnatal growth failure, syndactyly, and distinctive facial features, including a broad nasal bridge and underdeveloped alae nasi. Some affected individuals have intellectual disability, seizures, undescended testicles in males, and teeth and hair abnormalities. We performed homozygosity mapping and whole-exome sequencing in a Sardinian family with two affected children and identified a homozygous frameshift mutation, c.571dupA (p.Ile191Asnfs^∗6), in CKAP2L, encoding the protein cytoskeleton-associated protein 2-like (CKAP2L). The function of this protein was unknown until it was rediscovered in mice as Radmis (radial fiber and mitotic spindle) and shown to play a pivotal role in cell division of neural progenitors. Sanger sequencing of CKAP2L in a further eight unrelated individuals with clinical features consistent with Filippi syndrome revealed biallelic mutations in four subjects. In contrast to wild-type lymphoblastoid cell lines (LCLs), dividing LCLs established from the individuals homozygous for the c.571dupA mutation did not show CKAP2L at the spindle poles. Furthermore, in cells from the affected individuals, we observed an increase in the number of disorganized spindle microtubules owing to multipolar configurations and defects in chromosome segregation. The observed cellular phenotypes are in keeping with data from in vitro and in vivo knockdown studies performed in human cells and mice, respectively. Our findings show that loss-of-function mutations in CKAP2L are a major cause of Filippi syndrome.