Expression of p97/VCP and ubiquitin during postnatal development of the degenerating rat retina

In this study, we aimed to investigate the distribution pattern of ubiquitin and p97/VCP in the rat retina during postnatal development. Eyeballs from 1-, 4-, 10-, 36- and 72-week-old rats were examined by immunohistochemistry, and protein colocalization was determined by immunofluorescence microscopy. In the 1-week-old rat retina, p97/VCP was strongly expressed in the neuroblast layer, however no ubiquitin immunoreactivity was observed. p97/VCP immunoreactivity was present in the ganglion cell layer (GCL), inner nuclear layer (INL), outer nuclear layer (ONL), inner segment (IS) of the photoreceptor layer, and retinal pigment epithelium in the 4- and 10-week-old rat retinas. p97/VCP immunoreactivity increased significantly in the 10-week-old rat retinas. Ubiquitin was barely seen in the 4-week-old rat retinas, and ubiquitin expression was weak in the GCL and the IPL of the 10-week-old rat retinas. In the 36- and 72-week-old rats, the presence of ubiquitin was remarkable in the IS, INL, IPL and GCL, however, p97/VCP immunoreactivity was significantly decreased. Colocalization of ubiquitin and p97/VCP was also observed in the INL, IS, GCL and ONL of 36- and 72-week-old rat retinas. Our results indicate that p97/VCP immunoreactivity in the retina significantly decreases after rats reach 10 weeks of age, whereas ubiquitin immunoreactivity increases with aging. These results suggest that an altered expression pattern of p97/VCP and ubiquitin in the developing rat retina may associate with age-related retinal degeneration.     

To die or not to die: that is the autophagic question

Macroautophagy (commonly referred to as autophagy) is the process by which intact organelles and/or large portions of the cytoplasm are engulfed within double-membraned autophagic vacuoles for degradation. Whereas basal levels of autophagy ensure the physiological turnover of old and damaged organelles, the massive accumulation of autophagic vacuoles may represent either an alternative pathway of cell death or an ultimate attempt for cells to survive by adapting to stress. The activation of the autophagic pathway beyond a certain threshold may promote cell death directly, by causing the collapse of cellular functions as a result of cellular atrophy (autophagic, or type II, cell death). Alternatively, autophagy can lead to the execution of apoptotic (type I) or necrotic (type III) cell death programs, presumably via common regulators such as proteins from the Bcl-2 family. On the other hand, limited self-eating can provide cells with metabolic substrates to meet their energetic demands under stressful conditions, such as nutrient deprivation, or favor the selective elimination of damaged (and potentially dangerous) organelles. In these instances, autophagy operates as a pro-survival mechanism. The coordinate regulation of these opposite effects of autophagy relies upon a complex network of signal transducers, most of which also participate in non-autophagic signaling cascades. Thus, autophagy occupies a crucial position within the cell's metabolism, and its modulation may represent an alternative therapeutic strategy in several pathological settings including cancer and neurodegeneration. Here, we present a general outline of autophagy followed by a detailed analysis of organelle-specific autophagic pathways and of their intimate connections with cell death.     

Effects of cadmium on antioxidant enzyme and photosynthetic activities in leaves of two maize cultivars

Effects of cadmium (Cd(2+)) on photosynthetic and antioxidant activities of maize (Zea mays L.) cultivars (3223 and 32D99) were investigated. Fourteen-day-old cultivar seedlings were exposed to different Cd concentrations [0, 0.3, 0.6 and 0.9mM Cd(NO(3))(2).4H(2)O] for 8 days. The results of chlorophyll fluorescence indicated that different levels of Cd affected photochemical efficiency in 3223 much more than that in 32D99. In parallel, the level of Cd at 0.9mM caused oxidative damage but did not indicate cessation of PSII activity of the cultivars; plant death was not observed at highly toxic Cd levels. Additionally, the increase in Cd concentration caused loss of chlorophylls and carotenoid and membrane damage in both cultivars, but greater membrane damage was observed in 3223 than in 32D99. Depending on Cd accumulation, a significant reduction in dry biomass was observed in both cultivars at all Cd concentrations. The accumulation of Cd was higher in roots than in leaves for both cultivars. Nevertheless, cultivar 3223 transferred more Cd from roots to leaves than did 32D99. On the other hand, our results suggest that there were similar responses in SOD, APX and GR activities with increasing Cd concentrations for both cultivars. However, POD activity significantly increased at highly toxic Cd levels in 32D99. This result may be regarded as an indication of better tolerance of the Z. mays L. cultivar 32D99 to Cd contamination.     

Effect of acute maximal exercise on lymphocyte subgroups in type 1 diabetes

The essential therapy of diabetes mellitus includes medical nutrition therapy (MNT), exercise and medical therapy. Exercise, besides its metabolic effects, has positive influence on the immune system, but some forms of exercise may cause trauma for muscle and skeletal systems, they may also support negative effects on the immune system. Nineteen type 1 diabetic patients (mean age 22.1 +/- 2.8 yrs), followed by Diabetes Outpatient Clinic and twenty age matched male control subjects were included into the study, to demonstrate the effects of maximal, acute exercise on the immune system. The exercise test was performed according to Bruce protocol on treadmill. In diabetic subjects, increased CD19 and CD23 expressions were observed before exercise. In both groups (diabetic/control) CD3, CD4 expressions and CD4/CD8 ratio were decreased following the exercise, however expression of natural killer (NK) cells increased. Compared to type 1 diabetic patients healthy subjects had longer acute exercise that caused the increased level of CD8 expression, however type 1 diabetic patients did not show any difference. These results indicate that submaximal aerobic exercise might be recommended for type 1 diabetics without any complications because of its positive reflection on metabolic control and no negative effects on the immune system.     

Antioxidant status in cerebrovascular accident

Ischemia is associated with the pathological changes caused by the accumulation of reactive oxygen metabolites (ROM) in cerebrovascular accident (CVA). The aim of this study was to determine red cell copper/zinc-superoxide dismutase (Cu/Zn-SOD) and catalase activities and copper and zinc concentrations both in plasma and in red cells in CVA. Cu/Zn-SOD and catalase activities of 16 patients, with an average age of 64 yr, were measured spectrophotometrically; copper and zinc concentrations were determined by atomic absorption spectrophotometer. The results showed that Cu/Zn-SOD activity was increased markedly in patients compared to the young controls and reached a peak on the d 5 of the disease, whereas the catalase activity of the patients on d 3 and d 5 were in the normal range, but higher on d 10. The enzyme activities of the elderly group were generally increased compared to the young controls. Copper and zinc concentrations showed corresponding alterations. These findings suggested that the effects of oxidative stress in CVA might be reflected in red cell and plasma parameters. Presented at the III International Congress of Pathophysiology, Lahti, Finland, 28 June–3 July, 1998.     

MicroRNA Expression Patterns of CD8+ T Cells in Acute and Chronic Brucellosis

Although our knowledge about Brucella virulence factors and the host response increase rapidly, the mechanisms of immune evasion by the pathogen and causes of chronic disease are still unknown. Here, we aimed to investigate the immunological factors which belong to CD8+ T cells and their roles in the transition of brucellosis from acute to chronic infection. Using miRNA microarray, more than 2000 miRNAs were screened in CD8+ T cells of patients with acute or chronic brucellosis and healthy controls that were sorted from peripheral blood with flow cytometry and validated through qRT-PCR. Findings were evaluated using GeneSpring GX (Agilent) 13.0 software and KEGG pathway analysis. Expression of two miRNAs were determined to display a significant fold change in chronic group when compared with acute or control groups. Both miRNAs (miR-126-5p and miR-4753-3p) were decreased (p <0.05 or fold change > 2). These miRNAs have the potential to be the regulators of CD8+ T cell-related marker genes for chronic brucellosis infections. The differentially expressed miRNAs and their predicted target genes are involved in MAPK signaling pathway, cytokine-cytokine receptor interactions, endocytosis, regulation of actin cytoskeleton, and focal adhesion indicating their potential roles in chronic brucellosis and its progression. It is the first study of miRNA expression analysis of human CD8+ T cells to clarify the mechanism of inveteracy in brucellosis.     

Deciphering the “Fuzzy” Interaction of FG Nucleoporins and Transport Factors Using Small-Angle Neutron Scattering

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The effects of sex and season on the metal levels and proximate composition of red mullet (Mullus barbatus Linnaeus 1758) caught from the Middle Black Sea

The effects of seasonal and sexual differences on the levels of macro, trace element, and toxic metal levels in Mullus barbatus were investigated using the ICP-MS. The quantity relationships of macro elements were found as K>P>Na>Ca>Mg for male, P>K>Na>Ca>Mg in female; the quantity relationships of trace elements were determined as Fe>Zn>Mn>Mo>Se>Cu>Ni>Co in male, Fe>Zn>Mn>Se>Cu>Ni>Mo>Co in female; and the quantity relationship of toxic elements were found as As>Pb>Cd in both male and female. Macro, trace, and toxic metal levels showed no significant differences (p > .05) in terms of sexuality, but demonstrated seasonal differences (p > .05). Overall, the highest level of macro elements was determined in the autumn, while the high level of trace elements was measured in the winter. The As, Cd, and Pb levels in the muscle tissue of red mullet fish were higher than acceptable limits. However, when the Estimated Daily Intake (EDI) and Estimated Weekly Intake (EWI) of both toxic metals are considered, they appear to be below acceptable limits. As a result, it was determined that the red mullet had been contaminated with toxic metals (Cd and Pb) but their levels according to EDI and EWI were below the limit.     

Electrophysiological and neuropsychological outcomes of severe obstructive sleep apnea: effects of hypoxemia on cognitive performance

Obstructive sleep apnea syndrome (OSAS) is a sleep disorder characterized with upper airway obstructions. Some studies showed cognitive and electrophysiological changes in patients with OSAS; however, contradictory results were also reported. The purpose of the present study was twofold: (1) to investigate cognitive changes in severe OSAS patients by using neuropsychological tests and electrophysiological methods together, (2) to investigate influence of hypoxemia levels on cognition. Fifty-four severe OSAS patients and 34 age-, gender- and education matched healthy subjects were participated. OSAS patients were further divided into two subgroups according to minimum oxygen saturation levels. All participants underwent a detailed neuropsychological test battery. A classical visual oddball task was used to elicit ERP P300 and mean P300 amplitudes were measured from F_z, C_z and P_z electrode sites. OSAS patients showed reduced mean P300 amplitudes up to 43–51% on all electrode sites compared to healthy controls. Subgroup analysis revealed significant differences in neuropsychological test scores between healthy controls and high hypoxemia OSAS group, as well as between low and high hypoxemia groups. Moreover, both low and high hypoxemia OSAS groups had lower P300 amplitudes compared with healthy controls. P300 amplitudes showed a gradual decline in parallel with increasing hypoxemia severity; however, the difference between high and low hypoxemia OSAS groups did not reach significance. Moderate correlations were found between sleep parameters, neuropsychological test scores and P300 amplitudes. These results suggest that electrophysiological measures could be better indicators of cognitive changes than neuropsychological tests in OSAS, particularly in mildly affected patients.