The cohesin ring concatenates sister DNA molecules

Sister chromatid cohesion, which is essential for mitosis, is mediated by a multi-subunit protein complex called cohesin whose Scc1, Smc1, and Smc3 subunits form a tripartite ring structure. It has been proposed that cohesin holds sister DNAs together by trapping them inside its ring. To test this, we used site-specific cross-linking to create chemical connections at the three interfaces between the ring’s three constituent polypeptides, thereby creating covalently closed cohesin rings. As predicted by the ring entrapment model, this procedure produces dimeric DNA/cohesin structures that are resistant to protein denaturation. We conclude that cohesin rings concatenate individual sister minichromosome DNAs

To GP or not to GP: a natural experiment in children triaged to see a GP in a tertiary paediatric emergency department (ED)

Objective: To evaluate the impact of integrating a general practitioner (GP) into a tertiary paediatric emergency department (ED) on admissions, waiting times and antibiotic prescriptions. Design: Retrospective cohort study. Setting: Alder Hey Children’s NHS Foundation Trust, a tertiary paediatric hospital in Liverpool, UK. Participants: From October 2014, a GP was colocated within the ED, from 14:00 to 22:00 hours, 7 days a week. Children triaged green on the Manchester Triage System without any comorbidities were classed as ‘GP appropriate’. The natural experiment compared patients triaged as ‘GP appropriate’ and able to be seen by a GP between 14:00 and 22:00 hours (GP group) to patients triaged as ‘GP appropriate’ seen outside of the hours when a GP was available (ED group). Intention-to-treat (ITT) analysis was used to assess the main outcomes. Results: 5223 patients were designated as ‘GP appropriate’—18.2% of the total attendances to the ED over the study period. There were 2821 (54%) in the GP group and 2402 (46%) in the ED group. The median duration of stay in the ED was 94 min (IQR 63–141) for the GP group compared with 113 min (IQR 70–167) for the ED group (p<0.0005). Using the ITT analysis equivalent, we demonstrated that the GP group were less likely to: be admitted to hospital (2.2% vs 6.5%, OR 0.32, 95% CI 0.24 to 0.44), wait longer than 4 hours (2.3% vs 5.1%, OR 0.45, 95% CI 0.33 to 0.61) or leave before being seen (3.1% vs 5.7%, OR 0.53, 95% CI 0.41 to 0.70), but more likely to receive antibiotics (26.1% vs 20.5%, OR 1.37, 95% CI 1.10 to 1.56). Sensitivity analyses yielded similar results. Conclusions: Introducing a GP to a paediatric ED service can significantly reduce waiting times and admissions, but may lead to more antibiotic prescribing. This study demonstrates a novel, potentially more efficient ED care pathway in the current context of rising demand for children’s emergency services

Improve protective efficacy of a TB DNA-HSP65 vaccine by BCG priming

Vaccines are considered by many to be one of the most successful medical interventions against infectious diseases. But many significant obstacles remain, such as optimizing DNA vaccines for use in humans or large animals. The amount of doses, route and easiness of administration are also important points to consider in the design of new DNA vaccines. Heterologous prime-boost regimens probably represent the best hope for an improved DNA vaccine strategy. In this study, we have shown that heterologous prime-boost vaccination against tuberculosis (TB) using intranasal BCG priming/DNA-HSP65 boosting (BCGin/DNA) provided significantly greater protection than that afforded by a single subcutaneous or intranasal dose of BCG. In addition, BCGin/DNA immunization was also more efficient in controlling bacterial loads than were the other prime-boost schedules evaluated or three doses of DNA-HSP65 as a naked DNA. The single dose of DNA-HSP65 booster enhanced the immunogenicity of a single subcutaneous BCG vaccination, as evidenced by the significantly higher serum levels of anti-Hsp65 IgG2a Th1-induced antibodies, as well as by the significantly greater production of IFN-γ by antigen-specific spleen cells. The BCG prime/DNA-HSP65 booster was also associated with better preservation of lung parenchyma

Diagnosing Causes of Water Scarcity in Complex Water Resources Systems and Identifying Risk Management Actions

From the water management perspective, water scarcity is an unacceptable risk of facing water shortages to serve water demands in the near future. Water scarcity may be temporary and related to drought conditions or other accidental situation, or may be permanent and due to deeper causes such as excessive demand growth, lack of infrastructure for water storage or transport, or constraints in water management. Diagnosing the causes of water scarcity in complex water resources systems is a precondition to adopt effective drought risk management actions. In this paper we present four indices which have been developed to evaluate water scarcity. We propose a methodology for interpretation of index values that can lead to conclusions about the reliability and vulnerability of systems to water scarcity, as well as to diagnose their possible causes and to propose solutions. The described methodology was applied to the Ebro river basin, identifying existing and expected problems and possible solutions. System diagnostics, based exclusively on the analysis of index values, were compared with the known reality as perceived by system managers, validating the conclusions in all case

Assistência pré-natal à adolescente e os atributos da Atenção Primária à Saúde

OBJECTIVE: evaluate prenatal care for adolescents in health units, in accordance with the attributes of Primary Health Care (PHC) guidelines. METHOD: quantitative study conducted with health professionals, using the Primary Care Assessment Tool-Brazil to assess the presence and extent of PHC attributes. RESULTS: for all the participating units, the attribute Access scored =6.6; the attributes Longitudinality, Coordination (integration of care), Coordination (information systems) and Integrality scored =6.6, and the Essential Score =6.6. Comparing basic units with family health units, the attribute scores were equally distributed; Accessibility scored =6.6, the others attributes scored =6.6; however, in the basic units, the Essential Score was =6.6 and, in the family health units, =6.6. CONCLUSION: expanding the coverage of family health units and the training of professionals can be considered strategies to qualify health care.OBJETIVO: evaluar la atención prenatal a las adolescentes en unidades de salud, según los atributos de la Atención Primaria a la Salud. MÉTODO: estudio de abordaje cuantitativo, realizado con profesionales de la salud, utilizando el instrumento Primary Care Assessment Tool-Brasil para analizar la presencia y extensión de los atributos vinculados a la APS en las unidades de salud. RESULTADOS: para todas las unidades participantes, el atributo Acceso obtuvo un puntaje =6,6; los atributos Longitudinalidad, Coordinación (integración de cuidados), Coordinación (sistemas de información) e Integralidad obtuvieron puntajes =6,6 y el Puntaje Esencial fue =6,6. Comparando las unidades básicas de salud y las unidades de salud de la familia, los puntajes están igualmente distribuidos: Accesibilidad =6,6 y los demás atributos con puntajes =6,6; sin embargo, el puntaje Esencial en las unidades básicas fue =6,6 y el de las unidades de salud de la familia fue =6,6. CONCLUSIÓN: la ampliación de la cobertura de las unidades de salud de la familia y la capacitación profesional pueden ser estrategias para calificar la atención a la salud.OBJETIVO: avaliar a atenção pré-natal às adolescentes em unidades de saúde, segundo os atributos da Atenção Primária à Saúde. MÉTODO: estudo de abordagem quantitativa, realizado com profissionais de saúde, utilizando-se o instrumento Primary Care Assessment Tool-Brasil, para analisar a presença e extensão dos atributos. RESULTADOS: para todas as unidades participantes, o atributo acesso obteve escore =6,6; os atributos longitudinalidade, coordenação (integração de cuidados), coordenação (sistemas de informação) e integralidade obtiveram escores =6,6 e escore essencial =6,6. Comparando-se as unidades básicas e as unidades de saúde da família, os escores estão igualmente distribuídos: acessibilidade: =6,6 e os demais atributos com escores =6,6, no entanto, o escore essencial nas unidades básicas foi =6,6 e nas unidades de saúde da família foi =6,6. CONCLUSÃO: a ampliação da cobertura das unidades de saúde da família e a capacitação profissional podem ser estratégias para qualificar a atenção à saúde

Marcadores sorológicos de hepatite B em indivíduos submetidos a exames de sangue em unidades de saúde

OBJECTIVE: To study some of the epidemiological aspects of hepatitis B in a non-representative sample of patients seen in health care clinics. METHODS: The study population comprised 632 patients who were seen at health care clinics in the city of Ribeirão Preto, Brazil, for the purpose of blood testing, regardless the reason. After signing a written consent, an additional amount of blood was drawn from the same venous puncture site used to collect the original sample for the testing assigned to the patient at the health care clinic. A questionnaire was applied to each participant, looking for the presence of risk factors for hepatitis B. The blood samples were tested for HBV markers, using immunoenzimatic techniques. RESULTS: The prevalences of HBsAg and anti-HBcAg were 0.3% and 13.9%, respectively. By a logistic regression model, the following variables were significantly associated with the infection: age, time of residency in the city (higher risk among those living for a period less than one year), past history of hepatitis, incarceration and sexual behavior (higher risk among homosexual and bisexual males). CONCLUSIONS: The growing difficulties in obtaining blood samples from a representative group of patients, as done in classic surveys, make it necessary to look for alternative methodologies which can provide information concerning the presence of infectious agents in a community. Though the results cannot be generalized to the population as a whole, the methodology used conveyed some knowledge regarding the circulation of hepatitis B virus. In addition, it makes much easier to obtain agreement from the participants, since it does not add any invasive procedure. Despite the limitations, this methodology may be helpful in epidemiological surveillance of infectious agents known as producing asymptomatic infections in much of the population.OBJETIVO: Estudar aspectos da epidemiologia da hepatite B em pessoas submetidas à coleta de sangue em unidades de saúde. MÉTODOS: Indivíduos dos quais se coletou sangue em unidades de saúde de Ribeirão Preto, independentemente do motivo, foram solicitados a fornecer uma quantidade adicional de material, obtida no momento da coleta e submetida à detecção de marcadores de hepatite B. Simultaneamente, por meio de questionário padronizado, foram obtidas informações de possíveis fatores de risco para a doença. Os dados foram analisados por meio de um modelo de regressão logística. RESULTADOS: As prevalências de HBsAg e de anti-HBcAg foram de 0,3% e 13,9%, respectivamente. Os fatores de risco associados à infecção foram: idade, residência na cidade há menos de um ano, antecedente de hepatite, exposição prévia a casas de correção e homo/bissexualismo masculino. CONCLUSÕES: Devido a dificuldades crescentes de obtenção de sangue de indivíduos sadios, essa pode ser uma alternativa para estudos que objetivem fornecer informações sobre a circulação de agentes infecciosos na população. Embora não se possa generalizar os dados obtidos pela metodologia usada, ela traz conhecimento referente à circulação do vírus de hepatite B

Activation of Type 1 Cannabinoid Receptor (CB1R) promotes neurogenesis in murine subventricular zone cell cultures

The endocannabinoid system has been implicated in the modulation of adult neurogenesis. Here, we describe the effect of type 1 cannabinoid receptor (CB1R) activation on self-renewal, proliferation and neuronal differentiation in mouse neonatal subventricular zone (SVZ) stem/progenitor cell cultures. Expression of CB1R was detected in SVZ-derived immature cells (Nestin-positive), neurons and astrocytes. Stimulation of the CB1R by (R)-(+)-Methanandamide (R-m-AEA) increased self-renewal of SVZ cells, as assessed by counting the number of secondary neurospheres and the number of Sox2+/+ cell pairs, an effect blocked by Notch pathway inhibition. Moreover, R-m-AEA treatment for 48 h, increased proliferation as assessed by BrdU incorporation assay, an effect mediated by activation of MAPK-ERK and AKT pathways. Surprisingly, stimulation of CB1R by R-m-AEA also promoted neuronal differentiation (without affecting glial differentiation), at 7 days, as shown by counting the number of NeuN-positive neurons in the cultures. Moreover, by monitoring intracellular calcium concentrations ([Ca2+](i)) in single cells following KCl and histamine stimuli, a method that allows the functional evaluation of neuronal differentiation, we observed an increase in neuronal-like cells. This proneurogenic effect was blocked when SVZ cells were co-incubated with R-m-AEA and the CB1R antagonist AM 251, for 7 days, thus indicating that this effect involves CB1R activation. In accordance with an effect on neuronal differentiation and maturation, R-m-AEA also increased neurite growth, as evaluated by quantifying and measuring the number of MAP2-positive processes. Taken together, these results demonstrate that CB1R activation induces proliferation, self-renewal and neuronal differentiation from mouse neonatal SVZ cell cultures.Fundacao para a Ciencia e a Tecnologia - Portugal [POCTI/SAU-NEU/68465/2006, PTDC/SAU-NEU/104415/2008, PTDC/SAU-NEU/101783/2008, POCTI/SAU-NEU/110838/2009]; Fundacao Calouste Gulbenkian [96542]; Fundacao para a Ciencia e Tecnologiainfo:eu-repo/semantics/publishedVersio

Resistance to autosomal dominant Alzheimer's disease in an APOE3 Christchurch homozygote: a case report.

We identified a PSEN1 (presenilin 1) mutation carrier from the world's largest autosomal dominant Alzheimer's disease kindred, who did not develop mild cognitive impairment until her seventies, three decades after the expected age of clinical onset. The individual had two copies of the APOE3 Christchurch (R136S) mutation, unusually high brain amyloid levels and limited tau and neurodegenerative measurements. Our findings have implications for the role of APOE in the pathogenesis, treatment and prevention of Alzheimer's disease

Seascape genetics of the Atlantic Spotted Dolphin (Stenella frontalis) based on mitochondrial DNA

The Atlantic spotted dolphin (Stenella frontalis) is endemic to tropical, subtropical, and warm temperate waters of the Atlantic Ocean. Throughout its distribution, both geographic distance and environmental variation may contribute to population structure of the species. In this study, we follow a seascape genetics approach to investigate population differentiation of Atlantic spotted dolphins based on a large worldwide dataset and the relationship with marine environmental variables. The results revealed that the Atlantic spotted dolphin exhibits population genetic structure across its distribution based on mitochondrial DNA control region (mtDNA-CR) data. Analyses based on the contemporary landscape suggested, at both the individual and population level, that the population genetic structure is consistent with the isolation-by-distance model. However, because geography and environmental matrices were correlated, and because in some, but not all analyses, we found a significant effect for the environment, we cannot rule out the addition contribution of environmental factors in structuring genetic variation. Future analyses based on nuclear data are needed to evaluate whether local processes, such as social structure and some level of philopatry within populations, may be contributing to the associations among genetic structure, geographic, and environmental distance.info:eu-repo/semantics/acceptedVersio