Ghrelin and growth hormone secretagogues (GHS): modulation of growth hormone secretion and therapeutic applications

Growth hormone-releasing hormone (GHRH) and somatostatin modulate growth hormone (GH) secretion. A third mechanism was discovered in the last decade, involving the action of growth hormone secretagogues (GHS). Ghrelin, the endogenous ligand of the GHS-receptor, is an acylated peptide mainly produced by the stomach, but also synthesized in the hypothalamus. This compound increases both GH release and food intake. Endogenous ghrelin might amplify the basic pattern of GH secretion, optimizing somatotroph responsiveness to GHRH, activating multiple interdependent intracellular pathways. However, its main site of action is the hypothalamus. In the current paper it is reviewed the available data on the discovery of this peptide, the mechanisms of action and possible physiological roles of the GHS and ghrelin on GH secretion, and finally, the possible therapeutic applications of these compounds.A secreção do hormônio de crescimento (GH) é modulada pelo hormônio liberador de hormônio de crescimento (GHRH) e pela somatostatina. Na última década foi descoberto um terceiro mecanismo de controle, envolvendo os secretagogos de GH (GHS). A ghrelina, o ligante endógeno do receptor dos GHS, é um peptídeo acilado produzido no estômago, que também é sintetizado no hipotálamo. Este peptídeo é capaz de liberar GH, além de aumentar a ingesta alimentar. A ghrelina endógena parece amplificar o padrão básico de secreção de GH, ampliando a resposta do somatotrofo ao GHRH, estimulando múltiplas vias intracelulares interdependentes. Entretanto, seu local de atuação predominante é o hipotálamo. Neste trabalho, será apresentada revisão sobre a descoberta da ghrelina, os mecanismos de ação e o possível papel fisiológico dos GHS e da ghrelina na secreção de GH e, finalmente, as possíveis aplicações terapêuticas destes compostos.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUNIFESP, EPMSciEL

Influência do tamanho do recipiente no crescimento de plantas de mangueira sob condições de campo.

Este estudo tem como objetivo avaliar sob condicao de campo, em sequeiro, o crescimento de plantas de mangueira (Mangifera indica L.) formadas em tres diferentes tamanhos de recipiente.bitstream/CNPAT-2010/5398/1/Pa-054.pd

Cloud impacts on photochemistry: Building a climatology of photolysis rates from the Atmospheric Tomography mission

Abstract. Measurements from actinic flux spectroradiometers on board the NASA DC-8 during the Atmospheric Tomography (ATom) mission provide an extensive set of statistics on how clouds alter photolysis rates (J values) throughout the remote Pacific and Atlantic Ocean basins. J values control tropospheric ozone and methane abundances, and thus clouds have been included for more than three decades in tropospheric chemistry modeling. ATom made four profiling circumnavigations of the troposphere capturing each of the seasons during 2016–2018. This work examines J values from the Pacific Ocean flights of the first deployment, but publishes the complete Atom-1 data set (29 July to 23 August 2016). We compare the observed J values (every 3 s along flight track) with those calculated by nine global chemistry–climate/transport models (globally gridded, hourly, for a mid-August day). To compare these disparate data sets, we build a commensurate statistical picture of the impact of clouds on J values using the ratio of J-cloudy (standard, sometimes cloudy conditions) to J-clear (artificially cleared of clouds). The range of modeled cloud effects is inconsistently large but they fall into two distinct classes: (1) models with large cloud effects showing mostly enhanced J values aloft and or diminished at the surface and (2) models with small effects having nearly clear-sky J values much of the time. The ATom-1 measurements generally favor large cloud effects but are not precise or robust enough to point out the best cloud-modeling approach. The models here have resolutions of 50–200 km and thus reduce the occurrence of clear sky when averaging over grid cells. In situ measurements also average scattered sunlight over a mixed cloud field, but only out to scales of tens of kilometers. A primary uncertainty remains in the role of clouds in chemistry, in particular, how models average over cloud fields, and how such averages can simulate measurements. NERC ACSIS LTSM projec

Efeito da implantação de uma floresta mista sobre a população de microrganismos celulolíticos em solos do semi-árido mineiro.

Na recuperacao e manutencao da fertilidade dos solos degradados, a decomposicao apresenta-se particularmente importante sendo a razao celulose/N um dos principais fatores que influenciam a efetividade desses processo. Neste trabalho avaliou-se a ocorrencia e a dinamica da populacao de microorganismos celuloliticos nos solos de diferentes modelos de reflorestamento de uma area degradada do Projeto Jaiba/MG. Esses modelos incluiram especies arboreas de eucalipto, leguminosas e nao leguminosas nativas. Observaram-se diferencas significativas no numero de celuloliticos entre as estacoes e os locais estudados. Nas areas impactadas ocorreu elevacao menos intensa dos microrganismos evidenciando o efeito limitante do impacto sobre essa populacao microbiana. Nos modelos de plantio avaliados o numero de celuloliticos diferiu significativamente, sendo o mais elevado no modelo representado pelo plantio do maior numero de especies. em todos os experimentos, a maior populacao de celuloliticos ocorreu nos consorcios entre leguminosas e outras especies vegetais nativas e a menor nas areas de plantio de eucalipto, sugerindo uma acao limitante dessa planta sobre o crescimento desses microrganismos. Esses resultados evidenciaram o papel dos celuloliticos como bioindicadores da qualidade do solo e da resposta as diferentes praticas de manejo

Field theories with anisotropic scaling in 2D, solitons and the microscopic entropy of asymptotically Lifshitz black holes

Field theories with anisotropic scaling in 1+1 dimensions are considered. It is shown that the isomorphism between Lifshitz algebras with dynamical exponents z and 1/z naturally leads to a duality between low and high temperature regimes. Assuming the existence of gap in the spectrum, this duality allows to obtain a precise formula for the asymptotic growth of the number of states with a fixed energy which depends on z and the energy of the ground state, and reduces to the Cardy formula for z=1. The holographic realization of the duality can be naturally inferred from the fact that Euclidean Lifshitz spaces in three dimensions with dynamical exponents and characteristic lengths given by z, l, and 1/z, l/z, respectively, are diffeomorphic. The semiclassical entropy of black holes with Lifshitz asymptotics can then be recovered from the generalization of Cardy formula, where the ground state corresponds to a soliton. An explicit example is provided by the existence of a purely gravitational soliton solution for BHT massive gravity, which precisely has the required energy that reproduces the entropy of the analytic asymptotically Lifshitz black hole with z=3. Remarkably, neither the asymptotic symmetries nor central charges were explicitly used in order to obtain these results.Comment: 17 pages, no figures, references corrected and update

Update on HER-2 as a target for cancer therapy: HER2/neu peptides as tumour vaccines for T cell recognition

During the past decade there has been renewed interest in the use of vaccine immunotherapy for the treatment of cancer. This review focuses on HER2/neu, a tumour-associated antigen that is overexpressed in 10–40% of breast cancers and other carcinomata. Several immunogenic HER2/neu peptides recognized by T lymphocytes have been identified to be included in cancer vaccines. Some of these peptides have been assessed in clinical trials of patients with breast and ovarian cancer. Although it has been possible to detect immunological responses against the peptides in the immunized patients, no clinical responses have so far been described. Immunological tolerance to self-antigens like HER2/neu may limit the functional immune responses against them. It will be of interest to determine whether immune responses against HER2/neu epitopes can be of relevance to cancer treatment

miR-132/212 knockout mice reveal roles for these miRNAs in regulating cortical synaptic transmission and plasticity

miR-132 and miR-212 are two closely related miRNAs encoded in the same intron of a small non-coding gene, which have been suggested to play roles in both immune and neuronal function. We describe here the generation and initial characterisation of a miR-132/212 double knockout mouse. These mice were viable and fertile with no overt adverse phenotype. Analysis of innate immune responses, including TLR-induced cytokine production and IFNβ induction in response to viral infection of primary fibroblasts did not reveal any phenotype in the knockouts. In contrast, the loss of miR-132 and miR-212, while not overtly affecting neuronal morphology, did affect synaptic function. In both hippocampal and neocortical slices miR-132/212 knockout reduced basal synaptic transmission, without affecting paired-pulse facilitation. Hippocampal long-term potentiation (LTP) induced by tetanic stimulation was not affected by miR-132/212 deletion, whilst theta burst LTP was enhanced. In contrast, neocortical theta burst-induced LTP was inhibited by loss of miR-132/212. Together these results indicate that miR-132 and/or miR-212 play a significant role in synaptic function, possibly by regulating the number of postsynaptic AMPA receptors under basal conditions and during activity-dependent synaptic plasticity

Paternal obesity is associated with IGF2 hypomethylation in newborns: results from a Newborn Epigenetics Study (NEST) cohort

Data from epidemiological and animal model studies suggest that nutrition during pregnancy may affect the health status of subsequent generations. These transgenerational effects are now being explained by disruptions at the level of the epigenetic machinery. Besides in vitro environmental exposures, the possible impact on the reprogramming of methylation profiles at imprinted genes at a much earlier time point, such as during spermatogenesis or oogenesis, has not previously been considered. In this study, our aim was to determine associations between preconceptional obesity and DNA methylation profiles in the offspring, particularly at the differentially methylated regions (DMRs) of the imprinted Insulin-like Growth Factor 2 (IGF2) gene

Asymptotically Lifshitz wormholes and black holes for Lovelock gravity in vacuum

Static asymptotically Lifshitz wormholes and black holes in vacuum are shown to exist for a class of Lovelock theories in d=2n+1>7 dimensions, selected by requiring that all but one of their n maximally symmetric vacua are AdS of radius l and degenerate. The wormhole geometry is regular everywhere and connects two Lifshitz spacetimes with a nontrivial geometry at the boundary. The dynamical exponent z is determined by the quotient of the curvature radii of the maximally symmetric vacua according to n(z^2-1)+1=(l/L)^2, where L corresponds to the curvature radius of the nondegenerate vacuum. Light signals are able to connect both asymptotic regions in finite time, and the gravitational field pulls towards a fixed surface located at some arbitrary proper distance to the neck. The asymptotically Lifshitz black hole possesses the same dynamical exponent and a fixed Hawking temperature given by T=z/(2^z pi l). Further analytic solutions, including pure Lifshitz spacetimes with a nontrivial geometry at the spacelike boundary, and wormholes that interpolate between asymptotically Lifshitz spacetimes with different dynamical exponents are also found.Comment: 19 pages, 1 figur