Functional EF-hands in neuronal calcium sensor GCAP2 determine its phosphorylation state and subcellular distribution in vivo, and are essential for photoreceptor cell integrity

The neuronal calcium sensor proteins GCAPs (guanylate cyclase activating proteins) switch between Ca2+-free and Ca2+-bound conformational states and confer calcium sensitivity to guanylate cyclase at retinal photoreceptor cells. They play a fundamental role in light adaptation by coupling the rate of cGMP synthesis to the intracellular concentration of calcium. Mutations in GCAPs lead to blindness. The importance of functional EF-hands in GCAP1 for photoreceptor cell integrity has been well established. Mutations in GCAP1 that diminish its Ca2+ binding affinity lead to cell damage by causing unabated cGMP synthesis and accumulation of toxic levels of free cGMP and Ca2+. We here investigate the relevance of GCAP2 functional EF-hands for photoreceptor cell integrity. By characterizing transgenic mice expressing a mutant form of GCAP2 with all EF-hands inactivated (EF(-)GCAP2), we show that GCAP2 locked in its Ca2+-free conformation leads to a rapid retinal degeneration that is not due to unabated cGMP synthesis. We unveil that when locked in its Ca2+-free conformation in vivo, GCAP2 is phosphorylated at Ser201 and results in phospho-dependent binding to the chaperone 14-3-3 and retention at the inner segment and proximal cell compartments. Accumulation of phosphorylated EF(-)GCAP2 at the inner segment results in severe toxicity. We show that in wildtype mice under physiological conditions, 50% of GCAP2 is phosphorylated correlating with the 50% of the protein being retained at the inner segment. Raising mice under constant light exposure, however, drastically increases the retention of GCAP2 in its Ca2+-free form at the inner segment. This study identifies a new mechanism governing GCAP2 subcellular distribution in vivo, closely related to disease. It also identifies a pathway by which a sustained reduction in intracellular free Ca2+ could result in photoreceptor damage, relevant for light damage and for those genetic disorders resulting in 'equivalent-light'' scenarios.

Convergent Approaches for the Synthesis of the Anti-tumoral Peptide, Kahalalide F. Study of Orthogonal Protecting Groups

Kahalalide compounds are peptides that are isolated from a Hawaiian herbivorous marine species of mollusc, Elysia rufescens, and its diet, the green alga Bryopsis sp. Kahalalide F and its synthetic analogues are the most promising compounds of the Kahalalide family because they show anti-tumoral activity. Linear solid-phase syntheses of Kahalalide F have been reported. Here we describe several new improved synthetic routes based on convergent approaches with distinct orthogonal protection schemes for the preparation of Kahaladide analogues. These strategies allow a better control and characterization of the intermediates because more reactions are performed in solution. Five derivatives of Kahalalide F were synthesized using several convergent approaches.

Profile, cost and pattern of prescriptions for polymedicated patients in Catalonia, Spain

OBJECTIVES: Polypharmacy is one of the main management issues in public health policies because of its financial impact and the increasing number of people involved. The polymedicated population according to their demographic and therapeutic profile and the cost for the public healthcare system were characterised. DESIGN: Cross-sectional study. SETTING: Primary healthcare in Barcelona Health Region, Catalonia, Spain (5 105 551 inhabitants registered). PARTICIPANTS: All insured polymedicated patients. Polymedicated patients were those with a consumption of ≥16 drugs/month. MAIN OUTCOMES MEASURES: The study variables were related to age, gender and medication intake obtained from the 2008 census and records of prescriptions dispensed in pharmacies and charged to the public health system. RESULTS: There were 36 880 polymedicated patients (women: 64.2%; average age: 74.5±10.9 years). The total number of prescriptions billed in 2008 was 2 266 830 (2 272 920 total package units). The most polymedicated group (up to 40% of the total prescriptions) was patients between 75 and 84 years old. The average number of prescriptions billed monthly per patient was 32±2, with an average cost of 452.7±27.5. The total cost of those prescriptions corresponded to 2% of the drug expenditure in Catalonia. The groups N, C, A, R and M represented 71.4% of the total number of drug package units dispensed to polymedicated patients. Great variability was found between the medication profiles of men and women, and between age groups; greater discrepancies were found in paediatric patients (5-14 years) and the elderly (≥65 years). CONCLUSIONS: This study provides essential information to take steps towards rational drug use and a structured approach in the polymedicated population in primary healthcare.

Osaamisen johtaminen Suomen kunnissa

Kunnissa eletään muutosten aikaa, ja osaamisen johtamisella pyritään vastaamaan kehityksen mukanaan tuomiin haasteisiin. Osaamisen johtamista pidetäänkin tärkeänä asiana kuntien kehittämisessä. Viime vuosina osaamisen johtaminen on ollut voimakkaasti esillä myös yksityisellä sektorilla, jossa se on nähty tärkeänä elementtinä kilpailukyvyn kehittämisessä. Osaamisen johtaminen on toimintaa, jolla kehitetään yksilöiden ja organisaation osaamista sekä organisaation yhteistyövalmiutta. Osaamisen johtamisessa huomioidaan myös organisaatiolle asetetut strategiset tavoitteet. Tässä tutkimuksessa osaamisen johtaminen ankkuroidaan tietojohtamisen, henkilöstövoimavarojen johtamisen (HRM:n) ja oppivan organisaation viitekehyksiin. Tutkimusotteeksi on valittu kvantitatiivinen tutkimusote. Kvantitatiivinen tutkimusote mahdollistaa osaamisen johtamisen rakenteellisen analyysin ja kuvaamisen. Tutkimuksen kohderyhmänä ovat kaikki Suomen 444 kuntaa vuonna 2004. Tutkimuksen tiedonkeruu suoritettiin lomakekyselyn avulla, ja tutkimus kohdistettiin kuntien henkilöstöasioiden asiantuntijoille. Tutkimuksen keskeisenä tavoitteena oli mallintaa ja kuvata osaamisen johtamista Suomen kunnissa. Tutkimusongelma liittyy kuntien osaamisen johtamisen nykytilaan ja tavoitteisiin sekä siihen, missä vaiheissa kunnat ovat osaamisen johtamisessaan. Kyselyn avulla tutkittiin myös kuntien halukkuutta kehittää osaamisen johtamistaan. Vastausten pohjalta analysoitiin lisäksi, mitkä asiat kunnissa vaikuttavat osaamisen johtamiseen. Tutkimuksen tuloksissa tulevat esille neljä erilaista kunnissa vallitsevaa osaamisen johtamisen orientaatiota: Strategiaohjattu yhteisöllinen orientaatio, Innovatiivinen orientaatio, Teknologinen orientaatio ja Strategialähtöinen järjestelmäorientaatio. Nämä neljä orientaatiota ovat tunnistettavissa myös taustakirjallisuudessa. Kunnat ryhmiteltiin orientaatioiden perusteella neljään ryhmään, jotka nimettiin seuraavasti: Innostuneet aloittelijat, Tekniset aloittelijat, Edistyneet ja Kehittyvät. Innostuneiden aloittelijoiden ryhmässä korostuu innovatiivinen orientaatio, mutta muut osaamisen johtamisen orientaatiot tulevat esille heikosti. Teknisten aloittelijoiden ryhmässä korostuu teknologinen orientaatio, mutta muut osaamisen johtamisen orientaatiot tulevat esille heikosti. Edistyneiden ryhmässä kaikki osaamisen johtamisen orientaatiot tulevat hyvin esille. Kehittyvien ryhmässä korostuvat sekä innovatiivinen että teknologinen orientaatio. Kuntien osaamisen johtamisen nykytilanne on murroksessa. Osaamisen johtaminen on suuressa osassa kunnista hyvässä vauhdissa, mutta kehitettävääkin on. Tietotekniset välineet osaamisen johtamisessa ovat hyvät useimmissa kunnissa. Tulevaisuuden osaamistarpeina pidetään erityisesti vuorovaikutustaitoja ja oman ammattialan osaamista. Kunnissa on myös huomioitu ainakin tavoitteiden tasolla tulevaisuus ja sen tuomat haasteet.

Strategic groups and performance: an empirical analysis of strategic groups in the wind energy industry in Europe

The strategic group theory provides an intermediate level of analysis between a single company and the whole industry for identifying issues about the company's competitive position and strategic choices. Strategic groups are companies within an industry with similar strategic characteristics or competing on similar bases. Strategic choices are aligned with the firms’ resources. The purpose of this study was to identify the strategic groups in the wind energy industry in Europe, and study, whether a certain group membership results in financial performance differences. Altogether 80 European wind energy companies were included in the study, which were clustered into four strategic groups according to their age and growth rate. Each group corresponds to a different strategy. The results show that the wind energy companies can be clustered according to the chosen strategic characteristics. Strategic decisions were investigated with characteristic variables. Performance variables were used in the analysis measuring profitability, liquidity and solvency of the groups. These strategic choices of the companies did not have a significant influence on the firms’ performance. The more mature and slower growing group proved to be the most successful. However, the differences between groups were generally not statistically significant. The only statistically significant difference found was in the solvency ratio between Mature Slow and Young Rapid groups. Measured with these variables, more mature and slower growing companies performed better. Therefore, a certain strategic group membership results in performance differences.

Produtos naturais para o controle da transmissão da dengue: atividade larvicida de Myroxylon balsamum (óleo vermelho) e de terpenóides e fenilpropanóides

The bioassay-guided fractionation of the hexane extract obtained from the medicinal plant Myroxylon balsamum (red oil) was conducted in preparative thin layer chromatography on silica gel. The obtained fractions and some terpenoids and phenylpropanoids were assayed as larvicidal on third instar Aedes aegypti larvae, NPPN colony. The results indicate that the sesquiterpene nerolidol was the active constituent in the extract and that the sesquiterpenes were more active than the monoterpenes and phenylpropanoids utilized in this study. Lipophilicity seems to be an important property for the activity since the compounds with hydroxyl, carbonyl and methoxyl groups were less active. The results confirm also that essential oils can be a good tool for the control of dengue.

Composition and antifungal activity of essential oils from Piper aduncum, Piper arboreum and Piper tuberculatum

The composition of essential oils from leaves, stems and fruits of Piper aduncum, P. arboreum and P. tuberculatum was examined by means of GC-MS and antifungal assay. There was a predominance of monoterpenes in P. aduncum and P. tuberculatum and of sesquiterpenes in P. arboreum. P. aduncum showed the richest essential oil composition, including linalool. The essential oils from fruits of P. aduncum and P. tuberculatum showed the highest antifungal activity with the MIC of 10 µg as determined against Cladosporium cladosporioides and C. sphaerospermum, respectively. This is the first report of the composition of essential oils from P. tuberculatum.

Variação química do óleo essencial de Hyptis suaveolens (L.) Poit., sob condições de cultivo

This study was performed to establish the correlation between the growth conditions and essential oil composition of Hyptis suaveolens from Alfenas (MG), Brazil. The plants were grown in a greenhouse, four treatments were used and they were harvested at two different periods of time (60 and 135-day-old plants). The essential oil composition was determined by GC-MS analysis. The terpenes spathulenol, globulol, dehydroabietol, a-cadinol and beta-phellandrene were the major constituents found in the essential oil. Oxygenated sesquiterpenes represented the main group of constituents in most of the treatments. The major changes in the essential oil composition were found in 135-day-old plants grown under NPK deficiency. We also identified three groups of volatile components that have not been previously described in H suaveolens.

The adequacy of different robust statistical tests in comparing two independent groups

In the current study, we evaluated various robust statistical methods for comparing two independent groups. Two scenarios for simulation were generated: one of equality and another of population mean differences. In each of the scenarios, 33 experimental conditions were used as a function of sample size, standard deviation and asymmetry. For each condition, 5000 replications per group were generated. The results obtained by this study show an adequate type error I rate but not a high power for the confidence intervals. In general, for the two scenarios studied (mean population differences and not mean population differences) in the different conditions analysed, the Mann-Whitney U-test demonstrated strong performance, and a little worse the t-test of Yuen-Welch.

Chemical composition and antimicrobial activity of the essential oil from Aeolanthus suaveolens Mart. ex Spreng

The essential oils from leaves (sample A) and flowers (sample B) of Aeolanthus suaveolens Mart. ex Spreng were obtained by hydrodistillation and analyzed by GC, GC-MS, and chiral phase gas chromatography (CPGC). Six compounds have been identified from the essential oils, representing ca 94.3 and 93% of the oils corresponding to samples A and B, respectively. The major constituents of samples A and B essential oils were respectively, linalool (34.2%/34.9%), (-)-massoialactone (25.9%/17.0%) and (E)-beta-farnesene (25.4%/29.1%). The enantiomeric distribution of the monoterpene linalool was established by analysis on heptakis- (6-O-methyl-2,3-di-O-pentyl)-beta-cyclodextrin capillary column. The antimicrobial activity of the essential oil from leaves and isolated compounds was also evaluated.

Xarxa digital multimèdia de pantalles i kioscs interactius

Internet s’ha alçat en poc temps com el mitjà més utilitzat pels turistes per a planificar, organitzar i comprar un viatge, és per això que es proposa donar les mateixes facilitats en el destí. La Publicitat Dinàmica o “Digital Signage” és un nou servei de comunicació que consisteix en un conjunt de tecnologies i aplicacions informàtiques que permeten emetre missatges multimèdia i comunicar-se així d’una manera innovadora amb el públic objectiu de cada empresa, si s’afegeix un sistema independent, multimèdia i interactiu que pot utilitzar-se per a proporcionar informació i/o permetre la realització de transaccions es potencia al màxim el servei. D’aquesta manera es proposa crear una Xarxa Digital Multimèdia de Kioscs Interactius recolzats amb una pantalla de plasma per a la tecnologia Digital Signage. La ubicació escollida estratègicament és en un dels punts de major afluència turística, tal com l’entrada dels hotels. Així es tracta de crear circuits tancats en àrees geogràfiques on es troben els principals nuclis turístics de Mallorca. La possibilitat d’accedir a segments de població altament interessants per al producte o servei es multiplica al ser una manera fàcil, eficaç i altament suggestiva de promocionar el què es pretén. Un avantatge és la simplicitat de la infraestructura tecnològica que es necessita, el dispositiu mitjançant el qual es visualitzaran els missatges serà una pantalla de plasma convencional, i un terminal de punt de venda instal.lat en un lloc de pas. Cada mòdul està connectat a la xarxa ADSL mitjançant un servidor local a Internet. La connexió a la xarxa és imprescindible per a que el manteniment i actualització dels continguts es puguin efectuar remotament. L’objectiu principal d’aquest treball és estudiar la viabilitat de la implantació de la xarxa, mitjançant la realització d’un estudi de mercat on s’analitzen els grups claus per a la implantació: els hotelers, la indústria turística i el Govern Balear. S’identifiquen els beneficis que aportarà al nou servei i les repercussions que tendrà la seva instal.lació. Entre els resultats més destacats d’aquest estudi cal remarcar l’acceptació que ha tengut la idea entre els hotelers entrevistats i la resposta positiva de la indústria turística. Es reconeix: una millora de la imatge del sector, l’ús com a eina de promoció turística pel Govern, i la contribució a la sostenibilitat econòmica pel fet que augmenta la competitivitat de les empreses i això millora la qualitat del servei.

Realització d'una aplicació de gestió de xarxes per a la xarxa sensefils de Manresa GuifiBages

En els últims anys, la popularitat de les xarxes sensefils (WIFI) ha anat en augment a un ritme incansable. Des de petits aparells instal•lats a les cases amb aquesta tecnologia com a complement dels routers d’accés a internet instal•lats per diverses companyies, fins a empreses fent petits desplegaments per comunicar entre si les seves seus. Al marge d’aquests escenaris, s’ha produït un fenomen social d’acolliment d’aquesta tecnologia a nivell mundial, en forma del que coneixem com a xarxes ciutadanes / xarxes lliures / xarxes socials. Aquestes xarxes han estat possibles gràcies a diverses raons que han fet assequible a col•lectius de persones, tant els aparells com els coneixements necessaris per dur a terme aquestes actuacions. Dintre d’aquest marc, al Bages, concretament a Manresa, es va començar a desenvolupar una d’aquestes xarxes. Les decisions d’aquesta xarxa d’utilitzar exclusivament hardware i software de codi obert, i determinats aspectes tècnics de la xarxa, ha comportat que la xarxa fos incompatible amb algunes de les aplicacions de gestió de xarxes existents desenvolupades per comunicats com gufi.net a Osona. És per això que per garantir el creixement, la supervivència i l’èxit d’aquesta xarxa en el temps, és indispensable poder comptar amb una eina de gestió que s’adigui a les característiques de GuifiBages. L’objectiu principal d’aquest treball és dotar a la xarxa GuifiBages de les eines necessàries per poder gestionar tota la informació referent a l’estructura de la seva xarxa, tant per facilitar l’accés a nous usuaris sense molts coneixements tècnics, com per facilitar nous desplegaments / reparacions / modificacions de la xarxa d’una manera automàtica. Com a conclusió d’aquest treball, podem afirmar que les avantatges que proporciones tecnologies com Plone, faciliten enormement la creació d’aplicacions de gestió de continguts en entorn web. Alhora, l’ús de noves tècniques de programació com AJAX o recursos com els que ofereix Google, permeten desenvolupar aplicacions web que no tenen res a envejar al software tradicional. D’altra banda, voldríem destacar l’ús exclusiu de programari lliure tant en els paquets de software necessaris pel desenvolupament, com en el sistema operatiu i programes dels ordinadors on s’ha dut a terme, demostrant que es poden desenvolupar sistemes de qualitat sense dependre de programari privatiu.

Lipídios estruturados obtidos a partir da mistura de gordura de frango, sua estearina e triacilgliceróis de cadeia média: I- Composição em ácidos graxos e em triacilgliceróis

The purpose of this study is to analyze the interactions that occur in binary and ternary fat blends between medium and long chain triacylglycerols and their structured lipids obtained by chemical interesterification through the analysis of their physico-chemical properties. The synthesized structured triacylglycerols presented from 14.8 to 58.4% medium chain fatty acids, from 15.7 to 37.2% saturated fatty acids, from 19.2 to 47.5% monounsaturated fatty acids, and from 6.7 to 15.2% essential fatty acids. Chemical interesterification modified the behavior of binary and ternary mixtures and new types of triacylglycerol groups were formed.

Essential oils from leaves of cryptocarya spp from the atlantic rain forest

The essential oils from leaves of four Cryptocarya spp endemic in the Brazilian Atlantic rain forest were obtained by hydrodistillation and shown by GC-MS analysis to contain mono and sesquiterpenes. The major components of the oil of Cryptocarya moschata were linalool (34.3%), a-terpinene (17.0%), g-terpinene (10.4%), 1,8-cineole (5.8%) and trans-ocimene (4.8%), whilst those of C. botelhensis were a-pinene (22.7%), b-pinene (9.2%), trans-verbenol (8.4%), trans-pinocarveol (5.5%) and myrtenal (5.4%). The principal compounds of C. mandioccana oil were b-caryophyllene (13.8%), spathulenol (10.2%), caryophyllene oxide (7.8%), d-cadinene (6.9%) and bicyclogermacrene (6.4%), whilst those of C. saligna were germacrene D (15.5%), bicyclogermacrene (13.8%), spathulenol (11.8%) and germacrene B (5.7%).