Fin ray branching is defined by TRAP+ osteolytic tubules in zebrafish.

The shaping of bone structures relies on various cell types and signaling pathways. Here, we use the zebrafish bifurcating fin rays during regeneration to investigate bone patterning. We found that the regenerating fin rays form via two mineralization fronts that undergo an osteoblast-dependent fusion/stitching until the branchpoint, and that bifurcation is not simply the splitting of one unit into two. We identified tartrate-resistant acid phosphatase-positive osteolytic tubular structures at the branchpoints, hereafter named osteolytic tubules (OLTs). Chemical inhibition of their bone-resorbing activity strongly impairs ray bifurcation, indicating that OLTs counteract the stitching process. Furthermore, by testing different osteoactive compounds, we show that the position of the branchpoint depends on the balance between bone mineralization and resorption activities. Overall, these findings provide a unique perspective on fin ray formation and bifurcation, and reveal a key role for OLTs in defining the proximo-distal position of the branchpoint.

What are the barriers and facilitators to participation of people with Down syndrome? A scoping review.

AIM: To determine the barriers and facilitators of active community participation of children, adolescents, and adults with Down syndrome. METHOD: Searches were completed in five electronic databases to identify original studies about participation of children, adolescents (ages < 18 years), and adults (ages 18-59 years) with Down syndrome. Barriers and facilitators to participation were categorized into four factors: personal, social, environmental, and policy and programme. Findings were analysed and validated by a young adult with Down syndrome and a family member, using the public and patient involvement strategy. RESULTS: Fourteen studies were included: eight with children and adolescents and six with adults. Of the 14 studies, 10 were qualitative and four quantitative. Most studies (n = 9) investigated participation in physical activities, while only a few examined participation in community/social activities (n = 3), daily activities (n = 2), and leisure activities (n = 1). The most commonly cited barriers and facilitators were the availability of programmes and specialized professionals, transportation, as well as attitudes and behaviours. Physical and psychological characteristics of people with Down syndrome and facilities were also frequently mentioned as barriers. On the other hand, the desire to stay active and personal interest in the activity were among the most frequently reported facilitators. INTERPRETATION: The participation of people with Down syndrome is mainly influenced by physical or psychological factors, the support and attitudes of parents/caregivers, and the availability of specialized programmes. Given the scarcity of research investigating the participation of people with Down syndrome in community activities, daily activities, and leisure, especially in adults, more studies are still needed.

Aberrant Splicing Caused by a Novel VPS16 Variant Linked to Dystonia Type 30.

Dystonia is a hyperkinetic movement disorder characterized by sustained or intermittent involuntary muscle contractions, causing abnormal postures and/or repetitive movements. In this report, we identified a novel heterozygous splice-site variant in VPS16 (NM_022575.4:c.240+3G>C) in a patient with cervical and upper limb dystonia without other neurological or extra-neurological features. Analysis of patient's blood mRNA showed disruption of exon 3/intron 3 donor splice-site, leading to exon 3 skipping, which predictably results in a frameshift [p.(Ala48Valfs*14)]. Despite the scarcity of splice-affecting variants described in VPS16-related dystonia, our report contributes with the first fully characterized variant at the mRNA level.

A systematic review of the use of bacteriophages for in vitro biofilm control.

Bacteriophages (phages) are very promising biological agents for the prevention and control of bacterial biofilms. However, little is known about the parameters that can influence the efficacy of phages on biofilms. This systematic review provides a summary and analysis of the published data about the use of phages to control pre-formed biofilms in vitro, suggesting recommendations for future experiments in this area. A total of 68 articles, containing data on 605 experiments addressing the efficacy of phages to control biofilms in vitro were included, after a search conducted in Web of Science, Embase, and Medline (PubMed). The data collected from each experiment included information about biofilm growth conditions, phage characteristics, treatment conditions and biofilm reduction. In most cases, biofilms were formed in the surface of microtiter plates (82.5%); the median time for biofilm formation was 24 h, as is the median treatment duration. Quantification of biofilm biomass (52.6%), viable cells (25.5%) and metabolic activity (17.9%) were the most common biofilm assessment methods. Correlation analysis revealed that some phage parameters can influence the treatment outcome: higher phage concentrations were strongly associated with improved biofilm control, leading to higher levels of biofilm reduction, and phages with higher burst sizes and shorter latent periods seem to be the best candidates to control biofilms in vitro. However, the great variability of the methodologies used prompts the need for the development of standardized in vitro methodologies to characterize phage/biofilm interactions and to assess the efficacy of phages to control biofilms.

Impact of phage predation on P. aeruginosa adhered to human airway epithelium: major transcriptomic changes in metabolism and virulence-associated genes.

Phage therapy is a promising adjunct therapeutic approach against bacterial multidrug-resistant infections, including Pseudomonas aeruginosa-derived infections. Nevertheless, the current knowledge about the phage-bacteria interaction within a human environment is limited. In this work, we performed a transcriptome analysis of phage-infected P. aeruginosa adhered to a human epithelium (Nuli-1 ATCC® CRL-4011™). To this end, we performed RNA-sequencing from a complex mixture comprising phage-bacteria-human cells at early, middle, and late infection and compared it to uninfected adhered bacteria. Overall, we demonstrated that phage genome transcription is unaltered by bacterial growth and phage employs a core strategy of predation through upregulation of prophage-associated genes, a shutdown of bacterial surface receptors, and motility inhibition. In addition, specific responses were captured under lung-simulating conditions, with the expression of genes related to spermidine syntheses, sulphate acquisition, biofilm formation (both alginate and polysaccharide syntheses), lipopolysaccharide (LPS) modification, pyochelin expression, and downregulation of virulence regulators. These responses should be carefully studied in detail to better discern phage-induced changes from bacterial responses against phage. Our results establish the relevance of using complex settings that mimics in vivo conditions to study phage-bacteria interplay, being obvious the phage versatility on bacterial cell invasion.

Randomized clinical study of injectable dextrin-based hydrogel as a carrier of a synthetic bone substitute.

OBJECTIVES: This study aimed to improve the performance and mode of administration of a glass-reinforced hydroxyapatite synthetic bone substitute, Bonelike by Biosckin® (BL®), by association with a dextrin-based hydrogel, DEXGEL, to achieve an injectable and moldable device named DEXGEL Bone. METHODS: Twelve participants requiring pre-molar tooth extraction and implant placement were enrolled in this study. BL® granules (250-500 µm) were administered to 6 randomized participants whereas the other 6 received DEXGEL Bone. After 6 months, a bone biopsy of the grafted area was collected for histological and histomorphometric evaluation, prior to implant placement. The performance of DEXGEL Bone and BL® treatments on alveolar preservation were further analyzed by computed tomography and Hounsfield density analysis. Primary implant stability was analyzed by implant stability coefficient technique. RESULTS: The healing of defects was free of any local or systemic complications. Both treatments showed good osseointegration with no signs of adverse reaction. DEXGEL Bone exhibited increased granule resorption (p = 0.029) accompanied by a tendency for more new bone ingrowth (although not statistically significant) compared to the BL® group. The addition of DEXGEL to BL® granules did not compromise bone volume or density, being even beneficial for implant primary stability (p = 0.017). CONCLUSIONS: The hydrogel-reinforced biomaterial exhibited an easier handling, a better defect filling, and benefits in implant stability. CLINICAL RELEVANCE: This study validates DEXGEL Bone safety and performance as an injectable carrier of granular bone substitutes for alveolar ridge preservation. TRIAL REGISTRATION: European Databank on Medical Devices (EUDAMED) No. CIV-PT-18-01-02,705; Registo Nacional de Estudos Clínicos, RNEC, No. 30122.

[Mapping public health training in Latin America: perspectives for training institutionsMapeamento da formação em saúde pública na América Latina: perspectivas para as instituições formadoras]. / Mapeo de la formación en salud pública en América Latina: perspectivas para las instituciones formadoras.

Objective: Map the public health training courses and programs offered in Latin America, and identify regional training strategies and competencies developed in health workers. Methods: An internet search was conducted to identify public health training courses and programs offered by Latin American institutions. The following data were collected: name, country, and province/state of the training institution; course name; type of institution; educational level; modality; accreditation; year first offered; periodicity; and contact information. The programs and curricula on offer were analyzed by training level using descriptive content analysis, and the main competencies developed were identified. Results: The mapping identified 2 296 public health training opportunities in all Latin American subregions, distributed across 29 of the Region's 33 countries; these were fairly heterogeneous, both conceptually and programmatically, with uneven geographical distribution within and between countries. In the analysis of curricula and programmatic contents, a need for greater linkage with essential public health functions was detected. Conclusion: It is necessary to adapt the competencies and skills developed by the courses and programs to the demands of users of the regional health services, programs, and systems in order to achieve programs aimed at tackling the socio-environmental determinants of health and the production and reproduction of inequalities.

Objetivo: Mapear os cursos e programas de formação em saúde pública oferecidos na América Latina e identificar estratégias de formação e competências desenvolvidas na formação regional de profissionais de saúde pública. Métodos: Foi realizada uma busca na internet para identificar cursos e programas de formação em saúde pública oferecidos por instituições latino-americanas. Foram coletados os seguintes dados: nome, país e estado ou província da instituição formadora; nome do curso; característica da instituição; nível de formação; modalidade; acreditação; ano da primeira turma; regularidade e detalhes de contato. Em seguida, os programas e currículos oferecidos foram analisados por nível de formação, por meio da técnica descritiva de análise de conteúdo, e foram identificadas as principais competências desenvolvidas. Resultados: O mapeamento permitiu identificar 2 296 ofertas de formação em saúde pública em todas as sub-regiões da América Latina, distribuídas em 29 dos 33 países da Região. As ofertas identificadas foram bastante heterogêneas, tanto do ponto de vista conceitual como programático, e com uma distribuição geográfica desproporcional nos países e entre as sub-regiões. A análise dos currículos e conteúdos programáticos detectou a necessidade de um maior vínculo com as funções essenciais da saúde pública. Conclusão: Observou-se a necessidade de adequar as competências e habilidades desenvolvidas pelos cursos e programas às demandas dos usuários dos serviços, programas e sistemas regionais de saúde, a fim de concretizar programas voltados para o enfrentamento dos processos de determinação socioambiental da saúde e de produção e reprodução de desigualdades.

Evaluation of the Cytotoxic Effect of Pd2Spm against Prostate Cancer through Vibrational Microspectroscopies.

Regarding the development of new antineoplastic agents, with a view to assess the selective antitumoral potential which aims at causing irreversible damage to cancer cells while preserving the integrity of their healthy counterparts, it is essential to evaluate the cytotoxic effects in both healthy and malignant human cell lines. In this study, a complex with two Pd(II) centers linked by the biogenic polyamine spermine (Pd2Spm) was tested on healthy (PNT-2) and cancer (LNCaP and PC-3) prostate human cell lines, using cisplatin as a reference. To understand the mechanisms of action of both cisplatin and Pd2Spm at a molecular level, Fourier Transform Infrared (FTIR) and Raman microspectroscopies were used. Principal component analysis was applied to the vibrational data, revealing the major metabolic changes caused by each drug, which were found to rely on DNA, lipids, and proteins, acting as biomarkers of drug impact. The main changes were observed between the B-DNA native conformation and either Z-DNA or A-DNA, with a higher effect on lipids having been detected in the presence of cisplatin as compared to Pd2Spm. In turn, the Pd-agent showed a more significant impact on proteins.

Effect of pH and titratable acidity on enamel and dentine erosion.

OBJECTIVES: The relative effect of pH and titratable acidity on tooth erosion remains unclear. We determined the effect of both properties on in vivo salivary pH recovery and on enamel and dentine early erosion in situ. METHODS: Solutions simulating acidic beverages with different pHs (2.5 or 3.5) and titratable acidities (0, 25, or 100 mM citric acid) were tested. In an in vivo study (n = 20 participants), the salivary pH was determined before, during, and up to 2 min after exposure to the tested solutions. In situ, 12 participants exposed enamel and root dentine slabs to the tested solutions simulating a beverage consumption; early erosion was assessed by percentage of surface hardness loss (%SHL). Groups were compared by ANOVA (p < 0.05). RESULTS: Saliva pH was lower after exposure to solutions at pH 2.5, irrespective of titratable acidity; pH recovery took longer for solutions with higher titratable acidities, irrespective of their pHs. In situ, the highest %SHL was observed for the solution with lower pH and higher titratable acidities. The addition of citric acid increased the %SHL by 2.5-3 times in enamel, and at least 5 times in dentine. CONCLUSIONS: Both pH and titratable acidity may play a role on the erosive potential of acidic beverages. CLINICAL RELEVANCE: Acidic beverages with lower pHs promote erosion by an initial acid etching of the surface; those with a higher titratable acidity slow down the salivary pH recovery. Both properties contribute to the overall erosive potential.

[Recommendations to strengthen nutritional care in the primary care setting in BrazilRecomendaciones para el fortalecimiento de la atención nutricional en la atención primaria de salud en Brasil]. / Recomendações para o fortalecimento da atenção nutricional na atenção primária à saúde brasileira.

Objective: To develop recommendations to strengthen nutritional care in the primary health care (PHC) setting in Brazil based on expert consensus. Method: A descriptive and exploratory study was performed using the Delphi technique. Of 172 invited PHC experts in nutrition, 116 accepted the invitation and 72 participated in the first Delphi round. The second round had 56 participants from the five Brazilian regions, including managers, healthcare professionals, representatives from civil society organizations, and researchers. The recommendations were developed based on thematic analysis of the responses to open-ended questions about barriers, strategies, actions, and initiatives from five components of the National Food and Nutrition Policy (food and nutrition surveillance, coordination of nutritional care, health promotion, intersectoral focus, and management of food and nutrition actions). In the second round, experts classified each proposed item regarding its pertinence and relevance for the purpose of recommendation. Results: A consensus was reached on 35 recommendations distributed in six categories: structure; PHC nutritional agenda; organization of the healthcare network and PHC; nutritional work processes in PHC; planning, monitoring and evaluation of nutritional actions in PHC; and information systems. These categories were further classified into two blocks: "PHC structuring actions to strengthen nutrition" and "nutrition structuring actions to strengthen PHC." Conclusions: The recommendations were developed by experienced participants who are familiar with both nutritional and PHC pathways from diverse perspectives, and will be useful for the management and proposition of public policies to strengthen nutritional care in the PHC setting in Brazil.

Objetivo: Elaborar recomendaciones para el fortalecimiento de la alimentación y la nutrición en la atención primaria de salud (APS) en Brasil a partir del consenso de especialistas. Métodos: Se realizó un estudio descriptivo y exploratorio con la técnica de Delfos. En total, 172 especialistas en alimentación y nutrición del sistema de APS recibieron una invitación para participar, 116 la aceptaron y 72 intervinieron en la primera ronda. En la segunda ronda hubo 56 participantes de las cinco macrorregiones brasileñas, entre gestores, profesionales de salud, representantes de la sociedad civil e investigadores. Las recomendaciones se formularon mediante un análisis temático de las respuestas a preguntas abiertas sobre obstáculos, estrategias, medidas e iniciativas referentes a cinco aspectos técnicos de la política nacional de alimentación y nutrición (vigilancia alimentaria y nutricional, atención y coordinación del cuidado nutricional, promoción de la salud, intersectorialidad y gestión de las medidas relativas a alimentación y nutrición). En la segunda ronda, los especialistas clasificaron cada punto propuesto según su pertinencia y relevancia para efecto de las recomendaciones. Resultados: Los especialistas formularon 35 recomendaciones, organizadas en seis categorías: estructura; agenda de alimentación y nutrición en la APS; organización en red y organización de la APS; procesos de trabajo relativos a la alimentación y nutrición en la APS; planificación, monitoreo y evaluación de las medidas relativas a la alimentación y nutrición en la APS; y sistema de información. Las categorías se dividieron en dos grupos: medidas estructurantes de la APS para el fortalecimiento de la alimentación y la nutrición y medidas estructurantes de alimentación y nutrición para el fortalecimiento de la APS. Conclusiones: Las recomendaciones provinieron de personas expertas que siguen la trayectoria tanto de la alimentación y la nutrición como de la APS desde diferentes puntos de vista, útiles para la gestión y la propuesta de políticas públicas destinadas a fortalecer la alimentación y la nutrición en la APS de Brasil.

Balance impairment and lower limbs strength in patients with COPD who fell in the previous year.

Fall-related causes in patients with COPD might be associated to functional balance impairments and greater disease severity. We aimed to evaluate the reasons for falls in patients with COPD who had presented any fall during the previous year. This is a cross-sectional study. All COPD's GOLD classifications (mild, moderate, severe, and very severe) patients were recruited. In order to participate, patients ought to be clinically stable and without any exacerbation within 30 days prior to study entry. History of falls was self-reported by patients through an interview. Pre and post bronchodilator (salbutamol 400 µg) spirometry was performed. All patients accomplished postural balance tests such as the Berg Balance Scale, Falls Efficacy Scale-International, Time up and Go, Functional Reach test, Tinetti test and Chalder Scale; furthermore, lower limbs muscle strength (muscle dynamometry) and the COPD Assessment Test (CAT) were assessed. Ninety-six patients with COPD were evaluated and divided into two groups stratified according to any positive history of falls in the previous year. Patients with COPD who had any fall in the previous year presented older age (p=0.01), higher BMI (p=0.04) and worse pulmonary function than those who did not fall. The risk of falls was increased in patients with lower muscle strength in the lower limbs (OR 2.9, CI 95%;1.6 to 3.9), age greater than 65 years (OR 2.7, CI 95%;1.3 to 3.4), BMI greater than 28.8 kg/m2 (OR 3.2, CI 95%;1.1 to 5.6), very severe airway obstruction (OR 3.9, CI 95%;2.2 to 3.9) and fatigue (OR 3.2, CI 95%;1.5 to 5.3). Impaired body balance, reduced lower limb strength, disease severity, presence of fatigue and elevated BMI are important factors for falls in patients with COPD.

Yap induces osteoblast differentiation by modulating Bmp signalling during zebrafish caudal fin regeneration.

Osteoblast differentiation is a key process for bone homeostasis and repair. Multiple signalling pathways have been associated with osteoblast differentiation, yet much remains unknown on how this process is regulated in vivo Previous studies have proposed that the Hippo pathway transcriptional co-activators YAP and TAZ (also known as YAP1 and WWTR1, respectively) maintain progenitor stemness and inhibit terminal differentiation of osteoblasts, whereas others suggest they potentiate osteoblast differentiation and bone formation. Here, we use zebrafish caudal fin regeneration as a model to clarify how the Hippo pathway regulates de novo bone formation and osteoblast differentiation. We demonstrate that Yap inhibition leads to accumulation of osteoprogenitors and prevents osteoblast differentiation in a cell non-autonomous manner. This effect correlates with a severe impairment of Bmp signalling in osteoblasts, likely by suppressing the expression of the ligand bmp2a in the surrounding mesenchymal cells. Overall, our findings provide a new mechanism of bone formation through the Hippo-Yap pathway, integrating Yap in the signalling cascade that governs osteoprogenitor maintenance and subsequent differentiation during zebrafish caudal fin regeneration.

Differential transcription profiling of the phage LUZ19 infection process in different growth media.

RNA sequencing of phage-infected bacterial cultures offers a snapshot of transcriptional events occurring during the infection process, providing insights into the phage transcriptional organization as well as the bacterial response. To better mimic real environmental contexts, we performed RNA-seq of Pseudomonas aeruginosa PAO1 cultures infected with phage LUZ19 in a mammalian cell culture medium to better simulate a phage therapy event and the data were compared to lysogeny broth medium. Regardless of the media, phage LUZ19 induces significant transcriptional changes in the bacterial host over time, particularly during early infection (t = 5 min) and gradually shuts down bacterial transcription. In a common response in both media, 56 P. aeruginosa PAO1 genes are differentially transcribed and clustered into several functional categories such as metabolism, translation and transcription. Our data allowed us to tease apart a medium-specific response during infection from the identified infection-associated responses. This reinforces the concept that phages overtake bacterial transcriptome in a strict manner to gain control of the bacterial machinery and reallocate resources for infection, in this case overcoming the nutritional limitations of the mammalian cell culture medium. From a phage therapy perspective, this study contributes towards a better understanding of phage-host interaction in human physiological conditions and demonstrates the versatility of phage LUZ19 to adapt to different environments.

Bacteriophage-receptor binding proteins for multiplex detection of Staphylococcus and Enterococcus in blood.

Healthcare-associated infections (HCAIs) affect hundreds of millions of patients, representing a significant burden for public health. They are usually associated to multidrug resistant bacteria, which increases their incidence and severity. Bloodstream infections are among the most frequent and life-threatening HCAIs, with Enterococcus and Staphylococcus among the most common isolated pathogens. The correct and fast identification of the etiological agents is crucial for clinical decision-making, allowing to rapidly select the appropriate antimicrobial and to prevent from overuse and misuse of antibiotics and the consequent increase in antimicrobial resistance. Conventional culture methods are still the gold standard to identify these pathogens, however, are time-consuming and may lead to erroneous diagnosis, which compromises an efficient treatment. (Bacterio)phage receptor binding proteins (RBPs) are the structures responsible for the high specificity conferred to phages against bacteria and thus are very attractive biorecognition elements with high potential for specific detection and identification of pathogens. Taking into account all these facts, we have designed and developed a new, fast, accurate, reliable and unskilled diagnostic method based on newly identified phage RBPs and spectrofluorometric techniques that allows the multiplex detection of Enterococcus and Staphylococcus in blood samples in less than 1.5 hr after an enrichment step.

[Public Health Training Program for Health Workers on the Brazil-Uruguay Border]. / Programa de Formación en Salud Pública para Trabajadores de Salud en la Frontera Brasil-Uruguay.

The main objective of the Public Health Training Program on the Brazil-Uruguay Border was to strengthen local training capacities in public health through the development of skills and competencies together with health workers from four border areas. The methodological design of the Program, based on workshops with the application of active methodologies in health training and mediated by educational technologies, favored the organization of a permanent dialogical setting between instructors, managers and practice professionals from both countries that, between 2017 and 2018, resulted in a) development of local capacities for the mapping of the main health surveillance problems in the four participating border areas; b) discussion of the limits and perspectives of action of the existing health services in both countries, within the principles and guidelines of the public health field; c) appropriation of pedagogical tools and processes that allowed for the incorporation of public health and health surveillance into the different organizational processes and settings of the local health sector; and d) building of a permanent capacity for the development of skills and competencies together with health workers, within a framework of permanent education in health. The Program's achievements and its contributions to local health services effectively qualify it as a strategic action for strengthening training and research capacities on the Brazil-Uruguay border.

Association between Tooth Loss and Stroke: A Systematic Review.

This systematic review aims to evaluate the association between tooth loss and stroke. The Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines were followed. The PECO strategy was used to limit the eligibility criteria. The following databases were used on searches: PubMed, Scopus, Web of Science, The Cochrane Library, LILACS and OpenGrey. We included observational studies performed in adults (Population), in which patients with tooth loss (Exposition) and patients without tooth loss (Comparison) were observed to investigate the association between tooth loss and stroke (Outcome). After searches, the results were submitted to a selection process, followed by data extraction, quality assessment and risk of bias evaluation. The certainty of the evidence was evaluated through GRADE approach. A total of 925 potential studies were retrieved by the searches and 9 were included in this review. Seven of the included articles described an association between tooth loss and stroke. Low risk of bias and a low certainty of the evidence were identified to all studies. The certainty of the evidence may be associated with the observational nature of the included studies. Even though an association between tooth loss and stroke was suggested, the low strength of the current evidence indicated the need for further investigations with a better methodological design to conclude this question.

Vascular impairment of adenosinergic system in hypertension: increased adenosine bioavailability and differential distribution of adenosine receptors and nucleoside transporters.

Adenosinergic system regulates vascular tonicity through the complex system of adenosine, adenosine receptors (ARs) and nucleoside transporters. This work aimed at evaluating the impact of hypertension on adenosine bioavailability and expression/distribution profile of AR subtypes (A1, A2A, A2B, A3) and equilibrative nucleoside transporters (ENT1, ENT2, ENT3, ENT4). Adenosine was measured in vascular tissue extracts by HPLC (fluorescence detection); immunoreactivities (ARs/ENTs) in mesenteric arteries/veins from normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) were analyzed by histomorphometry. Significantly higher adenosine bioavailability occurred in arteries than in veins. Adenosine bioavailability was even more increased in SHR vessels. Expression/distribution of ARs and ENTs observed in all vascular layers (intima, media, adventitia), with more intensified expression in arteries than in veins. In SHR arteries, a downregulation of all ENT along with downregulated and punctuated distribution of A1 and A2B receptors occurred comparatively to WKY arteries. By contrast, expressions of ARs and ENTs were unaltered, exception for an A2A receptor upregulation, and ENT2 downregulation in SHR veins relatively to WKY veins. Our data evidenced clear alterations of adenosinergic dynamics occurring in hypertension, particularly in arterial vessels. An increased adenosine bioavailability was observed, for the first time, in hypertensive vascular tissues.

Steroid hormone signaling is essential to regulate innate immune cells and fight bacterial infection in Drosophila.

Coupling immunity and development is essential to ensure survival despite changing internal conditions in the organism. Drosophila metamorphosis represents a striking example of drastic and systemic physiological changes that need to be integrated with the innate immune system. However, nothing is known about the mechanisms that coordinate development and immune cell activity in the transition from larva to adult. Here, we reveal that regulation of macrophage-like cells (hemocytes) by the steroid hormone ecdysone is essential for an effective innate immune response over metamorphosis. Although it is generally accepted that steroid hormones impact immunity in mammals, their action on monocytes (e.g. macrophages and neutrophils) is still not well understood. Here in a simpler model system, we used an approach that allows in vivo, cell autonomous analysis of hormonal regulation of innate immune cells, by combining genetic manipulation with flow cytometry, high-resolution time-lapse imaging and tissue-specific transcriptomic analysis. We show that in response to ecdysone, hemocytes rapidly upregulate actin dynamics, motility and phagocytosis of apoptotic corpses, and acquire the ability to chemotax to damaged epithelia. Most importantly, individuals lacking ecdysone-activated hemocytes are defective in bacterial phagocytosis and are fatally susceptible to infection by bacteria ingested at larval stages, despite the normal systemic and local production of antimicrobial peptides. This decrease in survival is comparable to the one observed in pupae lacking immune cells altogether, indicating that ecdysone-regulation is essential for hemocyte immune functions and survival after infection. Microarray analysis of hemocytes revealed a large set of genes regulated at metamorphosis by EcR signaling, among which many are known to function in cell motility, cell shape or phagocytosis. This study demonstrates an important role for steroid hormone regulation of immunity in vivo in Drosophila, and paves the way for genetic dissection of the mechanisms at work behind steroid regulation of innate immune cells.

Enhancing electrochemical performance by control of transport properties in buffer layers--solid oxide fuel/electrolyser cells.

The current work demonstrates how tailoring the transport properties of thin ceria-based buffer layers in solid oxide fuel or electrolyser cells can provide the necessary phase stability against chemical interaction at the electrolyte/electrode interface, while also providing radical improvements in the electrochemical performance of the oxygen electrode. Half cells of Ce0.8R0.2O2-δ + 2 mol% Co buffer layers (where R = Gd, Pr) with Nd2NiO4+δ electrodes were fabricated by spin coating on dense YSZ electrolyte supports. Dramatic decreases in polarization resistance, Rp, of up to an order of magnitude, could be achieved in the order, Pr ≪ Gd < no buffer layer. The current article shows how this improvement can be related to increased levels of ambipolar conductivity in the mixed conducting buffer layer, which provides an additional parallel path for electrochemical reaction. This is an important breakthrough as it shows how electrode polarization resistance can be substantially improved, in otherwise identical electrochemical cells, solely by tailoring the transport properties of thin intermediate buffer layers.