Sequential and compartmentalized action of Rabs, SNAREs, and MAL in the apical delivery of fusiform vesicles in urothelial umbrella cells

Uroplakins (UPs) are major differentiation products of urothelial umbrella cells and play important roles in forming the permeability barrier and in the expansion/stabilization of the apical membrane. Further, UPIa serves as a uropathogenic Escherichia coli receptor. Although it is understood that UPs are delivered to the apical membrane via fusiform vesicles (FVs), the mechanisms that regulate this exocytic pathway remain poorly understood. Immunomicroscopy of normal and mutant mouse urothelia show that the UP-delivering FVs contained Rab8/11 and Rab27b/Slac2-a, which mediate apical transport along actin filaments. Subsequently a Rab27b/Slp2-a complex mediated FV–membrane anchorage before SNARE-mediated and MAL-facilitated apical fusion. We also show that keratin 20 (K20), which forms a chicken-wire network ∼200 nm below the apical membrane and has hole sizes allowing FV passage, defines a subapical compartment containing FVs primed and strategically located for fusion. Finally, we show that Rab8/11 and Rab27b function in the same pathway, Rab27b knockout leads to uroplakin and Slp2-a destabilization, and Rab27b works upstream from MAL. These data support a unifying model in which UP cargoes are targeted for apical insertion via sequential interactions with Rabs and their effectors, SNAREs and MAL, and in which K20 plays a key role in regulating vesicular trafficking

The AFLOW Fleet for Materials Discovery

The traditional paradigm for materials discovery has been recently expanded to incorporate substantial data driven research. With the intent to accelerate the development and the deployment of new technologies, the AFLOW Fleet for computational materials design automates high-throughput first principles calculations, and provides tools for data verification and dissemination for a broad community of users. AFLOW incorporates different computational modules to robustly determine thermodynamic stability, electronic band structures, vibrational dispersions, thermo-mechanical properties and more. The AFLOW data repository is publicly accessible online at aflow.org, with more than 1.7 million materials entries and a panoply of queryable computed properties. Tools to programmatically search and process the data, as well as to perform online machine learning predictions, are also available.Comment: 14 pages, 8 figure

Food allergy, airborne allergies, and allergic sensitisation among adolescents living in two disparate socioeconomic regions in Ecuador: A cross-sectional study

Background Allergic diseases are under-investigated and overlooked health conditions in developing countries. We measured the prevalence of food allergy (FA), airborne allergic disease, and allergic sensitisation among adolescents living in 2 socio-demographically disparate regions in Ecuador. We investigated which risk factors are associated with these conditions. Methods A cross-sectional study involved 1338 students (mean age: 13 ± 0.9 years old) living in Cuenca (n = 876) and Santa Isabel (n = 462). History of allergic symptoms (noted by parents or doctor) to food, house dust mites (HDM), pollen, and pets were recorded. Sociodemographic characteristics, environmental exposures, and parental history of allergic disorders data were collected. Sensitisation to 19 food and 20 aeroallergens was measured by skin-prick testing (SPT). FA and airborne allergic diseases (to HDM, pollen, cat, or dog) were defined as a report of allergic symptoms noted by doctor, together with a positive SPT (wheal size ≥3 mm). Logistic regression models were used to identify environmental and parental factors associated with allergic conditions. Results FA was prevalent among 0.4% (95% CI 0.2%–0.9%), and food sensitisation among 19.1% of the adolescents. Shrimp was the most frequent food linked with FA and food sensitisation. Risk factors associated with FA could not be evaluated due to the low prevalence. Food sensitisation was higher among adolescents exposed to family smoking (OR 1.63, 95% CI 1.14–2.34, p = 0.008) and those with parental history of allergic disorders (OR 1.68, 95% CI 1.13–2.49, p = 0.01), but less common among adolescents owning dogs (OR 0.59, 95% CI 0.41–0.84, p = 0.003). Airborne allergic diseases were prevalent amongst 12.0% of the adolescents (95% CI: 10.4–13.9, n = 1321), with HDM as the primary allergen (11.2%). Airborne allergic diseases were less common among adolescents with more siblings (OR 0.79, 95% CI 0.65–0.96, p = 0.02) and those who lived with farm animals in the first year of life (OR 0.47, 95% CI 0.23–0.95, p = 0.04), but, most common among adolescents with a smoking family (OR 1.67, 95% CI 1.04–2.70, p = 0.03) and with a parental history of allergic disorders (OR self-perceived: 2.62, 95% CI 1.46–4.71, p = 0.001; OR diagnosed by a doctor: 4.07, 95% CI 2.44–6.80, p < 0.001). Conclusions FA and airborne allergies are less prevalent in Ecuador than in developed regions; there is a great dissociation between the prevalence of allergic disease and allergic sensitisation. Shrimp and HDM were the most prevalent allergens. Risk factors identified in this study to be related to allergic diseases should be considered by physicians, health practitioners, and epidemiologists in Ecuador

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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Surveillance programs for detection and characterization of emergent pathogens and antimicrobial resistance: results from the Division of Infectious Diseases, UNIFESP

Several epidemiological changes have occurred in the pattern of nosocomial and community acquired infectious diseases during the past 25 years. Social and demographic changes possibly related to this phenomenon include a rapid population growth, the increase in urban migration and movement across international borders by tourists and immigrants, alterations in the habitats of animals and arthropods that transmit disease, as well as the raise of patients with impaired host defense abilities. Continuous surveillance programs of emergent pathogens and antimicrobial resistance are warranted for detecting in real time new pathogens, as well as to characterize molecular mechanisms of resistance. In order to become more effective, surveillance programs of emergent pathogens should be organized as a multicenter laboratory network connected to the main public and private infection control centers. Microbiological data should be integrated to guide therapy, adapting therapy to local ecology and resistance patterns. This paper presents an overview of data generated by the Division of Infectious Diseases, Federal University of São Paulo, along with its participation in different surveillance programs of nosocomial and community acquired infectious diseases.Várias alterações epidemiológicas ocorreram no perfil das doenças infecciosas hospitalares e comunitárias nos últimos 25 anos. Mudanças sociais e demográficas possivelmente relacionadas com esse fenômeno incluem o rápido crescimento populacional, o aumento da migração urbana e deslocamento através de fronteiras internacionais por turistas e imigrantes, alterações nos habitats de animais e artrópodes que transmitem doença assim como o aumento no número de pacientes com deficiências nas respostas de defesa. Os programas contínuos de vigilância de patógenos emergentes e resistência antimicrobiana são necessários para a detecção em tempo real de novos patógenos assim como para caracterizar mecanismos moleculares de resistência. Para serem mais efetivos, os programasde vigilância dos patógenos emergentes devem ser organizados em uma rede de laboratórios multicêntricos ligados aos principais centros de controle de infecções, públicos e privados. Os dados microbiológicos devem ser integrados a guias terapêuticos adaptando práticas terapêuticas à ecologia local eaos padrões de resistência. O artigo apresenta uma revisão dos dados gerados pela Disciplina de Infectologia, Universidade Federal de São Paulo (UNIFESP), contemplando sua participação nos diferentes programas de vigilância de doenças infecciosas hospitalares e adquiridas na comunidade.Universidade Federal de São Paulo (UNIFESP) Departamento de Medicina Divisão de Doenças InfecciosasUniversidade Federal de São Paulo (UNIFESP) Departamento de Microbiologia, Imunologia e ParasitologiaUNIFESP, Depto. de Medicina Divisão de Doenças InfecciosasUNIFESP, Depto. de Microbiologia, Imunologia e ParasitologiaSciEL

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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Population ecology of the sea lamprey (Petromyzon marinus) as an invasive species in the Laurentian Great Lakes and an imperiled species in Europe

The sea lamprey Petromyzon marinus (Linnaeus) is both an invasive non-native species in the Laurentian Great Lakes of North America and an imperiled species in much of its native range in North America and Europe. To compare and contrast how understanding of population ecology is useful for control programs in the Great Lakes and restoration programs in Europe, we review current understanding of the population ecology of the sea lamprey in its native and introduced range. Some attributes of sea lamprey population ecology are particularly useful for both control programs in the Great Lakes and restoration programs in the native range. First, traps within fish ladders are beneficial for removing sea lampreys in Great Lakes streams and passing sea lampreys in the native range. Second, attractants and repellants are suitable for luring sea lampreys into traps for control in the Great Lakes and guiding sea lamprey passage for conservation in the native range. Third, assessment methods used for targeting sea lamprey control in the Great Lakes are useful for targeting habitat protection in the native range. Last, assessment methods used to quantify numbers of all life stages of sea lampreys would be appropriate for measuring success of control in the Great Lakes and success of conservation in the native range

Measurement of quarkonium production in proton–lead and proton–proton collisions at 5.02 TeV with the ATLAS detector

The modification of the production of J/ψ, ψ(2S), and Υ(nS) (n=1,2,3) in p+Pb collisions with respect to their production in pp collisions has been studied. The p+Pb and pp datasets used in this paper correspond to integrated luminosities of 28 nb−1 and 25 pb−1 respectively, collected in 2013 and 2015 by the ATLAS detector at the LHC, both at a centre-of-mass energy per nucleon pair of 5.02 TeV. The quarkonium states are reconstructed in the dimuon decay channel. The yields of J/ψ and ψ(2S) are separated into prompt and non-prompt sources. The measured quarkonium differential cross sections are presented as a function of rapidity and transverse momentum, as is the nuclear modification factor, RpPb for J/ψ and Υ(nS). No significant modification of the J/ψ production is observed while Υ(nS) production is found to be suppressed at low transverse momentum in p+Pb collisions relative to pp collisions. The production of excited charmonium and bottomonium states is found to be suppressed relative to that of the ground states in central p+Pb collisions