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Find video protocols related to scientific articles indexed in Pubmed.
Spectral method for fast measurement of twisted nematic liquid crystal cell parameters.
Appl Opt
PUBLISHED: 10-17-2014
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We present an experimental approach for the fast measurement of twisted nematic (TN) liquid crystal (LC) cells' parameters. It is based on the spectral measurements of the light transmitted by the system polarizer-reference wave plate-LC cell-analyzer. The cell parameters are obtained by fitting the theoretical model to the experimental data. This method allows determining the rubbing angle, the twist angle and its sense, and the spectral dispersion of the LC cell retardation, simultaneously, with few measurements and without the need of applying voltage or any specific analytical conditions. The method is validated by characterizing two different TN cells with retardations of about 0.91 and 1.85 ?m. The birefringence relative error is less than 1.3%.
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MR imaging-based assessment of the female pelvic floor.
Radiographics
PUBLISHED: 09-11-2014
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Pelvic floor weakness is a functional condition that affects the anatomic structures supporting the pelvic organs: fasciae, ligaments, and muscles. It is a prevalent disorder among people older than 50 years, especially women, and may substantially diminish their quality of life. Many complex causes of pelvic floor weakness have been described, but the greatest risk factors are aging and female sex. Pelvic floor weakness can provoke a wide range of symptoms, including pain, urinary and fecal incontinence, constipation, difficulty in voiding, a sense of pressure, and sexual dysfunction. When the condition is diagnosed solely on the basis of physical and clinical examination, the compartments involved and the site of prolapse are frequently misidentified. Such errors contribute to a high number of failed interventions. Magnetic resonance (MR) imaging, which allows visualization of all three compartments, has proved a reliable technique for accurate diagnosis, especially when involvement of multiple compartments is suspected. MR imaging allows precise evaluation of ligaments, muscles, and pelvic organs and provides accurate information for appropriate surgical treatment. Moreover, dynamic MR imaging with steady-state sequences enables the evaluation of functional disorders of the pelvic floor. The authors review the pelvic floor anatomy, describe the MR imaging protocol used in their institutions, survey common MR imaging findings in the presence of pelvic floor weakness, and highlight key details that radiologists should provide surgeons to ensure effective treatment and improved outcomes.
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Infarct volume prediction using apparent diffusion coefficient maps during middle cerebral artery occlusion and soon after reperfusion in the rat.
Brain Res.
PUBLISHED: 08-14-2014
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Middle cerebral artery occlusion (MCAO) in rodents causes brain infarctions of variable sizes that depend on multiple factors, particularly in models of ischemia/reperfusion. This is a major problem for infarct volume comparisons between different experimental groups since unavoidable variability can induce biases in the results and imposes the use of large number of subjects. MRI can help to minimize these difficulties by ensuring that the severity of ischemia is comparable between groups. Furthermore, several studies showed that infarct volumes can be predicted with MRI data obtained soon after ischemia onset. However, such predictive studies require multiparametric MRI acquisitions that cannot be routinely performed, and data processing using complex algorithms that are often not available. The aim here was to provide a simplified method for infarct volume prediction using apparent diffusion coefficient (ADC) data in a model of transient MCAO in rats. ADC images were obtained before, during MCAO and after 60 min of reperfusion. Probability histograms were generated using ADC data obtained either during MCAO, after reperfusion, or both combined. The results were compared to real infarct volumes, i.e.T2 maps obtained at day 7. Assessment of the performance of the estimations showed better results combining ADC data obtained during occlusion and at reperfusion. Therefore, ADC data alone can provide sufficient information for a reasonable prediction of infarct volume if the MRI information is obtained both during the occlusion and soon after reperfusion. This approach can be used to check whether drug administration after MRI acquisition can change infarct volume prediction.
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Living in a coastal lagoon environment: Photosynthetic and biochemical mechanisms of key marine macroalgae.
Mar. Environ. Res.
PUBLISHED: 08-07-2014
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The physiological status of Cystoseira compressa, Padina pavonica and Palisada tenerrima was studied by in vivo chlorophyll fluorescence, pigment content, stoichiometry (C:N), accumulation of UV photoprotectors and antioxidant activity; comparing their photosynthetic response in a coastal lagoon (Mar Menor) and in Mediterranean coastal waters. In general, the specimens reached their highest ETRmax in spring in the Lagoon, but in summer in the Mediterranean, coinciding with their maximum biomass peak. The species exhibited a dynamic photoinhibition. Except C. compressa, they showed a lower decrease in Fv/Fm and higher recovery rates in the Mediterranean populations when exposed to high irradiance. The higher salinity and temperature of the lagoon could impair the photoprotection mechanisms. The acclimation to lagoon environments is species-specific and involves complex regulatory mechanisms. The results underline the importance of N in repair, avoidance, quenching and scavenging mechanisms. In general, Lagoon specimens showed higher pigment concentration. Although xanthophylls play important photo-protective and antioxidant roles, the observed trend is more likely to be explained by the higher temperatures reached in the lagoon compared to Mediterranean. Therefore the studied photosynthetic and biochemical mechanisms can be effective not only for high irradiance, but also for higher temperatures in a climate change scenario, but are highly dependent on nutrient availability.
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Breast milk metabolome characterization in a single-phase extraction, multiplatform analytical approach.
Anal. Chem.
PUBLISHED: 08-06-2014
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Breast milk (BM) is a biofluid that has a fundamental role in early life nutrition and has direct impact on growth, neurodevelopment, and health. Global metabolic profiling is increasingly being utilized to characterize complex metabolic changes in biological samples. However, in order to achieve broad metabolite coverage, it is necessary to employ more than one analytical platform, typically requiring multiple sample preparation protocols. In an effort to improve analytical efficiency and retain comprehensive coverage of the metabolome, a new extraction methodology was developed that successfully retains metabolites from BM in a single-phase using an optimized methyl-tert-butyl ether solvent system. We conducted this single-phase extraction procedure on a representative pool of BM, and characterized the metabolic composition using LC-QTOF-MS and GC-Q-MS for polar and lipidic metabolites. To ensure that the extraction method was reproducible and fit-for-purpose, the analytical procedure was evaluated on both platforms using 18 metabolites selected to cover a range of chromatographic retention times and biochemical classes. Having validated the method, the metabolic signature of BM composition was mapped as a metabolic reaction network highlighting interconnected biological pathways and showing that the LC-MS and GC-MS platforms targeted largely different domains of the network. Subsequently, the same protocol was applied to ascertain compositional differences between BM at week 1 (n = 10) and 4 weeks (n = 9) post-partum. This single-phase approach is more efficient in terms of time, simplicity, cost, and sample volume than the existing two-phase methods and will be suited to high-throughput metabolic profiling studies of BM.
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Hierarchical management of carbon sources is regulated similarly by the CbrA/B systems in Pseudomonas aeruginosa and Pseudomonas putida.
Microbiology (Reading, Engl.)
PUBLISHED: 07-16-2014
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The CbrA/B system in pseudomonads is involved in the utilization of carbon sources and carbon catabolite repression (CCR) through the activation of the small RNAs crcZ in Pseudomonas aeruginosa, and crcZ and crcY in Pseudomonas putida. Interestingly, previous works reported that the CbrA/B system activity in P. aeruginosa PAO1 and P. putida KT2442 responded differently to the presence of different carbon sources, thus raising the question of the exact nature of the signal(s) detected by CbrA. Here, we demonstrated that the CbrA/B/CrcZ(Y) signal transduction pathway is similarly activated in the two Pseudomonas species. We show that the CbrA sensor kinase is fully interchangeable between the two species and, moreover, responds similarly to the presence of different carbon sources. In addition, a metabolomics analysis supported the hypothesis that CCR responds to the internal energy status of the cell, as the internal carbon/nitrogen ratio seems to determine CCR and non-CCR conditions. The strong difference found in the 2-oxoglutarate/glutamine ratio between CCR and non-CCR conditions points to the close relationship between carbon and nitrogen availability, or the relationship between the CbrA/B and NtrB/C systems, suggesting that both regulatory systems sense the same sort or interrelated signal.
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GluN3A promotes dendritic spine pruning and destabilization during postnatal development.
J. Neurosci.
PUBLISHED: 07-11-2014
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Synaptic rearrangements during critical periods of postnatal brain development rely on the correct formation, strengthening, and elimination of synapses and associated dendritic spines to form functional networks. The correct balance of these processes is thought to be regulated by synapse-specific changes in the subunit composition of NMDA-type glutamate receptors (NMDARs). Among these, the nonconventional NMDAR subunit GluN3A has been suggested to play a role as a molecular brake in synaptic maturation. We tested here this hypothesis using confocal time-lapse imaging in rat hippocampal organotypic slices and assessed the role of GluN3A-containing NMDARs on spine dynamics. We found that overexpressing GluN3A reduced spine density over time, increased spine elimination, and decreased spine stability. The effect of GluN3A overexpression could be further enhanced by using an endocytosis-deficient GluN3A mutant and reproduced by silencing the adaptor protein PACSIN1, which prevents the endocytosis of endogenous GluN3A. Conversely, silencing of GluN3A reduced spine elimination and favored spine stability. Moreover, reexpression of GluN3A in more mature tissue reinstated an increased spine pruning and a low spine stability. Mechanistically, the decreased stability in GluN3A overexpressing neurons could be linked to a failure of plasticity-inducing protocols to selectively stabilize spines and was dependent on the ability of GluN3A to bind the postsynaptic scaffold GIT1. Together, these data provide strong evidence that GluN3A prevents the activity-dependent stabilization of synapses thereby promoting spine pruning, and suggest that GluN3A expression operates as a molecular signal for controlling the extent and timing of synapse maturation.
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[Patient advice].
Aten Primaria
PUBLISHED: 07-07-2014
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In wound care, knowing what to do is as important as knowing what not to do. The first step is to evaluate the severity of the lesion and to know whether it is necessary to attend a health center or not. If the wound is simple, the recommended course of action is cleansing with serum or water after washing one's hands, followed by wound disinfection with the most appropriate antiseptic. Antiseptics not should be used for wound cleansing (physiological serum or tap water should be used) or for wound healing with granulation tissue. Equally, antiseptics should not be used in the ear or near the eyes; if there is accidental application, the eye should be washed in abundant water. Povidone iodine should not be used in pregnant women, nor should iodine preparations be used in neonates, in patients with thyroid alterations or in those allergic to iodine. Currently, merbromine/mercurochrome is not used because of its mercury content. Before an antiseptic is applied, all inorganic residues (foreign bodies) and dead tissue should be removed; detritus, slough, purulent exudate, scabs… This will aid healing and the action of antiseptics, since they become inactive in the presence of organic material.
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[Antiseptic use in primary care].
Aten Primaria
PUBLISHED: 07-07-2014
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Wounds can be classified according to their mechanism of action into surgical or traumatic (which may be incision wounds, such as those provoked by a sharp object; contusions, caused by a blunt force; puncture wounds, caused by long, sharp objects; lacerations, caused by tears to the tissue; or bites, which have a high risk of infection and consequently should not be sutured). Wounds can also be classified by their healing process into acute or chronic (pressure ulcers, vascular ulcers, neuropathic ulcers, acute wounds with torpid clinical course). The use of antiseptics in any of these wounds is usually limited to cleaning and initial care -up to 48 hours- and to washing of hands and instruments. The use of antiseptics in chronic or persistent wounds is more debatable. The same is true of burns, in which the use of formulations that encourage hydration is recommended. In the pediatric population, the use of antiseptics with a known safety profile and low absorption is usually recommended, especially in the care of the umbilical cord, in which evidence supports the use of chlorhexidine gluconate. Another use of antiseptics is the care of wounds produced by procedures used in body esthetics, such as piercings; in these procedures, it is advisable to use transparent antiseptics that allow visualization of the technique.
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[Introduction to antiseptics].
Aten Primaria
PUBLISHED: 07-07-2014
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Antiseptics are anti-infectious agents for local use on the skin or mucosa, which distinguishes them from disinfectants, which are used on inanimate surfaces usually because of their toxicity. The present article explains the differences among the multiple possible antiseptics; special attention is paid to the most common, such as alcohol, chlorhexidine, povidone iodine, and oxygenated water. Finally, we stress the different antiseptic formulations, which increase the usefulness of these agents in specific indications.
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[Right of access to healthcare in the context of the Royal Decree-Law 16/2012: the perspective of civil society organizations and professional associations.]
Gac Sanit
PUBLISHED: 06-23-2014
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The recent publication of the Royal Decree-Law 16/2012 (RDL 16/2012), which introduces structural changes in the Spanish Public Healthcare System, can be placed in the broader context of budgetary adjustments in response to the current economic crisis. An analysis of the interrelationships among economic crisis, healthcare policies, and health reveals that citizen participation is one of several potential strategies for reducing the impact of this situation on the population. This observation raises the interest to know the citizens' perspectives on the modifications introduced by the RDL 16/2012.
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In vitro anti-proliferative effects on NB4 human leukemia cells and physicochemical screening of Pleurotus sp. (higher Basidiomycetes) mycelia from Cuba.
Int J Med Mushrooms
PUBLISHED: 06-19-2014
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This study examined the phytochemical profile and the in vitro anti-proliferative effects of a hot water mycelial extract from the edible mushroom Pleurotus sp. on NB4 human leukemia cells. Flow-cytometry analyses were used to measure cell viability, cell cycle, and apoptosis in cells incubated 24 h with the extract at doses of 100 and 200 µg/mL. Pleurotus sp. extract reduced cell viability, particularly at the concentration of 200 µg/mL to 82% compared to control cells, and induced apoptosis demonstrated by an increase in the number of annexin V-FITC+ cells (25% at 200 µg/mL). The NB4 cells were arrested in the G2/M phase thus supporting a cell-cycle dependent anticancer mechanism. Although carbohydrates (76.8%, w/w) appear to be the most important antitumor compound, secondary metabolites-like phenolics would also contribute to the anti-proliferative activity. The results indicate that Pleurotus sp. mycelia obtained by submerged fermentation may be an interesting renewable resource for developing functional foods and new antitumor therapeutic agents.
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Influence of vitamin D status on the effect of statins on bone mineral density and bone turnover markers in postmenopausal women.
J. Clin. Endocrinol. Metab.
PUBLISHED: 05-30-2014
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This study sought to assess whether the association between statin use and bone mineral density (BMD) and bone turnover markers is modulated by serum 25-hydroxyvitamin D (25OHD) levels in postmenopausal women. Design, Participants, and Settings: Approximately 1422 postmenopausal women were recruited from the Camargo Cohort after excluding those with any known medical disorder or drug that might affect bone metabolism. Participants were categorized into four groups: 25OHD levels of 20 ng/mL or less and not taking statins (group 1; n = 492); 25OHD levels greater than 20 ng/mL and on statins (group 2; n = 143); 25OHD levels of 20 ng/mL or less and using statins (group 3; n = 112); and 2OHD levels greater than 20 ng/mL and non-statin use (group 4; n = 675). Multivariate analyses were performed to compare BMD and bone turnover markers between groups.
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Characteristics and effectiveness of diabetes self-management educational programs targeted to racial/ethnic minority groups: a systematic review, meta-analysis and meta-regression.
BMC Endocr Disord
PUBLISHED: 05-06-2014
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It is not clear to what extent educational programs aimed at promoting diabetes self-management in ethnic minority groups are effective. The aim of this work was to systematically review the effectiveness of educational programs to promote the self-management of racial/ethnic minority groups with type 2 diabetes, and to identify programs' characteristics associated with greater success.
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The right of access to health care for undocumented migrants: a revision of comparative analysis in the European context.
Eur J Public Health
PUBLISHED: 04-09-2014
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The recent introduction of adjustment measures in the Spanish context by means of the Royal Decree-law 16/2012 (RDL 16/2012), which limits access to health care for undocumented migrants, raises the question about the state of the matter in different European Union member states.
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Toronto alexithymia scale for patients with eating disorder: of performance using the non-parametric item response theory.
Compr Psychiatry
PUBLISHED: 03-24-2014
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The aim of this study was to investigate the performance of the Toronto Alexithymia Scale (TAS-20) in patients with eating disorders. As a secondary objective, we analyzed a subset of items in order to determine whether the total score is a good tool for classifying these patients and whether the items are ordered according to the difficulty of choosing a particular answer depending on the severity of the patient's condition.
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The role of working memory in inferential sentence comprehension.
Cogn Process
PUBLISHED: 03-11-2014
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Existing literature on inference making is large and varied. Trabasso and Magliano (Discourse Process 21(3):255-287, 1996) proposed the existence of three types of inferences: explicative, associative and predictive. In addition, the authors suggested that these inferences were related to working memory (WM). In the present experiment, we investigated whether WM capacity plays a role in our ability to answer comprehension sentences that require text information based on these types of inferences. Participants with high and low WM span read two narratives with four paragraphs each. After each paragraph was read, they were presented with four true/false comprehension sentences. One required verbatim information and the other three implied explicative, associative and predictive inferential information. Results demonstrated that only the explicative and predictive comprehension sentences required WM: participants with high verbal WM were more accurate in giving explanations and also faster at making predictions relative to participants with low verbal WM span; in contrast, no WM differences were found in the associative comprehension sentences. These results are interpreted in terms of the causal nature underlying these types of inferences.
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Night shifts, sleep deprivation, and attention performance in medical students.
Int J Med Educ
PUBLISHED: 03-08-2014
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To determine attention performance of medical students after sleep deprivation due to night shift work.
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A novel cyanide-inducible gene cluster helps protect Pseudomonas aeruginosa from cyanide.
Environ Microbiol Rep
PUBLISHED: 03-06-2014
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Pseudomonas aeruginosa produces the toxic secondary metabolite hydrogen cyanide (HCN) at high cell population densities and low aeration. Here, we investigated the impact of HCN as a signal in cell-cell communication by comparing the transcriptome of the wild-type strain PAO1 to that of an HCN-negative mutant under cyanogenic conditions. HCN repressed four genes and induced 12 genes. While the individual functions of these genes are unknown, with one exception (i.e. a ferredoxin-dependent reductase), a highly inducible six-gene cluster (PA4129-PA4134) was found to be crucial for protection of P. aeruginosa from external HCN intoxication. A double mutant deleted for PA4129-PA4134 and cioAB (encoding cyanide-insensitive oxidase) did not grow with 100 ?M KCN, whereas the corresponding single mutants were essentially unaffected, suggesting a synergistic action of the PA4129-PA4134 gene products and cyanide-insensitive oxidase.
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New insights into the role of indole-3-acetic acid in the virulence of Pseudomonas savastanoi pv. savastanoi.
FEMS Microbiol. Lett.
PUBLISHED: 02-27-2014
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Indole-3-acetic acid (IAA) is a widespread phytohormone among plant-associated bacteria, including the tumour-inducing pathogen of woody hosts, Pseudomonas savastanoi pv. savastanoi. A phylogenetic analysis of the iaaM/iaaH operon, which is involved in the biosynthesis of IAA, showed that one of the two operons encoded by Pseudomonas savastanoi pv. savastanoi NCPPB 3335, iaaM-1/iaaH-1, is horizontally transferred among bacteria belonging to the Pseudomonas syringae complex. We also show that biosynthesis of the phytohormone, virulence and full fitness of this olive pathogen depend only on the functionality of the iaaM-1/iaaH-1 operon. In contrast, the iaaM-2/iaaH-2 operon, which carries a 22-nt insertion in the iaaM-2 gene, does not contribute to the production of IAA by this bacterium. A residual amount of IAA was detected in the culture supernatants of a double mutant affected in both iaaM/iaaH operons, suggesting that a different pathway might also contribute to the total pool of the phytohormone produced by this pathogen. Additionally, we show that exogenously added IAA negatively and positively regulates the expression of genes related to the type III and type VI secretion systems, respectively. Together, these results suggest a role of IAA as a signalling molecule in this pathogen.
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The urinary proteome and metabonome differ from normal in adults with mitochondrial disease.
Kidney Int.
PUBLISHED: 02-19-2014
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We studied the extent and nature of renal involvement in a cohort of 117 adult patients with mitochondrial disease, by measuring urinary retinol-binding protein (RBP) and albumin; established markers of tubular and glomerular dysfunction, respectively. Seventy-five patients had the m.3243A>G mutation and the most frequent phenotypes within the entire cohort were 14 with MELAS, 33 with MIDD, and 17 with MERRF. Urinary RBP was increased in 29 of 75 of m.3243A>G patients, whereas albumin was increased in 23 of the 75. The corresponding numbers were 16 and 14, respectively, in the 42 non-m.3243A>G patients. RBP and albumin were higher in diabetic m.3243A>G patients than in nondiabetics, but there were no significant differences across the three major clinical phenotypes. The urine proteome (mass spectrometry) and metabonome (nuclear magnetic resonance) in a subset of the m.3243A>G patients were markedly different from controls, with the most significant alterations occurring in lysosomal proteins, calcium-binding proteins, and antioxidant defenses. Differences were also found between asymptomatic m.3243A>G carriers and controls. No patients had an elevated serum creatinine level, but 14% had hyponatremia, 10% had hypophosphatemia, and 14% had hypomagnesemia. Thus, abnormalities in kidney function are common in adults with mitochondrial disease, exist in the absence of elevated serum creatinine, and are not solely explained by diabetes.Kidney International advance online publication, 10 September 2014; doi:10.1038/ki.2014.297.
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Influence of surface-imprinted nanoparticles on trypsin activity.
Adv Healthc Mater
PUBLISHED: 02-18-2014
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Here, the modulation of enzyme activity is presented by protein-imprinted nanoparticles produced using a solid-phase approach. Using trypsin as target, binding of the nanoparticles to the enzyme results in its inhibition or in stabilization, depending on the orientation of the immobilized enzyme used during imprinting.
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Introducing MINA--The Molecularly Imprinted Nanoparticle Assay.
Small
PUBLISHED: 02-06-2014
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A new ELISA- (enzyme-linked immunosorbent assay)-like assay is demonstrated in which no elements of biological origin are used for molecular recognition or signaling. Composite imprinted nanoparticles that contain a catalytic core and which are synthesized by using a solid-phase approach can simultaneously act as recognition/signaling elements, and be used with minimal modifications to standard assay protocols. This assay provides a new route towards replacement of unstable biomolecules in immunoassays.
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Nuke-sparing regimens as a main simplification strategy and high level of toxicity resolution after antiretroviral switch: the SWITCHART Study.
J Int AIDS Soc
PUBLISHED: 01-01-2014
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The advent of combined antiretroviral therapy (ART) in the past decade has led to HIV suppression in most cases. Virological failure was the main reason for ART switch a few years ago; however, toxicity and treatment simplification have now gained importance due to the availability of more effective and convenient drugs. This study assessed the reasons for ART switch in daily practice.
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Lipid changes in HIV-patients switching to the coformulated single tablet FTC/RPV/TDF (Eviplera®). Efficacy and safety analysis. GeSida Study 8114.
J Int AIDS Soc
PUBLISHED: 01-01-2014
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Rilpivirine (RPV) has a better lipid profile than efavirenz (EFV) in naïve patients (1). Switching to RPV may be convenient for many patients, while maintaining a good immunovirological control (2). The aim of this study was to analyze lipid changes in HIV-patients at 24 weeks after switching to Eviplera® (emtricitabine/RPV/tenofovir disoproxil fumarate [FTC/RPV/TDF]).
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Should screening for Chlamydia trachomatis and Neisseria gonorrhoeae in HIV-men who have sex with men be recommended?
J Int AIDS Soc
PUBLISHED: 01-01-2014
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Sexually transmitted infections (STI) like Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) have been associated with increased risk of HIV acquisition (1). It has been also described as a high prevalence of asymptomatic CT and NG infections in men who have sex with men (MSM) (2). The aim of this study was to know the prevalence of CT and/or NG infections in asymptomatic HIV-MSM and the related factors.
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Inhibiting and facilitating factors to end a violent relationship: patterns of behavior among women in Spain.
Violence Vict
PUBLISHED: 12-25-2013
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The objective of this study are (a) to explore the factors, which facilitate or inhibit womens responses to intimate partner violence (IPV) and their ability to leave a violent relationship; (b) to identify patterns of behavior in abused women based on their perception of the violence and the actions they take to find help or a solution to the problems derived from IPV. Semistructured interviews were carried out. The critical path is defined as the sequence of decisions and actions taken by affected women to address the violence they experienced. Based on this concept, we identified several factors that affect womens responses to violence, and categorized them into inhibiting and facilitating factors. We also identified three patterns of behavior: the first one is theoretically as the ideal critical path, whereas in the third pattern the process is less like the ideal critical path.
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[Polio vaccines, eradication and posterradication].
Rev. Esp. Salud Publica
PUBLISHED: 12-11-2013
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Vaccination against polio generates herd immunity (both with the attenuated (OPV) and inactivated (IPV) vaccines) and this will allow the eradication of the disease. The OPV vaccine produces 2-4 polio cases per cohort of one million children and therefore IPV is used in countries that can afford its cost (about 15 times more expensive than OPV). In 1988 the World Health Assembly established the polio eradication goal as "interruption of wild poliovirus transmission". If the elimination of wild poliovirus were achieved, the use of OPV will produce annually between 250 and 500 cases of polio in the world. From 1999, it was clear that eradication would require ending of immunization with OPV. On the 25th of January, 2013 it is approved the plan for the eradication and containment of all polioviruses, wild or not, so that no child suffers paralytic poliomyelitis. The most important landmarks include the lack of wild polio cases after 2014, the introduction of at least one dose of IPV in all immunization programs and to cease the type 2 OPV vaccination by the end of 2016 and to stop the use of the oral bivalent vaccine in 2019. To achieve all this, a complex scientific work and economic solidarity will be required.
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GluN3A expression restricts spine maturation via inhibition of GIT1/Rac1 signaling.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 12-02-2013
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NMDA-type glutamate receptors (NMDARs) guide the activity-dependent remodeling of excitatory synapses and associated dendritic spines during critical periods of postnatal brain development. Whereas mature NMDARs composed of GluN1 and GluN2 subunits mediate synapse plasticity and promote spine growth and stabilization, juvenile NMDARs containing GluN3A subunits are thought to inhibit these processes via yet unknown mechanisms. Here, we report that GluN3A binds G protein-coupled receptor kinase-interacting protein (GIT1), a postsynaptic scaffold that assembles actin regulatory complexes, including the Rac1 guanine nucleotide exchange factor ?PIX, to promote Rac1 activation in spines. Binding to GluN3A limits the synaptic localization of GIT1 and its ability to complex ?PIX, leading to decreased Rac1 activation and reduced spine density and size in primary cultured neurons. Conversely, knocking out GluN3A favors the formation of GIT1/?PIX complexes and increases the activation of Rac1 and its main effector p21-activated kinase. We further show that binding of GluN3A to GIT1 is regulated by synaptic activity, a response that might restrict the negative regulatory effects of GluN3A on actin signaling to inactive synapses. Our results identify inhibition of Rac1/p21-activated kinase actin signaling pathways as an activity-dependent mechanism mediating the inhibitory effects of GluN3A on spine morphogenesis.
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Intimate partner violence in older women in Spain: prevalence, health consequences, and service utilization.
J Women Aging
PUBLISHED: 10-15-2013
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The purpose of this study is to estimate the prevalence of lifetime intimate partner violence (IPV) in older women and to analyze its effect on womens health and Healthcare Services utilization. Women aged 55 years and over (1,676) randomly sampled from Primary Healthcare Services around Spain were included. Lifetime IPV prevalence, types, and duration were calculated. Descriptive and multivariate procedures using logistic and multiple lineal regression models were used. Of the women studied, 29.4% experienced IPV with an average duration of 21 years. Regardless of the type of IPV experienced, abused women showed significantly poorer health and higher healthcare services utilization compared to women who had never been abused. The high prevalence detected long standing duration, negative health impact, and high healthcare services utilization, calling attention to a need for increased efforts aimed at addressing IPV in older women.
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E1a promotes c-Myc-dependent replicative stress: Implications in glioblastoma radiosensitization.
Cell Cycle
PUBLISHED: 10-11-2013
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The E1a gene from adenovirus is known to be a potent inducer of chemo/radiosensitivity in a wide range of tumors. However, the molecular bases of its radiosensitizer properties are still poorly understood. In an attempt to study this effect, U87MG cells, derived from a radio-resistant tumor as glioblastoma, where infected with lentivirus carrying E1a gene developing an acute sensitivity to ionizing radiation. The induction of radiosensitivity correlated with a marked G 2/M phase accumulation and a potent apoptotic response. Our findings demonstrate that c-Myc plays a pivotal role in E1a-associated radiosensitivity through the induction of a replicative stress situation, as our data support by genetic approaches, based in interference and overexpression in U87MG cells. In fact, we present evidence showing that Chk1 is a novel transcriptional target of E1a gene through the effect exerted by this adenoviral protein onto c-Myc. Moreover, c-Myc upregulation also explains the marked phosphorylation of H2AX associated to E1a expression in the absence of DNA damage. Indeed, all these observations were applicable to other experimental models, such as T98G, LN-405 and A172, rendering the same pattern in terms of radiosensitivity, cell cycle distribution, upregulation of Chk1, c-Myc, and phosphorylation pattern of H2AX. In summary, our data propose a novel mechanism to explain how E1a mediates radiosensitivity through the signaling axis E1a?c-Myc? replicative stress situation. This novel mechanism of E1a-mediated radiosensitivity could be the key to open new possibilities in the current therapy of glioblastoma.
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Dietary and urinary metabonomic factors possibly accounting for higher blood pressure of black compared with white Americans: results of International Collaborative Study on macro-/micronutrients and blood pressure.
Hypertension
PUBLISHED: 10-07-2013
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Black compared with non-Hispanic white Americans have higher systolic and diastolic blood pressure and rates of prehypertension/hypertension. Reasons for these adverse findings remain obscure. Analyses here focused on relations of foods/nutrients/urinary metabolites and higher black blood pressure for 369 black compared with 1190 non-Hispanic white Americans aged 40 to 59 years from 8 population samples. Multiple linear regression, standardized data from four 24-hour dietary recalls per person, two 24-hour urine collections, and 8 blood pressure measurements were used to quantitate the role of foods, nutrients, and metabolites in higher black blood pressure. Compared with non-Hispanic white Americans, blacks average systolic/diastolic pressure was higher by 4.7/3.4 mm Hg (men) and 9.0/4.8 mm Hg (women). Control for higher body mass index of black women reduced excess black systolic/diastolic pressure to 6.8/3.8 mm Hg. Lesser intake of vegetables, fruits, grains, vegetable protein, glutamic acid, starch, fiber, minerals, and potassium, and higher intake of processed meats, pork, eggs, and sugar-sweetened beverages, along with higher cholesterol and higher Na/K ratio, related to in higher black blood pressure. Control for 11 nutrient and 10 non-nutrient correlates reduced higher black systolic/diastolic pressure to 2.3/2.3 mm Hg (52% and 33% reduction in men) and to 5.3/2.8 mm Hg (21% and 27% reduction in women). Control for foods/urinary metabolites had little further influence on higher black blood pressure. Less favorable multiple nutrient intake by blacks than non-Hispanic white Americans accounted, at least in part, for higher black blood pressure. Improved dietary patterns can contribute to prevention/control of more adverse black blood pressure levels.
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Direct replacement of antibodies with molecularly imprinted polymer nanoparticles in ELISA--development of a novel assay for vancomycin.
Anal. Chem.
PUBLISHED: 08-22-2013
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A simple and straightforward technique for coating microplate wells with molecularly imprinted polymer nanoparticles (nanoMIPs) to develop assays similar to the enzyme-linked immunosorbent assay (ELISA) is presented here for the first time. NanoMIPs were synthesized by a solid-phase approach with an immobilized vancomycin (template) and characterized using Biacore 3000, dynamic light scattering, and electron microscopy. Immobilization, blocking, and washing conditions were optimized in microplate format. The detection of vancomycin was achieved in competitive binding experiments with a horseradish peroxidase-vancomycin conjugate. The assay was capable of measuring vancomycin in buffer and in blood plasma within the range of 0.001-70 nM with a detection limit of 0.0025 nM (2.5 pM). The sensitivity of the assay was 3 orders of magnitude better than a previously described ELISA based on antibodies. In these experiments, nanoMIPs have shown high affinity and minimal interference from blood plasma components. Immobilized nanoMIPs were stored for 1 month at room temperature without any detrimental effects to their binding properties. The high affinity of nanoMIPs and the lack of a requirement for cold chain logistics make them an attractive alternative to traditional antibodies used in ELISA.
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Expression of Cocaine-Evoked Synaptic Plasticity by GluN3A-Containing NMDA Receptors.
Neuron
PUBLISHED: 07-30-2013
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Drug-evoked synaptic plasticity in the mesolimbic dopamine (DA) system reorganizes neural circuits that may lead to addictive behavior. The first cocaine exposure potentiates AMPAR excitatory postsynaptic currents (EPSCs) onto DA neurons of the VTA but reduces the amplitude of NMDAR-EPSCs. While plasticity of AMPAR transmission is expressed by insertion of calcium (Ca(2+))-permeable GluA2-lacking receptors, little is known about the expression mechanism for altered NMDAR transmission. Combining ex vivo patch-clamp recordings, mouse genetics, and subcellular Ca(2+) imaging, we observe that cocaine drives the insertion of NMDARs that are quasi-Ca(2+)-impermeable and contain GluN3A and GluN2B subunits. These GluN3A-containing NMDARs appear necessary for the expression of cocaine-evoked plasticity of AMPARs. We identify an mGluR1-dependent mechanism to remove these noncanonical NMDARs that requires Homer/Shank interaction and protein synthesis. Our data provide insight into the early cocaine-driven reorganization of glutamatergic transmission onto DA neurons and offer GluN3A-containing NMDARs as new targets in drug addiction.
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Seroprevalence of anti-N-methyl-D-aspartate receptor antibodies in women with ovarian teratoma.
J. Neurol.
PUBLISHED: 07-12-2013
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Recently antibodies against neuronal receptors have been identified as cause of a new type of encephalitis. The anti-N-methyl-D-aspartate receptor (anti-NMDA-R) encephalitis is the prototype of these disorders. Patients have a high incidence of teratomata. Removal of teratoma is considered the essential treatment of anti-NMDA-R encephalitis. Here, we aimed to investigate whether neurologically asymptomatic individuals suffering from ovarian teratomata may have positive anti-NMDA-R antibodies to be detected by an established assay. Over a time period of 15 months, all patients suffering from ovarian teratomata without neurological symptoms were included in this prospective study. Twenty consecutive patients were pair matched to patients with other benign ovarian disease and healthy controls. Preoperatively, patients had a gynaecological examination, transvaginal ultrasound, neurological examination and determination of anti-NMDA-R antibodies. None of the patients or controls presented with neurological symptoms. All tumours could be removed completely by laparoscopy. Anti-NMDA-R antibodies were absent in the group of patients with teratomata as well as in patients with benign ovarian tumours and healthy controls. Testing for anti-NMDA-R antibodies revealed negative findings in well-characterised patients with ovarian teratomata lacking neurological symptoms. Our data support the current clinical practice that a systematic screening for anti-NMDA-R antibodies in teratoma patients is not indicated.
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Mechanical properties and microstructure of frozen carrots during storage as affected by blanching in water and sugar solutions.
Food Chem
PUBLISHED: 07-03-2013
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Raw carrots and carrots blanched in water and in 4% trehalose and maltose solutions at 75°C for 3 (A) and 10 min (C) and at 90°C for 3 (B) and 10 min (D) were frozen and stored at -18°C for eight months. The effects of heating conditions and exogenous added sugars on the mechanical properties and microstructure of the vegetable after blanching and during frozen storage were studied. By scanning electron microscopy (SEM) analysis no significant differences were observed among samples A and B water-blanched and raw carrot while a thermo-protective effect due to the sugars addition was evidenced in sample D, undergone to the most severe thermal treatment. Freezing and frozen storage determined several fractures on both raw and blanched carrots due to ice crystals formation and re-crystallisation. The cryo-protective effect of the sugars on the vegetable microstructure was observed only in the over-blanched sample D. The mechanical properties of carrots were affected by blanching which caused a hardness decrease but after freezing and one month of frozen storage, all samples showed a further dramatic reduction of hardness. Only samples characterised by a pectinesterase residual activity showed a softening also after one month of frozen storage likely for a competitive effect of the thermo-protective ability of trehalose on this enzyme. The exogenous trehalose was able to limit the hardness loss of carrots undergone to B, C and D blanching pre-treatments.
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Prevalence and factors associated with a prolonged QTc interval in a cohort of asymptomatic HIV-infected patients.
AIDS Res. Hum. Retroviruses
PUBLISHED: 05-31-2013
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We aimed to determine the prevalence of a prolonged QTc interval in HIV-infected patients and its related factors through an observational study of a cohort of asymptomatic HIV-infected outpatients. All patients underwent a standard 12-lead electrocardiogram and a transthoracic echocardiogram. Prolonged QTc was considered if it was >440?ms in men and >450?ms in women. Epidemiological, clinical, and laboratory data were collected and the patients completed a questionnaire about cardiovascular risk factors. The analysis of the potential risk factors for prolonged QTc was done by multivariate logistic regression. The study included 194 patients, 84% men, with a mean age of 46.3 years. The mean duration of HIV infection was 122.6 months and 27.8% had AIDS. Antiretroviral therapy was being taken by 185 (96.4%) patients, and 92.4% of them had an undetectable viral load. The mean CD4 lymphocyte count was 553/mm(3). A total of 24 (12.4%) patients had a prolonged QTc interval, with a mean QTc of 456?ms. The factors associated with a prolonged QTc were hyperlipidemia (OR 3.7, 95% CI: 1.3-10.3; p=0.01) and diastolic dysfunction (OR 6.7, 95% CI: 2.4-18.3; p=0.0001), while the use of atazanavir was associated with a lower likelihood of having a prolonged QTc (OR 0.11, 95% CI: 0.02-0.5; p=0.008). A prolonged QTc syndrome was not uncommon in this cohort of asymptomatic HIV-infected patients with good immunovirological control. It was associated with hyperlipidemia and diastolic dysfunction. The use of atazanavir, compared with other protease inhibitors, was associated with a lower likelihood of having a prolonged QTc.
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[Isokinetic and functional lumbar evaluation in workers pensioned with disability].
Rev Med Inst Mex Seguro Soc
PUBLISHED: 05-23-2013
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there were 13,371 disability reports in Jalisco during 2008 about lumbar spine injuries; most of them were permanent and required evaluation of lumbar capabilities. The objective was to evaluate the functionality of the lumbar spine through the Oswestry questionnaire and isokinetic evaluation in pensioners with lumbar injury.
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Transcriptional activation of the CrcZ and CrcY regulatory RNAs by the CbrB response regulator in Pseudomonas putida.
Mol. Microbiol.
PUBLISHED: 05-17-2013
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The CbrAB two-component system has been described as a high-ranked element in the regulatory hierarchy of Pseudomonas putida that controls a variety of metabolic and behavioural traits required for adaptation to changing environmental conditions. We show that the response regulatory protein CbrB, an activator of ?(N) -dependent promoters, directly controls the expression of the small RNAs CrcZ and CrcY in P.?putida. These two RNAs sequester the protein Crc, which is a translational repressor of multiple pathways linked to carbon catabolite repression. We characterized the in vivo and in vitro activation by CbrB at both crcZ and crcY promoters, and identified new DNA sequences where the protein binds. IHF, a co-activator at many ?(N) -dependent promoters, also binds to the promoter regions and contributes to the activation of the sRNAs. CbrB phosphorylation is necessary at physiological activation conditions, but a higher dose of the protein allows in vitro transcriptional activation in its non-phosphorylated form. We also show there is some production of CrcY coming from an upstream promoter independent of CbrB. Thus, CbrAB constitute a global signal transduction pathway integrated in a higher regulatory network that also controls catabolite repression through the expression of the two regulatory RNAs CrcZ and CrcY.
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IL-10 deficiency exacerbates the brain inflammatory response to permanent ischemia without preventing resolution of the lesion.
J. Cereb. Blood Flow Metab.
PUBLISHED: 04-27-2013
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Stroke induces inflammation that can aggravate brain damage. This work examines whether interleukin-10 (IL-10) deficiency exacerbates inflammation and worsens the outcome of permanent middle cerebral artery occlusion (pMCAO). Expression of IL-10 and IL-10 receptor (IL-10R) increased after ischemia. From day 4, reactive astrocytes showed strong IL-10R immunoreactivity. Interleukin-10 knockout (IL-10 KO) mice kept in conventional housing showed more mortality after pMCAO than the wild type (WT). This effect was associated with the presence of signs of colitis in the IL-10 KO mice, suggesting that ongoing systemic inflammation was a confounding factor. In a pathogen-free environment, IL-10 deficiency slightly increased infarct volume and neurologic deficits. Induction of proinflammatory molecules in the IL-10 KO brain was similar to that in the WT 6?hours after ischemia, but was higher at day 4, while differences decreased at day 7. Deficiency of IL-10 promoted the presence of more mature phagocytic cells in the ischemic tissue, and enhanced the expression of M2 markers and the T-cell inhibitory molecule CTLA-4. These findings agree with a role of IL-10 in attenuating local inflammatory reactions, but do not support an essential function of IL-10 in lesion resolution. Upregulation of alternative immunosuppressive molecules after brain ischemia can compensate, at least in part, the absence of IL-10.
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Molecular characterization of carbamoyl-phosphate synthetase (CPS1) deficiency using human recombinant CPS1 as a key tool.
Hum. Mutat.
PUBLISHED: 04-18-2013
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The urea cycle disease carbamoyl-phosphate synthetase deficiency (CPS1D) has been associated with many mutations in the CPS1 gene [Häberle et al., 2011. Hum Mutat 32:579-589]. The disease-causing potential of most of these mutations is unclear. To test the mutations effects, we have developed a system for recombinant expression, mutagenesis, and purification of human carbamoyl-phosphate synthetase 1 (CPS1), a very large, complex, and fastidious enzyme. The kinetic and molecular properties of recombinant CPS1 are essentially the same as for natural human CPS1. Glycerol partially replaces the essential activator N-acetyl-l-glutamate (NAG), opening possibilities for treating CPS1D due to NAG site defects. The value of our expression system for elucidating the effects of mutations is demonstrated with eight clinical CPS1 mutations. Five of these mutations decreased enzyme stability, two mutations drastically hampered catalysis, and one vastly impaired NAG activation. In contrast, the polymorphisms p.Thr344Ala and p.Gly1376Ser had no detectable effects. Site-limited proteolysis proved the correctness of the working model for the human CPS1 domain architecture generally used for rationalizing the mutations effects. NAG and its analogue and orphan drug N-carbamoyl-l-glutamate, protected human CPS1 against proteolytic and thermal inactivation in the presence of MgATP, raising hopes of treating CPS1D by chemical chaperoning with N-carbamoyl-l-glutamate.
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Different impact of pretransplant anti-HLA antibodies detected by Luminex in highly sensitized renal transplanted patients.
Biomed Res Int
PUBLISHED: 04-05-2013
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It is well know that anti-HLA antibodies are an important obstacle in kidney transplantation. Our aim was to study the clinical impact of pretransplant donor specific anti-HLA antibodies (HLA-DSA), in highly sensitized (HS) patients. We analyzed retrospectively the day-of-transplant sera by Luminex Single Antigen Assay (LSA) in HS patients, and the results were correlated with episodes of humoral and cellular rejection as well as with graft and patient survival. All HS subjects received the same induction therapy and rejection episodes were biopsy proven. Thirteen patients (56.5%) preformed HLA-DSA, and we observed higher incidence of acute rejection in aforementioned patients than in the pre-transplant negatives DSA recipients (77% versus 30%, P = 0.03). The one-year graft survival was significantly reduced in positive pre-transplant HLA-DSA patients (60% versus 100%, P = 0.01 Breslow). The positive predicted value of HLA-DSA in relation to rejection reached 100% if patients lost their previous graft in the first year after transplant. Among anti-HLA antibodies present in patients before transplant, HLA-DSA were significantly associated with high risk of acute humoral and cellular rejection and reduced graft survival in posttransplant outcome. The negative impact of these antibodies was even higher when patients suffered an early loss of the previous transplant.
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Human Drg1 is a potassium-dependent GTPase enhanced by Lerepo4.
FEBS J.
PUBLISHED: 03-22-2013
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Human Drg1, a guanine nucleotide binding protein conserved in archaea and eukaryotes, is regulated by Lerepo4. Together they form a complex which interacts with translating ribosomes. Here we have purified and characterized the GTPase activity of Drg1 and three variants, a shortened mutant depleted of the TGS domain, a phosphomimicking mutant and a construct with the two combined mutations. Our data reveal that potassium strongly stimulates the GTPase activity, without changing the monomeric status of Drg1 and that this activity is notably reduced in the mutants. The nature of Lerepo4 association has also been investigated. Dissecting the role of the different domains revealed that Dfrp domain is the sole responsible for the Drg1 increase in thermal stability and the four fold stimulation over its catalytic activity. Lerepo4 action leaves Drg1 affinity for nucleotides unaffected, feasibly favoring a switch I reorientation, mainly via the TGS domain. Drg1 displayed a high temperature optimum of activity at 42°C, suggesting the ability of being active under possible heat stress conditions.
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Surface-modified multifunctional MIP nanoparticles.
Nanoscale
PUBLISHED: 03-15-2013
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The synthesis of core-shell molecularly imprinted polymer nanoparticles (MIP NPs) has been performed using a novel solid-phase approach on immobilised templates. The same solid phase also acts as a protective functionality for high affinity binding sites during subsequent derivatisation/shell formation. This procedure allows for the rapid synthesis, controlled separation and purification of high-affinity materials, with each production cycle taking just 2 hours. The aim of this approach is to synthesise uniformly sized imprinted materials at the nanoscale which can be readily grafted with various polymers without affecting their affinity and specificity. For demonstration purposes we grafted anti-melamine MIP NPs with coatings which introduce the following surface characteristics: high polarity (PEG methacrylate); electro-activity (vinylferrocene); fluorescence (eosin acrylate); thiol groups (pentaerythritol tetrakis(3-mercaptopropionate)). The method has broad applicability and can be used to produce multifunctional imprinted nanoparticles with potential for further application in the biosensors, diagnostics and biomedical fields and as an alternative to natural receptors.
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Suppressing aberrant GluN3A expression rescues synaptic and behavioral impairments in Huntingtons disease models.
Nat. Med.
PUBLISHED: 03-06-2013
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Huntingtons disease is caused by an expanded polyglutamine repeat in the huntingtin protein (HTT), but the pathophysiological sequence of events that trigger synaptic failure and neuronal loss are not fully understood. Alterations in N-methyl-D-aspartate (NMDA)-type glutamate receptors (NMDARs) have been implicated. Yet, it remains unclear how the HTT mutation affects NMDAR function, and direct evidence for a causative role is missing. Here we show that mutant HTT redirects an intracellular store of juvenile NMDARs containing GluN3A subunits to the surface of striatal neurons by sequestering and disrupting the subcellular localization of the endocytic adaptor PACSIN1, which is specific for GluN3A. Overexpressing GluN3A in wild-type mouse striatum mimicked the synapse loss observed in Huntingtons disease mouse models, whereas genetic deletion of GluN3A prevented synapse degeneration, ameliorated motor and cognitive decline and reduced striatal atrophy and neuronal loss in the YAC128 Huntingtons disease mouse model. Furthermore, GluN3A deletion corrected the abnormally enhanced NMDAR currents, which have been linked to cell death in Huntingtons disease and other neurodegenerative conditions. Our findings reveal an early pathogenic role of GluN3A dysregulation in Huntingtons disease and suggest that therapies targeting GluN3A or pathogenic HTT-PACSIN1 interactions might prevent or delay disease progression.
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Endocytosis of synaptic ADAM10 in neuronal plasticity and Alzheimers disease.
J. Clin. Invest.
PUBLISHED: 03-05-2013
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A disintegrin and metalloproteinase 10 (ADAM10), a disintegrin and metalloproteinase that resides in the postsynaptic densities (PSDs) of excitatory synapses, has previously been shown to limit ?-amyloid peptide (A?) formation in Alzheimers disease (AD). ADAM10 also plays a critical role in regulating functional membrane proteins at the synapse. Using human hippocampal homogenates, we found that ADAM10 removal from the plasma membrane was mediated by clathrin-dependent endocytosis. Additionally, we identified the clathrin adaptor AP2 as an interacting partner of a previously uncharacterized atypical binding motif in the ADAM10 C-terminal domain. This domain was required for ADAM10 endocytosis and modulation of its plasma membrane levels. We found that the ADAM10/AP2 association was increased in the hippocampi of AD patients compared with healthy controls. Long-term potentiation (LTP) in hippocampal neuronal cultures induced ADAM10 endocytosis through AP2 association and decreased surface ADAM10 levels and activity. Conversely, long-term depression (LTD) promoted ADAM10 synaptic membrane insertion and stimulated its activity. ADAM10 interaction with the synapse-associated protein-97 (SAP97) was necessary for LTD-induced ADAM10 trafficking and required for LTD maintenance and LTD-induced changes in spine morphogenesis. These data identify and characterize a mechanism controlling ADAM10 localization and activity at excitatory synapses that is relevant to AD pathogenesis.
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Epidemiological Clinical Features and Evolution of Gastroduodenal Ulcer Bleeding in a Tertiary Care Hospital in Spain, during the Last Seven Years.
Gastroenterol Res Pract
PUBLISHED: 03-02-2013
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Background. Gastroduodenal ulcer bleeding is a common medical emergency. The aim of this study was to analyze the characteristics of bleeding episodes and to identify changes in the clinical trends over seven years. Methods. Retrospective observational clinical study on a cohort of 272 consecutive adult patients with peptic ulcer bleeding, during the 2006-2012 period. Results. Mean annual admission rate was 12.8 per 100.000 inhabitants. Men were predominant (71%), with a mean age of 66.6 years. Comorbidities were present in 131 cases (48.2%) and 156 patients (57.4%) had received ulcerogenic drugs. Duodenal ulcer was the commonest location (61%). Endoscopic therapy was necessary in 183 cases (67.3%) and rebleeding occurred in 30 patients (11%). Overall mortality rate was 5.5%, with a significant association with the presence of comorbidities (P < 0.01). There were no differences in trends of annual hospitalization, clinical features at presentation, and outcomes during this 7-years period. Conclusions. Annual hospitalization rates and prognosis of peptic ulcer bleeding have remained unchanged in the study period. This may be due to the fact that the effect of improved approach on this condition is probably counteracted by risk factors such as older age, severe comorbidities, and ulcerogenic drugs consumption, which have also remained stable over recent years.
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Tyrosine phosphorylation regulates the endocytosis and surface expression of GluN3A-containing NMDA receptors.
J. Neurosci.
PUBLISHED: 03-01-2013
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Selective control of receptor trafficking provides a mechanism for remodeling the receptor composition of excitatory synapses, and thus supports synaptic transmission, plasticity, and development. GluN3A (formerly NR3A) is a nonconventional member of the NMDA receptor (NMDAR) subunit family, which endows NMDAR channels with low calcium permeability and reduced magnesium sensitivity compared with NMDARs comprising only GluN1 and GluN2 subunits. Because of these special properties, GluN3A subunits act as a molecular brake to limit the plasticity and maturation of excitatory synapses, pointing toward GluN3A removal as a critical step in the development of neuronal circuitry. However, the molecular signals mediating GluN3A endocytic removal remain unclear. Here we define a novel endocytic motif (YWL), which is located within the cytoplasmic C-terminal tail of GluN3A and mediates its binding to the clathrin adaptor AP2. Alanine mutations within the GluN3A endocytic motif inhibited clathrin-dependent internalization and led to accumulation of GluN3A-containing NMDARs at the cell surface, whereas mimicking phosphorylation of the tyrosine residue promoted internalization and reduced cell-surface expression as shown by immunocytochemical and electrophysiological approaches in recombinant systems and rat neurons in primary culture. We further demonstrate that the tyrosine residue is phosphorylated by Src family kinases, and that Src-activation limits surface GluN3A expression in neurons. Together, our results identify a new molecular signal for GluN3A internalization that couples the functional surface expression of GluN3A-containing receptors to the phosphorylation state of GluN3A subunits, and provides a molecular framework for the regulation of NMDAR subunit composition with implications for synaptic plasticity and neurodevelopment.
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[Co-occurrence of anxiety and autism. The social error and allostatic load hypotheses].
Rev Neurol
PUBLISHED: 03-01-2013
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INTRODUCTION. The concept of comorbidity in neurodevelopmental disorders like autism is sometimes ambiguous. The co-occurrence of anxiety and autism is clinically significant, yet it is not always easy to determine whether it is a real comorbidity, where the two comorbid conditions are phenotypically and aetiologically identical to what that anxiety would mean in persons with a neurotypical development, whether it is an anxiety that has been phenotypically modified by the pathological processes of the autism spectrum disorders, thus resulting in a specific variant of these latter, or whether we are dealing with a false comorbidity resulting from rather inaccurate differential diagnoses. DEVELOPMENT. The article puts forward two hypotheses to explain this co-occurrence, which provide each other with feedback and are little more than our reflections on the scientific evidence we have available today, but expressed aloud. The first is the social error hypothesis, which considers that the maladjustments in the social behaviour of persons with autism (which arises from alterations affecting the processes involved in social cognition) help to aggravate anxiety in autism. The second hypothesis, referring to allostatic load, holds that anxiety is a response to chronic stress, wear or exhaustion that is produced by the hyperactivation of certain structures in the limbic system. CONCLUSIONS. The prototypical manifestations of anxiety present in the person with autism are not always related with the same biopsychosocial variables as those observed in persons without autism. Evidence points to hyper-reactive flee-or-fight responses (hypervigilance) when the person finds him or herself outside their comfort zone, and supports the hypotheses of social error and of decompensation of the allostatic mechanism that makes it possible to cope with stress.
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Effectiveness of two interventions based on improving patient-practitioner communication on diabetes self-management in patients with low educational level: study protocol of a clustered randomized trial in primary care.
BMC Health Serv Res
PUBLISHED: 02-24-2013
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In the last decades the presence of social inequalities in diabetes care has been observed in multiple countries, including Spain. These inequalities have been at least partially attributed to differences in diabetes self-management behaviours. Communication problems during medical consultations occur more frequently to patients with a lower educational level. The purpose of this cluster randomized trial is to determine whether an intervention implemented in a General Surgery, based in improving patient-provider communication, results in a better diabetes self-management in patients with lower educational level. A secondary objective is to assess whether telephone reinforcement enhances the effect of such intervention. We report the design and implementation of this on-going study.Methods/designThe study is being conducted in a General Practice located in a deprived neighbourhood of Granada, Spain. Diabetic patients 18 years old or older with a low educational level and inadequate glycaemic control (HbA1c > 7%) were recruited. General Practitioners (GPs) were randomised to three groups: intervention A, intervention B and control group. GPs allocated to intervention groups A and B received training in communication skills and are providing graphic feedback about glycosylated haemoglobin levels. Patients whose GPs were allocated to group B are additionally receiving telephone reinforcement whereas patients from the control group are receiving usual care. The described interventions are being conducted during 7 consecutive medical visits which are scheduled every three months. The main outcome measure will be HbA1c; blood pressure, lipidemia, body mass index and waist circumference will be considered as secondary outcome measures. Statistical analysis to evaluate the effectiveness of the interventions will include multilevel regression analysis with three hierarchical levels: medical visit level, patient level and GP level.
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Casein kinase 2 phosphorylation of protein kinase C and casein kinase 2 substrate in neurons (PACSIN) 1 protein regulates neuronal spine formation.
J. Biol. Chem.
PUBLISHED: 02-18-2013
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The PACSIN (protein kinase C and casein kinase 2 substrate in neurons) adapter proteins couple components of the clathrin-mediated endocytosis machinery with regulators of actin polymerization and thereby regulate the surface expression of specific receptors. The brain-specific PACSIN 1 is enriched at synapses and has been proposed to affect neuromorphogenesis and the formation and maturation of dendritic spines. In studies of how phosphorylation of PACSIN 1 contributes to neuronal function, we identified serine 358 as a specific site used by casein kinase 2 (CK2) in vitro and in vivo. Phosphorylated PACSIN 1 was found in neuronal cytosol and membrane fractions. This localization could be modulated by trophic factors such as brain-derived neurotrophic factor (BDNF). We further show that expression of a phospho-negative PACSIN 1 mutant, S358A, or inhibition of CK2 drastically reduces spine formation in neurons. We identified a novel protein complex containing the spine regulator Rac1, its GTPase-activating protein neuron-associated developmentally regulated protein (NADRIN), and PACSIN 1. CK2 phosphorylation of PACSIN 1 leads to a dissociation of the complex upon BDNF treatment and induces Rac1-dependent spine formation in dendrites of hippocampal neurons. These findings suggest that upon BDNF signaling PACSIN 1 is phosphorylated by CK2 which is essential for spine formation.
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The role of metabonomics as a tool for augmenting nutritional information in epidemiological studies.
Electrophoresis
PUBLISHED: 02-01-2013
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Most chronic diseases have been demonstrated to have a link to nutrition. Within food and nutritional research there is a major driver to understand the relationship between diet and disease in order to improve health of individuals. However, the lack of accurate dietary intake assessment in free-living populations, makes accurate estimation of how diet is associated with disease risk difficulty. Thus, there is a pressing need to find solutions to the inaccuracy of dietary reporting. Metabolic profiling of urine or plasma can provide an unbiased approach to characterizing dietary intake and various high-throughput analytical platforms have been used in order to implement targeted and nontargeted assays in nutritional clinical trials and nutritional epidemiology studies. This review describes first the challenges presented in interpreting the relationship between diet and health within individual and epidemiological frameworks. Second, we aim to explore how metabonomics can benefit different types of nutritional studies and discuss the critical importance of selecting appropriate analytical techniques in these studies. Third, we propose a strategy capable of providing accurate assessment of food intake within an epidemiological framework in order establish accurate associations between diet and health.
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Important functional role of residue x of the presenilin GxGD protease active site motif for APP substrate cleavage specificity and substrate selectivity of ?-secretase.
J. Neurochem.
PUBLISHED: 01-15-2013
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?-Secretase plays a central role in the generation of the Alzheimer disease-causing amyloid ?-peptide (A?) from the ?-amyloid precursor protein (APP) and is thus a major Alzheimers disease drug target. As several other ?-secretase substrates including Notch1 and CD44 have crucial signaling functions, an understanding of the mechanism of substrate recognition and cleavage is key for the development of APP selective ?-secretase-targeting drugs. The ?-secretase active site domain in its catalytic subunit presenilin (PS) 1 has been implicated in substrate recognition/docking and cleavage. Highly critical in this process is its GxGD active site motif, whose invariant glycine residues cannot be replaced without causing severe functional losses in substrate selection and/or cleavage efficiency. Here, we have investigated the contribution of the less well characterized residue x of the motif (L383 in PS1) to this function. Extensive mutational analysis showed that processing of APP was overall well-tolerated over a wide range of hydrophobic and hydrophilic mutations. Interestingly, however, most L383 mutants gave rise to reduced levels of A?37-39 species, and several increased the pathogenic A?42/43 species. Several of the A?42/43 -increasing mutants severely impaired the cleavages of Notch1 and CD44 substrates, which were not affected by any other L383 mutation. Our data thus establish an important, but compared with the glycine residues of the motif, overall less critical functional role for L383. We suggest that L383 and the flanking glycine residues form a spatial arrangement in PS1 that is critical for docking and/or cleavage of different ?-secretase substrates.
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Improving diabetes care in rural areas: a systematic review and meta-analysis of quality improvement interventions in OECD countries.
PLoS ONE
PUBLISHED: 01-01-2013
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Despite well documented disparities in health and healthcare in rural communities, evidence in relation to quality improvement (QI) interventions in those settings is still lacking. The main goals of this work were to assess the effectiveness of QI strategies designed to improve diabetes care in rural areas, and identify characteristics associated with greater success.
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Earthworms Produce phytochelatins in Response to Arsenic.
PLoS ONE
PUBLISHED: 01-01-2013
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Phytochelatins are small cysteine-rich non-ribosomal peptides that chelate soft metal and metalloid ions, such as cadmium and arsenic. They are widely produced by plants and microbes; phytochelatin synthase genes are also present in animal species from several different phyla, but there is still little known about whether these genes are functional in animals, and if so, whether they are metal-responsive. We analysed phytochelatin production by direct chemical analysis in Lumbricus rubellus earthworms exposed to arsenic for a 28 day period, and found that arsenic clearly induced phytochelatin production in a dose-dependent manner. It was necessary to measure the phytochelatin metabolite concentrations directly, as there was no upregulation of phytochelatin synthase gene expression after 28 days: phytochelatin synthesis appears not to be transcriptionally regulated in animals. A further untargetted metabolomic analysis also found changes in metabolites associated with the transsulfuration pathway, which channels sulfur flux from methionine for phytochelatin synthesis. There was no evidence of biological transformation of arsenic (e.g. into methylated species) as a result of laboratory arsenic exposure. Finally, we compared wild populations of earthworms sampled from the field, and found that both arsenic-contaminated and cadmium-contaminated mine site worms had elevated phytochelatin concentrations.
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A new kinetic framework for synaptic vesicle trafficking tested in synapsin knock-outs.
J. Neurosci.
PUBLISHED: 08-12-2011
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At least two rate-limiting mechanisms in vesicle trafficking operate at mouse Schaffer collateral synapses, but their molecular/physical identities are unknown. The first mechanism determines the baseline rate at which reserve vesicles are supplied to a readily releasable pool. The second causes the supply rate to depress threefold when synaptic transmission is driven hard for extended periods. Previous models invoked depletion of a reserve vesicle pool to explain the reductions in the supply rate, but the mass-action assumption at their core is not compatible with kinetic measurements of neurotransmission under maximal-use conditions. Here we develop a new theoretical model of rate-limiting steps in vesicle trafficking that is compatible with previous and new measurements. A physical interpretation is proposed where local reserve pools consisting of four vesicles are tethered to individual release sites and are replenished stochastically in an all-or-none fashion. We then show that the supply rate depresses more rapidly in synapsin knock-outs and that the phenotype can be fully explained by changing the value of the single parameter in the model that would specify the size of the local reserve pools. Vesicle-trafficking rates between pools were not affected. Finally, optical imaging experiments argue against alternative interpretations of the theoretical model where vesicle trafficking is inhibited without reserve pool depletion. This new conceptual framework will be useful for distinguishing which of the multiple molecular and cell biological mechanisms involved in vesicle trafficking are rate limiting at different levels of synaptic throughput and are thus candidates for physiological and pharmacological modulation.
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Refractory iron-deficiency anemia and gluten intolerance - Response to gluten-free diet.
Rev Esp Enferm Dig
PUBLISHED: 07-21-2011
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refractory iron-deficiency anemia has a multifactorial origin related to various gastrointestinal conditions, with celiac disease plus malabsorption and IBD together with isolated gluten intolerance being most common.
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Sequence and role in virulence of the three plasmid complement of the model tumor-inducing bacterium Pseudomonas savastanoi pv. savastanoi NCPPB 3335.
PLoS ONE
PUBLISHED: 07-19-2011
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Pseudomonas savastanoi pv. savastanoi NCPPB 3335 is a model for the study of the molecular basis of disease production and tumor formation in woody hosts, and its draft genome sequence has been recently obtained. Here we closed the sequence of the plasmid complement of this strain, composed of three circular molecules of 78,357 nt (pPsv48A), 45,220 nt (pPsv48B), and 42,103 nt (pPsv48C), all belonging to the pPT23A-like family of plasmids widely distributed in the P. syringae complex. A total of 152 coding sequences were predicted in the plasmid complement, of which 38 are hypothetical proteins and seven correspond to putative virulence genes. Plasmid pPsv48A contains an incomplete Type IVB secretion system, the type III secretion system (T3SS) effector gene hopAF1, gene ptz, involved in cytokinin biosynthesis, and three copies of a gene highly conserved in plant-associated proteobacteria, which is preceded by a hrp box motif. A complete Type IVA secretion system, a well conserved origin of transfer (oriT), and a homolog of the T3SS effector gene hopAO1 are present in pPsv48B, while pPsv48C contains a gene with significant homology to isopentenyl-diphosphate delta-isomerase, type 1. Several potential mobile elements were found on the three plasmids, including three types of MITE, a derivative of IS801, and a new transposon effector, ISPsy30. Although the replication regions of these three plasmids are phylogenetically closely related, their structure is diverse, suggesting that the plasmid architecture results from an active exchange of sequences. Artificial inoculations of olive plants with mutants cured of plasmids pPsv48A and pPsv48B showed that pPsv48A is necessary for full virulence and for the development of mature xylem vessels within the knots; we were unable to obtain mutants cured of pPsv48C, which contains five putative toxin-antitoxin genes.
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eIF4F complex disruption causes protein synthesis inhibition during hypoxia in nerve growth factor (NGF)-differentiated PC12 cells.
Biochim. Biophys. Acta
PUBLISHED: 07-13-2011
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Poor oxygenation (hypoxia) influences important physiological and pathological situations, including development, ischemia, stroke and cancer. Hypoxia induces protein synthesis inhibition that is primarily regulated at the level of initiation step. This regulation generally takes place at two stages, the phosphorylation of the subunit ? of the eukaryotic initiation factor (eIF) 2 and the inhibition of the eIF4F complex availability by dephosphorylation of the inhibitory protein 4E-BP1 (eukaryotic initiation factor 4E-binding protein 1). The contribution of each of them is mainly dependent of the extent of the oxygen deprivation. We have evaluated the regulation of hypoxia-induced translation inhibition in nerve growth factor (NGF)-differentiated PC12 cells subjected to a low oxygen concentration (0.1%) at several times. Our findings indicate that protein synthesis inhibition occurs primarily by the disruption of eIF4F complex through 4E-BP1 dephosphorylation, which is produced by the inhibition of the mammalian target of rapamycin (mTOR) activity via the activation of REDD1 (regulated in development and DNA damage 1) protein in a hypoxia-inducible factor 1 (HIF1)-dependent manner, as well as the translocation of eIF4E to the nucleus. In addition, this mechanism is reinforced by the increase in 4E-BP1 levels, mainly at prolonged times of hypoxia.
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Prevalence and clinical correlates of restless legs syndrome among psychogeriatric patients.
Int J Geriatr Psychiatry
PUBLISHED: 07-11-2011
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To evaluate the prevalence, clinical features, and comorbidities of restless legs syndrome (RLS) among psychogeriatric patients in an out-patient clinical setting.
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The influence of the energy absorbed from microwave pretreatment on biogas production from secondary wastewater sludge.
Bioresour. Technol.
PUBLISHED: 06-21-2011
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In this study, microwave treatment is analyzed as a way to accelerate the hydrolysis in anaerobic digestion of municipal wastewater sludge. The influence of the absorbed energy, power and athermal microwave effect on organic matter solubilization and biogas production has been studied. In addition, a novel method that considers the absorbed energy in the microwave system is proposed, in order to obtain comparable experimental results. The absorbed energy is calculated from an energy balance. The highest solubilization was achieved using 0.54 kJ/ml at 1000 W, where an increment of 7.1% was observed in methane production, compared to the untreated sample. Using a higher energy value (0.83 kJ/ml), methane production further increased (to 15.4%), but solubilization decreased. No power influence was found when 0.54 kJ/ml was applied at 1000, 600 and 440 W. Microwave heating was compared to conventional heating in two different experimental setups, providing similar methane yields in all cases.
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The relationship between reproductive work and sociodemographic and psychosocial factors in regard to psychological distress in men and women in Spain.
Prev Sci
PUBLISHED: 06-10-2011
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Studies have shown that some sociodemographic factors, such as marital status, employment status or social class, can affect mental health in different ways for each gender. However, up until now, few research projects have tried to ascertain if the role that reproductive work or psychosocial factors play in mental health is different for men and women. The aim of this study is to assess the differences between men and women in terms of how reproductive work, sociodemographic and psychosocial factors are linked to psychological distress in Spain. A cross-sectional study of 29,478 male and female adults using data gathered for the Spanish National Health Survey 2006 was carried out. Psychological distress was measured using the GHQ-12. The independent variables analyzed were: sociodemographic, psychosocial (family functionality and functional social support) and those related to reproductive work (living with or being in charge of different types of people needing care and number of hours devoted to caregiver tasks). Different independent logistic regression models were developed for men and women. In general, with the exception of men who were more prone to psychological distress if they were signed off work for 3 months or more, no major differences were observed regarding the effect of sociodemographic and psychosocial characteristics on psychological distress. With regard to reproductive work, the likelihood of psychological distress doubles in both sexes when the person lives with someone who needs care. In women, a greater number of hours devoted to caring for another person is associated with an increase in distress. Men play a less frequent role in caregiving, but the impact on psychological distress is similar to that in women. Women experienced more psychological distress when they had to live with or be in charge of a disabled person or different types of persons needing care, while men were not affected by this. Major differences have been identified in terms of psychological distress in women and men in several aspects of reproductive work to date unexplored.
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Differences between pediatric and adult celiac disease.
Rev Esp Enferm Dig
PUBLISHED: 05-31-2011
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Celiac disease (CD) is a common autoimmune condition (involves 1-2% of the general population) that develops at any age in life but manifests differently in children and adults.
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Effect of exposure to p,p-DDE on male hormone profile in Mexican flower growers.
Occup Environ Med
PUBLISHED: 05-10-2011
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p,p-Dichlorodiphenyldichloroethene (p,p-DDE) acts as an androgen receptor antagonist, however data regarding its hormonal effects in men are limited. The objective of this study was to evaluate the association between serum levels of p,p-DDE and reproductive hormone profile in Mexican male flower growers.
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[Application of an OPT model in a paediatric nursing clinical case in primary health care].
Enferm Clin
PUBLISHED: 05-04-2011
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This article describes the assessment and nursing diagnostic hypothesis generation on a 10 years old child with a parietal contusion who attended the health care centre with his mother. The health centre is located in a rural area in Catalonia, and a paediatric nurse was placed in charge of the child. In the assessment and the subsequent information analysis, the nurse identified an unhealthy situation for the correct development of the child. The situation required the mothers intervention and a change in her habits and behaviours. For the approach of the case study, the OPT model (Outcome Present-state Testing) by Pesut and Herdman was used. The assessment was made by using Marjory Gordons Functional Health Patterns assessment, and the NANDA-I nursing diagnoses taxonomy, NOC Outcomes taxonomy and NIC Interventions taxonomy was used for the diagnoses and planning.
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Physical and structural changes in liquid whole egg treated with high-intensity pulsed electric fields.
J. Food Sci.
PUBLISHED: 05-04-2011
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Liquid whole egg (LWE) is currently pasteurized through the application of heat; however, this treatment entails deleterious effects against some of the functional and technological properties of the product. In this study, the effect of high-intensity pulsed electric fields (HIPEF) processing (field strength: 19, 32, and 37 kV/cm) was compared to the traditional heat pasteurization (66 °C for 4.5 min). Different physical and structural characteristics of LWE, subjected or not to homogenization, were evaluated and compared, having the untreated LWE as a reference. Thermal treatment caused an increase in the viscosity of LWE, especially in nonhomogenized samples. HIPEF treatments did not modify the original color of LWE, whereas thermally treated samples developed an opaque appearance. LWE treated at 19 and 32 kV/cm exhibited a similar foaming capacity as fresh untreated egg, whereas thermal processing and PEF treatments of 37 kV/cm caused a substantial decrease in the foaming capacity of untreated liquid egg. Regarding the microstructure, the lipoprotein matrix appeared to be less affected by the HIPEF than by heat treatment if compared to the control. In addition, heat pasteurization had a significant impact on both the water-soluble protein content of the LWE samples (19.5% to 23.6% decrease) and the mechanical properties of the egg gels (up to 21.3% and 14.5% increase in hardness and cohesiveness, respectively). On the other hand, these parameters were not substantially affected in the HIPEF-treated samples. Heat-induced gels obtained from HIPEF-treated samples did not exhibit remarkable differences in the water-holding capacity (WHC) with respect to heat-pasteurized samples.
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Depressive dimensions and item response analysis of the Hamilton Depression Rating Scale-17 in eating disorders.
Compr Psychiatry
PUBLISHED: 05-03-2011
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Most patients having eating disorders (EDs) experience depressive symptoms. To date, there have been few reports about the different depressive dimensions in EDs.
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Azithromycin inhibits expression of the GacA-dependent small RNAs RsmY and RsmZ in Pseudomonas aeruginosa.
Antimicrob. Agents Chemother.
PUBLISHED: 05-02-2011
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Azithromycin at clinically relevant doses does not inhibit planktonic growth of the opportunistic pathogen Pseudomonas aeruginosa but causes markedly reduced formation of biofilms and quorum-sensing-regulated extracellular virulence factors. In the Gac/Rsm signal transduction pathway, which acts upstream of the quorum-sensing machinery in P. aeruginosa, the GacA-dependent untranslated small RNAs RsmY and RsmZ are key regulatory elements. As azithromycin treatment and mutational inactivation of gacA have strikingly similar phenotypic consequences, the effect of azithromycin on rsmY and rsmZ expression was investigated. In planktonically growing cells, the antibiotic strongly inhibited the expression of both small RNA genes but did not affect the expression of the housekeeping gene proC. The azithromycin treatment resulted in reduced expression of gacA and rsmA, which are known positive regulators of rsmY and rsmZ, and of the PA0588-PA0584 gene cluster, which was discovered as a novel positive regulatory element involved in rsmY and rsmZ expression. Deletion of this cluster resulted in diminished ability of P. aeruginosa to produce pyocyanin and to swarm. The results of this study indicate that azithromycin inhibits rsmY and rsmZ transcription indirectly by lowering the expression of positive regulators of these small RNA genes.
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Note: Phase-locked loop with a voltage controlled oscillator based on a liquid crystal cell as variable capacitance.
Rev Sci Instrum
PUBLISHED: 04-18-2011
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A phase-locked loop is demonstrated using a twisted-nematic liquid crystal cell as a capacitance that can be varied as a function of applied voltage. The system is formed by a phase detector, a low-pass filter, as well as a voltage controlled oscillator including such variable capacitance. A theoretical study is proposed and experimentally validated. Capture and locked ranges of hundreds of kHz have been obtained for the configuration used in this circuit. An application as frequency demodulator using a practical implementation of this circuit has been demonstrated.
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