Munc13-1 is a Ca2+-phospholipid-dependent vesicle priming hub that shapes synaptic short-term plasticity and enables sustained neurotransmission

During ongoing presynaptic action potential (AP) firing, transmitter release is limited by the availability of release-ready synaptic vesicles (SVs). The rate of SV recruitment (SVR) to release sites is strongly upregu- lated at high AP frequencies to balance SV consumption. We show that Munc13-1—an essential SV priming protein—regulates SVR via a Ca2+-phospholipid-dependent mechanism. Using knockin mouse lines with point mutations in the Ca2+-phospholipid-binding C2B domain of Munc13-1, we demonstrate that abolishing Ca2+-phospholipid binding increases synaptic depression, slows recovery of synaptic strength after SV pool depletion, and reduces temporal fidelity of synaptic transmission, while increased Ca2+-phospholipid binding has the opposite effects. Thus, Ca2+-phospholipid binding to the Munc13-1-C2B domain accelerates SVR, reduces short-term synaptic depression, and increases the endurance and temporal fidelity of neurotrans- mission, demonstrating that Munc13-1 is a core vesicle priming hub that adjusts SV re-supply to demand

Substratum selection in coral reef sponges and their interactions with other benthic organisms

Substratum preferences and contact interactions among sessile organisms can be a major determinant of biotic gradients in the structure of benthic communities on coral reefs. Sponges are a substantial component of these communities, but their substratum requirements and interactions with other benthic taxa are poorly understood. Here, we quantified sponge substratum preferences and interactions from 838 randomly selected photo-quadrats across different depths (5, 10 and 15 m), exposure (sheltered and exposed), and substratum topography (horizontal, inclined and vertical surfaces) on coastal coral reefs in Kimbe Bay. A high proportion (55%) of sponge colonies were associated with dead coral, unconsolidated coral rubble (7%) and calcium carbonate rock (CaCO3 rock) (7%), even though they represented only 10%, 4% and 1% of the available substratum, respectively. Sponges interacted most frequently with algae (~ 34%), corals (~ 30%) and crustose coralline algae (CCA ~ 19%) that represented ~ 46%, ~ 18% and ~ 14% of the substratum cover, respectively. The microhabitat preferences of sponges and frequency of interactions with other taxa were mostly consistent across various exposure, depth and substratum topography conditions. Most interactions appeared to be “stand-offs” (71%) which are interactions with no clear winner or loser. However, when overgrowth occurred, sponges were usually winners, overgrowing corals (92%), CCA (81%) and macroalgae (65%). Three sponge species Dysidea sp1, Lamellodysidea cf. chlorea and Lamellodysidea chlorea accounted for 51% to 96% of the overgrowth of sponges over algae, corals and CCA, but there was no one species found to always win or lose. Our results suggest that sponges avoid other biological substrata by preferentially settling on dead coral, coral rubble and CaCO3 rock, but when they do come into contact with algae and corals, they frequently overgrow their spacial competitors

Epidemiology of seasonal coronaviruses: establishing the context for the emergence of coronavirus disease 2019

Public health preparedness for coronavirus (CoV) disease 2019 (COVID-19) is challenging in the absence of setting-specific epidemiological data. Here we describe the epidemiology of seasonal CoVs (sCoVs) and other cocirculating viruses in the West of Scotland, United Kingdom. We analyzed routine diagnostic data for >70 000 episodes of respiratory illness tested molecularly for multiple respiratory viruses between 2005 and 2017. Statistical associations with patient age and sex differed between CoV-229E, CoV-OC43, and CoV-NL63. Furthermore, the timing and magnitude of sCoV outbreaks did not occur concurrently, and coinfections were not reported. With respect to other cocirculating respiratory viruses, we found evidence of positive, rather than negative, interactions with sCoVs. These findings highlight the importance of considering cocirculating viruses in the differential diagnosis of COVID-19. Further work is needed to establish the occurrence/degree of cross-protective immunity conferred across sCoVs and with COVID-19, as well as the role of viral coinfection in COVID-19 disease severity

Llave maestra y escudo de la verdad : explicacion de las Bulas de... Inocencio Dezimo y de la Santa Cruzada...

"Escudo de la verdad y defensa general de la religion de los frayles menores Capuchinos..., constituciones..." corresponde a las últimas 107 p.Copia digital. Madrid : Ministerio de Cultura. Subdirección General de Coordinación Bibliotecaria, 2008Sign. : [calderón-3 calderones]\p4\s, [3 calderones]\p4\s, [4 calderones]\p2\s, A\p8\s, B-M\p4\s, N\p2\s, A-N\p4\s, O\p2\s.Error en paginación: se repiten las p. 73 y 74.Texto a dos col

Estimation of temporal covariances in pathogen dynamics using Bayesian multivariate autoregressive models

It is well recognised that animal and plant pathogens form complex ecological communities of interacting organisms within their hosts, and there is growing interest in the health implications of such pathogen interactions. Although community ecology approaches have been used to identify pathogen interactions at the within-host scale, methodologies enabling robust identification of interactions from population-scale data such as that available from health authorities are lacking. To address this gap, we developed a statistical framework that jointly identifies interactions between multiple viruses from contemporaneous non-stationary infection time series. Our conceptual approach is derived from a Bayesian multivariate disease mapping framework. Importantly, our approach captures within- and between-year dependencies in infection risk while controlling for confounding factors such as seasonality, demographics and infection frequencies, allowing genuine pathogen interactions to be distinguished from simple correlations. We validated our framework using a broad range of synthetic data. We then applied it to diagnostic data available for five respiratory viruses co-circulating in a major urban population between 2005 and 2013: adenovirus, human coronavirus, human metapneumovirus, influenza B virus and respiratory syncytial virus. We found positive and negative covariances indicative of epidemiological interactions among specific virus pairs. This statistical framework enables a community ecology perspective to be applied to infectious disease epidemiology with important utility for public health planning and preparedness

Estimation of temporal covariances in pathogen dynamics using Bayesian multivariate autoregressive models

It is well recognised that animal and plant pathogens form complex ecological communities of interacting organisms within their hosts, and there is growing interest in the health implications of such pathogen interactions. Although community ecology approaches have been used to identify pathogen interactions at the within-host scale, methodologies enabling robust identification of interactions from population-scale data such as that available from health authorities are lacking. To address this gap, we developed a statistical framework that jointly identifies interactions between multiple viruses from contemporaneous non-stationary infection time series. Our conceptual approach is derived from a Bayesian multivariate disease mapping framework. Importantly, our approach captures within- and between-year dependencies in infection risk while controlling for confounding factors such as seasonality, demographics and infection frequencies, allowing genuine pathogen interactions to be distinguished from simple correlations. We validated our framework using a broad range of synthetic data. We then applied it to diagnostic data available for five respiratory viruses co-circulating in a major urban population between 2005 and 2013: adenovirus, human coronavirus, human metapneumovirus, influenza B virus and respiratory syncytial virus. We found positive and negative covariances indicative of epidemiological interactions among specific virus pairs. This statistical framework enables a community ecology perspective to be applied to infectious disease epidemiology with important utility for public health planning and preparedness

Are Neurotrophin Genes Involved in the Pathophysiology of Gambling Disorder?

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Social, clinical, and policy implications of ultra-processed food addiction

Key messages Ultra-processed foods high in refined carbohydrates and added fats are highly rewarding, appealing, and consumed compulsively and may be addictive Behaviours around ultra-processed food may meet the criteria for diagnosis of substance use disorder in some people •   Ultra-processed food addiction is estimated to occur in 14% of adults and 12% of children and is associated with biopsychological mechanisms of addiction and clinically significant problems Understanding of these foods as addictive could lead to novel approaches in the realm of social justice, clinical care, and policy approache

Breve e clara exposiçam e declaraçam da primeira regra da gloriosa S. Clara ... em que se tratao e resolvem muitas difficultdades que pertencem ao estado das religiosas de todas as ordens ... / composta pelo Rev. Padre Fr. Leandro de Murcia ... da ordem dos frades menores Capuchinhos ... ; traduzida ao noslo idioma por huma religiosa do convento do Santíssimo Crucifixo desta cidade ..

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