Div-BLAST: Diversification of Sequence Search Results

Sequence similarity tools, such as BLAST, seek sequences most similar to a query from a database of sequences. They return results significantly similar to the query sequence and that are typically highly similar to each other. Most sequence analysis tasks in bioinformatics require an exploratory approach, where the initial results guide the user to new searches. However, diversity has not yet been considered an integral component of sequence search tools for this discipline. Some redundancy can be avoided by introducing non-redundancy during database construction, but it is not feasible to dynamically set a level of non-redundancy tailored to a query sequence. We introduce the problem of diverse search and browsing in sequence databases that produce non-redundant results optimized for any given query. We define diversity measures for sequences and propose methods to obtain diverse results extracted from current sequence similarity search tools. We also propose a new measure to evaluate the diversity of a set of sequences that is returned as a result of a sequence similarity query. We evaluate the effectiveness of the proposed methods in post-processing BLAST and PSI-BLAST results. We also assess the functional diversity of the returned results based on available Gene Ontology annotations. Additionally, we include a comparison with a current redundancy elimination tool, CD-HIT. Our experiments show that the proposed methods are able to achieve more diverse yet significant result sets compared to static non-redundancy approaches. In both sequence-based and functional diversity evaluation, the proposed diversification methods significantly outperform original BLAST results and other baselines. A web based tool implementing the proposed methods, Div-BLAST, can be accessed at cedar.cs.bilkent.edu.tr/Div-BLAST     

The expression of HER-2/neu (c-erbB2), survivin and cycline D1 in serous ovarian neoplasms: their correlation with clinicopathological variables

Ovarian cancer is the most common cause of death among all gynecologic malignancies and a result of complex interaction of multiple oncogenes and tumor suppressor genes. The aim of this study was to evaluate expression of HER-2/neu (c-erbB2), survivin and cycline D1 biomarkers in serous ovarian neoplasms and their correlations with clinicopathological variables in serous ovarian cancers. We analyzed pathological specimens of 62 patients with benign (n = 25), borderline (n = 14) and malignant (n = 23) serous ovarian neoplasms. Immunohistochemical analysis was performed on formalin-fixed paraffin-embedded specimens. Significantly more immunoreactivity with HER-2/neu was detected in malignant tumors (100 %) compared to borderline (78.6 %) and benign tumors (48 %) (P < 0.01). Survivin expression was significantly higher in malignant tumors (91.3 %) than those found in borderline (71.4 %) and benign tumors (24 %) (P < 0.001). Similarly, higher cyclin D1 expression was observed in malignant tumors (95.6 %) compared to borderline (85.7 %) and benign tumors (48 %) (P < 0.001). Expression of all biomarkers analyzed significantly and gradually increased from benign to borderline and borderline to malignant serous tumors. In terms of clinicopathological variables, only tumor grade was associated with the expression of all biomarkers others exhibited different correlations in serous ovarian cancers. The expressions of HER-2/neu (c-erbB2), survivin and cycline D1 are positively correlated with the malignant potential of serous ovarian neoplasms.     

Responsivenes of total content changes of magnesium and zinc status in patients infected with Giardia intestinalis

The aim of the study was to investigate the changes of total content of the essential elements of zinc and magnesium levels in patients infected with Giardia intestinalis. Zinc and magnesium concentrations were measured in 64 patients who were positive for the intestinal parasite G. intestinalis. Scores were obtained for the positives and their 60 age- and sex-matched G. intestinalis-negative healthy controls. The mean concentration of magnesium in blood was significantly lower in G. intestinalis-positive patients than in their controls both in females (p<0.05) and males (p<0.05). The average zinc concentration in G. intestinalis-positive female patients was 0.76±0.3 mg/L and it was 0.60±0.2 mg/L in controls (p>0.05). The mean values of the zinc in blood were 0.73±0.2 mg/L in G. intestinalis-positive male patients and 0.82±0.1 mg/L in controls (p>0.05). No correlation could be demonstrated between age and mean values of zinc and magnesium in both G. intestinalis-positive females/males and controls (p>0.05). No significant correlation could be found between blood zinc and magnesium levels in G. intestinalis-positive female/male patients and controls (p>0.05). Magnesium levels were found to be clearly decreased, whereas no change was observed in zinc level in the patients infected with G. intestinalis compared to controls.     

Serum zinc and magnesium levels in patients with blastocystosis

The aim of the study was to investigate the total content of the essential elements of zinc and magnesium levels in patients infected with Blastocystis hominis. Zinc and magnesium concentrations were measured in 52 patients who were positive for the intestinal parasite Blastocystis hominis. Scores were obtained for the positives and their age- and sex-matched 60 Blastocystis hominis-negative healthy controls. For comparison of two groups of continuous variables, the independent samples t-test was used. The mean concentration of magnesium in blood was significantly lower in Blastocystis hominis-positive patients than in their controls both in females (p<0.05) and males (p<0.05). The average zinc concentration in Blastocystis hominis-positive female patients was 0.61±0.2 mg/L and 0.60±0.2 mg/L in controls (p>0.05). The mean values of the zinc in blood were 0.62±0.2 mg/L in Blastocystis hominis-positive male patients and 0.82±0.1 in controls (p>0.05). No correlation could be demonstrated between age and mean values of zinc and magnesium in Blastocystis-positive females/males and controls (p>0.05). No significant correlation could be found between blood zinc and magnesium levels in Blastocystis-positive female/male patients and controls (p>0.05). Magnesium levels were found to be clearly decreased, whereas no change was observed in zinc levels in the patients with Blastocystis compared to controls.     

Cell type-specific activation of mitogen-activated protein kinases by CpG-DNA controls interleukin-12 release from antigen-presenting cells

Activation of antigen-presenting cells (APCs) by invariant constituents of pathogens such as lipopolysaccharide (LPS) or bacterial DNA (CpG-DNA) initiates immune responses. We have analyzed the mitogen-activated protein kinase (MAPK) pathways triggered by CpG-DNA and their significance for cytokine production in two subsets of APCs, i.e. macrophages and dendritic cells (DCs). We found that CpG-DNA induced extracellular signal-regulated kinase (ERK) activity in macrophages in a classic MEK-dependent way. This pathway up-regulated tumor necrosis factor production but down-regulated interleukin (IL)-12 production. However, in DCs, which produce large amounts of IL-12, CpG-DNA and LPS failed to induce ERK activity. Consistent with a specific negative regulatory role for ERK in macrophages, chemical activation of this pathway in DCs suppressed CpG-DNA-induced IL-12 production. Overall, these results imply that differential activation of MAP kinase pathways is a basic mechanism by which distinct subsets of innate immune cells regulate their effector functions.     

The effect of melatonin on lipid peroxidation and nitrite/nitrate levels, and on superoxide dismutase and catalase activities in kainic acid-induced injury

Kainic acid (KA) initiates neuronal injury and death by inducing oxidative stress and nitric oxide release from various regions of the brain. It was recently shown that melatonin has free radical-scavenging action and may protect against kainate-induced toxicity. In order to assess the possible supportive effect of melatonin treatment in KA-induced injury in the rat brain cortex, we determined malondialdehyde (MDA) levels as an index of lipid peroxidation, and assessed the activities of catalase (CAT) and superoxide dismutase (SOD) and the levels of nitrite/nitrate 35 male rats were divided into five groups, each receiving a different intraperitoneal treatment: saline solution (0.2 ml), kainic acid (15 mg/kg), melatonin (20 mg/kg), KA then melatonin (each as above, 15 min apart), or melatonin then KA (each as above, 30 min apart). Administration of KA caused an about five-fold increase in the catalase activity and an increase in the SOD activity in the cortex relative to the activities for the controls. Treatment with melatonin 15 min after KA injection kept malondialdehyde levels and catalase and superoxide dismutase activities at the normal levels, and led to an increase in the levels of nitrite/nitrate. Our data suggests that melatonin treatment following KA administration has a protective effect on antioxidant enzyme activities and thus supports the role of melatonin and oxidative stress in the regulation of antioxidative enzyme activity.