Proinsulin: From Hormonal Precursor to Neuroprotective Factor

In the last decade, non-canonical functions have been described for several molecules with hormone-like activities in different stages of vertebrate development. Since its purification in the 1960s, proinsulin has been one of the best described hormonal precursors, though it has been overwhelmingly studied in the context of insulin, the mature protein secreted by the pancreas. Beginning with our discovery of the presence and precise regulation of proinsulin mRNA in early neurulation and neurogenesis, we uncovered a role for proinsulin in cell survival in the developing nervous system. We subsequently demonstrated the ability of proinsulin to prevent pathological cell death and delay photoreceptor degeneration in a mouse model of retinitis pigmentosa. In this review, we focus on the evolution of proinsulin/insulin, beginning with insulin-like peptides expressed in mainly the neurosecretory cells of some invertebrates. We summarize findings related to the regulation of proinsulin expression during development and discuss the possible effects of proinsulin in neural cells or tissue, and its potential as a neuroprotective molecule

Bravo/Nr-CAM Is Closely Related to the Cell Adhesion Molecules L1 and Ng-CAM and Has a Similar Heterodimer Structure

Diverse cell-surface molecules of the nervous system play an important role in specifying cell interactions during development. Using a method designed to generate mAbs against neural surface molecules of defined molecular weight, we have previously reported on the surface protein, Bravo, found in the developing avian retinotectal system. Bravo is immunologically detected on developing optic fibers in the retina, but absent from distal regions of the same fibers in the tectum. We have isolated cDNA clones encompassing the entire coding region of Bravo, including clones containing five alternative sequences of cDNA. These putative alternatively spliced sequences encode stretches of polypeptide ranging in length from 10-93 amino acids and are predicted to be both extra- and intracellular. The deduced primary structure of Bravo reveals that, like the cell adhesion molecules (CAMs) chicken Ng- CAM and mouse L1, Bravo is composed of six Ig-like domains, five fibronectin type III repeats, a transmembrane domain, and a short cytoplasmic region. Recently, the cDNA sequence of a related molecule, Nr-CAM, was reported and its possible identity with Bravo discussed (Grumet, M., V. Mauro, M. P. Burgoon, G. E. Edelman, and B. A. Cunningham. 1991. J. Cell Biol. 113:1399-1412). Here we confirm this identity and moreover show that Bravo is found on Muller glial processes and end-feet in the developing retina. In contrast to the single polypeptide chain structure of Nr-CAM reported previously, we show that Bravo has a heterodimer structure composed of an alpha chain of M(r) 140/130 and a beta chain of 60-80 kD. As with L1 and Ng-CAM, the two chains of Bravo are generated from an intact polypeptide by cleavage at identical locations and conserved sites within all three molecules (Ser-Arg/Lys-Arg). The similar domain composition and heterodimer structure, as well as the 40% amino acid sequence identity of these molecules, defines them as an evolutionarily related subgroup of CAMs. The relationship of Bravo to molecules known to be involved in cell adhesion and process outgrowth, combined with its pattern of expression and numerous potential isoforms, suggests a complex role for this molecule in cell interactions during neural development

Estudio expeditivo de los suelos del _área prevista para ampliación en la zona negable de "Sierra Boyera"

7 páginas.-- 1 mapa esquemático de suelosEn el presente trabajo se lleva a cabo una definición somera de las unidades de suelo más sobresalientes, y su distribución se acompaña en un mapa esquemático a escala 1/20.000. Se ha programado como una primera aproximación que permita –después de un trabajo futuro de mayor detalle- efectuar una identificación y clasificación más ajustada de los suelos como base para el conocimiento de los problemas de su puesta en riego.N

On Velocity in several Complementary Currencies

We analyse the velocity of several complementary currencies, notably the WIR, RES, Chiemgauer, Sol, Berkshares dollars, and several other cases. Then we describe the diversity in their velocity of circulation, and seek potential explanations for these differences. For example, WIR velocity is 2.6 while RES velocity is 1.9 despite being similar currencies. The higher speed may be explained by WIR blended loans among other benefits or by the fact that there are nearly 20.000 unregistered members that contribute with their transactions. Using a comparative method between cases, the article explores a number of possible explanations on the increases in velocity, apart from prevailing demurrage approaches

Assessing Child Obesity and Physical Activity in a Hard-to-Reach Population in California's Central Valley, 2012-2013.

IntroductionIn California's agricultural Central Valley, the rate of childhood obesity is higher than the national average. Adequate physical activity contributes to obesity prevention and its assessment is useful to evaluate the impact of interventions.MethodsNiños Sanos, Familia Sana (Healthy Children, Healthy Family [NSFS]) uses community-based participatory research to implement an intervention program to reduce childhood obesity among people of Mexican origin in the Central Valley. Anthropometric measurements were conducted on more than 650 children enrolled in NSFS. Physical activity data from a subgroup of children aged 4 to 7 years (n = 134) were collected via a wearable accelerometer.ResultsChildren were classified on the basis of age and sex-adjusted body mass index as healthy weight (57.7%); overweight (19.3%), or obese (23%). Logistic regression showed that moderate to vigorous physical activity (MVPA) was associated with a child's likelihood of having a healthy BMI (odds ratio: 1.03; 95% CI, 1.01-1.05; P = .017).ConclusionNSFS's community-based participatory approach resulted in successful use of a commercial electronic device to measure physical activity quantity and quality in this hard-to-reach population. Promotion of adequate daily MVPA is an appropriate and necessary component of NSFS's childhood obesity prevention strategy

Topologically Restricted Appearance in the Developing Chick Retinotectal System of Bravo, a Neural Surface Protein: Experimental Modulation by Environmental Cues

A novel neural surface protein, Bravo, shows a pattern of topological restriction in the embryonic chick retinotectal system. Bravo is present on the developing optic fibers in the retina; however, retinal axons in the tectum do not display Bravo. The appearance of Bravo in vitro is modulated by environmental cues. Axons growing out from retinal explants on retinal basal lamina, their natural substrate, express Bravo, whereas such axons growing on collagen do not. Retinal explants provide a valuable system to characterize the mechanism of Bravo restriction, as well as the cellular signals controlling it. Bravo was identified with monoclonal antibodies from a collection generated against exposed molecules isolated by using a selective cell surface biotinylation procedure. The NH2-terminal sequence of Bravo shows similarity with L1, a neural surface molecule which is a member of the immunoglobulin superfamily. This possible relationship to L1, together with its restricted appearance, suggests an involvement of Bravo in axonal growth and guidance