Nitric Oxide Released From Luminal S-nitroso-n-acetylcysteine Increases Gastric Mucosal Blood Flow

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Nitric oxide (NO)-mediated vasodilation plays a key role in gastric mucosal defense, and NO-donor drugs may protect against diseases associated with gastric mucosal blood flow (GMBF) deficiencies. In this study, we used the ex vivo gastric chamber method and Laser Doppler Flowmetry to characterize the effects of luminal aqueous NO-donor drug S-nitroso-N-acetylcysteine (SNAC) solution administration compared to aqueous NaNO2 and NaNO3 solutions (pH 7.4) on GMBF in Sprague-Dawley rats. SNAC solutions (600 mu M and 12 mM) led to a rapid threefold increase in GMBF, which was maintained during the incubation of the solutions with the gastric mucosa, while NaNO2 or NaNO3 solutions (12 mM) did not affect GMBF. SNAC solutions (600 mu M and 12 mM) spontaneously released NO at 37 degrees C at a constant rate of 0.3 or 14 nmol center dot mL(-1)center dot min(-1), respectively, while NaNO2 (12 mM) released NO at a rate of 0.06 nmol center dot mL(-1)center dot min(-1) and NaNO3 (12 mM) did not release NO. These results suggest that the SNAC-induced GMBF increase is due to their higher rates of spontaneous NO release compared to equimolar NaNO2 solutions. Taken together, our data indicate that oral SNAC administration is a potential approach for gastric acid-peptic disorder prevention and treatment.20341094123Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP [2011/50514-5, 2013/07173-8]CNPq [309390/2011-7]FAPESP [2008/57560-0

The histone methyltransferase SUV420H2 and Heterochromatin Proteins HP1 interact but show different dynamic behaviours

<p>Abstract</p> <p>Background</p> <p>Histone lysine methylation plays a fundamental role in chromatin organization and marks distinct chromatin regions. In particular, trimethylation at lysine 9 of histone H3 (H3K9) and at lysine 20 of histone H4 (H4K20) governed by the histone methyltransferases SUV39H1/2 and SUV420H1/2 respectively, have emerged as a hallmark of pericentric heterochromatin. Controlled chromatin organization is crucial for gene expression regulation and genome stability. Therefore, it is essential to analyze mechanisms responsible for high order chromatin packing and in particular the interplay between enzymes involved in histone modifications, such as histone methyltransferases and proteins that recognize these epigenetic marks.</p> <p>Results</p> <p>To gain insights into the mechanisms of SUV420H2 recruitment at heterochromatin, we applied a tandem affinity purification approach coupled to mass spectrometry. We identified heterochromatin proteins HP1 as main interacting partners. The regions responsible for the binding were mapped to the heterochromatic targeting module of SUV420H2 and HP1 chromoshadow domain. We studied the dynamic properties of SUV420H2 and the HP1 in living cells using fluorescence recovery after photobleaching. Our results showed that HP1 proteins are highly mobile with different dynamics during the cell cycle, whereas SUV420H2 remains strongly bound to pericentric heterochromatin. An 88 amino-acids region of SUV420H2, the heterochromatic targeting module, recapitulates both, HP1 binding and strong association to heterochromatin.</p> <p>Conclusion</p> <p>FRAP experiments reveal that in contrast to HP1, SUV420H2 is strongly associated to pericentric heterochromatin. Then, the fraction of SUV420H2 captured and characterized by TAP/MS is a soluble fraction which may be in a stable association with HP1. Consequently, SUV420H2 may be recruited to heterochromatin in association with HP1, and stably maintained at its heterochromatin sites in an HP1-independent fashion.</p

Deficits in emotion recognition as markers of frontal behavioral dysfunction in Amyotrophic Lateral Sclerosis

Objective: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with prominent motor symptoms. Patients with ALS may also manifest frontal behavior symptoms and cognitive decline, including impairment in facial emotion recognition. The authors aimed to investigate whether deficits in emotion recognition were associated with frontal behavior symptoms in ALS. Methods: Participants were patients with probable or definite sporadic ALS (N521; male:female ratio, 11:10; median age, 62 years; median disease duration, 3 years) and agematched and education-matched healthy control subjects (N525; male:female ratio, 14:11; median age, 61 years). The Facial Emotion Recognition Test (FERT) was administered to all participants. Patients with ALS were assessed using the Cambridge Behavior Inventory-Revised and were classified into two groups according to the presence of frontal behavioral symptoms: ALS with no behavioral symptom (ALSns; N59) and ALS with at least one behavioral symptom (ALSbs; N512). Results: Apathy and mood symptoms were the most frequent neuropsychiatric symptoms in the patient group. Patients with ALS performed worse than control subjects in the recognition of sadness (p,0.004). There were no differences between control subjects and patients in the ALSns group in all FERT scores, but the ALSbs group had lower performance than control subjects in sadness (p,0.003). Conclusions: Emotion recognition deficit may be a marker of frontal behavior in ALS

Integration of miRNA and mRNA expression profles reveals microRNA-regulated networks during muscle wasting in cardiac cachexia

Cardiac cachexia (CC) is a common complication of heart failure (HF) associated with muscle wasting and poor patient prognosis. Although different mechanisms have been proposed to explain muscle wasting during CC, its pathogenesis is still not understood. Here, we described an integrative analysis between miRNA and mRNA expression profiles of muscle wasting during CC. Global gene expression profiling identified 1,281 genes and 19 miRNAs differentially expressed in muscle wasting during CC. Several of these deregulated genes are known or putative targets of the altered miRNAs, including miR-29a-3p, miR-29b-3p, miR-210-5p, miR-214, and miR-489. Gene ontology analysis on integrative mRNA/miRNA expression profiling data revealed miRNA interactions affecting genes that regulate extra-cellular matrix (ECM) organization, proteasome protein degradation, citric acid cycle and respiratory electron transport. We further identified 11 miRNAs, including miR-29a-3p and miR-29b-3p, which target 21 transcripts encoding the collagen proteins related to ECM organization. Integrative miRNA and mRNA global expression data allowed us to identify miRNA target genes involved in skeletal muscle wasting in CC. Our functional experiments in C2C12 cells confirmed that miR-29b down-regulates collagen genes and contributes to muscle cell atrophy. Collectively, our results suggest that key ECM-associated miRNAs and their target genes may contribute to CC in HF

Comparative study of the atmospheric chemical composition of three South American cities

PM10 samples were collected in 2008 at three sites in South America in the framework of an international project (South American Emissions Megacities, and Climate; SAEMC). The concentration of metals, metalloids, ion and organic compounds of most PM10 samples collected at three sites (Buenos Aires (BAI), Bogotá (BOG) and São Paulo (SPA)) is below the air quality standard of the respective countries. At the sites n-alkanes and carbon preference index distribution indicated the influence of petroleum residues derived from vehicular emissions. Most PAH detected are attributed to light-duty gasoline vehicles and to stationary sources. At all sites benzo[a]pyrene equivalent values mean a significant cancer risk. Sulfate, nitrate, ammonium, calcium and sodium are the most abundant water-soluble ions at the three sites. Ammonium sulfate is likely the form presented for these species formed by photochemical reactions of precursors emitted mainly by vehicles. At BAI and SPA, formate/acetate ratios indicated the contribution of photochemical reactions; on the contrary, at BOG site, acetate is predominant, indicating strong contribution of vehicular emissions. São Paulo samples showed the highest concentrations of elements among all the sites. None of the toxic or potentially toxic elements exceed the guideline values of the World Health Organization. At BAI site earth crust seems to be the major source of Fe and Mn; at SPA, anthropogenic source is responsible for Pb and Zn presences. Traffic related element is well correlated at the three sites.Fil: Vasconcellos, Pérola C.. Universidade de Sao Paulo; BrasilFil: Souza, Davi Z.. Instituto Nacional de Pesquisas Nucleares; BrasilFil: Ávila, Simone G.. Universidade de Sao Paulo; BrasilFil: Araújo, Maria P.. Universidade de Sao Paulo; BrasilFil: Naoto, Edson. Universidade de Sao Paulo; BrasilFil: Nascimento, Kátia H.. Universidade de Sao Paulo; BrasilFil: Cavalcante, Fernando S.. Universidade de Sao Paulo; BrasilFil: Dos Santos, Marina. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Smichowski, Patricia Nora. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Behrentz, Eduardo. Universidad de los Andes; Colombi

Dual-energy X-ray absorptiometry study of body composition in patients with lipodystrophy

Inst Estadual Diabet & Endocrinol, Metab Unit, Rio de Janeiro, BrazilUniversidade Federal de São Paulo, Dept Endocrinol & Metab, São Paulo, BrazilDENSSO, Rio de Janeiro, BrazilUniversidade Federal de São Paulo, Dept Endocrinol & Metab, São Paulo, BrazilWeb of Scienc

The role of maternal infection in preterm birth: evidence from the Brazilian Multicentre Study on Preterm Birth (EMIP)

OBJECTIVES: Evidence suggests that infection or inflammation is a major contributor to early spontaneous preterm birth (sPTB). Therefore, this study aimed to investigate the development and causes of maternal infection associated with maternal and neonatal outcomes in women with sPTB. METHODS: This was a secondary analysis of a multicenter cross-sectional study with a nested case–control component, the Brazilian Multicentre Study on Preterm Birth (EMIP), conducted from April 2011 to July 2012 in 20 Brazilian referral obstetric hospitals. Women with preterm birth (PTB) and their neonates were enrolled. In this analysis, 2,682 women undergoing spontaneous preterm labor and premature pre-labor rupture of membranes were included. Two groups were identified based on self-reports or prenatal or hospital records: women with at least one infection factor and women without any maternal infection (vulvovaginitis, urinary tract infection, or dental infection). A bivariate analysis was performed to identify potential individual risk factors for PTB. The odds ratios (ORs) with their respective 95% confidence intervals were calculated. RESULTS: The majority of women with sPTB fulfilled at least one criterion for the identification of maternal infection (65.9%), and more than half reported having urinary tract infection during pregnancy. Approximately 9.6% of women with PTB and maternal infection were classified as having periodontal infection only. Apart from the presence of a partner, which was more common among women with infectious diseases (p=0.026; OR, 1.28 [1.03–1.59]), other variables did not show any significant difference between groups. CONCLUSION: Maternal infection was highly prevalent in all cases of sPTBs, although it was not clearly associated with the type of PTB, gestational age, or any adverse neonatal outcomes

Tremor in Patients with Inflammatory Bowel Disease

The spectrum of neurological manifestations of Crohn’s disease (CD) and ulcerative colitis (UC) is diverse and not fully understood. In addition to peripheral neuropathy, mild autonomic impairment has been reported. These problems themselves could also result in secondary neurological consequences, such as the exacerbation of enhanced physiological tremor. Indeed, some patients in our cohort complained of tremor. Hence, we hypothesized that enhanced physiological tremor would be more severe in patients with inflammatory bowel disease (IBD) than controls

Molecular Genetic Variability, Population Structure and Mating System in Tropical Forages

Microsatellite (SSR) markers were developed for the following tropical forage species, using accessions available from the plant genetic resources (PGR) collections held by EMBRAPA (Brazilian Agricultural Research Corporation): Brachiaria brizantha, B. humidicola, Panicum maximum, Paspalum spp., Stylosanthes capitata, S. guianensis, S. macrocephala, Calopogonium mucunoides and Centrosema spp. The markers were used to analyse population structure and genetic diversity, evolution and origin of the genetic variability in the centre of origin, mating systems and genetic resources in EMBRAPA’s germplasm bank. The results shed light on the amount of genetic variation within and between populations, revealed the need in some cases for further plant collection to adequately represent the species in PGR collections, allowed us to assemble core collections (subsets of the total collections) that should contain most of the available diversity and (in the case of the legumes) showed the need to avoid unwanted outcrossing when regenerating conserved material. The data will allow plant breeders to better select accessions for hybrid production, discriminate between genotypes and use marker-assisted selection in breeding programs. Our results will also underpin the construction of genetic maps, mapping of genes of agronomic interest and numerous other studies on genetic variability, population structure, gene flow and reproductive systems for the tropical forage species studied in this work