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71.
Pena V Hothorn M Eberth A Kaschau N Parret A Gremer L Bonneau F Ahmadian MR Scheffzek K 《EMBO reports》2008,9(4):350-355
The brain-specific synaptic guanosine triphosphatase (GTPase)-activating protein (SynGAP) is important in synaptic plasticity. It shows dual specificity for the small guanine nucleotide-binding proteins Rap and Ras. Here, we show that RapGAP activity of SynGAP requires its C2 domain. In contrast to the isolated GAP domain, which does not show any detectable RapGAP activity, a fragment comprising the C2 and GAP domains (C2-GAP) stimulates the intrinsic GTPase reaction of Rap by approximately 1 x 10(4). The C2-GAP crystal structure, complemented by modelling and biochemical analyses, favours a concerted movement of the C2 domain towards the switch II region of Rap to assist in GTPase stimulation. Our data support a catalytic mechanism similar to that of canonical RasGAPs and distinct from the canonical RapGAPs. SynGAP presents the first example, to our knowledge, of a GAP that uses a second domain for catalytic activity, thus pointing to a new function of C2 domains. 相似文献
72.
Suárez-Varela MM García-Marcos Alvarez L Kogan MD González AL Gimeno AM Aguinaga Ontoso I Díaz CG Pena AA Aurrecoechea BD Monge RM Quiros AB Garrido JB Canflanca IM Varela AL 《International journal of biometeorology》2008,52(8):833-840
Atopic eczema (AE) is a chronic skin disease. Recent reports indicate that the worldwide prevalence of AE is increasing and
that various environmental factors are implicated in its aetiology. Climatic conditions have been related with AE prevalence,
and Spain has varying climatic conditions. The aim of this study is to document the possible climatic influence on the prevalence
of AE in schoolchildren aged 6–7 years in three different climatic regions in Spain. We conducted a cross-sectional population-based
survey of 28,394 schoolchildren aged 6–7 years from 10 Spanish centres in three different climatic regions. The mean participation
rate was 76.5%. AE prevalence was assessed using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire
and the Spanish Academy of Dermatology criteria used in Spain to diagnose AE. The data, including annual temperature, precipitation,
relative humidity and the annual number of sunny hours per climatic region, were obtained from the Spanish National Institute
of Meteorology. Different AE prevalences were found in all three climatic regions studied: Atlantic, 32.9; Mediterranean 28.3;
and Continental 31.2 per 100 children studied (p < 0.005). AE was positively associated with precipitation and humidity, and was negatively associated with temperature and
the number of sunny hours. The results show that AE is significantly dependent on meteorological conditions. 相似文献
73.
Sylvanne M Daniels Carlos E Melendez-Peña Robert J Scarborough Aïcha Daher Helen S Christensen Mohamed El Far Damian FJ Purcell Sébastien Lainé Anne Gatignol 《BMC molecular biology》2009,10(1):38-13
Background
Dicer, Ago2 and TRBP are the minimum components of the human RNA-induced silencing complex (RISC). While Dicer and Ago2 are RNases, TRBP is the double-stranded RNA binding protein (dsRBP) that loads small interfering RNA into the RISC. TRBP binds directly to Dicer through its C-terminal domain. 相似文献74.
The cellular prion protein (PrPC) is a membrane-bound glycoprotein especially abundant in the central nervous system (CNS). The scrapie prion protein (PrPSc, also termed prions) is responsible of transmissible spongiform encephalopathies (TSE), a group of neurodegenerative diseases which affect humans and other mammal species, although the presence of PrPC is needed for the establishment and further evolution of prions.The present work compares the expression and localization of PrPC between healthy human brains and those suffering from Alzheimer disease (AD).In both situations we have observed a rostrocaudal decrease in the amount of PrPC within the CNS, both by immunoblotting and immunohistochemistry techniques. PrPC is higher expressed in our control brains than in AD cases. There was a neuronal loss and astogliosis in our AD cases. There was a tendency of a lesser expression of PrPC in AD cases than in healthy ones. And in AD cases, the intensity of the expression of the unglycosylated band is higher than the di- and monoglycosylated bands.With regards to amyloid plaques, those present in AD cases were positively labeled for PrPC, a result which is further supported by the presence of PrPC in the amyloid plaques of a transgenic line of mice mimicking AD.The work was done according to Helsinki Declaration of 1975, and approved by the Ethics Committee of the Faculty of Medicine of the University of Navarre.Key words: cellular prion protein, Alzheimer disease, transgenic mice 相似文献
75.
María V. Niklison-Chirou Fernando Dupuy Liliana B. Pena Susana M. Gallego Maria Laura Barreiro-Arcos Cesar Avila Clarisa Torres-Bugeau Beatriz E. Arcuri Augusto Bellomio Carlos Minahk Roberto D. Morero 《The international journal of biochemistry & cell biology》2010,42(2):273-281
We previously showed that the antimicrobial peptide microcin J25 induced the over-production of reactive oxygen species with the concomitant release of cytochrome c from rat heart mitochondria via the opening of the mitochondrial permeability transition pore. Here, we were able to demonstrate that indeed, as a consequence of the oxidative burst, MccJ25 induces carbonylation of mitochondrial proteins, which may explain the irreversible inhibition of complex III and the partial inhibition of superoxide dismutase and catalase. Moreover, the peptide raised the levels of oxidized membrane lipids, which triggers the release of cytochrome c. From in silico analysis, we hypothesize that microcin would elicit these effects through interaction with heme c1 at mitochondrial complex III. On the other hand, under an excess of l-arginine, MccJ25 caused nitric oxide overproduction with no oxidative damage and a marked inhibition in oxygen consumption. Therefore, a beneficial anti-oxidative activity could be favored by the addition of l-arginine. Conversely, MccJ25 pro-oxidative–apoptotic effect can be unleashed in either an arginine-free medium or by suppressing the nitric oxide synthase activity. 相似文献
76.
77.
Fernandez-Rodriguez A Munoz M Fernandez A Pena RN Tomas A Noguera JL Ovilo C Fernandez AI 《Biology of reproduction》2011,84(2):299-307
Previous results from a genome scan in an F(2) Iberian × Meishan pig intercross showed several chromosome regions associated with litter size traits in this species. In order to identify candidate genes underlying these quantitative trait loci (QTL), we performed an ovary gene expression analysis during the sow's pregnancy. F(2) sows were ranked by their estimated breeding values for prolificacy: six sows with the highest estimated breeding value (EBV) (i.e., high prolificacy) and six sows with the lowest EBV (low prolificacy) were selected. Samples were hybridized using an Affymetrix GeneChip porcine genome array. Statistical analysis with a mixed model approach identified 221 differentially expressed probes, representing 189 genes. These genes were functionally annotated in order to identify genetic pathways overrepresented in this list. Among the functional groups most represented was, in first position, immune system response activation against external stimulus. The second group consisted of integrated genes that regulate maternal homeostasis by complement and coagulation cascades. A third group was involved in lipid and fatty acid enzymes of metabolic processes, which participate in the steroidogenesis pathway. In order to identify powerful candidate genes for prolificacy, the second approach of this study was to merge microarray data with the QTL positional information affecting litter size, previously detected in the same experimental cross. As a result, we have identified 27 differentially expressed genes colocalizing with QTL for litter size traits, which fulfill the biological, positional, and functional criteria. 相似文献
78.
José Luis Durán Mariño Francisco Javier Rielo AriasEva Prado Miranda Juan Pena HolguínCarola Rubio Taboada Lucía Martínez Gallego 《Revista espa?ola de geriatría y gerontología》2011,46(3):121
Introduction
Forty-five per cent of stoke patients have a surgically accessible stenosis. The objective of our study is to describe the response to carotid endarterectomy (EA) in patients of advanced age compared to younger ones.Material and method
Retrospective evaluation of the clinical history of all patients who underwent an endarterectomy in a tertiary hospital between January 1995 and December 2006. The patients were grouped into those 75 years or older and those less than this age. The incidence of peri-operative complications in the first month after surgery, and the long-term mortality was evaluated using a survival analysis.Results
Data were collected on 147 EA in 134 patients of 75 years or more, and on 201 EA in 177 patients less than 75 years-old. The incidence of peri-operative complications was similar in both groups, with a mortality of 2% in the older age group and a stroke incidence of 2.6% (half transient ischaemic accidents). The older patients had a mean follow-up of 4.1 years, with a survival of 86% at one year and 54% at 5 years and with the main cause of death being heart disease.Conclusions
Carotid EA is a safe and effective technique for the treatment of extracranial carotid stenosis in the elderly, having the same peri-operative morbidity and mortality as younger ones. Age must not affect our therapeutic attitude, although an exhaustive cardiology study must be made in the elderly prior to the operation. 相似文献79.
Pena OM Pistolic J Raj D Fjell CD Hancock RE 《Journal of immunology (Baltimore, Md. : 1950)》2011,186(12):7243-7254
Classical (M1) and alternative (M2) polarization of mononuclear cells (MNCs) such as monocyte and macrophages is known to occur in response to challenges within a microenvironment, like the encounter of a pathogen. LPS, also known as endotoxin, is a potent inducer of inflammation and M1 polarization. LPS can also generate an effect in MNCs known as endotoxin tolerance, defined as the reduced capacity of a cell to respond to LPS activation after an initial exposure to this stimulus. Using systems biology approaches in PBMCs, monocytes, and monocyte-derived macrophages involving microarrays and advanced bioinformatic analysis, we determined that gene responses during endotoxin tolerance were similar to those found during M2 polarization, featuring gene and protein expression critical for the development of key M2 MNC functions, including reduced production of proinflammatory mediators, expression of genes involved in phagocytosis, as well as tissue remodeling. Moreover, expression of different metallothionein gene isoforms, known for their role in the control of oxidative stress and in immunomodulation, were also found to be consistently upregulated during endotoxin tolerance. These results demonstrate that after an initial inflammatory stimulus, human MNCs undergo an M2 polarization probably to control hyperinflammation and heal the affected tissue. 相似文献
80.
D Taruscio C Morciano P Laricchiuta P Mincarone F Palazzo CG Leo S Sabina R Guarino J Auld T Sejersen D Gavhed K Ritchie M Hilton-Boon J Manson PG Kanavos D Tordrup V Tzouma Y Le Cam J Senecat G Filippini S Minozzi C Del Giovane H Schünemann JJ Meerpohl B Prediger L Schell R Stefanov G Iskrov T Miteva-Katrandzhieva P Serrano-Aguilar L Perestelo-Perez MM Trujillo-Martín J Pérez-Ramos A Rivero-Santana A Brand H van Kranen K Bushby A Atalaia J Ramet L Siderius M Posada I Abaitua-Borda V Alonso Ferreira M Hens-Pérez FJ Manzanares 《Orphanet journal of rare diseases》2014,9(Z1):O14