A population of gut epithelial enterochromaffin cells is mechanosensitive and requires Piezo2 to convert force into serotonin release

Enterochromaffin (EC) cells constitute the largest population of intestinal epithelial enteroendocrine (EE) cells. EC cells are proposed to be specialized mechanosensory cells that release serotonin in response to epithelial forces, and thereby regulate intestinal fluid secretion. However, it is unknown whether EE and EC cells are directly mechanosensitive, and if so, what the molecular mechanism of their mechanosensitivity is. Consequently, the role of EE and EC cells in gastrointestinal mechanobiology is unclear. Piezo2 mechanosensitive ion channels are important for some specialized epithelial mechanosensors, and they are expressed in mouse and human EC cells. Here, we use EC and EE cell lineage tracing in multiple mouse models to show that Piezo2 is expressed in a subset of murine EE and EC cells, and it is distributed near serotonin vesicles by superresolution microscopy. Mechanical stimulation of a subset of isolated EE cells leads to a rapid inward ionic current, which is diminished by Piezo2 knockdown and channel inhibitors. In these mechanosensitive EE cells force leads to Piezo2-dependent intracellular Ca(2+) increase in isolated cells as well as in EE cells within intestinal organoids, and Piezo2-dependent mechanosensitive serotonin release in EC cells. Conditional knockout of intestinal epithelial Piezo2 results in a significant decrease in mechanically stimulated epithelial secretion. This study shows that a subset of primary EE and EC cells is mechanosensitive, uncovers Piezo2 as their primary mechanotransducer, defines the molecular mechanism of their mechanotransduction and mechanosensitive serotonin release, and establishes the role of epithelial Piezo2 mechanosensitive ion channels in regulation of intestinal physiology

The consolidation and effectiveness of matrix support in mental health in Brazil - bottlenecks and challenges

Passados dez anos da implementação do apoio matricial nas redes de saúde por meio dos Núcleos de Apoio à Saúde da Família, ainda sente-se a falta de dados consistentes quanto à consolidação e efetividade desse arranjo. Nesse sentido, este estudo teve como objetivo revisar a bibliografia nacional dos últimos dez anos a fim de identificar os impasses e desafios vivenciados no apoio matricial em saúde mental na Atenção Primária, classificando-os a partir de uma reconstrução teórico-conceitual e fazendo uma articulação destes com os desafios pontuados em congêneres internacionais do apoio matricial. Entre os principais pontos levantados pelo estudo, destacou-se a necessidade de delineamentos claros para prática de matriciamento; investimento maciço em formação e capacitação dos profissionais; e criação de espaços institucionalizados com encontros sistemáticos dos profissionais para discussão dos casos e avaliação conjunta do andamento das atividades23COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESsem informaçãoTen years on from the introduction of matrix support in health networks through the creation of Family Health Support Centers, there is still a lack of consistent data to measure the success of consolidation and effectiveness of this arrangement. With this in mind, we conducted a literature review of national articles produced over the last ten years to identify the bottlenecks and challenges faced by matrix support in mental health in Primary Care. The problems were classified using a theoretical and conceptual reconstruction and drawing on similar experiences with matrix support in other countries. The following key points emerged from the review: the need to provide clear guidelines for matrix support; the need for major investment in training and capacity building; and the need to create institutionalized spaces to foster systematic communication between professionals to discuss cases and promote joint evaluation of the progress of activitie

Produção de biogás por digestão em fase sólida de cama de frango.

RESUMO: A cama de frango é um resíduo da atividade avícola, que é gerado em grandes quantidades, e quando mal manuseado tem elevado potencial poluidor. No entanto, é possível aproveitar este resíduo para geração de biogás, contudo este substrato apresenta desafios devido a baixa umidade e composição química. Diante deste contexto, a digestão em fase sólida se destaca como um processo promissor pelo fato de evitar o manejo ou póstratamento da água derivada do processo. O objetivo do presente estudo foi avaliar a eficiência da produção de biogás de cama de frango em um reator anaeróbio de fase sólida (RDFS) operado em batelada. Ao realizar o processo de digestão em fase sólida, verificouse que este sistema apresentou um rendimento de biogás de 90,30 mLNbiogás.gSVadic -1 ,quando comparado ao valor de referência do teste do potencial bioquímico de biogás que foi de 281 mLNbiogás.gSVadic -1 , a eficiência foi de 32 % após 30 dias de digestão. No entanto, o teor de sólidos totais que o RDFS pode operar é de 30 %, enquanto que a digestão úmida a concentração de sólidos totais é em média de 10%. Neste caso utilizando o RDFS estaremos economizando líquido para diluição do substrato, e este é um sistema robusto, de fácil monitoramento que pode ser utilizado pelos avicultores, podendo ainda ser otimizado para melhoria do sistema e assim aumentar a eficiência de produção de biogás. ABSTRACT: The poultry litter is a residue from poultry activity, which is generated in large quantities and, when poorly handled, presents a high polluting potential. It is possible to take advantage of this residue to generate biogas, however this substrate consists in a challenging material due to its humidity and chemical composition. In this context, solid-state digestion stands out as a promising process because it prevents the handling or post-treatment of water derived from the process. The goal of the present study was to evaluate the efficiency of production of poultry litter biogas in a solid phase anaerobic reactor operated in batch. When carrying out the solid phase digestion process, it was verified that this system presented a biogas production of 90,30 mLNbiogas.gSVadd -1 . When comparing this to the reference value of the biochemical potential of biogas test, which is 281 mLNbiogas.gSVadd -1 , the efficiency attained was 32% at the 30-day of digestion However, the total solids content that the RDFS can operate is 30%, while the wet digestion at the total solids concentration is on average 10%. In this case using the RDFS we will be saving liquid for dilution of the substrate, and this is a robust system, easy to monitor that can be used by poultry farmers and can be optimized for system improvement and thus increase biogas production efficiency

Liver-Targeting of Interferon-Alpha with Tissue-Specific Domain Antibodies

PMCID: PMC3581439This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

A Spectacular Bow Shock in the 11 keV Galaxy Cluster Around 3C 438

This is a pre-copyedited, author-produced pdf of an article accepted for publication in The Astrophysical Journal following peer review. The version of record, Deanna L. Emery; Ákos Bogdán; Ralph P. Kraft; Felipe Andrade-Santos; William R. Forman; Martin Hardcastle; and Christine Jones, ‘A spectacular bow shock in the 11 keV galaxy cluster around 3C 438’, The Astrophysical Journal (2017) 834(2):159 (7pp), published 10 January 2017, is available at doi: 10.3847/1538-4357/834/2/159 © 2017. The American Astronomical Society. All rights reserved.We present results of deep 153 ks Chandra observations of the hot, 11 keV, galaxy cluster associated with the radio galaxy 3C 438. By mapping the morphology of the hot gas and analyzing its surface brightness and temperature distributions, we demonstrate the presence of a merger bow shock. We identify the presence of two jumps in surface brightness and in density located at $\sim$400 kpc and $\sim$800 kpc from the cluster's core. At the position of the inner jump, we detect a factor of $2.3\pm 0.2$ density jump, while at the location of the outer jump, we detect a density drop of a factor of $3.5 \pm 0.7$. Combining this with the temperature distribution within the cluster, we establish that the pressure of the hot gas is continuous at the 400 kpc jump, while there is a factor of $6.2 \pm 2.8$ pressure discontinuity at 800 kpc jump. From the magnitude of the outer pressure discontinuity, using the Rankine-Hugoniot jump conditions, we determine that the sub-cluster is moving at $M = 2.3\pm 0.5$, or approximately $2600\pm 565$ km/s through the surrounding intracluster medium, creating the conditions for a bow shock. Based on these findings, we conclude that the pressure discontinuity is likely the result of an ongoing major merger between two massive clusters. Since few observations of bow shocks in clusters have been made, this detection can contribute to the study of the dynamics of cluster mergers, which offers insight on how the most massive clusters may have formed.Peer reviewe

The damming of the Narmadā River : progress, technology and the sacred.

Pressure on the limited amount of available natural resources is growing rapidly and primarily stems from population growth and individual/national aspirations for development. Harnessing more water is seen as the best available way to meet the increasing demands. However, despite often the best intentions and the use of widely accepted tools to assess the likely impacts (such as Environmental Impact Assessment – EIA) water “development projects” are not without costs. In this thesis I will address the global issue of the over-¬-use of natural resources by looking at the specific example of the Narmada River. The Narmada is a sacred river in India and as such, has a long culturally significant history. The Narmada is currently experiencing a large development project being built along its course. This project proposed over 3000 dams, though only a fraction of those have been built. This thesis employs a case study of the Narmada River in India to explore the rationale and approaches taken for development, as well as the costs that this development has incurred such as environmental and social impacts. Specific attention has been given to the description of the religious impacts, cultural transformations and impact upon minority indigenous groups; aspects frequently ignored or given little attention. An improved recognition of the religious and cultural significance of freshwater is needed to enable more positive local acceptance of developments such as dams as well as protecting national identity. These components are critical for sustainable development. I use the terms ‘development’ and ‘sacred’ in this thesis. These are widely interpreted terms and as such mean different things to different people. The definition of ‘development’ I have used is: “the process of converting land to a new purpose by constructing buildings or making use of its resources.” The term ‘sacred’ is also widely interpreted. In terms of this thesis, I will use Mircea Eliade’s definition of sacred. He defines it as a cover-¬-term for that category of ‘objects' constituted in the mind of the believer as both 'ultimately real' and as distinct from the profane world. A sacred river is real in a physical sense but also separate from other rivers because of its divine origins

Atmospheric Muon Flux at Sea Level, Underground, and Underwater

The vertical sea-level muon spectrum at energies above 1 GeV and the underground/underwater muon intensities at depths up to 18 km w.e. are calculated. The results are particularly collated with a great body of the ground-level, underground, and underwater muon data. In the hadron-cascade calculations, the growth with energy of inelastic cross sections and pion, kaon, and nucleon generation in pion-nucleus collisions are taken into account. For evaluating the prompt muon contribution to the muon flux, we apply two phenomenological approaches to the charm production problem: the recombination quark-parton model and the quark-gluon string model. To solve the muon transport equation at large depths of homogeneous medium, a semi-analytical method is used. The simple fitting formulas describing our numerical results are given. Our analysis shows that, at depths up to 6-7 km w. e., essentially all underground data on the muon intensity correlate with each other and with predicted depth-intensity relation for conventional muons to within 10%. However, the high-energy sea-level data as well as the data at large depths are contradictory and cannot be quantitatively decribed by a single nuclear-cascade model.Comment: 47 pages, REVTeX, 15 EPS figures included; recent experimental data and references added, typos correcte

Synaptic vesicle release regulates pre-myelinating oligodendrocyte-axon interactions in a neuron subtype-specific manner

Oligodendrocyte-lineage cells are central nervous system (CNS) glia that perform multiple functions including the selective myelination of some but not all axons. During myelination, synaptic vesicle release from axons promotes sheath stabilization and growth on a subset of neuron subtypes. In comparison, it is unknown if pre-myelinating oligodendrocyte process extensions selectively interact with specific neural circuits or axon subtypes, and whether the formation and stabilization of these neuron–glia interactions involves synaptic vesicle release. In this study, we used fluorescent reporters in the larval zebrafish model to track pre-myelinating oligodendrocyte process extensions interacting with spinal axons utilizing in vivo imaging. Monitoring motile oligodendrocyte processes and their interactions with individually labeled axons revealed that synaptic vesicle release regulates the behavior of subsets of process extensions. Specifically, blocking synaptic vesicle release decreased the longevity of oligodendrocyte process extensions interacting with reticulospinal axons. Furthermore, blocking synaptic vesicle release increased the frequency that new interactions formed and retracted. In contrast, tracking the movements of all process extensions of singly-labeled oligodendrocytes revealed that synaptic vesicle release does not regulate overall process motility or exploratory behavior. Blocking synaptic vesicle release influenced the density of oligodendrocyte process extensions interacting with reticulospinal and serotonergic axons, but not commissural interneuron or dopaminergic axons. Taken together, these data indicate that alterations to synaptic vesicle release cause changes to oligodendrocyte-axon interactions that are neuron subtype specific