Spectral variability in phycocyanin cryptophyte antenna complexes is controlled by changes in the α‐polypeptide chains

Quantitative models of light harvesting in photosynthetic antenna complexes depend sensitively on the challenging determination of the relative site energies of the pigments. Here we analyze the basis of the light harvesting properties of four antennae from cryptophyte algae, phycocyanines PC577, PC612, PC630 and PC645, by comparing two alternative theoretical strategies to derive the excitonic Hamiltonian. The first is based on molecular dynamics simulations and subsequent polarizable quantum/molecular mechanics (QM/MMPol) calculations, whereas the second is based on three-layer QM/MMPol/ddCOSMO calculations performed on optimized geometries of the pigments, where the water solvent is described using the ddCOSMO continuum model. We find the latter approach to be remarkably accurate, suggesting that these four phycobiliproteins share a common energetic ordering PCB82 < PCB158 < DBV51/61 for pigments located in the highly-conserved β chains, whereas bilins in the more divergent α chains originate their spectral differences. In addition, we predict a strong screening of the coupling among central DBVs in 'open' form complexes PC577 and PC612 compared to 'closed' form ones, which together with the increased interpigment separation explains the attenuation of coherence beatings observed for these complexes

Determination of the protonation preferences of bilin pigments in cryptophyte antenna complexes

The light-harvesting mechanisms of cryptophyte antenna complexes have attracted considerable attention due to their ability to exhibit maximal photosynthetic activity under very low-light conditions and to display several colors, as well as the observation of vibronic coherent features in their two-dimensional electronic spectra. However, detailed investigations on the interplay between the protein environment and their light-harvesting properties are hampered by the uncertainty related to the protonation state of the underlying bilin pigments. Here we study the protonation preferences of four types of bilin pigments including 15,16-dihydrobiliverdin (DBV), phycoerythrobilin (PEB), phycocyanobilin (PCB) and mesobiliverdin (MBV), which are found in phycoerythrin PE545 and phycocyanin PC577, PC612, PC630 and PC645 complexes. We apply quantum chemical calculations coupled to continuum solvation calculations to predict the intrinsic acidity of bilins in aqueous solution, and then combine molecular dynamics simulations with empirical pKa estimates to investigate the impact of the local protein environment on the acidity of the pigments. We also report measurements of the absorption spectra of the five complexes in a wide range of pH in order to validate our simulations and investigate possible changes in the light harvesting properties of the complexes in the range of physiological pH found in the lumen (pH ∼ 5-7). The results suggest a pKa > 7 for DBV and MBV pigments in the α polypeptide chains of PE545 and PC630/PC645 complexes, which are not coordinated to a negatively charged amino acid. For the other PEB, DBV and PCB pigments, which interact with a Glu or Asp side chain, higher pKa values (pKa > 8) are estimated. Overall, the results support a preferential population of the fully protonated state for bilins in cryptophyte complexes under physiological conditions regardless of the specific type of pigment and local protein environment

Angiotensin II type 1/adenosine A2A receptor oligomers: a novel target for tardive dyskinesia

Tardive dyskinesia (TD) is a serious motor side effect that may appear after long-term treatment with neuroleptics and mostly mediated by dopamine D2 receptors (D2Rs). Striatal D2R functioning may be finely regulated by either adenosine A2A receptor (A2AR) or angiotensin receptor type 1 (AT1R) through putative receptor heteromers. Here, we examined whether A2AR and AT1R may oligomerize in the striatum to synergistically modulate dopaminergic transmission. First, by using bioluminescence resonance energy transfer, we demonstrated a physical AT1R-A2AR interaction in cultured cells. Interestingly, by protein-protein docking and molecular dynamics simulations, we described that a stable heterotetrameric interaction may exist between AT1R and A2AR bound to antagonists (i.e. losartan and istradefylline, respectively). Accordingly, we subsequently ascertained the existence of AT1R/A2AR heteromers in the striatum by proximity ligation in situ assay. Finally, we took advantage of a TD animal model, namely the reserpine-induced vacuous chewing movement (VCM), to evaluate a novel multimodal pharmacological TD treatment approach based on targeting the AT1R/A2AR complex. Thus, reserpinized mice were co-treated with sub-effective losartan and istradefylline doses, which prompted a synergistic reduction in VCM. Overall, our results demonstrated the existence of striatal AT1R/A2AR oligomers with potential usefulness for the therapeutic management of TD

Adaptació al català de l'enquesta per malalties respiratòries ATS-DLD-78: validació preliminar

L'objectiu del treball és validar un instrument de mesura per conèixer, més endavant, la prevalença de les bronquitis més cròniques en el nostre medi. Es tracta de l'enquesta per malalties respiratòries de l'American Thoracic Society for the Division of Lung Disease, que hem traduït al català. Respecte a les preguntes del test que defineixen les bronquitis cròniques, hem trobat una sensibilitat del 63,33% i una especificitat del 100% per la referida a la tos i una sensibilitat del 63,33% i una especificitat del 90% per la referida a l'expectoració. De les 124 preguntes, 55 s'hagueren de repetir. D'aquestes, 7 dues vegades i la resta (48) només una. La mitjana aritmètica de la durada del qüestionari és de 17,15 minuts. Pensem que aquesta enquesta, traduïda al català, és una bona eina per estudis de prevalença de malalties respiratòries en el nostre medi

A set of quality and safety indicators for hospitals of the «Agencia Valenciana de Salud»

Objetivos: Elaborar un conjunto de indicadores de calidad y seguridad en el contexto de los hospitales de la Agencia Valenciana de Salud. Material y métodos: Se utilizó la técnica Metaplan® para identificar propuestas sobre sostenibilidad y enfermería. Se empleó el catálogo de la Sociedad Espanola ˜ de Calidad Asistencial como punto de partida para los indicadores clínicos. Utilizando la Técnica Delphi 207 profesionales fueron invitados a participar en el proceso para identificar los indicadores más fiables y factibles. Finalmente, la propuesta resultante fue validada por los directivos de 12 hospitales, teniendo en cuenta la variabilidad, objetividad, factibilidad, fiabilidad y sensibilidad de los indicadores. Resultados: La tasa de participación osciló entre el 66,67 y 80,71%. De los 159 indicadores de la propuesta inicial se priorizaron y seleccionaron 68 (21 económicos o de gestión, 22 de cuidados de enfermería y 25 clínicos). De ellos 3 eran comunes a las 3 categorías y 2 no cumplían los criterios específicos de la fase de validación, por lo que el conjunto final consta de 63 indicadores. Conclusiones: Se ha elaborado un conjunto de indicadores de calidad y seguridad. El sistema de información actual permite su monitorización.Objectives: To prepare a set of quality and safety indicators for Hospitals of the «Agencia Valenciana de Salud». Material and methods: The qualitative technique Metaplan® was applied in order to gather proposals on sustainability and nursing. The catalogue of the «Spanish Society of Quality in Healthcare» was adopted as a starting point for clinical indicators. Using the Delphi technique, 207 professionals were invited to participate in the selecting the most reliable and feasible indicators. Lastly, the resulting proposal was validated with the managers of 12 hospitals, taking into account the variability, objectivity, feasibility, reliability and sensitivity, of the indicators. Results: Participation rates varied between 66.67% and 80.71%. Of the 159 initial indicators, 68 were prioritized and selected (21 economic or management indicators, 22 nursing indicators, and 25 clinical or hospital indicators). Three of them were common to all three categories and two did not match the specified criteria during the validation phase, thus obtaining a final catalogue of 63 indicators. Conclusions: A set of quality and safety indicators for Hospitals was prepared. They are currently being monitored using the hospital information systems.Medicin

Viscerotropic disease: case definition and guidelines for collection, analysis, and presentation of immunization safety data

Viscerotropic disease (VTD) is defined as acute multiple organ system dysfunction that occurs following vaccination. The severity of VTD ranges from relatively mild multisystem disease to severe multiple organ system failure and death. The term VTD was first used shortly after the initial published reports in 2001 of febrile multiple organ system failure following yellow fever (YF) vaccination. To date, VTD has been reported only in association with YF vaccine and has been thus referred to as YF vaccine-associated viscerotropic disease (YEL-AVD)

Performance issues in optical burst/packet switching

The final publication is available at Springer via http://dx.doi.org/10.1007/978-3-642-01524-3_8This chapter summarises the activities on optical packet switching (OPS) and optical burst switching (OBS) carried out by the COST 291 partners in the last 4 years. It consists of an introduction, five sections with contributions on five different specific topics, and a final section dedicated to the conclusions. Each section contains an introductive state-of-the-art description of the specific topic and at least one contribution on that topic. The conclusions give some points on the current situation of the OPS/OBS paradigms

Effectiveness of Motivational Interviewing in improving lipid level in patients with dyslipidemia assisted by general practitioners: Dislip-EM study protocol

<p>Abstract</p> <p>Background</p> <p>The non-pharmacological approach to cholesterol control in patients with hyperlipidemia is based on the promotion of a healthy diet and physical activity. Thus, to help patients change their habits, it is essential to identify the most effective approach. Many efforts have been devoted to explain changes in or adherence to specific health behaviors. Such efforts have resulted in the development of theories that have been applied in prevention campaigns, and that include brief advice and counseling services. Within this context, Motivational Interviewing has proven to be effective in changing health behaviors in specific cases. However, more robust evidence is needed on the effectiveness of Motivational Interviewing in treating chronic pathologies -such as dyslipidemia- in patients assisted by general practitioners. This article describes a protocol to assess the effectiveness of MI as compared with general practice (brief advice), with the aim of improving lipid level control in patients with dyslipidemia assisted by a general practitioner.</p> <p>Methods/Design</p> <p>An open, two-arm parallel, multicentre, cluster, controlled, randomized, clinical trial will be performed. A total of 48-50 general practitioners from 35 public primary care centers in Spain will be randomized and will recruit 436 patients with dyslipidemia. They will perform an intervention based either on Motivational Interviewing or on the usual brief advice. After an initial assessment, follow-ups will be performed at 2, 4, 8 and 12 months. Primary outcomes are lipid levels (total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides) and cardiovascular risk. The study will assess the degree of dietary and physical activity improvement, weight loss in overweight patients, and adherence to treatment guidelines.</p> <p>Discussion</p> <p>Motivational interview skills constitute the primary strategies GPs use to treat their patients. Having economical, simple, effective and applicable techniques is essential for primary care professionals to help their patients change their lifestyle and improve their health. This study will provide scientific evidence on the effectiveness of Motivational interviewing, and will be performed under strict control over the data collected, ensuring the maintenance of therapeutic integrity.</p> <p>Trials Registration</p> <p>ClinicalTrials.gov (<a href="http://www.clinicaltrials.gov/ct2/show/NCT01282190">NCT01282190</a>).</p

Activation of PKR Causes Amyloid ß-Peptide Accumulation via De-Repression of BACE1 Expression

BACE1 is a key enzyme involved in the production of amyloid ß-peptide (Aß) in Alzheimer's disease (AD) brains. Normally, its expression is constitutively inhibited due to the presence of the 5′untranslated region (5′UTR) in the BACE1 promoter. BACE1 expression is activated by phosphorylation of the eukaryotic initiation factor (eIF)2-alpha, which reverses the inhibitory effect exerted by BACE1 5′UTR. There are four kinases associated with different types of stress that could phosphorylate eIF2-alpha. Here we focus on the double-stranded (ds) RNA-activated protein kinase (PKR). PKR is activated during viral infection, including that of herpes simplex virus type 1 (HSV1), a virus suggested to be implicated in the development of AD, acting when present in brains of carriers of the type 4 allele of the apolipoprotein E gene. HSV1 is a dsDNA virus but it has genes on both strands of the genome, and from these genes complementary RNA molecules are transcribed. These could activate BACE1 expression by the PKR pathway. Here we demonstrate in HSV1-infected neuroblastoma cells, and in peripheral nervous tissue from HSV1-infected mice, that HSV1 activates PKR. Cloning BACE1 5′UTR upstream of a luciferase (luc) gene confirmed its inhibitory effect, which can be prevented by salubrinal, an inhibitor of the eIF2-alpha phosphatase PP1c. Treatment with the dsRNA analog poly (I∶C) mimicked the stimulatory effect exerted by salubrinal over BACE1 translation in the 5′UTR-luc construct and increased Aß production in HEK-APPsw cells. Summarizing, our data suggest that PKR activated in brain by HSV1 could play an important role in the development of AD

Wetlands for wastewater treatment and subsequent recycling of treated effluent : a review

Due to water scarcity challenges around the world, it is essential to think about non-conventional water resources to address the increased demand in clean freshwater. Environmental and public health problems may result from insufficient provision of sanitation and wastewater disposal facilities. Because of this, wastewater treatment and recycling methods will be vital to provide sufficient freshwater in the coming decades, since water resources are limited and more than 70% of water are consumed for irrigation purposes. Therefore, the application of treated wastewater for agricultural irrigation has much potential, especially when incorporating the reuse of nutrients like nitrogen and phosphorous, which are essential for plant production. Among the current treatment technologies applied in urban wastewater reuse for irrigation, wetlands were concluded to be the one of the most suitable ones in terms of pollutant removal and have advantages due to both low maintenance costs and required energy. Wetland behavior and efficiency concerning wastewater treatment is mainly linked to macrophyte composition, substrate, hydrology, surface loading rate, influent feeding mode, microorganism availability, and temperature. Constructed wetlands are very effective in removing organics and suspended solids, whereas the removal of nitrogen is relatively low, but could be improved by using a combination of various types of constructed wetlands meeting the irrigation reuse standards. The removal of phosphorus is usually low, unless special media with high sorption capacity are used. Pathogen removal from wetland effluent to meet irrigation reuse standards is a challenge unless supplementary lagoons or hybrid wetland systems are used