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Find video protocols related to scientific articles indexed in Pubmed.
CXCR4 and a cell-extrinsic mechanism control immature B lymphocyte egress from bone marrow.
J. Exp. Med.
PUBLISHED: 11-19-2014
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Leukocyte residence in lymphoid organs is controlled by a balance between retention and egress-promoting chemoattractants sensed by pertussis toxin (PTX)-sensitive G?i protein-coupled receptors (GPCRs). Here, we use two-photon intravital microscopy to show that immature B cell retention within bone marrow (BM) was strictly dependent on amoeboid motility mediated by CXCR4 and CXCL12 and by ?4?1 integrin-mediated adhesion to VCAM-1. However, B lineage cell egress from BM is independent of PTX-sensitive GPCR signaling. B lineage cells expressing PTX rapidly exited BM even though their motility within BM parenchyma was significantly reduced. Our experiments reveal that when immature B cells are near BM sinusoids their motility is reduced, their morphology is predominantly rounded, and cells reverse transmigrate across sinusoidal endothelium in a largely nonamoeboid manner. Immature B cell egress from BM was dependent on a twofold CXCR4 down-regulation that was antagonized by antigen-induced BCR signaling. This passive mode of cell egress from BM also contributes significantly to the export of other hematopoietic cells, including granulocytes, monocytes, and NK cells, and is reminiscent of erythrocyte egress.
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NMR metabolomics of human lung tumours reveals distinct metabolic signatures for adenocarcinoma and squamous cell carcinoma.
Carcinogenesis
PUBLISHED: 11-05-2014
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Lung tumour subtyping, particularly the distinction between adenocarcinoma (AdC) and squamous cell carcinoma (SqCC), is a critical diagnostic requirement. In this work, the metabolic signatures of lung carcinomas were investigated through (1)H NMR metabolomics, with a view to provide additional criteria for improved diagnosis and treatment planning. High Resolution Magic Angle Spinning (HRMAS) NMR spectroscopy was used to analyse matched tumour and adjacent control tissues from 56 patients undergoing surgical excision of primary lung carcinomas. Multivariate modelling allowed tumour and control tissues to be discriminated with high accuracy (97% classification rate), mainly due to significant differences in the levels of 13 metabolites. Notably, the magnitude of those differences were clearly distinct for AdC and SqCC: major alterations in AdC were related to phospholipid metabolism (increased phosphocholine, glycerophosphocholine and phosphoethanolamine, together with decreased acetate) and protein catabolism (increased peptide moieties), whereas SqCC had stronger glycolytic and glutaminolytic profiles (negatively correlated variations in glucose and lactate and positively correlated increases in glutamate and alanine). Other tumour metabolic features were increased creatine, GSH, taurine and uridine nucleotides, the first two being especially prominent in SqCC and the latter in AdC. Furthermore, multivariate analysis of AdC and SqCC profiles allowed their discrimination with a 94% classification rate, thus showing great potential for aiding lung tumours subtyping. Overall, this study has provided new, clear evidence of distinct metabolic signatures for lung AdC and SqCC, which can potentially impact on diagnosis and provide important leads for future research on novel therapeutic targets or imaging tracers.
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Concomitant Unipolar Radiofrequency Ablation of Nonparoxysmal Atrial Fibrillation in Rheumatic and Degenerative Valve Disease.
J Card Surg
PUBLISHED: 10-21-2014
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The aim of this study was to compare the results of concomitant unipolar radiofrequency ablation of nonparoxysmal atrial fibrillation (AF) between rheumatic and degenerative valve disease (RHD versus DVD).
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A NEW ACANTHOCEPHALAN SPECIES (ARCHIACANTHOCEPHALA: OLIGACANTHORHYNCHIDAE) FROM CERDOCYON THOUS, A CRAB-EATING FOX IN THE BRAZILIAN PANTANAL WETLANDS.
J. Parasitol.
PUBLISHED: 10-08-2014
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Abstract A new species of Oligancanthorhynchidae (Acanthocephala) Prosthenochis cerdocyonys n. sp. is described from 17 specimens collected from the small intestine of the crab-eating fox Cerdocyon thous Linnaeus, 1766 (Canidae: Carnivora) found in the Brazilian Pantanal Wetlands. The new species were studied using light and scanning electron microscopy. Characteristic features distinguishing the new species from others already described were presented, such as size of the body, the position of lemnisci, size of the eggs, host, and geographical distribution. Therefore, details of the body surface obtained by scanning electron microscopy, such as the presence of 2 lateral papillae in the proximal region of the proboscis, the presence of barbs in hooks, a robust and festooned collar, helped to identify the species. Until now, specimens of the genus Prosthenorchis were reported to parasitize Cerdocyon thous but had not been identified. Furthermore, the new species is the first to be recorded in C. thous found in the Pantanal Wetlands.
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Milk Fermented with a 15-Lipoxygenase-1-Producing Lactococcus Lactis Alleviates Symptoms of colitis in a Murine Model.
Curr Pharm Biotechnol
PUBLISHED: 09-26-2014
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Inflammatory bowel disease (IBD), such as Crohn's disease and ulcerative colitis, are characterized by extensive inflammation due to dysregulation of the innate and adaptive immune system whose exact etiology is not yet completely understood. Currently there is no cure for IBD, thus the search for new molecules capable of controlling IBD and their delivery to the site of inflammation are the goal of many researchers. The aim of this work was to evaluate the anti-inflammatory effect of the administration of milks fermented by a Lactococcus (L.) lactis strain producing 15-lipoxygenase-1 (15-LOX-1) using a trinitrobenzenesulfonic acid-induced IBD mouse model. The results obtained demonstrated that 15-LOX-1 producing L. lactis was effective in the prevention of the intestinal damage associated to inflammatory bowel disease in a murine model. The work also confirmed previous studies showing that fermented milk is an effective form of administration of recombinant lactic acid bacteria expressing beneficial molecules.
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Controlled pericardiocentesis in patients with cardiac tamponade complicating aortic dissection: Experience of a centre without cardiothoracic surgery.
Eur Heart J Acute Cardiovasc Care
PUBLISHED: 09-02-2014
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Cardiac tamponade has been reported in 18.7% of patients with acute type A aortic dissection and its presence is associated with worse outcomes. Emergency aortic repair together with intra-operative pericardial drainage is the recommended treatment approach. However, controversy surrounds how to manage patients with haemopericardium and cardiac tamponade who cannot survive until surgery.
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Dopamine signaling leads to loss of Polycomb repression and aberrant gene activation in experimental parkinsonism.
PLoS Genet.
PUBLISHED: 09-01-2014
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Polycomb group (PcG) proteins bind to and repress genes in embryonic stem cells through lineage commitment to the terminal differentiated state. PcG repressed genes are commonly characterized by the presence of the epigenetic histone mark H3K27me3, catalyzed by the Polycomb repressive complex 2. Here, we present in vivo evidence for a previously unrecognized plasticity of PcG-repressed genes in terminally differentiated brain neurons of parkisonian mice. We show that acute administration of the dopamine precursor, L-DOPA, induces a remarkable increase in H3K27me3S28 phosphorylation. The induction of the H3K27me3S28p histone mark specifically occurs in medium spiny neurons expressing dopamine D1 receptors and is dependent on Msk1 kinase activity and DARPP-32-mediated inhibition of protein phosphatase-1. Chromatin immunoprecipitation (ChIP) experiments showed that increased H3K27me3S28p was accompanied by reduced PcG binding to regulatory regions of genes. An analysis of the genome wide distribution of L-DOPA-induced H3K27me3S28 phosphorylation by ChIP sequencing (ChIP-seq) in combination with expression analysis by RNA-sequencing (RNA-seq) showed that the induction of H3K27me3S28p correlated with increased expression of a subset of PcG repressed genes. We found that induction of H3K27me3S28p persisted during chronic L-DOPA administration to parkisonian mice and correlated with aberrant gene expression. We propose that dopaminergic transmission can activate PcG repressed genes in the adult brain and thereby contribute to long-term maladaptive responses including the motor complications, or dyskinesia, caused by prolonged administration of L-DOPA in Parkinson's disease.
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Affective and Cognitive Determinants of Women's Sexual Response to Erotica.
J Sex Med
PUBLISHED: 08-15-2014
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The specific cognitive-affective mechanisms involved in the activation and regulation of the subjective and genital components of sexual arousal are not fully understood yet.
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An integrative omics strategy to assess the germ cell secretome and to decipher sertoli-germ cell crosstalk in the Mammalian testis.
PLoS ONE
PUBLISHED: 08-11-2014
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Mammalian spermatogenesis, which takes place in complex testicular structures called seminiferous tubules, is a highly specialized process controlled by the integration of juxtacrine, paracrine and endocrine information. Within the seminiferous tubules, the germ cells and Sertoli cells are surrounded by testicular fluid (TF), which probably contains most of the secreted proteins involved in crosstalk between these cells. It has already been established that germ cells can modulate somatic Sertoli cell function through the secretion of diffusible factors. We studied the germ cell secretome, which was previously considered inaccessible, by analyzing the TF collected by microsurgery in an "integrative omics" strategy combining proteomics, transcriptomics, genomics and interactomics data. This approach identified a set of proteins preferentially secreted by Sertoli cells or germ cells. An interaction network analysis revealed complex, interlaced cell-cell dialog between the secretome and membranome of seminiferous cells, mediated via the TF. We then focused on germ cell-secreted candidate proteins, and we identified several potential interacting partners located on the surface of Sertoli cells. Two interactions, APOH/CDC42 and APP/NGFR, were validated in situ, in a proximity ligation assay (PLA). Our results provide new insight into the crosstalk between germ cells and Sertoli cells occurring during spermatogenesis. Our findings also demonstrate that this "integrative omics" strategy is powerful enough for data mining and highlighting meaningful cell-cell communication events between different types of cells in a complex tissue, via a biological fluid. This integrative strategy could be applied more widely, to gain access to secretomes that have proved difficult to study whilst avoiding the limitations of in vitro culture.
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Predictors of Men's Sexual Response to Erotic Film Stimuli: The Role of Affect and Self-Reported Thoughts.
J Sex Med
PUBLISHED: 08-08-2014
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Both emotions and cognitions seem to play a role in determining sexual arousal. However, no studies to date have tested the effects of self-reported thoughts on subjective sexual arousal and genital response using psychophysiological methods.
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The relationship between dehydroepiandrosterone (DHEA), working memory and distraction--a behavioral and electrophysiological approach.
PLoS ONE
PUBLISHED: 08-08-2014
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Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulphate (DHEAS) have been reported to have memory enhancement effects in humans. A neuro-stimulatory action and an anti-cortisol mechanism of action may contribute to that relation. In order to study DHEA, DHEAS and cortisol relations to working memory and distraction, we recorded the electroencephalogram of 23 young women performing a discrimination (no working memory load) or 1-back (working memory load) task in an audio-visual oddball paradigm. We measured salivary DHEA, DHEAS and cortisol both before each task and at 30 and 60 min. Under working memory load, a higher baseline cortisol/DHEA ratio was related to higher distraction as indexed by an enhanced novelty P3. This suggests that cortisol may lead to increased distraction whereas DHEA may hinder distraction by leading to less processing of the distractor. An increased DHEA production with consecutive cognitive tasks was found and higher DHEA responses attributed to working memory load were related to enhanced working memory processing as indexed by an enhanced visual P300. Overall, the results suggest that in women DHEA may oppose cortisol effects reducing distraction and that a higher DHEA response may enhance working memory at the electrophysiological level.
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Anti-inflammatory effects of Lactococcus lactis NCDO 2118 during the remission period of chemically induced colitis.
Gut Pathog
PUBLISHED: 07-29-2014
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Many probiotic bacteria have been described as promising tools for the treatment and prevention of inflammatory bowel diseases (IBDs). Most of these bacteria are lactic acid bacteria, which are part of the healthy human microbiota. However, little is known about the effects of transient bacteria present in normal diets, including Lactococcus lactis.
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A protein kinase screen of Neurospora crassa mutant strains reveals that the SNF1 protein kinase promotes glycogen synthase phosphorylation.
Biochem. J.
PUBLISHED: 07-24-2014
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Glycogen functions as a carbohydrate reserve in a variety of organisms and its metabolism is highly regulated. The activities of glycogen synthase and glycogen phosphorylase, the rate-limiting enzymes of the synthesis and degradation processes, respectively, are regulated by allosteric modulation and by reversible phosphorylation. To identify the protein kinases affecting glycogen metabolism in N. crassa, we performed a screen of 84 serine/threonine kinase knockout strains. We identified multiple kinases that have already been described as controlling glycogen metabolism in different organisms, such as NcSNF1, NcPHO85, NcGSK3, NcPKA, PSK2 homologue, and NcATG1. In addition, many hypothetical kinases have been implicated in the control of glycogen metabolism. Two kinases, NcIME-2 and NcNIMA already functionally characterized but with no functions related to glycogen metabolism regulation, were also identified. Among the kinases identified, it is important to mention the role of NcSNF1. We showed here that this kinase was implicated in glycogen synthase phosphorylation, as demonstrated by the higher levels of glycogen accumulated during growth, along with a higher glycogen synthase -/+ G6P activity ratio and a lesser set of phosphorylated GSN isoforms in strain Ncsnf1KO, when compared to the wild-type strain. The results led us to conclude that, in N. crassa, this kinase promotes phosphorylation of glycogen synthase either directly or indirectly, which is the opposite of what is described for S. cerevisiae. The kinases also play a role in gene expression regulation in that gdn, the gene encoding debranching enzyme, was down-regulated by the proteins identified in the screen. Some kinases affected growth and development suggesting a connection linking glycogen metabolism with cell growth and development.
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Assessment of the efficacy of the utilisation of conventional and electric toothbrushes by the elderly.
Gerodontology
PUBLISHED: 07-22-2014
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Objective:? To evaluate the efficacy of electric and conventional toothbrushes for a group of elderly individuals. Background:? Although the electric toothbrush has been recommended for elderly individuals, there had previously never been a study regarding its efficacy. Material and methods:? Sixty independent elders of both genders with different oral conditions from the Center Adult Day Vitória, Espírito Santo, Brazil, were randomly divided into two groups of 30 individuals. One group received the Oral B CrossAction Power electric toothbrush, whereas the other received a conventional Bitufo Class 32 soft toothbrush to perform oral hygiene. The bacterial plaque index (O'Leary Plaque Index) and DMFT index were assessed as a measure of oral hygiene and oral health. The data were analysed using the Shapiro-Wilk, Mann-Whitney and Wilcoxon tests. Results:? The results of the efficacy of the Oral B Cross Action Power electric toothbrush demonstrated that on the 7th and 15th days, the bacterial plaque indexes were 24.91?±?12.81 and 22.11?±?14.46, respectively, which corresponds to a 50.24% removal of bacterial plaque on the 7th and 55.83% on the 15th days. Although the electric toothbrush removed more bacterial plaque than the conventional toothbrush, the difference was not statistically significant. Conclusion:? Both the conventional and the electric toothbrushes were effective in removing bacterial plaque within the elderly group. More studies are necessary to test the efficacy of electric toothbrushes in relation to conventional toothbrushes for elderly patients.
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Cultivar variability of iron uptake mechanisms in rice (Oryza sativa L.).
Plant Physiol. Biochem.
PUBLISHED: 07-01-2014
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Rice (Oryza sativa L.) is the most important staple food in the world. It is rich in genetic diversity and can grow in a wide range of environments. Iron (Fe) deficiency is a major abiotic stress in crop production and in aerobic soils, where Fe forms insoluble complexes, and is not readily available for uptake. To cope with Fe deficiency, plants developed mechanisms for Fe uptake, and although rice was described as a Strategy II plant, recent evidence suggests that it is capable of utilizing mechanisms from both Strategies. The main objective of this work was to compare two cultivars, Bico Branco (japonica) and Nipponbare (tropical japonica), to understand if the regulation of Fe uptake mechanisms could be cultivar (cv.) dependent. Plants of both cultivars were grown under Fe-deficient and -sufficient conditions and physiological and molecular responses to Fe deficiency were evaluated. Bico Branco cv. developed more leaf chlorosis and was more susceptible to Fe deficiency, retaining more nutrients in roots, than Nipponbare cv., which translocated more nutrients to shoots. Nipponbare cv. presented higher levels of Fe reductase activity, which was significantly up-regulated by Fe deficiency, and had higher expression levels of the Strategy I-OsFRO2 gene in roots, while Bico Branco cv. induced more genes involved in Strategy II. These new findings show that rice cultivars have different responses to Fe deficiency and that the induction of Strategy I or II may be rice cultivar-dependent, although the utilization of the reduction mechanisms seems to be an ubiquitous advantage.
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Association between nutritional status, C-reactive protein, adiponectin and HOMA-AD in Brazilian children.
Nutr Hosp
PUBLISHED: 07-01-2014
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In children, the presence of obesity is a major risk factor for the occurrence of cardiovascular diseases on the adulthood.
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Global abundance of planktonic heterotrophic protists in the deep ocean.
ISME J
PUBLISHED: 06-10-2014
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The dark ocean is one of the largest biomes on Earth, with critical roles in organic matter remineralization and global carbon sequestration. Despite its recognized importance, little is known about some key microbial players, such as the community of heterotrophic protists (HP), which are likely the main consumers of prokaryotic biomass. To investigate this microbial component at a global scale, we determined their abundance and biomass in deepwater column samples from the Malaspina 2010 circumnavigation using a combination of epifluorescence microscopy and flow cytometry. HP were ubiquitously found at all depths investigated down to 4000?m. HP abundances decreased with depth, from an average of 72±19 cells?ml(-1) in mesopelagic waters down to 11±1 cells?ml(-1) in bathypelagic waters, whereas their total biomass decreased from 280±46 to 50±14?pg C?ml(-1). The parameters that better explained the variance of HP abundance were depth and prokaryote abundance, and to lesser extent oxygen concentration. The generally good correlation with prokaryotic abundance suggested active grazing of HP on prokaryotes. On a finer scale, the prokaryote:HP abundance ratio varied at a regional scale, and sites with the highest ratios exhibited a larger contribution of fungi molecular signal. Our study is a step forward towards determining the relationship between HP and their environment, unveiling their importance as players in the dark ocean's microbial food web.The ISME Journal advance online publication, 7 October 2014; doi:10.1038/ismej.2014.168.
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Treatment with Evasin-3 abrogates neutrophil-mediated inflammation in mouse acute pancreatitis.
Eur. J. Clin. Invest.
PUBLISHED: 05-30-2014
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Acute pancreatitis is characterized by inflammatory processes affecting not only the pancreas, but also the lung. Here, we investigated timing of leucocyte infiltration and chemokine expression within lung and pancreas during pancreatitis and whether treatments selectively inhibiting chemokines (using Evasins) could improve organ injury.
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The Sirt1 activator SRT3025 provides atheroprotection in Apoe-/- mice by reducing hepatic Pcsk9 secretion and enhancing Ldlr expression.
Eur. Heart J.
PUBLISHED: 03-08-2014
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The deacetylase sirtuin 1 (Sirt1) exerts beneficial effects on lipid metabolism, but its roles in plasma LDL-cholesterol regulation and atherosclerosis are controversial. Thus, we applied the pharmacological Sirt1 activator SRT3025 in a mouse model of atherosclerosis and in hepatocyte culture.
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Phosphoinositide metabolism links cGMP-dependent protein kinase G to essential Ca²? signals at key decision points in the life cycle of malaria parasites.
PLoS Biol.
PUBLISHED: 03-01-2014
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Many critical events in the Plasmodium life cycle rely on the controlled release of Ca²? from intracellular stores to activate stage-specific Ca²?-dependent protein kinases. Using the motility of Plasmodium berghei ookinetes as a signalling paradigm, we show that the cyclic guanosine monophosphate (cGMP)-dependent protein kinase, PKG, maintains the elevated level of cytosolic Ca²? required for gliding motility. We find that the same PKG-dependent pathway operates upstream of the Ca²? signals that mediate activation of P. berghei gametocytes in the mosquito and egress of Plasmodium falciparum merozoites from infected human erythrocytes. Perturbations of PKG signalling in gliding ookinetes have a marked impact on the phosphoproteome, with a significant enrichment of in vivo regulated sites in multiple pathways including vesicular trafficking and phosphoinositide metabolism. A global analysis of cellular phospholipids demonstrates that in gliding ookinetes PKG controls phosphoinositide biosynthesis, possibly through the subcellular localisation or activity of lipid kinases. Similarly, phosphoinositide metabolism links PKG to egress of P. falciparum merozoites, where inhibition of PKG blocks hydrolysis of phosphatidylinostitol (4,5)-bisphosphate. In the face of an increasing complexity of signalling through multiple Ca²? effectors, PKG emerges as a unifying factor to control multiple cellular Ca²? signals essential for malaria parasite development and transmission.
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PTH-C1: a rat continuous cell line expressing the parathyroid phenotype.
Endocrine
PUBLISHED: 02-26-2014
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The lack of a continuous cell line of epithelial parathyroid cells able to produce parathyroid hormone (PTH) has hampered the studies on in vitro evaluation of the mechanisms involved in the control of parathyroid cell function and proliferation. The PT-r cell line was first established from rat parathyroid tissue in 1987, but these cells were known to express the parathyroid hormone-related peptide (Pthrp) gene, but not the Pth gene. In an attempt to subclone the PT-r cell line, a rat parathyroid cell strain was isolated and named PTH-C1. During 3 years, in culture, PTH-C1 cells maintained an epithelioid morphology, displaying a diploid chromosome number, a doubling time around 15 h during the exponential phase of growth, and parathyroid functional features. PTH-C1 cell line produces PTH and expresses the calcium sensing receptor (Casr) gene and other genes known to be involved in parathyroid function. Most importantly, the PTH-C1 cells also exhibit an in vitro secretory response to calcium. Altogether these findings indicate the uniqueness of the PTH-C1 cell line as an in vitro model for cellular and molecular studies on parathyroid physiopathology.
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Qualitative and quantitative peptidomic and proteomic approaches to phenotyping chicken semen.
J Proteomics
PUBLISHED: 02-24-2014
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Understanding of the avian male gamete biology is essential to improve the conservation of genetic resources and performance in farming. In this study, the chicken semen peptidome/proteome and the molecular phenotype related to sperm quality were investigated. Spermatozoa (SPZ) and corresponding seminal plasma (SP) from 11 males with different fertilizing capacity were analyzed using three quantitative strategies (fluid and intact cells MALDI-MS, SDS-PAGE combined to LC-MS/MS with spectral counting and XIC methods). Individual MALDI profiling in combination with top-down MS allowed to characterize specific profiles per male and to identify 16 biomolecules (e.g.VMO1, AvBD10 and AvBD9 including polymorphism). Qualitative analysis identified 1165 proteins mainly involved in oxidoreduction mechanisms, energy processes, proteolysis and protein localization. Comparative analyses between the most and the least fertile males were performed. The enzymes involved in energy metabolism, respiratory chain or oxido-reduction activity were over-represented in SPZ of the most fertile males. The SP of the most and the least fertile males differed also on many proteins (e.g. ACE, AvBD10 and AvBD9, NEL precursor, acrosin). Thus proteomic is a "phenomic molecular tool" that may help to discriminate avian males on their reproductive capacity. The data have been deposited with ProteomeXchange (identifier PXD000287).
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SRT2104 extends survival of male mice on a standard diet and preserves bone and muscle mass.
Aging Cell
PUBLISHED: 02-24-2014
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Increased expression of SIRT1 extends the lifespan of lower organisms and delays the onset of age-related diseases in mammals. Here, we show that SRT2104, a synthetic small molecule activator of SIRT1, extends both mean and maximal lifespan of mice fed a standard diet. This is accompanied by improvements in health, including enhanced motor coordination, performance, bone mineral density, and insulin sensitivity associated with higher mitochondrial content and decreased inflammation. Short-term SRT2104 treatment preserves bone and muscle mass in an experimental model of atrophy. These results demonstrate it is possible to design a small molecule that can slow aging and delay multiple age-related diseases in mammals, supporting the therapeutic potential of SIRT1 activators in humans.
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Urethral dysfunction due to alloxan-induced diabetes. Urodynamic and morphological evaluation.
Acta Cir Bras
PUBLISHED: 02-20-2014
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To evaluate the effect of short and long term alloxan-induced diabetes on bladder and urethral function of female rats, and also describing its correlated morphological alterations.
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Functional modifications associated with gastrointestinal tract organogenesis during metamorphosis in Atlantic halibut (Hippoglossus hippoglossus).
BMC Dev. Biol.
PUBLISHED: 02-19-2014
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Flatfish metamorphosis is a hormone regulated post-embryonic developmental event that transforms a symmetric larva into an asymmetric juvenile. In altricial-gastric teleost fish, differentiation of the stomach takes place after the onset of first feeding, and during metamorphosis dramatic molecular and morphological modifications of the gastrointestinal (GI-) tract occur. Here we present the functional ontogeny of the developing GI-tract from an integrative perspective in the pleuronectiforme Atlantic halibut, and test the hypothesis that the multiple functions of the teleost stomach develop synchronously during metamorphosis.
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Synthesis, structural elucidation, and catalytic properties in olefin epoxidation of the polymeric hybrid material [Mo3O9(2-[3(5)-pyrazolyl]pyridine)]n.
Inorg Chem
PUBLISHED: 02-12-2014
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The reaction of [MoO2Cl2(pzpy)] (1) (pzpy = 2-[3(5)-pyrazolyl]pyridine) with water in an open reflux system (16 h), in a microwave synthesis system (120 °C, 2 h), or in a Teflon-lined stainless steel digestion bomb (100 °C, 19 h) gave the molybdenum oxide/pyrazolylpyridine polymeric hybrid material [Mo3O9(pzpy)]n (2) as a microcrystalline powder in yields of 72–79%. Compound 2 can also be obtained by the hydrothermal reaction of MoO3, pzpy, and H2O at 160 °C for 3 d. Secondary products isolated from the reaction solutions included the salt (pzpyH)2(MoCl4) (3) (pzpyH = 2-[3(5)-pyrazolyl]pyridinium), containing a very rare example of the tetrahedral MoCl4(2–) anion, and the tetranuclear compound [Mo4O12(pzpy)4] (4). Reaction of 2 with excess tert-butylhydroperoxide (TBHP) led to the isolation of the oxodiperoxo complex [MoO(O2)2(pzpy)] (5). Single-crystal X-ray structures of 3 and 5 are described. Fourier transform (FT)-IR and FT Raman spectra for 1, 4, and 5 were assigned based on density functional theory calculations. The structure of 2 was determined from synchrotron powder X-ray diffraction data in combination with other physicochemical information. In 2, a hybrid organic–inorganic one-dimensional (1D) polymer, ?(1)[Mo3O9(pzpy)], is formed by the connection of two very distinct components: a double ladder-type inorganic core reminiscent of the crystal structure of MoO3 and 1D chains of corner-sharing distorted {MoO4N2} octahedra. Compound 2 exhibits moderate activity and high selectivity when used as a (pre)catalyst for the epoxidation of cis-cyclooctene with TBHP. Under the reaction conditions used, 2 is poorly soluble and is gradually converted into 5, which is at least partly responsible for the catalytic reaction.
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Genetic and chemical analyses reveal that trypanothione synthetase but not glutathionylspermidine synthetase is essential for Leishmania infantum.
Free Radic. Biol. Med.
PUBLISHED: 02-10-2014
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Trypanothione is a unique and essential redox metabolite of trypanosomatid parasites, the biosynthetic pathway of which is regarded as a promising target for antiparasitic drugs. Synthesis of trypanothione occurs by the consecutive conjugation of two glutathione molecules to spermidine. Both reaction steps are catalyzed by trypanothione synthetase (TRYS), a molecule known to be essential in Trypanosoma brucei. However, other trypanosomatids (including some Leishmania species and Trypanosoma cruzi) potentially express one additional enzyme, glutathionylspermidine synthetase (GSPS), capable of driving the first step of trypanothione synthesis yielding glutathionylspermidine. Because this monothiol can substitute for trypanothione in some reactions, the possibility existed that TRYS was redundant in parasites harboring GSPS. To clarify this issue, the functional relevance of both GSPS and TRYS was investigated in Leishmania infantum (Li). Employing a gene-targeting approach, we generated a gsps(-/-) knockout line, which was viable and capable of replicating in both life cycle stages of the parasite, thus demonstrating the superfluous role of LiGSPS. In contrast, elimination of both LiTRYS alleles was not possible unless parasites were previously complemented with an episomal copy of the gene. Retention of extrachromosomal LiTRYS in the trys(-/-)/+TRYS line after several passages in culture further supported the essentiality of this gene for survival of L. infantum (including its clinically relevant stage), hence ruling out the hypothesis of functional complementation by LiGSPS. Chemical targeting of LiTRYS with a drug-like compound was shown to also lead to parasite death. Overall, this study disqualifies GSPS as a target for drug development campaigns and, by genetic and chemical evidence, validates TRYS as a chemotherapeutic target in a parasite endowed with GSPS and, thus, probably along the entire trypanosomatid lineage.
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Clinical comparison of the effectiveness of single-file reciprocating systems and rotary systems for removal of endotoxins and cultivable bacteria from primarily infected root canals.
J Endod
PUBLISHED: 02-02-2014
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This clinical study was conducted to compare the effectiveness of single-file reciprocating systems and rotary systems in removing endotoxins and cultivable bacteria from primarily infected root canals.
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N-cinnamoylation of antimalarial classics: quinacrine analogues with decreased toxicity and dual-stage activity.
ChemMedChem
PUBLISHED: 01-30-2014
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Plasmodium falciparum, the causative agent of the most lethal form of malaria, is becoming increasingly resistant to most available drugs. A convenient approach to combat parasite resistance is the development of analogues of classical antimalarial agents, appropriately modified in order to restore their relevance in antimalarial chemotherapy. Following this line of thought, the design, synthesis and in vitro evaluation of N-cinnamoylated quinacrine surrogates, 9-(N-cinnamoylaminobutyl)-amino-6-chloro-2-methoxyacridines, is reported. The compounds were found to be highly potent against both blood-stage P.falciparum, chloroquine-sensitive 3D7 (IC50 =17.0-39.0 nM) and chloroquine-resistant W2 and Dd2 strains (IC50 =3.2-41.2 and 27.1-131.0 nM, respectively), and liver-stage P.berghei (IC50 =1.6-4.9 ?M) parasites. These findings bring new hope for the possible future "rise of a fallen angel" in antimalarial chemotherapy, with a potential resurgence of quinacrine-related compounds as dual-stage antimalarial leads.
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P-glycoprotein induction in Caco-2 cells by newly synthetized thioxanthones prevents paraquat cytotoxicity.
Arch. Toxicol.
PUBLISHED: 01-22-2014
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The induction of P-glycoprotein (P-gp), an ATP-dependent efflux pump, has been proposed as a strategy against the toxicity induced by P-gp substrates such as the herbicide paraquat (PQ). The aim of this study was to screen five newly synthetized thioxanthonic derivatives, a group known to interact with P-gp, as potential inducers of the pump's expression and/or activity and to evaluate whether they would afford protection against PQ-induced toxicity in Caco-2 cells. All five thioxanthones (20 µM) caused a significant increase in both P-gp expression and activity as evaluated by flow cytometry using the UIC2 antibody and rhodamine 123, respectively. Additionally, it was demonstrated that the tested compounds, when present only during the efflux of rhodamine 123, rapidly induced an activation of P-gp. The tested compounds also increased P-gp ATPase activity in MDR1-Sf9 membrane vesicles, indicating that all derivatives acted as P-gp substrates. PQ cytotoxicity was significantly reduced in the presence of four thioxanthone derivatives, and this protective effect was reversed upon incubation with a specific P-gp inhibitor. In silico studies showed that all the tested thioxanthones fitted onto a previously described three-feature P-gp induction pharmacophore. Moreover, in silico interactions between thioxanthones and P-gp in the presence of PQ suggested that a co-transport mechanism may be operating. Based on the in vitro activation results, a pharmacophore model for P-gp activation was built, which will be of further use in the screening for new P-gp activators. In conclusion, the study demonstrated the potential of the tested thioxanthonic compounds in protecting against toxic effects induced by P-gp substrates through P-gp induction and activation.
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Oral combined therapy with probiotics and alloantigen induces B cell-dependent long-lasting specific tolerance.
J. Immunol.
PUBLISHED: 01-22-2014
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Allogeneic hematopietic stem cell transplantation (aHSCT) is widely used for the treatment of hematologic malignancies. Although aHSCT provides a good response against the malignant cells (graft-versus-leukemia [GVL]), it also leads to the development of graft-versus-host disease (GVHD), a severe disease with high mortality and morbidity rates. Therapy for GVHD is commonly based on nonspecific immunosupression of the transplanted recipient, resulting in the concomitant inhibition of the GVL effect. In this study, we propose an alternative approach to specifically suppress GVHD while sparing the GVL, based on oral treatment of transplant donors with recipient Ags, associated with the intake of probiotic Lactococcus lactis as tolerogenic adjuvant (combined therapy). We show that treatment of C57BL/6 donor mice with combined therapy before the transplant protects the recipients F1 (C57BL/6 × BAL/c) mice from clinical and pathological manifestations of disease, resulting in 100% survival rate. Importantly, the animals keep the immunological competence maintaining the GVL response as well as the response to third-party Ags. The protection is specific, long lasting and dependent on donor IL-10-sufficient B cells activity, which induces regulatory T cells in the host. These data suggest that combined therapy is a promising strategy for prevention of GVHD with preservation of GVL, opening new possibilities to treat human patients subjected to transplantation.
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Surgical treatment of atrial fibrillation: an updated review.
Eur J Cardiothorac Surg
PUBLISHED: 01-19-2014
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The first Cox-maze procedure was performed in 1987, demonstrating the feasibility of a non-pharmacological treatment for atrial fibrillation (AF). Since then, surgery for AF has changed over time, in parallel with technological advances. Replacement of surgical incisions with linear ablation lines made a previously cumbersome procedure accessible to most surgeons, without compromising success. On the other hand, new ablation technologies paved the way for the development of minimally invasive surgery, which may potentially extend the scope of surgery to patients who would otherwise be deemed unsuitable. Nonetheless, literature on minimally invasive surgery is still scarce and randomized clinical trials currently under way are expected to shed light on some controversial issues. Moreover, successful AF treatment will probably rely on close collaboration between surgery and electrophysiology. Indeed, the hybrid procedure, though still in its very beginning, seems to combine the best of catheter and surgical ablation. However, further studies are warranted to determine the effectiveness of this promising strategy, especially in patients with persistent and longstanding persistent AF. Better understanding of AF pathophysiology as well as more accurate preoperative localization of AF triggers will bring about the possibility of tailoring specific lesion sets and ablation modalities to individual patients. This, in turn, will increase recovery and maintenance of sinus rhythm, with significant benefits in long-term outcomes.
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Geroncogenesis: metabolic changes during aging as a driver of tumorigenesis.
Cancer Cell
PUBLISHED: 01-18-2014
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Why does cancer risk increase as we age? Frequently attributed to the multi-hit hypothesis and the time required to accumulate genomic mutations, this question is a matter of ongoing debate. Here, we propose that the normal decline in oxidative metabolism during aging constitutes an early and important "hit" that drives tumorigenesis. Central to these metabolic changes are the sirtuins, a family of NAD(+)-dependent deacylases that have evolved as coordinators of physiological responses to nutrient intake and energetic demand. Thus, the modulation of sirtuins might be a fruitful approach to reversing the age-related metabolic changes that could underlie tumorigenesis.
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Optimization of the production of solid Witepsol nanoparticles loaded with rosmarinic acid.
Colloids Surf B Biointerfaces
PUBLISHED: 01-14-2014
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During the last decade there has been a growing interest in the formulation of new food and nutraceutical products containing compounds with antioxidant activity. Unfortunately, due to their structure, certain compounds such as polyphenols, in particular rosmarinic acid (RA) are not stable and may interact easily with matrices in which they are incorporated. To overcome such limitations, the formulation of loaded polyphenols nanoparticles can offer an efficient solution to protect such compounds. Based on this rationale, the aim of this study was to prepare solid lipid nanoparticles (SLNs) loaded with RA using a hot melt ultrasonication method, where Witepsol H15 was used as lipid and Polysorbate 80 (Tween 80) as surfactant, following a 3(2) fractional factorial design, resulting in the use of 3 different percentages of surfactant (viz. 1, 2 and 3%, v/v) and lipid (0.5, 1.0 and 1.5%, w/v). The stability of the nanoparticles systems were tested during 28 d in aqueous solution stored at refrigeration temperature (ca. 5 °C), tracking the mean particle size of different formulations by photon correlation spectroscopy. To confirm RA entrapment, thermal analyses of the nanoparticles by DSC and FTIR were performed. The association efficiencies percentages (AE%) were determined using HPLC to quantitatively assess the RA in supernatants. Results showed that Witepsol H15 produced nanoparticles with initial mean diameters between 270 and 1000 nm, yet over time, a slight increase occurred, but without occurrence of aggregation. The AE% showed a high percentage of encapsulation (ca. 99%), which reveals low polyphenol releases from SLNs throughout storage time. In general, results showed a successful production of SLNs with properties that can be used to food applications.
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Local and systemic immune mechanisms underlying the anti-colitis effects of the dairy bacterium Lactobacillus delbrueckii.
PLoS ONE
PUBLISHED: 01-01-2014
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Several probiotic bacteria have been proposed for treatment or prevention of inflammatory bowel diseases (IBD), showing a protective effect in animal models of experimental colitis and for some of them also in human clinical trials. While most of these probiotic bacteria are isolated from the digestive tract, we recently reported that a Lactobacillus strain isolated from cheese, L. delbrueckii subsp. lactis CNRZ327 (Lb CNRZ327), also possesses anti-inflammatory effects in vitro and in vivo, demonstrating that common dairy bacteria may be useful in the treatment or prevention of IBD. Here, we studied the mechanisms underlying the protective effects of Lb CNRZ327 in vivo, in a mouse dextran sodium sulfate (DSS) colitis model. During colitis, Lb CNRZ327 modulated the production of TGF-?, IL-6, and IL-12 in colonic tissue and of TGF-? and IL-6 in the spleen, and caused an expansion of CD4+Foxp3+ regulatory T cells in the cecal lymph nodes. Moreover, a strong tendency to CD4+Foxp3+ expansion was also observed in the spleen. The results of this study for the first time show that orally administered dairy lactobacilli can not only modulate mucosal but also systemic immune responses and constitute an effective treatment of IBD.
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Unravelling the diversity of grapevine microbiome.
PLoS ONE
PUBLISHED: 01-01-2014
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Vitis vinifera is one of the most widely cultivated fruit crops with a great economic impact on the global industry. As a plant, it is naturally colonised by a wide variety of both prokaryotic and eukaryotic microorganisms that interact with grapevine, having either beneficial or phytopathogenic effects, who play a major role in fruit yield, grape quality and, ultimately, in the evolution of grape fermentation and wine production. Therefore, the objective of this study was to extensively characterize the natural microbiome of grapevine. Considering that the majority of microorganisms are uncultivable, we have deeply studied the microflora of grapevine leaves using massive parallel rDNA sequencing, along its vegetative cycle. Among eukaryotic population the most abundant microorganisms belonged to the early diverging fungi lineages and Ascomycota phylum, whereas the Basidiomycota were the least abundant. Regarding prokaryotes, a high diversity of Proteobacteria, Firmicutes and Actinobacteria was unveiled. Indeed, the microbial communities present in the vineyard during its vegetative cycle were shown to be highly structured and dynamic. In all cases, the major abundant microorganisms were the yeast-like fungus Aureobasidium and the prokaryotic Enterobacteriaceae. Herein, we report the first complete microbiome landscape of the vineyard, through a metagenomic approach, and highlight the analysis of the microbial interactions within the vineyard and its importance for the equilibrium of the microecosystem of grapevines.
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Evaluation of life quality of patients submitted to orthognathic surgery.
Dental Press J Orthod
PUBLISHED: 12-20-2013
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To compare changes related to self-esteem and appearance satisfaction between pre and postsurgical phases in patients undergoing orthognathic surgery and to assess the quality of life and psychosocial changes of these patients six months after surgery.
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The Malarial Serine Protease SUB1 Plays an Essential Role in Parasite Liver Stage Development.
PLoS Pathog.
PUBLISHED: 12-01-2013
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Transmission of the malaria parasite to its vertebrate host involves an obligatory exoerythrocytic stage in which extensive asexual replication of the parasite takes place in infected hepatocytes. The resulting liver schizont undergoes segmentation to produce thousands of daughter merozoites. These are released to initiate the blood stage life cycle, which causes all the pathology associated with the disease. Whilst elements of liver stage merozoite biology are similar to those in the much better-studied blood stage merozoites, little is known of the molecular players involved in liver stage merozoite production. To facilitate the study of liver stage biology we developed a strategy for the rapid production of complex conditional alleles by recombinase mediated engineering in Escherichia coli, which we used in combination with existing Plasmodium berghei deleter lines expressing Flp recombinase to study subtilisin-like protease 1 (SUB1), a conserved Plasmodium serine protease previously implicated in blood stage merozoite maturation and egress. We demonstrate that SUB1 is not required for the early stages of intrahepatic growth, but is essential for complete development of the liver stage schizont and for production of hepatic merozoites. Our results indicate that inhibitors of SUB1 could be used in prophylactic approaches to control or block the clinically silent pre-erythrocytic stage of the malaria parasite life cycle.
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miR-363-5p regulates endothelial cell properties and their communication with hematopoietic precursor cells.
J Hematol Oncol
PUBLISHED: 11-06-2013
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Recent findings have shown that the blood vessels of different organs exert an active role in regulating organ function. In detail, the endothelium that aligns the vasculature of most organs is fundamental in maintaining organ homeostasis and in promoting organ recovery following injury. Mechanistically, endothelial cells (EC) of tissues such as the liver, lungs or the bone marrow (BM) have been shown to produce "angiocrine" factors that promote organ recovery and restore normal organ function. Controlled production of angiocrine factors following organ injury is therefore essential to promote organ regeneration and to restore organ function. However, the molecular mechanisms underlying the coordinated production and function of such "angiocrine" factors are largely undisclosed and were the subject of the present study. In detail, we identified for the first time a microRNA (miRNA) expressed by BM EC that regulates the expression of angiocrine genes involved in BM recovery following irradiation. Using a microarray-based approach, we identified several miRNA expressed by irradiated BMEC. After validating the variations in miRNA expression by semi-quantitative PCR, we chose to study further the ones showing consistent variations between experiments, and those predicted to regulate (directly or indirectly) angiogenic and angiocrine factors. Of the mi-RNA that were chosen, miR-363-5p (previously termed miR-363*) was subsequently shown to modulate the expression of numerous EC-specific genes including some angiocrine factors. By luciferase reporter assays, miR-363-5p is shown to regulate the expression of angiocrine factors tissue inhibitor of metalloproteinases-1 (Timp-1) and thrombospondin 3 (THBS3) at post-transcriptional level. Moreover, miR-363-5p reduction using anti-miR is shown to affect EC angiogenic properties (such as the response to angiogenic factors stimulation) and the interaction between EC and hematopoietic precursors (particularly relevant in a BM setting). miR-363-5p reduction resulted in a significant decrease in EC tube formation on matrigel, but increased hematopoietic precursor cells adhesion onto EC, a mechanism that is shown to involve kit ligand-mediated cell adhesion. Taken together, we have identified a miRNA induced by irradiation that regulates angiocrine factors expression on EC and as such modulates EC properties. Further studies on the importance of miR-363-5p on normal BM function and in disease are warranted.
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Influence of EDTA and dentine in tissue dissolution ability of sodium hypochlorite.
Aust Endod J
PUBLISHED: 11-01-2013
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This study verified whether ethylenediaminetetraacetic acid (EDTA) influences the pulp tissue dissolution capability of different concentrations of NaOCl, in the presence of dentine. NaOCl and EDTA solutions were simultaneously mixed in flasks either containing a dentine disc or those not containing a dentine disc. Previously weighed bovine pulp tissues were immersed in the solutions for 5, 15 and 30?min. The weight loss was measured. The dissolution tests were performed in triplicate. Univariate analysis of variance, along with further Tukeys honestly significant difference pairwise comparisons, was used to verify the effect of EDTA, different concentrations of NaOCl, dentine and time of incubation on the tissue dissolution. Higher concentrations of NaOCl increased the tissue dissolution. EDTA reduced the capacity of NaOCl to dissolve pulp tissue, even in presence of dentine. Dentine negatively affects the capacity of NaOCl to dissolve pulp tissue. In conclusion, the presence of EDTA and dentine negatively affects the tissue dissolution ability of NaOCl.
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Declining NAD(+) Induces a Pseudohypoxic State Disrupting Nuclear-Mitochondrial Communication during Aging.
Cell
PUBLISHED: 10-25-2013
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Ever since eukaryotes subsumed the bacterial ancestor of mitochondria, the nuclear and mitochondrial genomes have had to closely coordinate their activities, as each encode different subunits of the oxidative phosphorylation (OXPHOS) system. Mitochondrial dysfunction is a hallmark of aging, but its causes are debated. We show that, during aging, there is a specific loss of mitochondrial, but not nuclear, encoded OXPHOS subunits. We trace the cause to an alternate PGC-1?/?-independent pathway of nuclear-mitochondrial communication that is induced by a decline in nuclear NAD(+) and the accumulation of HIF-1? under normoxic conditions, with parallels to Warburg reprogramming. Deleting SIRT1 accelerates this process, whereas raising NAD(+) levels in old mice restores mitochondrial function to that of a young mouse in a SIRT1-dependent manner. Thus, a pseudohypoxic state that disrupts PGC-1?/?-independent nuclear-mitochondrial communication contributes to the decline in mitochondrial function with age, a process that is apparently reversible.
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Preparation of crystal-like periodic mesoporous phenylene-silica derivatized with ferrocene and its use as a catalyst for the oxidation of styrene.
Dalton Trans
PUBLISHED: 08-30-2013
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The surface silanol groups in crystal-like mesoporous phenylene-silica have been derivatized with trimethylsilyl, benzyldimethylsilyl and dimethylsilyl(ferrocene) groups by performing a post-synthetic grafting reaction with the corresponding chlorosilane precursors. The success of the grafting procedure was demonstrated by transmission FT-IR spectroscopy and diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), and (13)C and (29)Si magic-angle spinning (MAS) NMR spectroscopy. Powder X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM) and N2 adsorption data for the modified materials indicated preservation of the mesostructure as well as the molecular-scale periodicity in the pore walls. Ferrocene and the ferrocenyl-modified periodic mesoporous organosilica (PMO) were employed in the catalytic oxidation of styrene at 55 °C using either hydrogen peroxide or tert-butylhydroperoxide as an oxidant. The main reaction product was always benzaldehyde (BzCHO), and other products included styrene oxide, benzoic acid and 2-hydroxyacetophenone. Using a styrene:H2O2 molar ratio of 1:5, the highest BzCHO yields at 24 h were 65% (85% selectivity) for ferrocene (semibatch conditions involving stepwise addition of H2O2, 1 mol% Fe) and 34% (83% selectivity) for the modified PMO (batch conditions, 0.06 mol% Fe). The modified PMO could be recovered and reused, albeit with a drop in catalytic activity due to partial metal leaching during the first catalytic run.
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Update on selective treatments targeting neutrophilic inflammation in atherogenesis and atherothrombosis.
Thromb. Haemost.
PUBLISHED: 08-29-2013
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Atherosclerosis is the most common pathological process underlying cardiovascular diseases. Current therapies are largely focused on alleviating hyperlipidaemia and preventing thrombotic complications, but do not completely eliminate risk of suffering recurrent acute ischaemic events. Specifically targeting the inflammatory processes may help to reduce this residual risk of major adverse cardiovascular events in atherosclerotic patients. The involvement of neutrophils in the pathophysiology of atherosclerosis is an emerging field, where evidence for their causal contribution during various stages of atherosclerosis is accumulating. Therefore, the identification of neutrophils as a potential therapeutic target may offer new therapeutic perspective to reduce the current atherosclerotic burden. This narrative review highlights the expanding role of neutrophils in atherogenesis and discusses on the potential treatment targeting neutrophil-related inflammation and associated atherosclerotic plaque vulnerability.
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Carboxamide SIRT1 inhibitors block DBC1 binding via an acetylation-independent mechanism.
Cell Cycle
PUBLISHED: 07-30-2013
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SIRT1 is an NAD (+) -dependent deacetylase that counteracts multiple disease states associated with aging and may underlie some of the health benefits of calorie restriction. Understanding how SIRT1 is regulated in vivo could therefore lead to new strategies to treat age-related diseases. SIRT1 forms a stable complex with DBC1, an endogenous inhibitor. Little is known regarding the biochemical nature of SIRT1-DBC1 complex formation, how it is regulated and whether or not it is possible to block this interaction pharmacologically. In this study, we show that critical residues within the catalytic core of SIRT1 mediate binding to DBC1 via its N-terminal region, and that several carboxamide SIRT1 inhibitors, including EX-527, can completely block this interaction. We identify two acetylation sites on DBC1 that regulate its ability to bind SIRT1 and suppress its activity. Furthermore, we show that DBC1 itself is a substrate for SIRT1. Surprisingly, the effect of EX-527 on SIRT1-DBC1 binding is independent of DBC1 acetylation. Together, these data show that protein acetylation serves as an endogenous regulatory mechanism for SIRT1-DBC1 binding and illuminate a new path to developing small-molecule modulators of SIRT1.
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Metformin improves healthspan and lifespan in mice.
Nat Commun
PUBLISHED: 06-26-2013
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Metformin is a drug commonly prescribed to treat patients with type 2 diabetes. Here we show that long-term treatment with metformin (0.1% w/w in diet) starting at middle age extends healthspan and lifespan in male mice, while a higher dose (1% w/w) was toxic. Treatment with metformin mimics some of the benefits of calorie restriction, such as improved physical performance, increased insulin sensitivity, and reduced low-density lipoprotein and cholesterol levels without a decrease in caloric intake. At a molecular level, metformin increases AMP-activated protein kinase activity and increases antioxidant protection, resulting in reductions in both oxidative damage accumulation and chronic inflammation. Our results indicate that these actions may contribute to the beneficial effects of metformin on healthspan and lifespan. These findings are in agreement with current epidemiological data and raise the possibility of metformin-based interventions to promote healthy aging.
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Forkhead box proteins: tuning forks for transcriptional harmony.
Nat. Rev. Cancer
PUBLISHED: 06-25-2013
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Forkhead box (FOX) proteins are multifaceted transcription factors that are responsible for fine-tuning the spatial and temporal expression of a broad range of genes both during development and in adult tissues. This function is engrained in their ability to integrate a multitude of cellular and environmental signals and to act with remarkable fidelity. Several key members of the FOXA, FOXC, FOXM, FOXO and FOXP subfamilies are strongly implicated in cancer, driving initiation, maintenance, progression and drug resistance. The functional complexities of FOX proteins are coming to light and have established these transcription factors as possible therapeutic targets and putative biomarkers for specific cancers.
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EFSAs scientific activities and achievements on the risk assessment of genetically modified organisms (GMOs) during its first decade of existence: looking back and ahead.
Transgenic Res.
PUBLISHED: 06-19-2013
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Genetically modified organisms (GMOs) and derived food and feed products are subject to a risk analysis and regulatory approval before they can enter the market in the European Union (EU). In this risk analysis process, the role of the European Food Safety Authority (EFSA), which was created in 2002 in response to multiple food crises, is to independently assess and provide scientific advice to risk managers on any possible risks that the use of GMOs may pose to human and animal health and the environment. EFSAs scientific advice is elaborated by its GMO Panel with the scientific support of several working groups and EFSAs GMO Unit. This review presents EFSAs scientific activities and highlights its achievements on the risk assessment of GMOs for the first 10 years of its existence. Since 2002, EFSA has issued 69 scientific opinions on genetically modified (GM) plant market registration applications, of which 62 for import and processing for food and feed uses, six for cultivation and one for the use of pollen (as or in food), and 19 scientific opinions on applications for marketing products made with GM microorganisms. Several guidelines for the risk assessment of GM plants, GM microorganisms and GM animals, as well as on specific issues such as post-market environmental monitoring (PMEM) were elaborated. EFSA also provided scientific advice upon request of the European Commission on safeguard clause and emergency measures invoked by EU Member States, annual PMEM reports, the potential risks of new biotechnology-based plant breeding techniques, evaluations of previously assessed GMOs in the light of new scientific publications, and the use of antibiotic resistance marker genes in GM plants. Future challenges relevant to the risk assessment of GMOs are discussed. EFSAs risk assessments of GMO applications ensure that data are analysed and presented in a way that facilitates scientifically sound decisions that protect human and animal health and the environment.
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An unusual cause of glomerular hematuria and acute kidney injury in a chronic kidney disease patient during warfarin therapy.
Nefrologia
PUBLISHED: 05-29-2013
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Warfarin is a well-established cause of gross hematuria. However, impaired kidney function does not occur except in the rare instance of severe blood loss or clot formation that obstructs the urinary tract. It has been recently described an entity called warfarin-related nephropathy, in which acute kidney injury is caused by glomerular hemorrhage and renal tubular obstruction by red blood cell casts. We report a patient under warfarin treatment with chronic kidney disease, macroscopic hematuria and acute kidney injury. A renal biopsy showed massive occlusion of renal tubules by red blood cells and casts. The possible relationship of the warfarin therapy, intratubular hemorrhage and acute kidney injury is discussed.
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Role and regulation of the forkhead transcription factors FOXO3a and FOXM1 in carcinogenesis and drug resistance.
Chin J Cancer
PUBLISHED: 05-27-2013
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The FOXO3a and FOXM1 forkhead transcription factors are key players in cancer initiation, progression, and drug resistance. Recent research shows that FOXM1 is a direct transcriptional target of FOXO3a, a vital downstream effector of the PI3K-AKT-FOXO signaling cascade. In addition, FOXM1 and FOXO3a also antagonize each others activity by competitively binding to the same target genes, which are involved in chemotherapeutic drug sensitivity and resistance. Understanding the role and regulation of the FOXO-FOXM1 axis will provide insight into chemotherapeutic drug action and resistance in patients, and help to identify novel therapeutic approaches as well as diagnostic and predictive biomarkers.
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Development and evaluation of a novel topical treatment for acne with azelaic acid-loaded nanoparticles.
Microsc. Microanal.
PUBLISHED: 05-15-2013
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Azelaic acid (AzA) is used in the treatment of acne. However, side effects and low compliance have been associated with several topical treatments with AzA. Nanotechnology presents a strategy that can overcome these problems. Polymeric nanoparticles can control drug release and targeting and reduce local drug toxicity. The aim of this study was to produce and evaluate an innovative topical treatment for acne with AzA-loaded poly-DL-lactide/glycolide copolymer nanoparticles. A soft white powder of nanoparticles was prepared. The mean size of loaded nanoparticles was < 400 nm and zeta potential was negative. Spherical nanoparticles were observed by scanning electron microscopy. Encapsulation efficiency was around 80% and a strong interaction between the polymer and the drug was confirmed by differential scanning calorimetric analysis. In vitro drug release studies suggested a controlled and pulsatile release profile. System efficacy tests suggested similar results between the loaded nanoparticles and the nonencapsulated drug against the most common bacteria associated with acne. Cytotoxicity of AzA-loaded nanoparticles was concentration dependent, although not pronounced. The occluded patch test seemed to indicate that the formulation excipients were safe and thus AzA-loaded nanoparticles appear to be an efficient and safe treatment for acne.
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Intercalation of a molybdenum ?3-allyl dicarbonyl complex in a layered double hydroxide and catalytic performance in olefin epoxidation.
Dalton Trans
PUBLISHED: 04-16-2013
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A Zn-Al layered double hydroxide (LDH) intercalated by [Mo(?(3)-C3H5)Cl(CO)2(bpdc)](2-) anions (bpdc = 2,2-bipyridine-5,5-dicarboxylate) has been prepared by coprecipitation from aqueous solution and characterised by various techniques. The one-pot method gives rise to a highly organised intercalate with an interlayer spacing of 18.3 Å and up to six (00l) basal reflections in the powder X-ray diffraction pattern. Spectroscopic studies (FT-IR, FT-Raman, (13)C CP MAS NMR and UV-Vis) confirm the presence of structurally intact [Mo(?(3)-C3H5)Cl(CO)2(bpdc)](2-) anions. The interlayer spacing of 18.3 Å indicates that the material contains a monolayer of guest anions positioned in such a way that the bpdc ligands are arranged with their longest dimension roughly perpendicular to the hydroxide layers of the host. Thermal properties were studied by thermogravimetric analysis and differential scanning calorimetry. The intracrystalline reactivity of intercalated dicarbonyl complexes was probed by using the hybrid nanocomposite as a precatalyst in the liquid phase epoxidation of cis-cyclooctene with tert-butylhydroperoxide as oxidant. Under the reaction conditions used, oxidative decarbonylation of the guest molecules takes place (with release of CO and CO2 as confirmed by on-line gas chromatography experiments) to give intercalated molybdenum oxide/bipyridine species that selectively catalyse the epoxidation reaction. The intracrystalline oxidative decarbonylation reaction is topotactic in nature.
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Hysteroscopic sterilization of patient with intrauterine device Mirena®.
Einstein (Sao Paulo)
PUBLISHED: 04-13-2013
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Tubal sterilization is the definitive procedure most often used worldwide to control fecundity. Laparoscopic ligature is safe, but invasive and with possible surgical and anesthetic risks. The hysteroscopic approach enables tubal occlusion at outpatients setting without the need of incisions or anesthesia. A microdevice (Essure®) is inserted directly into the tubes and its polyethelene fibers cause obstruction of tubes in about three months. During this period, it is recommended that patients continue the use of a temporary birth control method. Several women use the levonorgestrel-releasing intrauterine system, which is called in the market as Mirena®. This report evaluated the possibility of inserting Essure® without remove the intrauterine device; patient tolerance to the procedure was also assessed. The tubal device was successfully placed in the patient without the need to remove Mirena®. After three months the intrauterine device was removed with no intercurrent events.
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Prevalence of sexual problems in portugal: results of a population-based study using a stratified sample of men aged 18 to 70 years.
J Sex Res
PUBLISHED: 04-10-2013
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Despite the use of different methodologies, target populations, and clinical definitions of sexual problems, recent epidemiological studies have shown that the occurrence of sexual difficulties is a very common experience among men from the general population regardless of their age. The objective of this study was to present epidemiological data on the prevalence of sexual difficulties in a community sample of 650 sexually active Portuguese men, stratified by age, marital status, and educational level. Participants completed a self-reported questionnaire assessing sexual function in the previous four weeks (International Index of Erectile Function). Results showed that sexual difficulties were relatively common among this sample. Rapid ejaculation was the most frequently reported sexual difficulty (23.2%), followed by erectile difficulties (10.2%), orgasm problems (8.2%), and low desire (2.9%) in the previous four weeks. With the exception of rapid ejaculation, all categories showed age-specific prevalence rates, with sexual difficulties increasing gradually in men above age 45. Age was a significant predictor of all sexual difficulties except rapid ejaculation, and lower educational levels were related to orgasm difficulties. Findings are consistent with the majority of epidemiological studies indicating a high prevalence of sexual difficulties among men in the general population and highlight the importance and the need to implement sexual health promotion programs in the target population.
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Is positive affect in pregnancy protective of postpartum depression?
Rev Bras Psiquiatr
PUBLISHED: 04-10-2013
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To investigate the predictive/protective role of negative affect/positive affect in late pregnancy on the outcome of postpartum depression.
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PTHrP-induced modifications of the sea bream (Sparus auratus) vertebral bone proteome.
Gen. Comp. Endocrinol.
PUBLISHED: 04-03-2013
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Endocrine factors play an essential role in the formation and turnover of the skeleton in vertebrates. In the present study sea bream vertebral bone transcripts for PTH1R and PTH3R were identified and the action of intermittent administration of parathyroid hormone related protein (PTHrP) on the proteome of vertebral bone was analysed. Treatment of immature sea bream (Sparus auratus, n=6) for 5days with homologous recombinant PTHrP(1-125; 150ng/g body weight) modified bone metabolism and caused a significant (p<0.05) reduction in both tartrate resistant acid phosphatase (TRACP) and alkaline phosphatase (ALP) in relation to control fish. However, the ratio of TRACP: ALP in PTHrP treated fish (1.3 to 2.2 cf. control) suggested it had an anabolic response. A sea bream vertebral bone proteome of 157 protein spots was generated and putative identity assigned to 118 (75.2%) proteins of which 72% had homology to proteins/transcripts from teleosts many of which have not previously been reported in teleost bone. Classification of bone proteins using gene ontology revealed those with protein or metal/ion (e.g., calcium, magnesium, zinc) binding (?53%) activities were most abundant. The expression of eight proteins was significantly (p<0.05) modified in the vertebra of PTHrP treated compared to control fish; three were up-regulated, betainehomocystein S-methyltransferase, glial fibrillary acidic protein, parvalbumin beta and five were down-regulated, annexin A5, apolipoprotein A1, myosin light chain 2, fast skeletal myosin light chain 3, troponin C. In conclusion, intermittent administration of PTHrP to sea bream is associated with an anabolic response in vertebral bone metabolism and modifies calcium binding proteins in the proteome.
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Destructive aneurysmal bone cyst of the mandible.
J Craniofac Surg
PUBLISHED: 03-26-2013
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Aneurysmal bone cyst (ABC) is an uncommon osteolytic lesion of the bones, usually affecting the long bones and spine. The lesion is rare in the jaws and is found most commonly in the body and ramus of the mandible. In some cases, ABCs may be present as rdestructive lesions simulating malignancies. In these cases, a careful diagnosis should be done, including in the differential diagnosis malignant tumors such as telangiectasic osteosarcoma and intraosseous fibrosarcoma. Removing the lesion is usually easy if it is confined within the bone, but it may prove difficult if the lesions are multilocular, expansive, divided by multiple bony septa, or destructive or when the cortical is perforated. Therefore, the surgical treatment of the destructive ABCs should be more radical.
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SIRT6 modulates paclitaxel and epirubicin resistance and survival in breast cancer.
Carcinogenesis
PUBLISHED: 03-20-2013
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In this study, we report the identification of a novel role of SIRT6 in both epirubicin and paclitaxel resistance in breast cancer. We found that SIRT6 protein levels are elevated in paclitaxel- and epirubicin-resistant MCF-7 cells compared with the parental sensitive cells. SIRT6 knockout and depletion sensitized cells to both paclitaxel and epirubicin treatment, whereas SIRT6 ectopic overexpression led to increased resistance to paclitaxel and epirubicin. Moreover, our data suggest that SIRT6 could be mediating epirubicin resistance through enhancing the DNA repair response to epirubicin-induced DNA damage. Clonogenic assays also revealed that mouse embryonic fibroblasts (MEFs) lacking SIRT6 have decreased long-term viability in response to epirubicin. The tumour suppressor FOXO3a increases its levels of acetylation in MEFs depleted of SIRT6, whereas its induction by epirubicin is attenuated in breast cancer cells overexpressing SIRT6. Further cell viability studies demonstrate that deletion of FOXO1/3/4 in MEFs can confer sensitivity to both paclitaxel and epirubicin, suggesting that SIRT6 reduces paclitaxel and epirubicin sensitivity, at least in part, through modulating FOXO acetylation and expression. Consistently, immunohistochemical analysis of 118 breast cancer patient samples revealed that high SIRT6 nuclear staining is significantly associated with poorer overall survival (P = 0.018; Kaplan-Meier analysis). Multivariate Cox analysis demonstrated that nuclear SIRT6 staining remained associated with death after correcting for tumour stage and lymph-node involvement (P = 0.033). Collectively, our data suggest that SIRT6 has a role in paclitaxel and epirubicin sensitivity via targeting FOXO proteins and that SIRT6 could be a useful biomarker and therapeutic target for paclitaxel- and epirubicin-resistant cancer.
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Evidence for a common mechanism of SIRT1 regulation by allosteric activators.
Science
PUBLISHED: 03-09-2013
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A molecule that treats multiple age-related diseases would have a major impact on global health and economics. The SIRT1 deacetylase has drawn attention in this regard as a target for drug design. Yet controversy exists around the mechanism of sirtuin-activating compounds (STACs). We found that specific hydrophobic motifs found in SIRT1 substrates such as PGC-1? and FOXO3a facilitate SIRT1 activation by STACs. A single amino acid in SIRT1, Glu(230), located in a structured N-terminal domain, was critical for activation by all previously reported STAC scaffolds and a new class of chemically distinct activators. In primary cells reconstituted with activation-defective SIRT1, the metabolic effects of STACs were blocked. Thus, SIRT1 can be directly activated through an allosteric mechanism common to chemically diverse STACs.
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Strategies based on silica monoliths for removing pollutants from wastewater effluents: a review.
Sci. Total Environ.
PUBLISHED: 03-07-2013
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Silica monoliths have been used for more than half a century in a wide variety of applications, such as stationary phases for microextraction fibers, capillary columns for chromatography, in the encapsulation of biomolecules for affinity chromatography and for microfluidic or microarray chips and, more recently, and less well known for wastewater treatment. The main objective of this review article is to specifically overview the strategies that use silica monoliths for the removal of chemical pollutants from wastewater effluents or prepared solutions. The discussion of advantages and drawbacks of such strategies will be supported with the main studies carried out so far which have been performed in laboratory environment only. The application and potential research interest in several strategies using composites and biocomposites based silica monoliths as cleaning systems are also discussed.
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Principles for the risk assessment of genetically modified microorganisms and their food products in the European Union.
Int. J. Food Microbiol.
PUBLISHED: 02-28-2013
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Genetically modified microorganisms (GMMs) are involved in the production of a variety of food and feed. The release and consumption of these products can raise questions about health and environmental safety. Therefore, the European Union has different legislative instruments in place in order to ensure the safety of such products. A key requirement is to conduct a scientific risk assessment as a prerequisite for the product to be placed on the market. This risk assessment is performed by the European Food Safety Authority (EFSA), through its Scientific Panels. The EFSA Panel on Genetically Modified Organisms has published complete and comprehensive guidance for the risk assessment of GMMs and their products for food and/or feed use, in which the strategy and the criteria to conduct the assessment are explained, as well as the scientific data to be provided in applications for regulated products. This Guidance follows the main risk assessment principles developed by various international organisations (Codex Alimentarius, 2003; OECD, 2010). The assessment considers two aspects: the characterisation of the GMM and the possible effects of its modification with respect to safety, and the safety of the product itself. Due to the existing diversity of GMMs and their products, a categorisation is recommended to optimise the assessment and to determine the extent of the required data. The assessment starts with a comprehensive characterisation of the GMM, covering the recipient/parental organism, the donor(s) of the genetic material, the genetic modification, and the final GMM and its phenotype. Evaluation of the composition, potential toxicity and/or allergenicity, nutritional value and environmental impact of the product constitute further cornerstones of the process. The outcome of the assessment is reflected in a scientific opinion which indicates whether the product raises any safety issues. This opinion is taken into account by the different European regulatory authorities prior to a decision regarding authorisation to commercialise the product.
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Bioactivity of probiotic whey cheese: characterization of the content of peptides and organic acids.
J. Sci. Food Agric.
PUBLISHED: 02-11-2013
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Probiotic whey cheeses have been produced for several years. It is recognized that several bacterium-mediated metabolic activities contribute differently to the final sensory and nutritional profiles of dairy products. Hence the metabolic activity of probiotic strains in a whey cheese and their contribution to the bioactivity of such matrices were investigated here, including in particular Bifidobacterium animalis, Lactobacillus acidophilus and Lactobacillus casei.
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Paraneoplastic neurological syndrome as an initial indicator of small cell carcinoma of the lung.
BMJ Case Rep
PUBLISHED: 02-09-2013
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Paraneoplastic syndromes are indirect manifestations of cancer due to functional peptides/hormones produced by a tumour, or due to cross reactivity between tumour and host antigens. Here the case of a 58-year-old woman presenting with ataxia, paraesthesia and subacute and progressive loss of vision is reported. The patient exhibited strong serum positivity for anti-Hu and anti-CV2 antibodies, and a chest CT scan showed a hypodense nodule in proximity of the right upper lobe bronchus and an enlarged ipsilateral paratracheal lymph node that was not visible on a lung x-ray. Histopathological examination of a biopsy specimen from this lymph node showed that small cell carcinoma of the lung was present. The patients deficits were subsequently diagnosed as three coexisting paraneoplastic neurological syndromes (PNSs): subacute cerebellar ataxia, sensory neuropathy and retinopathy, respectively. Although rare, PNSs can be the first manifestations of cancer, and their rapid recognition facilitates an early treatment.
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Tenascin and fibronectin expression after pulp capping with different hemostatic agents: a preliminary study.
Braz Dent J
PUBLISHED: 01-24-2013
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This study investigated the expression of extracellular matrix glycoproteins tenascin (TN) and fibronectin (FN) in pulp repair after capping with calcium hydroxide (CH), following different hemostasis protocols. Class I cavities with a pulp exposure were prepared in 42 human third molars scheduled for extraction. Different hemostatic agents (0.9% saline solution, 5.25% sodium hypochlorite and 2% chlorhexidine digluconate) were used and pulps were capped with CH cement. After 7, 30 or 90 days, teeth were extracted, formalin-fixed, and prepared for immunohistochemical technique. Hemostatic agents did not influence the expression of TN and FN. Both glycoproteins were found in the entire the pulp tissue and around collagen fibers, but were absent in the mineralized tissues. In the predentin, TN showed positive immunostaining and FN had a variable expression. Within 7 days post-treatment, a slightly more pronounced immunostaining on the pulp exposure site was observed. Within 30 days, TN and FN demonstrated a positive expression around the dentin barrier and at 90 days, a thin and linear expression of TN and FN was delimitating the reparative dentin. In conclusion, hemostatic agents did not influence TN and FN expression. Immunostaining for TN and FN was seen in different regions and periods, demonstrating their role in pulp repair.
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Food components and the immune system: from tonic agents to allergens.
Front Immunol
PUBLISHED: 01-01-2013
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The intestinal mucosa is the major site of contact with antigens, and it houses the largest lymphoid tissue in the body. In physiological conditions, microbiota and dietary antigens are the natural sources of stimulation for the gut-associated lymphoid tissues (GALT) and for the immune system as a whole. Germ-free models have provided some insights on the immunological role of gut antigens. However, most of the GALT is not located in the large intestine, where gut microbiota is prominent. It is concentrated in the small intestine where protein absorption takes place. In this review, we will address the involvement of food components in the development and the function of the immune system. Studies in mice have already shown that dietary proteins are critical elements for the developmental shift of the immature neonatal immune profile into a fully developed immune system. The immunological effects of other food components (such as vitamins and lipids) will also be addressed. Most of the cells in the GALT are activated and local pro-inflammatory mediators are abundant. Regulatory elements are known to provide a delicate yet robust balance that maintains gut homeostasis. Usually antigenic contact in the gut induces two major immune responses, oral tolerance and production of secretory IgA. However, under pathological conditions mucosal homeostasis is disturbed resulting in inflammatory reactions such as food hypersensitivity. Food allergy development depends on many factors such as genetic predisposition, biochemical features of allergens, and a growing array of environmental elements. Neuroimmune interactions are also implicated in food allergy and they are examples of the high complexity of the phenomenon. Recent findings on the gut circuits triggered by food components will be reviewed to show that, far beyond their role as nutrients, they are critical players in the operation of the immune system in health and disease.
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Effect of calcium hydroxide on ph changes of the external medium after intracoronal bleaching.
J Contemp Dent Pract
PUBLISHED: 12-22-2011
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This in vitro study evaluated the effect of calcium hydroxide on pH changes of the external medium after intracoronal bleaching.
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Phosphorylation of FOXO3a on Ser-7 by p38 promotes its nuclear localization in response to doxorubicin.
J. Biol. Chem.
PUBLISHED: 11-29-2011
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FOXO3a is a forkhead transcription factor that regulates a multitude of important cellular processes, including proliferation, apoptosis, differentiation, and metabolism. Doxorubicin treatment of MCF-7 breast carcinoma cells results in FOXO3a nuclear relocation and the induction of the stress-activated kinase p38 MAPK. Here, we studied the potential regulation of FOXO3a by p38 in response to doxorubicin. Co-immunoprecipitation studies in MCF-7 cells demonstrated a direct interaction between p38 and FOXO3a. We also showed that p38 can bind and phosphorylate a recombinant FOXO3a directly in vitro. HPLC-coupled phosphopeptide mapping and mass spectrometric analyses identified serine 7 as a major site for p38 phosphorylation. Using a phosphorylated Ser-7 FOXO3a antibody, we demonstrated that FOXO3a is phosphorylated on Ser-7 in response to doxorubicin. Immunofluorescence staining studies showed that upon doxorubicin treatment, the wild-type FOXO3a relocalized to the nucleus, whereas the phosphorylation-defective FOXO3a (Ala-7) mutant remained largely in the cytoplasm. Treatment with SB202190 also inhibits the doxorubicin-induced FOXO3a Ser-7 phosphorylation and nuclear accumulation in MCF-7 cells. In addition, doxorubicin caused the nuclear translocation of FOXO3a in wild-type but not p38-depleted mouse fibroblasts. Together, our results suggest that p38 phosphorylation of FOXO3a on Ser-7 is essential for its nuclear relocalization in response to doxorubicin.
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Sleep and academic performance in undergraduates: a multi-measure, multi-predictor approach.
Chronobiol. Int.
PUBLISHED: 11-15-2011
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The present study examined the associations of sleep patterns with multiple measures of academic achievement of undergraduate university students and tested whether sleep variables emerged as significant predictors of subsequent academic performance when other potential predictors, such as class attendance, time devoted to study, and substance use are considered. A sample of 1654 (55% female) full-time undergraduates 17 to 25 yrs of age responded to a self-response questionnaire on sleep, academics, lifestyle, and well-being that was administered at the middle of the semester. In addition to self-reported measures of academic performance, a final grade for each student was collected at the end of the semester. Univariate analyses found that sleep phase, morningness/eveningness preference, sleep deprivation, sleep quality, and sleep irregularity were significantly associated with at least two academic performance measures. Among 15 potential predictors, stepwise multiple regression analysis identified 5 significant predictors of end-of-semester marks: previous academic achievement, class attendance, sufficient sleep, night outings, and sleep quality (R(2)=0.14 and adjusted R(2)=0.14, F(5, 1234)= 40.99, p < .0001). Associations between academic achievement and the remaining sleep variables as well as the academic, well-being, and lifestyle variables lost significance in stepwise regression. Together with class attendance, night outings, and previous academic achievement, self-reported sleep quality and self-reported frequency of sufficient sleep were among the main predictors of academic performance, adding an independent and significant contribution, regardless of academic variables and lifestyles of the students.
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?-Oxido-bis-[chlorido(4,4-di-tert-butyl-2,2-bipyridine-?N,N)dioxido-molybdenum(VI)] 0.2-hydrate.
Acta Crystallogr Sect E Struct Rep Online
PUBLISHED: 11-04-2011
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The title hydrate, [Mo(2)Cl(2)O(5)(C(18)H(24)N(2))(2)]·0.2H(2)O, has been isolated as the oxidation product of [Mo(?(3)-C(3)H(5))Cl(CO)(2)(di-t-Bu-bipy)] (where di-t-Bu-bipy is 4,4-di-tert-butyl-2,2-bipyridine). A ?-oxide ligand bridges two similar MoCl(di-t-Bu-bipy)O(2) units, having the terminal oxide ligands mutually cis, and the chloride and ?-oxide trans to each other. In the binuclear complex, the coordination geometries of the metal atoms can be described as highly distorted octa-hedra. Individual complexes co-crystallize with a partially occupied water mol-ecule of crystallization (occupancy factor = 0.20; H atoms not located), with the crystal packing being mediated by the need to effectively fill the available space. A number of weak C-H?O and C-H?Cl inter-actions are present.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.