Effect of vagotomy on the duodenal mechanisms regulating gastric secretion

Gastric acid secretion, gastrin and secretin serum levels after duodenal acidification were studied in 6 dogs, before and after a troncular vagotomy was performed in each one. After duodenal acidification in normal dogs, a 45.2% inhibition of gastric acid secretion with parallel 55-84% increases in the serum secretin levels, without changes in the serum gastrin levels, was noted. When a troncular vagotomy was performed in the same dogs, duodenal acidification produced a 20% (non significant) inhibition of gastric acid secretion with parallel 34-72% increases in the serum secretin levels and without changes in the serum gastrin levels. It is concluded that vagus nerve is necessary to assess a physiological inhibition of gastric secretion after duodenal acidification and it is suggested that humoral and nervous factors are implicated and coexist in these mechanisms.     

Photoaffinity labeling of the adenosine transport system in adipocyte plasma membranes

A membrane component involved in the transport of adenosine in adipocytes has been identified utilizing the techniques of photoaffinity labeling with the adenosine derivative, 8-azidoadenosine. In the absence of light, adenosine and 8-azidoadenosine exhibited similar transport characteristics. In addition, adenosine was shown to be a competitive inhibitor of 8-azidoadenosine uptake, and the photoprobe, a competitive inhibitor of adenosine uptake. Analysis of the nucleotide metabolites indicated that the photoprobe was metabolized in a similar fashion to that observed for adenosine. Several nucleoside transport inhibitors were also equally effective in inhibiting the uptake of both nucleosides. These results suggest that 8-azidoadenosine is transported by the same membrane system as adenosine. Photolysis of 8-azido[2-³H]adenosine in the presence of adipocytes resulted in the covalent incorporation of the photoprobe into the plasma membrane fraction. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that essentially all of the radioactivity was incorporated into a glycoprotein with a molecular weight of 56,000. This labeling was inhibited by greater than 90% when the photolysis was carried out in the presence of excess adenosine or the transport inhibitors, persantin or theophylline. Fractionation of the labeled plasma membranes by dialysis against water (pH 9.5) indicated that approximately 75% of the radioactivity was associated with a glycoprotein which resisted solubilization by this procedure. These results suggest that the major labeled species is a 56,000 M_r intrinsic membrane glycoprotein which may function as a component of a transmembrane assembly involved in the transport of adenosine.     

Involving Motor Capabilities in the Formation of Sensory Space Representations

A goal of sensory coding is to capture features of sensory input that are behaviorally relevant. Therefore, a generic principle of sensory coding should take into account the motor capabilities of an agent. Up to now, unsupervised learning of sensory representations with respect to generic coding principles has been limited to passively received sensory input. Here we propose an algorithm that reorganizes an agent''s representation of sensory space by maximizing the predictability of sensory state transitions given a motor action. We applied the algorithm to the sensory spaces of a number of simple, simulated agents with different motor parameters, moving in two-dimensional mazes. We find that the optimization algorithm generates compact, isotropic representations of space, comparable to hippocampal place fields. As expected, the size and spatial distribution of these place fields-like representations adapt to the motor parameters of the agent as well as to its environment. The representations prove to be well suited as a basis for path planning and navigation. They not only possess a high degree of state-transition predictability, but also are temporally stable. We conclude that the coding principle of predictability is a promising candidate for understanding place field formation as the result of sensorimotor reorganization.     

Akt activity protects rheumatoid synovial fibroblasts from Fas-induced apoptosis by inhibition of Bid cleavage

Introduction  

Synovial hyperplasia is a main feature of rheumatoid arthritis pathology that leads to cartilage and bone damage in the inflamed joints. Impaired apoptosis of resident synoviocytes is pivotal in this process. Apoptosis resistance seems to involve defects in the extrinsic and intrinsic apoptotic pathways. The aim of this study was to investigate the association of PI3Kinase/Akt and the mitochondrial apoptotic pathway in the resistance of rheumatoid arthritis (RA) fibroblast like synovial cells (FLS) to Fas-mediated apoptosis.     

Viral Protein Inhibits RISC Activity by Argonaute Binding through Conserved WG/GW Motifs

RNA silencing is an evolutionarily conserved sequence-specific gene-inactivation system that also functions as an antiviral mechanism in higher plants and insects. To overcome antiviral RNA silencing, viruses express silencing-suppressor proteins. These viral proteins can target one or more key points in the silencing machinery. Here we show that in Sweet potato mild mottle virus (SPMMV, type member of the Ipomovirus genus, family Potyviridae), the role of silencing suppressor is played by the P1 protein (the largest serine protease among all known potyvirids) despite the presence in its genome of an HC-Pro protein, which, in potyviruses, acts as the suppressor. Using in vivo studies we have demonstrated that SPMMV P1 inhibits si/miRNA-programmed RISC activity. Inhibition of RISC activity occurs by binding P1 to mature high molecular weight RISC, as we have shown by immunoprecipitation. Our results revealed that P1 targets Argonaute1 (AGO1), the catalytic unit of RISC, and that suppressor/binding activities are localized at the N-terminal half of P1. In this region three WG/GW motifs were found resembling the AGO-binding linear peptide motif conserved in metazoans and plants. Site-directed mutagenesis proved that these three motifs are absolutely required for both binding and suppression of AGO1 function. In contrast to other viral silencing suppressors analyzed so far P1 inhibits both existing and de novo formed AGO1 containing RISC complexes. Thus P1 represents a novel RNA silencing suppressor mechanism. The discovery of the molecular bases of P1 mediated silencing suppression may help to get better insight into the function and assembly of the poorly explored multiprotein containing RISC.     

Induction of autocrine epidermal growth factor receptor ligands in human keratinocytes by insulin/insulin-like growth factor-1

Autocrine activation of the epidermal growth factor (EGF) receptor on keratinocytes has been recognized as an important growth regulatory mechanism involved in epithelial homeostasis, and, possibly, hyperproliferative diseases. Insulin-like growth factor (IGF)-1 and insulin have been shown to be paracrine keratinocyte mitogens that bind to the type I IGF receptor which is expressed on actively proliferating keratinocytes in situ. In this report, we demonstrate that IGF-1/insulin induced production of keratinocyte-derived autocrine growth factors that bind to the EGF receptor. Increased steady-state mRNA levels for transforming growth factor alpha (TGF-α) and for amphiregulin (AR) were observed upon incubation of keratinocytes with mitogenic concentrations of IGF-1. IGF-1 also induced production and secretion of TGF-α and AR proteins as detected by immunoassays. An EGF receptor antagonistic monoclonal antibody abolished the mitogenic effect of IGF-1 on cultured keratinocytes. These results suggest that stimulation of keratinocyte growth by IGF-1 requires activation of an EGF receptor-mediated autocrine loop. © 1995 Wiley-Liss, Inc.     

Existence of atrial natriuretic peptide in choroid, retina and ciliary body in rabbits]

The presence of atrial natriuretic factor (ANF) in choroid, retina and ciliary body of rabbit eyes has been studied. The peptide was extracted by reverse phase chromatography using Sep-Pak C18 cartridges. Immunoreactive ANF (Ir-ANF) was measured by a specific RIA. In the choroid, retina and ciliary body the ir-ANF concentrations were 444 +/- 94, 67 +/- 12 and 223 +/- 75 pg/g tissue weight (n = 16), respectively. The biological activity of the acid extract ANF was evaluated by a 125I-ANF binding assay to a retinal particulate preparation. Results demonstrate the existence of biological active ANF in choroid, retina and ciliary body of rabbit eyes. The presence of ANF and its specific receptors in the ocular tissues suggests that this hormone might play a physiological role in the intraocular fluid homeostasis.     

Cardiac myoglobin deficit has evolved repeatedly in teleost fishes

Myoglobin (Mb) is the classic vertebrate oxygen-binding protein present in aerobic striated muscles. It functions principally in oxygen delivery and provides muscle with its characteristic red colour. Members of the Antarctic icefish family (Channichthyidae) are widely thought to be extraordinary for lacking cardiac Mb expression, a fact that has been attributed to their low metabolic rate and unusual evolutionary history. Here, we report that cardiac Mb deficit, associated with pale heart colour, has evolved repeatedly during teleost evolution. This trait affects both gill- and air-breathing species from temperate to tropical habitats across a full range of salinities. Cardiac Mb deficit results from total pseudogenization in three-spined stickleback and is associated with a massive reduction in mRNA level in two species that evidently retain functional Mb. The results suggest that near or complete absence of Mb-assisted oxygen delivery to heart muscle is a common facet of teleost biodiversity, even affecting lineages with notable oxygen demands. We suggest that Mb deficit may affect how different teleost species deal with increased tissue oxygen demands arising under climate change.