Mitochondrial DNA common deletion is not associated with thyroid, breast and colorectal tumors in Turkish patients

Recently, efforts have been focused on mitochondrial DNA changes and their relation to human cancers. Among them, a 4977 bp deletion of mitochondrial DNA, named "common deletion", has been investigated in several types of tumors, with inconsistent results. In this study, we investigated the presence of the common deletion in tissues from 25 breast, 25 colorectal and 50 thyroid tumors and in the adjacent healthy tissues from Turkish patients. Samples from healthy volunteers were also evaluated for comparison. Two PCR-based methods were used for the detection of the common deletion. First, two pairs of primers were used to amplify wild-type and deleted mtDNA. Then, a highly sensitive nested-PCR was performed, to determine low amounts of deleted genomes. By the first method, wild-type mtDNAs were observed in all samples, but a deletion was observed in only six thyroid samples, by using the nested-PCR method. In conclusion, the mitochondrial common deletion was very rare in our study group and did not appear to be not related with cancer.     

Learning the topological properties of brain tumors

This work presents a graph-based representation (a.k.a., cell-graph) of histopathological images for automated cancer diagnosis by probabilistically assigning a link between a pair of cells (or cell clusters). Since the node set of a cell-graph can include a cluster of cells as well as individual ones, it enables working with low-cost, low-magnification photomicrographs. The contributions of this work are twofold. First, it is shown that without establishing a pairwise spatial relation between the cells (i.e., the edges of a cell-graph), neither the spatial distribution of the cells nor the texture analysis of the images yields accurate results for tissue level diagnosis of brain cancer called malignant glioma. Second, this work defines a set of global metrics by processing the entire cell-graph to capture tissue level information coded into the histopathological images. In this work, the results are obtained on the photomicrographs of 646 archival brain biopsy samples of 60 different patients. It is shown that the global metrics of cell-graphs distinguish cancerous tissues from noncancerous ones with high accuracy (at least 99 percent accuracy for healthy tissues with lower cellular density level, and at least 92 percent accuracy for benign tissues with similar high cellular density level such as nonneoplastic reactive/inflammatory conditions).     

Decreased Serum Selenium Levels are Correlated with Diminished Coronary Flow Reserve Among Hemodialysis Patients

Cardiovascular diseases are the main reason of high mortality among hemodialysis patients. Decreased serum selenium levels may have a role in accelerated atherosclerosis in this patient group. The hypothesis of this study was to show a correlation between decreased serum selenium levels and coronary flow reserve as an indicator of endothelial dysfunction and atherosclerosis in HD patients. Seventy-one chronic hemodialysis patients and age 65 and sex-matched healthy controls were included in the study. Plasma selenium levels were measured by spectrophotometry, and coronary flow reserve was assessed by transthoracic Doppler echocardiography. Serum selenium levels (34.16?±?6.15 ng/ml vs. 52.4?±?5.51 ng/ml, P?<?0.001) and coronary flow reserve values (1.73?±?0.11 vs. 2.32?±?0.28, P?<?0.001) were significantly lower in hemodialysis patients compared with controls, respectively. There was a significant positive correlation between coronary flow reserve and serum levels of selenium (r?=?0.676, P?<?0.001). A linear regression analysis showed that serum levels of selenium were independently and positively correlated with coronary flow reserve (regression coefficient?=?0.650, P?<?0.05). This study was the first to show a positive and independent correlation between decreased selenium levels and diminished coronary flow reserve as an indicator of endothelial dysfunction and atherosclerosis in hemodialysis patients. Our data suggest that decreased serum selenium levels may facilitate the development of endothelial dysfunction and disruption of coronary flow reserve which occur before the development of overt atherosclerosis.     

Recurrent distal 7q11.23 deletion including HIP1 and YWHAG identified in patients with intellectual disabilities, epilepsy, and neurobehavioral problems

We report 26 individuals from ten unrelated families who exhibit variable expression and/or incomplete penetrance of epilepsy, learning difficulties, intellectual disabilities, and/or neurobehavioral abnormalities as a result of a heterozygous microdeletion distally adjacent to the Williams-Beuren syndrome region on chromosome 7q11.23. In six families with a common recurrent ∼1.2 Mb deletion that includes the Huntingtin-interacting protein 1 (HIP1) and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma (YWHAG) genes and that is flanked by large complex low-copy repeats, we identified sites for nonallelic homologous recombination in two patients. There were no cases of this ∼1.2 Mb distal 7q11.23 deletion copy number variant identified in over 20,000 control samples surveyed. Three individuals with smaller, nonrecurrent deletions (∼180–500 kb) that include HIP1 but not YWHAG suggest that deletion of HIP1 is sufficient to cause neurological disease. Mice with targeted mutation in the Hip1 gene (Hip1^−/−) develop a neurological phenotype characterized by failure to thrive, tremor, and gait ataxia. Overall, our data characterize a neurodevelopmental and epilepsy syndrome that is likely caused by recurrent and nonrecurrent deletions, including HIP1. These data do not exclude the possibility that YWHAG loss of function is also sufficient to cause neurological phenotypes. Based on the current knowledge of Hip1 protein function and its proposed role in AMPA and NMDA ionotropic glutamate receptor trafficking, we believe that HIP1 haploinsufficiency in humans will be amenable to rational drug design for improved seizure control and cognitive and behavioral function.     

Mathematical modeling of the malignancy of cancer using graph evolution

We report a novel computational method based on graph evolution process to model the malignancy of brain cancer called glioma. In this work, we analyze the phases that a graph passes through during its evolution and demonstrate strong relation between the malignancy of cancer and the phase of its graph. From the photomicrographs of tissues, which are diagnosed as normal, low-grade cancerous and high-grade cancerous, we construct cell-graphs based on the locations of cells; we probabilistically generate an edge between every pair of cells depending on the Euclidean distance between them. For a cell-graph, we extract connectivity information including the properties of its connected components in order to analyze the phase of the cell-graph. Working with brain tissue samples surgically removed from 12 patients, we demonstrate that cell-graphs generated for different tissue types evolve differently and that they exhibit different phase properties, which distinguish a tissue type from another.     

Serum fetuin--a concentrations are inversely related to cytokine concentrations in patients with chronic renal failure

Background/Aims: A close relationship exists between inflammation and vascular calcification. Although fetuin-A is known to be an inhibitor of calcification, studies correlating levels of this glycoprotein to markers of inflammation are limited. To understand these relationships, we investigated the relationship between serum fetuin-A and proinflammatory cytokine levels in patients with chronic renal failure (CRF). Methods: Thirty-two patients on haemodialysis (HD), 32 conservatively managed chronic kidney disease (CKD) patients and a control group of 25 subjects with normal renal function were enrolled in this study. Serum fetuin-A, IL-1β, IL-6 and TNF-α levels were measured by ELISA. Correlations between serum fetuin-A and IL-1β, IL-6 and TNF-α concentrations were investigated by the Spearman correlation test. Results: In 64 CRF patients (on HD and with CKD), serum fetuin-A was significantly and inversely related to IL-1β (P < 0.001), IL-6 (P = 0.025) and TNF-α levels (P = 0.007), respectively. The serum fetuin-A levels of the control subjects were not significantly correlated to levels of the inflammatory markers IL-1β, IL-6 and TNF-α (P = 0.551, 0.985 and 0.984, respectively). Conclusion: The negative correlation between serum fetuin-A and cytokine concentrations in CRF patients supports the hypothesis of inflammation-dependent down-regulation of fetuin-A expression.     

Anaerobic digestion of whole stillage from dry-grind corn ethanol plant under mesophilic and thermophilic conditions

Anaerobic digestion of whole stillage from a dry-grind corn-based ethanol plant was evaluated by batch and continuous-flow digesters under thermophilic and mesophilic conditions. At whole corn stillage concentrations of 6348 to 50,786 mg total chemical oxygen demand (TCOD)/L, at standard temperature (0 °C) and pressure (1 atm), preliminary biochemical methane potential assays produced 88 ± 8 L (49 ± 5 L CH₄) and 96 ± 19 L (65 ± 14 L CH₄) biogas per L stillage from mesophilic and thermophilic digesters, respectively. Continuous-flow studies for the full-strength stillage (TCOD = 254 g/L) at organic loadings of 4.25, 6.30 and 9.05 g TCOD/L days indicated unstable performance for the thermophilic digester. Among the sludge retention times (SRTs) of 60, 45 and 30 days tested, the mesophilic digestion was successful only at 60 days-SRT which does not represent a practical operation time for a large scale bioethanol plant. Future laboratory studies will focus on different reactor configurations to reduce the SRT needed in the digesters.     

Effects of tamoxifen on myocardial ischemia-reperfusion injury model in ovariectomized rats

The purpose of this study is to examine the antiarrhythmic and antioxidant effects of tamoxifen, one of the selective estrogen modulators, in ovariectomized rats subjected to myocardial ischemia-reperfusion (I/R) injury. A month after ovariectomy, rats were divided into four groups: (I) ovariectomized controls without any treatment, (II) ovariectomized rats treated with vehicle dimethylsulfoxide (DMSO), (III)–(IV) ovariectomized rats treated with tamoxifen 1 or 10 mg/kg,sc daily for 14 days. To produce arrhythmia, the left main coronary artery was occluded for 7 min, followed by 7 min of reperfusion. The blood pressure (BP), heart rate (HR), electrocardiography (ECG) was recorded before and during the ischemia-reperfusion period. The blood levels of malondialdehyde (MDA), creatine kinase (CK), glutathione (GSH), glutathione peroxidase (GSH-Px), glutathione reductase (GR), and catalase (CAT) were measured after the rats were killed. Tamoxifen reduced the incidence of ventricular tachycardia (VT) on ischemia and reperfusion as well as the incidence and duration of reversible ventricular fibrillation (VF) on reperfusion. I/R injury caused a significant fall in GSH, GSH-Px as well as an increase in MDA and CK levels in the control group when compared to tamoxifen treated groups. The changes in levels of CAT and GR were however, not significant. In conclusion, our findings suggest that tamoxifen has cardioprotective effects against I/R injury in rats, likely its antioxidant properties.