Effect Of Inhibition Of Nitric Oxide Synthase On Blood Pressure And Renal Sodium Handling In Renal Denervated Rats.

The role of sympathetic nerve activity in the changes in arterial blood pressure and renal function caused by the chronic administration of N G-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthesis, was examined in sham and bilaterally renal denervated rats. Several studies have demonstrated that sympathetic nerve activity is elevated acutely after L-NAME administration. To evaluate the role of renal nerve activity in L-NAME-induced hypertension, we compared the blood pressure response in four groups (N = 10 each) of male Wistar-Hannover rats weighing 200 to 250 g: 1) sham-operated vehicle-treated, 2) sham-operated L-NAME-treated, 3) denervated vehicle-treated, and 4) denervated L-NAME-treated rats. After renal denervation or sham surgery, one control week was followed by three weeks of oral administration of L-NAME by gavage. Arterial pressure was measured weekly in conscious rats by a tail-cuff method and renal function tests were performed in individual metabolic cages 0, 7, 14 and 21 days after the beginning of L-NAME administration. L-NAME (60 mg kg-1 day-1) progressively increased arterial pressure from 108 +/- 6.0 to 149 +/- 12 mmHg (P<0.05) in the sham-operated group by the third week of treatment which was accompanied by a fall in creatinine clearance from 336 +/- 18 to 222 +/- 59 microl min-1 100 g body weight-1 (P<0. 05) and a rise in fractional urinary sodium excretion from 0.2 +/- 0. 04 to 1.62 +/- 0.35% (P<0.05) and in sodium post-proximal fractional excretion from 0.54 +/- 0.09 to 4.7 +/- 0.86% (P<0.05). The development of hypertension was significantly delayed and attenuated in denervated L-NAME-treated rats. This was accompanied by a striking additional increase in fractional renal sodium and potassium excretion from 0.2 +/- 0.04 to 4.5 +/- 1.6% and from 0.1 +/- 0.015 to 1.21 +/- 0.37%, respectively, and an enhanced post-proximal sodium excretion compared to the sham-operated group. These differences occurred despite an unchanged creatinine clearance and Na+ filtered load. These results suggest that bilateral renal denervation delayed and attenuated the L-NAME-induced hypertension by promoting an additional decrease in tubule sodium reabsorption in the post-proximal segments of nephrons. Much of the hypertension caused by chronic NO synthesis inhibition is thus dependent on renal nerve activity.33347-5

Influence of HOTAIR rs920778 and rs12826786 genetic variants on prostate cancer risk and progression-free survival

Aim: Evaluate the impact of the single nucleotide polymorphisms rs920778 and rs12826786 in the long noncoding RNA HOTAIR in the susceptibility and prognosis of prostate cancer (PCa) patients. Patients & methods: HOTAIR single nucleotide polymorphisms were genotyped by restriction fragment length polymorphism in 151 PCa cases and 180 cancer-free controls. Odds ratio, 95% CIs and prognostic significance were calculated. Results: Our data showed no statistically significant associations between HOTAIR polymorphic variants in rs920778 and rs12826786 and PCa susceptibility. However, the CC genotype in rs12826786 was significantly associated with shorter biochemical recurrence-free survival in pT3-stage PCa patients. Conclusion: Our results indicate that HOTAIR rs12826786 CC genotype may be an independent prognostic biomarker in a particular subset of PCa tumors.Fundação para a Ciência e Tecnologia (IF/00601/2012 to BM Costa; SFRH/BD/52287/2013 to AI Oliveira; SFRH/BD/88220/2012 to AX Magalhaes), Fundação Calouste Gulbenkian (BM Costa), Liga Portuguesa Contra o Cancro (BM Costa) and Inter-University Doctoral Programme in Ageing and Chronic Disease (PhDOC; to AI Oliveira and AX Magalhaes). Project co-financed by Programa Operacional Regional do Norte (ON.2-O Novo Norte), Quadro de Referencia Estratégico Nacional (QREN), Fundo Europeu de Desenvolvimento Regional (FEDER) and a grant (74-CI-IPOP) from Research Center of Portuguese Oncology Institute of Porto (C Jeronimo).info:eu-repo/semantics/publishedVersio

O Estado do Brasil na aurora do século XVII. Uma carta inédita do governador-geral Diogo Botelho (Olinda, 1602)

El artículo presenta y analiza una carta inédita del gobernador-general Diogo Botelho redactada en la villa de Olinda en 1602. El documento revela información desconocida acerca de las capitanías brasileñas, así como de los diversos proyectos que se estaban ejecutando en ellas dos décadas después de la Unión Dinástica. Su lectura también nos ofrece la perspectiva de un administrador colonial recién llegado desde Portugal a Brasil que buscaba conocer las particularidades de las diversas redes ya existentes desde el siglo XVI e interferir en ellas utilizando los mecanismos propios de la economía de mercedes, basada en premios y castigos.O artigo apresenta e analisa uma carta inédita do governador-geral Diogo Botelho redigida na vila de Olinda em 1602. O documento revela informações desconhecidas acerca das capitanias brasílicas, bem como dos diversos projetos que estavam sendo nelas executados em cada uma delas, duas décadas após o início da União das Coroas. A sua leitura também nos oferece a perspectiva de um administrador colonial recém-chegado do Reino, mas que buscava reconhecer as particularidades das diversas redes, previamente construídas desde o século XVI, e nelas interferir utilizando os mecanismos de poder próprios da economia de mercês, orientadas por prêmios e castigos.This paper presents and analyzes an unknown letter of Governor-general Diogo Botelho, written in Olinda in 1602. The manuscript provides unprecedented information about Colonial Brazil, describing several undertakings in progress during the beginning of the Iberian Union. The document offers the perspective of a high colonial official, newly arrived from Portugal. He gives insight on his attempts to identify the peculiarities of different networks formed during the sixteenth century and how he could interact with them, employing power resources such as Economy of Favors (economia de mercês), rewards and punishment

O Estado do Brasil na aurora do século XVII. Uma carta inédita do governador-geral Diogo Botelho (Olinda, 1602)

El artículo presenta y analiza una carta inédita del gobernador-general Diogo Botelho redactada en la villa de Olinda en 1602. El documento revela información desconocida acerca de las capitanías brasileñas, así como de los diversos proyectos que se estaban ejecutando en ellas dos décadas después de la Unión Dinástica. Su lectura también nos ofrece la perspectiva de un administrador colonial recién llegado desde Portugal a Brasil que buscaba conocer las particularidades de las diversas redes ya existentes desde el siglo XVI e interferir en ellas utilizando los mecanismos propios de la economía de mercedes, basada en premios y castigos.O artigo apresenta e analisa uma carta inédita do governador-geral Diogo Botelho redigida na vila de Olinda em 1602. O documento revela informações desconhecidas acerca das capitanias brasílicas, bem como dos diversos projetos que estavam sendo nelas executados em cada uma delas, duas décadas após o início da União das Coroas. A sua leitura também nos oferece a perspectiva de um administrador colonial recém-chegado do Reino, mas que buscava reconhecer as particularidades das diversas redes, previamente construídas desde o século XVI, e nelas interferir utilizando os mecanismos de poder próprios da economia de mercês, orientadas por prêmios e castigos.This paper presents and analyzes an unknown letter of Governor-general Diogo Botelho, written in Olinda in 1602. The manuscript provides unprecedented information about Colonial Brazil, describing several undertakings in progress during the beginning of the Iberian Union. The document offers the perspective of a high colonial official, newly arrived from Portugal. He gives insight on his attempts to identify the peculiarities of different networks formed during the sixteenth century and how he could interact with them, employing power resources such as Economy of Favors (economia de mercês), rewards and punishment

Mobilisation of data to stakeholder communities. Bridging the research-practice gap using a commercial shellfish species model

Knowledge mobilisation is required to “bridge the gap” between research, policy and practice. This activity is dependent on the amount, richness and quality of the data published. To understand the impact of a changing climate on commercial species, stakeholder communities require better knowledge of their past and current situations. The common cockle (Cerastoderma edule) is an excellent model species for this type of analysis, as it is well-studied due to its cultural, commercial and ecological significance in west Europe. Recently, C. edule harvests have decreased, coinciding with frequent mass mortalities, due to factors such as a changing climate and diseases. In this study, macro and micro level marine historical ecology techniques were used to create datasets on topics including: cockle abundance, spawning duration and harvest levels, as well as the ecological factors impacting those cockle populations. These data were correlated with changing climate and the Atlantic Multidecadal Oscillation (AMO) index to assess if they are drivers of cockle abundance and harvesting. The analyses identified the key stakeholder communities involved in cockle research and data acquisition. It highlighted that data collection was sporadic and lacking in cross-national/stakeholder community coordination. A major finding was that local variability in cockle populations is influenced by biotic (parasites) and abiotic (temperature, legislation and harvesting) factors, and at a global scale by climate (AMO Index). This comprehensive study provided an insight into the European cockle fishery but also highlights the need to identify the type of data required, the importance of standardised monitoring, and dissemination efforts, taking into account the knowledge, source, and audience. These factors are key elements that will be highly beneficial not only to the cockle stakeholder communities but to other commercial species

A novel molecular link between HOXA9 and WNT6 in glioblastoma identifies a subgroup of patients with particular poor prognosis

Despite much effort to improve treatments, patients with malignant glioma still present a very poor prognosis that has not changed significantly in the last decades. In this context, it is crucial to better understand glioma pathogenesis to identify new molecular prognostic subgroups and therapeutic targets. WNT6 was recently identified as a new oncogenic molecule in glioblastoma (GBM), with prognostic value in patients, but the mechanisms underlying WNT6 aberrant expression in glioma are still unknown. WNT6 was overexpressed in a subset of gliomas independently of IDH mutations, 1p/19q codeletion status, and WNT6 gene copy number. Interestingly, WNT6 expression is associated with the DNA methylation levels of particular CpG regions at both the WNT6 promoter and the gene body in glioma patient samples. HOXA9, a transcription factor previously associated with poorer clinical outcome in GBM, was identified as a novel transcriptional regulator of WNT6, activating the WNT/β-catenin pathway in vitro and in vivo. In various cohorts of glioma patients, mRNA levels of WNT6 and HOXA9 were significantly correlated, extending our in vitro and in vivo findings into the clinical setting. Interestingly, this novel molecular link between WNT6 and HOXA9 was not limited to glioma, as they were co-expressed also in patients with other tumor types. Clinically, WNT6 was a prognostic biomarker of shorter survival in GBM, independently of HOXA9 expression. Concomitant high expression of both WNT6 and HOXA9 identified a subgroup of patients with particularly dismal survival. These findings describe novel WNT6 regulatory mechanisms in GBM, establishing particular DNA methylation patterns and HOXA9 as critical regulators of WNT6 expression in glioma. This HOXA9-WNT6 molecular link supports WNT signaling in GBM cells and is a powerful prognostic biomarker, highlighting the clinical relevance of this axis in patients. Novel therapies targeting WNT6-HOXA9 signaling may thus be useful for this deadly disease.info:eu-repo/semantics/publishedVersio

Effects of the functional HOTAIR rs920778 and rs12826786 genetic variants in glioma susceptibility and patient prognosis

Abnormal expression of the long non-coding RNA HOX transcript antisense intergenic RNA (HOTAIR) is oncogenic in several human cancers, including gliomas. The HOTAIR single nucleotide polymorphisms (SNPs) rs920778 (C > T) and rs12826786 (C > T) present in the intronic enhancer and promoter regions of HOTAIR, respectively, are associated with expression, cancer susceptibility, and patient prognosis in some tumor types. However, the relevance of these HOTAIR SNPs has not been studied in glioma. Here, we report a case-control study comprising 177 Portuguese glioma patients and 199 cancer-free controls. All subjects were genotyped by PCR and restriction fragment length polymorphism (RFLP). No statistically significant differences were found in the genotype or allele distributions of either rs920778 or rs12826786 between glioma patients and controls, suggesting these SNPs are not associated with glioma risk. No significant associations were found between rs920778 variants and HOTAIR expression levels, while rs12826786 CT genotype was associated with increased intratumoral HOTAIR RNA levels when compared to TT genotype (p-value = 0.04). Univariate (Log-rank) and multivariate (Cox proportional) analyses showed both rs920778 CT and rs12826786 CT genotypes were significantly associated with longer overall survival of WHO grade III anaplastic oligodendroglioma patients. Our results suggest that HOTAIR SNPs rs920778 and rs12826786 do not play a significant role in glioma susceptibility, but may be important prognostic factors in anaplastic oligodendroglioma patients. Future studies are warranted to validate and expand these findings, and to further dissect the importance of these SNPs in glioma.info:eu-repo/semantics/publishedVersio