The Auto/paracrine regulation of endocrine functions: a history of TGF-β and the adrenal cortex

Aquesta breu revisió vol analitzar quinze anys de recerca que han portat a proposar el factor de creixement transformant beta (TGF-β) com un component endogen auto/paracrí de la regulació de les funcions diferenciades de teixits endocrins, com el còrtex adrenal. El TGF-β reuneix els criteris requerits per aquesta funció, és a dir: a) El pèptid TGF-β està produït per les cèll. ules adrenocorticals i expressat in situ en aquest teixit; b) el TGF-β reprimeix considerablement la capacitat esteroidogènica d'aquestes cèll. ules reprimint els marcadors clau de diferenciació; c) l'hormona sistèmica ACTH modula la resposta de les cèll. ules adrenocorticals al TGF-β; d) la supressió de la síntesi de TGF-β suprimeix la inhibició de l'activitat esteroidogènica d'aquestes cèll. ules. El sistema del TGF-β adrenocortical és, al nostre entendre, el primer circuit regulador (loop) clarament establert en un teixit endocrí. Aquest viatge històric és un tribut al nostre amic José Sáez, que va participar activament en el coneixement d'aquesta història.This brief review is intended as a flash-back spanning over fifteen years of research and finally leading to the proposal that TGF-β could be an endogenous, auto/paracrine component in the regulation of the differentiated functions of an endocrine tissue, i.e., the adrenal cortex. TGF-β meets the criteria required for such a function: (i) the peptide is produced by adrenocortical cells and expressed in the tissue in situ; (ii) TGF-β strikingly down-regulates the steroidogenic capacity of these cells by repressing key differentiation markers; (iii) the systemic hormone ACTH modulates the adrenocortical cells’ responsiveness to TGF-β, and (iv) the suppression of TGF-β synthesis releases the inhibition of the steroidogenic activity of these cells. The TGF-β adrenocortical cell system was, to our knowledge, the first autocrine regulatory loop clearly established in an endocrine tissue. This chronological account is a tribute to our friend, José Sáez, who actively contributed to this history

Review of progress in implementing the recommendations of Sir Gareth Roberts, regarding employability and career development of PhD students and research staff

The need for improvement in the development of research careers and researchers’ training in transferable skills was highlighted in two particular recommendations (numbers 4.2 and 5.3) in the 2002 report ‘SET for success: the report of Sir Gareth Roberts’ Review - the supply of people with science, technology, engineering and mathematics skills’ (Roberts, 2002). As a consequence of that review, Research Councils UK (RCUK)1 have invested about £120 million, usually referred to as ’Roberts’ Money’, in research organisations to address this concern in all research disciplines. The last ‘Roberts’ Money’ payment will be for the period up to March 2011; it was therefore proposed to assess the progress made with taking forward these specific recommendations. An independent panel was formed by RCUK to undertake this review in 2010. The terms of reference for the panel are in Annex A. In summary, the panel was asked to review progress made and to advise RCUK and the higher education (HE) sector about future requirements for the development and training of researchers. In the course of their review, the panel considered a wide range of existing reports, interviewed key stakeholders in the HE sector and elsewhere, as well as drawing on their own knowledge and expertise. This report presents the findings of the panel’s review

Neural correlates of socio-emotional perception in 22q11.2 deletion syndrome.

BACKGROUND: Social impairments are described as a common feature of the 22q11.2 deletion syndrome (22q11DS). However, the neural correlates underlying these impairments are largely unknown in this population. In this study, we investigated neural substrates of socio-emotional perception. METHODS: We used event-related functional magnetic resonance imaging (fMRI) to explore neural activity in individuals with 22q11DS and healthy controls during the visualization of stimuli varying in social (social or non-social) or emotional (positive or negative valence) content. RESULTS: Neural hyporesponsiveness in regions of the default mode network (inferior parietal lobule, precuneus, posterior and anterior cingulate cortex and frontal regions) in response to social versus non-social images was found in the 22q11DS population compared to controls. A similar pattern of activation for positive and negative emotional processing was observed in the two groups. No correlation between neural activation and social functioning was observed in patients with the 22q11DS. Finally, no social × valence interaction impairment was found in patients. CONCLUSIONS: Our results indicate atypical neural correlates of social perception in 22q11DS that appear to be independent of valence processing. Abnormalities in the social perception network may lead to social impairments observed in 22q11DS individuals

Sensing of Dietary Lipids by Enterocytes: A New Role for SR-BI/CLA-1

BACKGROUND: The intestine is responsible for absorbing dietary lipids and delivering them to the organism as triglyceride-rich lipoproteins (TRL). It is important to determine how this process is regulated in enterocytes, the absorptive cells of the intestine, as prolonged postprandial hypertriglyceridemia is a known risk factor for atherosclerosis. During the postprandial period, dietary lipids, mostly triglycerides (TG) hydrolyzed by pancreatic enzymes, are combined with bile products and reach the apical membrane of enterocytes as postprandial micelles (PPM). Our aim was to determine whether these micelles induce, in enterocytes, specific early cell signaling events that could control the processes leading to TRL secretion. METHODOLOGY/PRINCIPAL FINDINGS: The effects of supplying PPM to the apex of Caco-2/TC7 enterocytes were analyzed. Micelles devoid of TG hydrolysis products, like those present in the intestinal lumen in the interprandial period, were used as controls. The apical delivery of PPM specifically induced a number of cellular events that are not induced by interprandial micelles. These early events included the trafficking of apolipoprotein B, a structural component of TRL, from apical towards secretory domains, and the rapid, dose-dependent activation of ERK and p38MAPK. PPM supply induced the scavenger receptor SR-BI/CLA-1 to cluster at the apical brush border membrane and to move from non-raft to raft domains. Competition, inhibition or knockdown of SR-BI/CLA-1 impaired the PPM-dependent apoB trafficking and ERK activation. CONCLUSIONS/SIGNIFICANCE: These results are the first evidence that enterocytes specifically sense postprandial dietary lipid-containing micelles. SR-BI/CLA-1 is involved in this process and could be a target for further study with a view to modifying intestinal TRL secretion early in the control pathway

The effect of extended post-mortem ageing on the Warner–Brazler shear force of longissimus thoracis from beef heifers from two sire breeds, slaughtered at 20 or 25 mo of age

peer-reviewedwere examined. Spring-born Angus × Holstein-Friesian heifers (n = 48) and Belgian Blue × Holstein-Friesian heifers (n = 48) were slaughtered, within sire breed, at 20 or 25 mo of age. Approximately 48 h post-mortem, LT steaks (2.5 cm) were removed, and either stored at −20°C for chemical analysis or vacuum-packed, stored at 2°C for 7, 14 or 28 d post-mortem and then at −20°C pending Warner–Bratzler shear force (WBSF) analysis. Muscle from Angus-sired heifers had higher (P < 0.001) intramuscular fat (IMF) concentration, lower (P < 0.001) proportion of type IIX muscle fibres and higher (P < 0.001) proportion of type IIA and type I muscle fibres compared to muscle from Belgian Blue-sired heifers. Collagen characteristics did not differ between sire breeds. Later slaughter increased (P < 0.001) IMF concentration and decreased (P < 0.001) total and insoluble concentrations and collagen solubility. There were no interactions between the main effects for WBSF and no difference between sire breeds. Later slaughter and increasing the duration of ageing decreased (P < 0.05) WBSF. Based on threshold WBSF values in the literature, all samples would be considered tender (<39 N) after 7 d ageing. Untrained consumers are likely to detect the decrease in WBSF from 7 to 14 d ageing but not due to further ageing. Within the production system examined and based on WBSF data, extending LT ageing to 28 d is not necessary to ensure consumer satisfaction