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Spinocerebellar ataxia type-3 (SCA3) is among the most common dominantly inherited ataxias, and is one of nine devastating human neurodegenerative diseases caused by the expansion of a CAG repeat encoding glutamine within the gene. The polyglutamine domain confers toxicity on the protein Ataxin-3 leading to neuronal dysfunction and loss. Although modifiers of polyglutamine toxicity have been identified, little is known concerning how the modifiers function mechanistically to affect toxicity. To reveal insight into spinocerebellar ataxia type-3, we performed a genetic screen in Drosophila with pathogenic Ataxin-3-induced neurodegeneration and identified 25 modifiers defining 18 genes. Despite a variety of predicted molecular activities, biological analysis indicated that the modifiers affected protein misfolding. Detailed mechanistic studies revealed that some modifiers affected protein accumulation in a manner dependent on the proteasome, whereas others affected autophagy. Select modifiers of Ataxin-3 also affected tau, revealing common pathways between degeneration due to distinct human neurotoxic proteins. These findings provide new insight into molecular pathways of polyQ toxicity, defining novel targets for promoting neuronal survival in human neurodegenerative disease. 相似文献
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Loss of Bard1, the heterodimeric partner of the Brca1 tumor suppressor,results in early embryonic lethality and chromosomal instability
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The BRCA1 tumor suppressor has been implicated in many cellular pathways, but the mechanisms by which it suppresses tumor formation are not fully understood. In vivo BRCA1 forms a heterodimeric complex with the related BARD1 protein, and its enzymatic activity as a ubiquitin ligase is largely dependent upon its interaction with BARD1. To explore the genetic relationship between BRCA1 and BARD1, we have examined the phenotype of Bard1-null mice. These mice become developmentally retarded and die between embryonic day 7.5 (E7.5) and E8.5. Embryonic lethality results from a severe impairment of cell proliferation that is not accompanied by increased apoptosis. In the absence of p53, the developmental defects associated with Bard1 deficiency are partly ameliorated, and the lethality of Bard1; p53-nullizygous mice is delayed until E9.5. This result, together with the increased chromosomal aneuploidy of Bard1 mutant cells, indicates a role for Bard1 in maintaining genomic stability. The striking similarities between the phenotypes of Bard1-null, Brca1-null, and double Bard1; Brca1-null mice provide strong genetic evidence that the developmental functions of Brca1 and Bard1 are mediated by the Brca1/Bard1 heterodimer. 相似文献
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Ozan E Kükner A Canpolat L Oner H Gezen MR Yilmaz S Ozan S 《Acta physiologica Hungarica》2001,88(3-4):301-315
In this study, rats were made to inhale cigarette smoke in a specifically prepared container for different periods. The lung tissue samples of the subjects were examined by light microscopy, transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Malonaldehyde, one of the free oxygen radicals was determined in lungs and plasma. The catalase activity level of erythrocyte and arginase levels were determined. Three groups were formed. The rats in the Ist and IInd groups were made to inhale cigarette smoke for 30 and 60 minutes a day for a total period of 3 months. Control group, the rats in the IIIrd group (controls) were made to inhale clean air during the same periods. An increase in the number of macrophages was observed in the pulmonary tissue of the exposed groups. Especially in the group that inhaled the smoke for long periods, the number of macrophages and the inclusion bodies contained in them increased. These differences could easily be observed in TEM studies. In the light microscopy and SEM observations, it arouse attention that the alveolar macrophages occurred as sets and their activation increased. Depending on the length of the exposure to cigarette smoke, an increase in the number of macrophages was observed. Statistically significant increases were determined in the malonaldehyde levels of pulmonary tissue and plasma when compared to the control group. Besides significant increases were found in the catalase activity levels of erythrocytes in the experimental groups. 相似文献
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Mergen H Acar C Birben E Oner R Oner C 《Journal of biochemical and biophysical methods》2000,44(1-2):73-76
The study presented here describes a Southern blot hybridization technique which is performed in a shorter time and safer than the classical one. In this study DNA was isolated from a small amount of blood sample and the probe for hybridization was prepared with (35)S by polymerase chain reaction. 相似文献
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Elif Şahin Horasan Gülden Ersöz Musa Göksu Feza Otag Ahmet Oner Kurt Sevim Karaçorlu Ali Kaya 《Mycopathologia》2010,170(4):263-268
Objectives
We aimed to asses possible clinically significant differences between C. parapsilosis and other candida species candidemia receiving care in the intensive care unit (ICU) setting.Methods
The study included 118 adult patients diagnosed as candidemia after admission to the ICU of a university hospital between January 2004 and December 2009. Data about demographic characteristics, underlying diseases, and risk factors for ICU-related candidemia were collected.Results
During the study period, 118 patients with candidemia were identified among 2,853 patients admitted into the ICU. Candidemia was seen in 41.4 cases per 1,000 ICU admissions. The overall incidence of candidemia in ICU patients during the study period was 2.09 per 1,000 hospital admissions. Of the isolates, 18.6% were C. albicans and 81.4% were C. non-albicans. The species most frequently isolated was C. parapsilosis (66.1%, 78/118). The distribution of other Candida spp. was as follows: 15 had C. tropicalis (12.7%) and 3 had C. glabrata (2.5%). By Statistical analysis, when patients with candidemia who had C. parapsilosis were compared with other Candida spp., the following factors were found to be significantly associated with C. parapsilosis fungemia; intravascular catheters (p = 0.008), malignity (p = 0.049) and age (p = 0.039). Relationship was found between C. tropicalis and hematologic malignancies (p = 0.001).Conclusions
When infections with a high mortality such as candidemia is suspected in critically ill patients, it is important to know local risk factors and epidemiological distributions of causative agents in selection of empirical and effective antifungal treatment. 相似文献8.
Ultrastructural changes in the kidneys of rats after acute cadmium exposure and the effects of exogenous metallothionein (MT)
were studied by transmission electron microscopy. Thirty-six adult Wistar rats were divided into three groups. Cadmium chloride
(CdCl2) (3.5 mg/kg/day) was injected subcutaneously in the first group. In the second group, 30 μmol/kg MT was administered in addition
to CdCl2. Control rats received 0.5 ml subcutaneous saline solution. Four rats from each group were killed on days 1, 3, 5, and 7
after administration of the compounds. Kidney tissues were taken and fixed in 2.5% glutaraldehyde solution for electron microscopic
observations. Tissue damage in kidney increased as time passed since the administration of CdCl2 in the first group. Degeneration in the proximal and distal tubules was observed. Increased apoptosis was seen in the proximal
tubules epithelium, especially on day 7. Peritubular capillaries became dilated, there was degeneration of the endothelial
cells, and the amount of intertubular collagen fibers was increased. On day 1, irregular microvilli in the proximal tubules,
deepening of the basal striations, and myelin figures; on day 3, multiple vesicular mitochondria and regions of edema around
tubules; on days 5 and 7, increased apoptotic cell in the proximal tubules and widened rough endoplasmic reticulum of the
endothelial cells of glomerular capillaries were observed. We observed that the structural alterations that increased depending
on the day of Cd administration decreased after exogenous MT administration, the dilation of the peritubular capillaries persisted,
and there were degenerated proximal tubules. It was established that cadmium chloride was toxic for kidney cortex and caused
structural damage. Exogenous MT partly prevents CdCl2-induced damage. 相似文献
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Finore Ilaria Kasavi Ceyda Poli Annarita Romano Ida Oner Ebru Toksoy Kirdar Betul Dipasquale Laura Nicolaus Barbara Lama Licia 《World journal of microbiology & biotechnology》2011,27(10):2425-2433
This study reports the purification and biochemical characterization of a raw starch-digesting α-amylase from Geobacillus thermoleovorans subsp. stromboliensis subsp. nov. (strain PizzoT). The molecular weight was estimated to be 58 kDa by SDS–PAGE. The enzyme was highly active over a wide range of pH from
4.0–10.0. The optimum temperature of the enzyme was 70°C. It showed extreme thermostability in the presence of Ca2+, retaining 50% of its initial activity after 90 h at 70°C. The enzyme efficiently hydrolyzed 20% (w/v) of raw starches, concentration
normally used in starch industries. The α-amylase showed an high stability in presence of many organic solvents. In particular
the residual activity was of 73% in presence of 15% (v/v) ethyl alcohol, which corresponds to ethanol yield in yeast fermentation
process. By analyzing its complete amyA gene sequence (1,542 bp), the enzyme was proposed to be a new α-amylase. 相似文献
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Sam S Kucukasik F Yenigun O Nicolaus B Oner ET Yukselen MA 《Bioresource technology》2011,102(2):1788-1794
This study reports the first systematic investigation of the flocculation dynamics of exopolysaccharides (EPSs) produced by a halophilic bacterial strain grown on pretreated molasses as fermentation substrate. The potential use of these EPSs as an easily biodegradable, natural alternative for synthetic polyelectrolytes which are widely used and contain toxic and carcinogenic monomers was investigated. Flocculating activities of the EPS samples in synthetic water, synthetic sea water and natural sea water media which were used as model raw waters were monitored via the Photometric Dispersion Analyser (PDA 2000) instrument and removals were determined by measuring residual turbidities. One of the six EPS specimens, which formed the largest flocs thus performed highest turbidity removal, exhibited flocculation performance and particle removal efficiency comparable with commercial cationic, nonionic and anionic synthetic polyelectrolytes. 相似文献