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141.
Mayr JA Haack TB Graf E Zimmermann FA Wieland T Haberberger B Superti-Furga A Kirschner J Steinmann B Baumgartner MR Moroni I Lamantea E Zeviani M Rodenburg RJ Smeitink J Strom TM Meitinger T Sperl W Prokisch H 《American journal of human genetics》2012,90(2):314-320
Exome sequencing of an individual with congenital cataracts, hypertrophic cardiomyopathy, skeletal myopathy, and lactic acidosis, all typical symptoms of Sengers syndrome, discovered two nonsense mutations in the gene encoding mitochondrial acylglycerol kinase (AGK). Mutation screening of AGK in further individuals with congenital cataracts and cardiomyopathy identified numerous loss-of-function mutations in an additional eight families, confirming the causal nature of AGK deficiency in Sengers syndrome. The loss of AGK led to a decrease of the adenine nucleotide translocator in the inner mitochondrial membrane in muscle, consistent with a role of AGK in driving the assembly of the translocator as a result of its effects on phospholipid metabolism in mitochondria. 相似文献
142.
Girotto S Sturlese M Bellanda M Tessari I Cappellini R Bisaglia M Bubacco L Mammi S 《The Journal of biological chemistry》2012,287(22):18738-18749
The physiological role of DJ-1, a protein involved in familial Parkinson disease is still controversial. One of the hypotheses proposed indicates a sensor role for oxidative stress, through oxidation of a conserved cysteine residue (Cys-106). The association of DJ-1 mutations with Parkinson disease suggests a loss of function, specific to dopaminergic neurons. Under oxidative conditions, highly reactive dopamine quinones (DAQs) can be produced, which can modify cysteine residues. In cellular models, DJ-1 was found covalently modified by dopamine. We analyzed the structural modifications induced on human DJ-1 by DAQs in vitro. We described the structural perturbations induced by DAQ adduct formation on each of the three cysteine residues of DJ-1 using specific mutants. Cys-53 is the most reactive residue and forms a covalent dimer also in SH-SY5Y DJ-1-transfected cells, but modification of Cys-106 induces the most severe structural perturbations; Cys-46 is not reactive. The relevance of these covalent modifications to the several functions ascribed to DJ-1 is discussed in the context of the cell response to a dopamine-derived oxidative insult. 相似文献
143.
Tóth R Gerding-Reimers C Deeks MJ Menninger S Gallegos RM Tonaco IA Hübel K Hussey PJ Waldmann H Coupland G 《The Plant journal : for cell and molecular biology》2012,71(2):338-352
Chemical modulators are powerful tools to investigate biological processes. To identify circadian clock effectors, we screened a natural product library in the model plant Arabidopsis thaliana. Two compounds, prieurianin (Pri) and prieurianin acetate, were identified as causing a shorter circadian period. Recently, Pri was independently identified as a vesicle trafficking inhibitor and re-named endosidin 1 (ES1). Here we show that Pri primarily affects actin filament flexibility in vivo, later resulting in reduced severing and filament depolymerization. This stabilization of the actin cytoskeleton subsequently causes changes in vesicle trafficking. Pri also affected microfilaments in mammalian cells, indicating that its target is highly conserved; however, it did not alter actin dynamics in vitro, suggesting that its activity requires the presence of actin-associated proteins. Furthermore, well-characterized actin inhibitors shortened the period length of the Arabidopsis clock in a similar way to Pri, supporting the idea that Pri affects rhythms by altering the actin network. We conclude that actin-associated processes influence the circadian system in a light-dependent manner, but their disruption does not abolish rhythmicity. In summary, we propose that the primary effect of Pri is to stabilize the actin cytoskeleton system, thereby affecting endosome trafficking. Pri appears to stabilize actin filaments by a different mechanism from previously described inhibitors, and will be a useful tool to study actin-related cellular processes. 相似文献
144.
Minoli S Kauer I Colson V Party V Renou M Anderson P Gadenne C Marion-Poll F Anton S 《PloS one》2012,7(3):e34141
The effect of repeated exposure to sensory stimuli, with or without reward is well known to induce stimulus-specific modifications of behaviour, described as different forms of learning. In recent studies we showed that a brief single pre-exposure to the female-produced sex pheromone or even a predator sound can increase the behavioural and central nervous responses to this pheromone in males of the noctuid moth Spodoptera littoralis. To investigate if this increase in sensitivity might be restricted to the pheromone system or is a form of general sensitization, we studied here if a brief pre-exposure to stimuli of different modalities can reciprocally change behavioural and physiological responses to olfactory and gustatory stimuli. Olfactory and gustatory pre-exposure and subsequent behavioural tests were carried out to reveal possible intra- and cross-modal effects. Attraction to pheromone, monitored with a locomotion compensator, increased after exposure to olfactory and gustatory stimuli. Behavioural responses to sucrose, investigated using the proboscis extension reflex, increased equally after pre-exposure to olfactory and gustatory cues. Pheromone-specific neurons in the brain and antennal gustatory neurons did, however, not change their sensitivity after sucrose exposure. The observed intra- and reciprocal cross-modal effects of pre-exposure may represent a new form of stimulus-nonspecific general sensitization originating from modifications at higher sensory processing levels. 相似文献
145.
Annaratone L Marchiò C Renzulli T Castellano I Cantarella D Isella C Macrì L Mariscotti G Balmativola D Cantanna E Deambrogio C Pietribiasi F Arisio R Schmitt F Medico E Sapino A 《Translational oncology》2012,5(3):180-189
We investigated whether residual material from diagnostic smears of fine needle aspirations (FNAs) of mammographically detected breast lesions can be successfully used to extract RNA for reliable gene expression analysis. Twenty-eight patients underwent FNA of breast lesions under ultrasonographic guidance. After smearing slides for cytology, residual cells were rinsed with TRIzol to recover RNA. RNA yield ranged from 0.78 to 88.40 μg per sample. FNA leftovers from 23 nonpalpable breast cancers were selected for gene expression profiling using oligonucleotide microarrays. Clusters generated by global expression profiles partitioned samples in well-distinguished subgroups that overlapped with clusters obtained using "biologic scores" (cytohistologic variables) and differed from clusters based on "technical scores" (RNA/complementary RNA/microarray quality). Microarray profiling used to measure the grade of differentiation and estrogen receptor and ERBB2/HER2 status reflected the results obtained by histology and immunohistochemistry. Given that proliferative status in the FNA material is not always assessable, we designed and performed on FNA leftover a multiprobe genomic signature for proliferation genes that strongly correlated with the Ki67 index examined on histologic material. These findings show that cells residual to cytologic smears of FNA are suitable for obtaining high-quality RNA for high-throughput analysis even when taken from small nonpalpable breast lesions. 相似文献
146.
147.
Changes in the airways epithelium caused by environmental insults might play a role in the development of allergic rhinitis. We measured albumin and Clara cell protein (CC16) in the nasal lavage fluid (NALF) from 474 adolescents (263 girls and 211 boys). The NALF CC16/albumin ratio, integrating the permeability and cellular integrity of the nasal epithelium, decreased mostly with time spent in chlorinated pools. In boys, a lower CC16/albumin ratio in NALF was associated with an increased risk of house dust mite sensitization. The results suggest that the CC16/albumin ratio in NALF can be used to detect nasal epithelium alterations linked to allergic sensitization. 相似文献
148.
Mental distractions and physical impairments can increase the risk of accidents by affecting a driver's ability to control the vehicle. In this article, we developed a linear mathematical model that can be used to quantitatively predict drivers' performance over a variety of possible driving conditions. Predictions were not limited only to conditions tested, but also included linear combinations of these tests conditions. Two groups of 12 participants were evaluated using a custom drivers' reaction speed testing device to evaluate the effect of cell phone talking, texting, and a fixed knee brace on the components of drivers' reaction speed. Cognitive reaction time was found to increase by 24% for cell phone talking and 74% for texting. The fixed knee brace increased musculoskeletal reaction time by 24%. These experimental data were used to develop a mathematical model to predict reaction speed for an untested condition, talking on a cell phone with a fixed knee brace. The model was verified by comparing the predicted reaction speed to measured experimental values from an independent test. The model predicted full braking time within 3% of the measured value. Although only a few influential conditions were evaluated, we present a general approach that can be expanded to include other types of distractions, impairments, and environmental conditions. 相似文献
149.
Gianluca Isoardo Isabella Morra Giulia Chiarle Valentina Audrito Silvia Deaglio Antonio Melcarne Carola Junemann Michele Naddeo Maurizio Cogoni Maria Consuelo Valentini Andrea Limberti Federico Faccani Fabio Malavasi Giuliano Faccani 《Molecular medicine (Cambridge, Mass.)》2012,18(1):1147-1151
Aquaporin-4 (AQP-4), the most important water channel in the brain, is expressed by astrocyte end feet abutting microvessels. Altered expression levels of AQP-4 and redistribution of the protein throughout the membranes of cells found in glioblastoma multiforme (GBM) lead to development of the edema often found surrounding the tumor mass. Dysregulation of AQP-4 also occurs in hippocampal sclerosis and cortical dysplasia in patients with refractory partial epilepsy. This work reports on analysis of the relationship between AQP-4 expression and the incidence of epileptic seizures in patients with GBM. Immunohistochemical and polymerase chain reaction techniques were used to evaluate AQP-4 in biopsy specimens from 19 patients with GBM, 10 of who had a history of seizures before surgery. AQP-4 mRNA levels were identical in the two groups of patients, but AQP-4 expression was more frequently detected on the GBM membranes from specimens of patients with seizures than from individuals without (10 versus 2, P < 0.001). We conclude that reduced expression of cell surface AQP-4 is characteristic of GBM patients without seizures, likely attributable to a posttranslational mechanism. 相似文献
150.
Chiara Barbiero Isabella Lonciari Marcella Montico Lorenzo Monasta Roberta Penge Claudio Vio Patrizio Emanuele Tressoldi Valentina Ferluga Anna Bigoni Alessia Tullio Marco Carrozzi Luca Ronfani CENDi working group and for the Epidemiology of Dyslexia of Friuli Venezia Giulia working group 《PloS one》2012,7(10)