Expression and functional role of the prorenin receptor in the human adrenocortical zona glomerulosa and in primary aldosteronism.

OBJECTIVES: Prorenin can be detected in plasma of hypertensive patients. If detected in patients with primary aldosteronism could implicate prorenin in the development of primary aldosteronism. To address this issue, we measured the plasma prorenin levels in primary aldosteronism patients, the expression of the prorenin receptor (PRR) in the normal human adrenocortical zona glomerulosa and aldosterone-producing adenoma (APA), and we investigated the functional effects of PRR activation in human adrenocortical cells. METHOD: Plasma renin activity, aldosterone, and active and total trypsin-activated renin were measured in primary aldosteronism patients, essential hypertensive patients, and healthy individuals, and then prorenin levels were calculated. Localization and functional role of PRR were investigated in human and rat tissues, and aldosterone-producing cells. RESULTS: Primary aldosteronism patients had detectable plasma levels of prorenin. Using digital-droplet real-time PCR, we found a high PRR-to-porphobilinogen deaminase ratio in both the normal adrenal cortex and APAs. Marked expression of the PRR gene and protein was also found in HAC15 cells. Immunoblotting, confocal, and immunogold electron microscopy demonstrated PRR at the cell membrane and intracellularly. Renin and prorenin significantly triggered both CYP11B2 expression (aldosterone synthase) and ERK1/2 phosphorylation, but only CYP11B2 transcription was prevented by aliskiren. CONCLUSION: The presence of detectable plasma prorenin in primary aldosteronism patients, and the high expression of PRR in the normal human adrenal cortex, APA tissue, CD56+ aldosterone-producing cells, along with activation of CYP11B2 synthesis and ERK1/2 phosphorylation, suggest that the circulating and locally produced prorenin may contribute to the development or maintenance of human primary aldosteronism.

Dendrochronological study of the avalanche path Canal del Roc Roig: first results of the ALUDEX Project in the Pyrenees

Historical data about ancient avalanches are scarce in the Pyrenees. Dendrochronology can provide new data about past avalanches and their return period, but up to now little research has been carried out with this purpose. The Aludex project aims to obtain information about the frequency and extent of extreme avalanches, using a dendrochronological and a nivo-meteorological approach. In this paper, we present the results of a dendrochronological study of the Canal del Roc Roig avalanche path which was affected by two extreme avalanches in February 1996. This first dendrochronological study has permitted us to assess the tree-ring signals due to avalanche events in 53 out of 132 dated trees. The trees presented a variety of responses to the 1996 avalanche events. It is shown that the type of tree-ring signal depends on tree age. The methodology has proved successful in detecting the 1996 and 1972 documented avalanche events, and provided outstanding evidence of undocumented past events such as one in 1930.

The Control of the Edge Shrinkage in Board

Tämän diplomityön tavoitteena oli löytää prosessiparametrejä nestepakkauskartongin reuna-alueiden kuivatuskutistuman hallintaan ja saada tuotteen reuna-alueiden sileystaso paremmaksi. Tarkoituksena oli parantaa reuna-alueiden painettavuusominaisuuksia sekä saada koneen poikkisuunnassa laadultaan parempi tuote. Työn kirjallisuusosassa on tarkasteltu työn kannalta nestepakkauskartongin kriittisimpiä ominaisuuksia, sileyttä ja jäykkyyttä. Lisäksi kirjallisuusosassa on tarkasteltu kuitujen ominaisuuksia, sylinterikuivatusta ja kuivatuskutistumaa. Kokeellisessa osassa on etsitty esitutkimuksella prosessiparametrejä, jotka ovat aiheuttaneet poikkisuunnan sileyserojen kasvun kartonkikoneen investoinnin jälkeen. Suoria korrelaatioita prosessiparametrien ja kuivatuskutistuman välille ei löydetty. Kokeellisen osan tehdasmittakaavaisissa koeajoissa tutkittiin kahdeksan eri parametrin vaikutusta kuivatuskutistumaan, jotka perustuivat kirjallisuuteen. Tutkituista parametreistä huulisuihkun iskukulman muutoksella sekä konesuuntaisella kuivatusprofiililla ei ollut vaikutusta kuivatuskutistumaan. Runkokerroksen mäntysellun korvaaminen koivusellulla vähensi kuivatuskutistumaa ja lisäsi sileyttä, mutta tuotteen palstautumislujuus ei tällöin ollut riittävä. Retentiokemikaalien reseptimuutoksilla pinta- ja taustakerroksen välillä, kuivatusosan nollatason laskulla ja perälaatikkosakeuksien pienentämisellä oli vähän vaikutusta kuivatuskutistumaan. Vaikutus reuna-alueiden sileyteen oli kuitenkin vähemmän kuin 10 %. Diplomityön perusteella kuivatusosan nopeuseroilla ja kuivatusviirojen kireyksillä oli suurin vaikutusta kuivatuskutistumaan ja reuna-alueiden sileystasoon. Lisäämällä nopeuseroja ja kiristämällä kuivatusviiroja reuna-alueiden sileyttä pystyttiin parantamaan yli 20 %.

Diversity of the Quality Criteria in Qualitative Research in the Health Sciences: Lessons from a Lexicometric Analysis Composed of 133 Guidelines

A review of health sciences literature shows a substantial increase in qualitative publications. This work incorporates a certain number of research quality guidelines. We present the results of the Alceste® lexicometric analysis, which includes 133 quality grids for qualitative research covering five disciplinary fields of the health sciences: medicine and epidemiology, public health and health education, nursing, health sociology and anthropology, psychiatry and psychology. This analysis helped to cross-check the disciplinary fields with the various objectives assigned to the different criteria in the grids examined. The results obtained with Alceste® show the variability of the objectives sought by the authors of the guidelines. These discrepancies are not directly associated to disciplinary fields, and appear to be more closely linked to different qualitative research conceptualizations within the disciplines, and with essential qualitative research validation criteria. These conceptualizations must be clarified to help users better understand the objectives targeted by the grids, and promote more appreciation for qualitative research in the health sciences.

Sedimentology and Stratigraphy of the Pleistocene sediments in Lake Llauset (Southern Pyrenees, Spain)-a first approach

The high alpine valleys in the Southem Pyrenees are characterised by a many small lakes and ponds. They occur above 2000 m and are said to have been formed by glacial erosion. The sediments in these basins should, therefore, contain s t p tigraphic information since deglaciation, at least. An interesting and may be one of the most important of these basins is Lake Llauset in the Alta Ribagorca. The Llauset basin has recently been developped for hydsopower production. In conection with the construction of the retaining wall at the 'Riegel' the sedimentary filling of the lake basin could be investigated, and the first sedimentological and stratigraphicalresults are presented.

Development process and initial validation of the ethical conflict in nursing questionnaire-critical care version

Background: Ethical conflicts are arising as a result of the growing complexity of clinical care, coupled with technological advances. Most studies that have developed instruments for measuring ethical conflict base their measures on the variables"frequency" and"degree of conflict". In our view, however, these variables are insufficient for explaining the root of ethical conflicts. Consequently, the present study formulates a conceptual model that also includes the variable"exposure to conflict", as well as considering six"types of ethical conflict". An instrument was then designed to measure the ethical conflicts experienced by nurses who work with critical care patients. The paper describes the development process and validation of this instrument, the Ethical Conflict in Nursing Questionnaire Critical Care Version (ECNQ-CCV). Methods: The sample comprised 205 nursing professionals from the critical care units of two hospitals in Barcelona (Spain). The ECNQ-CCV presents 19 nursing scenarios with the potential to produce ethical conflict in the critical care setting. Exposure to ethical conflict was assessed by means of the Index of Exposure to Ethical Conflict (IEEC), a specific index developed to provide a reference value for each respondent by combining the intensity and frequency of occurrence of each scenario featured in the ECNQ-CCV. Following content validity, construct validity was assessed by means of Exploratory Factor Analysis (EFA), while Cronbach"s alpha was used to evaluate the instrument"s reliability. All analyses were performed using the statistical software PASW v19. Results: Cronbach"s alpha for the ECNQ-CCV as a whole was 0.882, which is higher than the values reported for certain other related instruments. The EFA suggested a unidimensional structure, with one component accounting for 33.41% of the explained variance. Conclusions: The ECNQ-CCV is shown to a valid and reliable instrument for use in critical care units. Its structure is such that the four variables on which our model of ethical conflict is based may be studied separately or in combination. The critical care nurses in this sample present moderate levels of exposure to ethical conflict. This study represents the first evaluation of the ECNQ-CCV.

Development process and initial validation of the ethical conflict in nursing questionnaire-critical care version

Background: Ethical conflicts are arising as a result of the growing complexity of clinical care, coupled with technological advances. Most studies that have developed instruments for measuring ethical conflict base their measures on the variables"frequency" and"degree of conflict". In our view, however, these variables are insufficient for explaining the root of ethical conflicts. Consequently, the present study formulates a conceptual model that also includes the variable"exposure to conflict", as well as considering six"types of ethical conflict". An instrument was then designed to measure the ethical conflicts experienced by nurses who work with critical care patients. The paper describes the development process and validation of this instrument, the Ethical Conflict in Nursing Questionnaire Critical Care Version (ECNQ-CCV). Methods: The sample comprised 205 nursing professionals from the critical care units of two hospitals in Barcelona (Spain). The ECNQ-CCV presents 19 nursing scenarios with the potential to produce ethical conflict in the critical care setting. Exposure to ethical conflict was assessed by means of the Index of Exposure to Ethical Conflict (IEEC), a specific index developed to provide a reference value for each respondent by combining the intensity and frequency of occurrence of each scenario featured in the ECNQ-CCV. Following content validity, construct validity was assessed by means of Exploratory Factor Analysis (EFA), while Cronbach"s alpha was used to evaluate the instrument"s reliability. All analyses were performed using the statistical software PASW v19. Results: Cronbach"s alpha for the ECNQ-CCV as a whole was 0.882, which is higher than the values reported for certain other related instruments. The EFA suggested a unidimensional structure, with one component accounting for 33.41% of the explained variance. Conclusions: The ECNQ-CCV is shown to a valid and reliable instrument for use in critical care units. Its structure is such that the four variables on which our model of ethical conflict is based may be studied separately or in combination. The critical care nurses in this sample present moderate levels of exposure to ethical conflict. This study represents the first evaluation of the ECNQ-CCV.

NMR chemical shifts of the rhodopsin chromophore in the dark state and in bathorhodopsin: a hybrid QM/MM molecular dynamics study.

We investigate nuclear magnetic resonance (NMR) parameters of the rhodopsin chromophore in the dark state of the protein and in the early photointermediate bathorhodopsin via first-principles molecular dynamics simulations and NMR chemical shift calculations in a hybrid quantum/classical (QM/MM) framework. NMR parameters are particularly sensitive to structural properties and to the chemical environment, which allows us to address different questions about the retinal chromophore in situ. Our calculations show that both the 13C and the 1H NMR chemical shifts are rather insensitive to the protonation state of Glu181, an ionizable amino acid side chain located in the vicinity of the isomerizing 11-cis bond. Thus, other techniques should be better suited to establish its protonation state. The calculated chemical shifts for bathorhodopsin further support our previously published theoretical structure, which is in very good agreement with more recent X-ray data.

Microtubule Associated Protein 1b (MAP1B) Is a Marker of the Microtubular Cytoskeleton in Podocytes but Is Not Essential for the Function of the Kidney Filtration Barrier in Mice.

Podocytes are essential for the function of the kidney glomerular filter. A highly differentiated cytoskeleton is requisite for their integrity. Although much knowledge has been gained on the organization of cortical actin networks in podocyte's foot processes, less is known about the molecular organization of the microtubular cytoskeleton in primary processes and the cell body. To gain an insight into the organization of the microtubular cytoskeleton of the podocyte, we systematically analyzed the expression of microtubule associated proteins (Maps), a family of microtubules interacting proteins with known functions as regulator, scaffold and guidance proteins. We identified microtubule associated protein 1b (MAP1B) to be specifically enriched in podocytes in human and rodent kidney. Using immunogold labeling in electron microscopy, we were able to demonstrate an enrichment of MAP1B in primary processes. A similar association of MAP1B with the microtubule cytoskeleton was detected in cultured podocytes. Subcellular distribution of MAP1B HC and LC1 was analyzed using a double fluorescent reporter MAP1B fusion protein. Subsequently we analyzed mice constitutively depleted of MAP1B. Interestingly, MAP1B KO was not associated with any functional or structural alterations pointing towards a redundancy of MAP proteins in podocytes. In summary, we established MAP1B as a specific marker protein of the podocyte microtubular cytoskeleton.