Age-related losses of cognitive function and motor skills in mice are associated with oxidative protein damage in the brain.

The hypothesis that age-associated impairment of cognitive and motor functions is due to oxidative molecular damage was tested in the mouse. In a blind study, senescent mice (aged 22 months) were subjected to a battery of behavioral tests for motor and cognitive functions and subsequently assayed for oxidative molecular damage as assessed by protein carbonyl concentration in different regions of the brain. The degree of age-related impairment in each mouse was determined by comparison to a reference group of young mice (aged 4 months) tested concurrently on the behavioral battery. The age-related loss of ability to perform a spatial swim maze task was found to be positively correlated with oxidative molecular damage in the cerebral cortex, whereas age-related loss of motor coordination was correlated with oxidative molecular damage within the cerebellum. These results support the view that oxidative stress is a causal factor in brain senescence. Furthermore, the findings suggest that age-related declines of cognitive and motor performance progress independently, and involve oxidative molecular damage within different regions of the brain.

The vertebrate alcohol dehydrogenase system: variable class II type form elucidates separate stages of enzymogenesis.

A mixed-class alcohol dehydrogenase has been characterized from avian liver. Its functional properties resemble the classical class I type enzyme in livers of humans and animals by exhibiting low Km and kcat values with alcohols (Km = 0.7 mM with ethanol) and low Ki values with 4-methylpyrazole (4 microM). These values are markedly different from corresponding parameters of class II and III enzymes. In contrast, the primary structure of this avian liver alcohol dehydrogenase reveals an overall relationship closer to class II and to some extent class III (69 and 65% residue identities, respectively) than to class I or the other classes of the human alcohol dehydrogenases (52-61%), the presence of an insertion (four positions in a segment close to position 120) as in class II but in no other class of the human enzymes, and the presence of several active site residues considered typical of the class II enzyme. Hence, the avian enzyme has mixed-class properties, being functionally similar to class I, yet structurally similar to class II, with which it also clusters in phylogenetic trees of characterized vertebrate alcohol dehydrogenases. Comparisons reveal that the class II enzyme is approximately 25% more variable than the "variable" class I enzyme, which itself is more variable than the "constant" class III enzyme. The overall extreme, and the unusual chromatographic behavior may explain why the class II enzyme has previously not been found outside mammals. The properties define a consistent pattern with apparently repeated generation of novel enzyme activities after separate gene duplications.

Analysis of homeodomain function by structure-based design of a transcription factor.

The homeodomain is a 60-amino acid module which mediates critical protein-DNA and protein-protein interactions for a large family of regulatory proteins. We have used structure-based design to analyze the ability of the Oct-1 homeodomain to nucleate an enhancer complex. The Oct-1 protein regulates herpes simplex virus (HSV) gene expression by participating in the formation of a multiprotein complex (C1 complex) which regulates alpha (immediate early) genes. We recently described the design of ZFHD1, a chimeric transcription factor containing zinc fingers 1 and 2 of Zif268, a four-residue linker, and the Oct-1 homeodomain. In the presence of alpha-transinduction factor and C1 factor, ZFHD1 efficiently nucleates formation of the C1 complex in vitro and specifically activates gene expression in vivo. The sequence specificity of ZFHD1 recruits C1 complex formation to an enhancer element which is not efficiently recognized by Oct-1. ZFHD1 function depends on the recognition of the Oct-1 homeodomain surface. These results prove that the Oct-1 homeodomain mediates all the protein-protein interactions that are required to efficiently recruit alpha-transinduction factor and C1 factor into a C1 complex. The structure-based design of transcription factors should provide valuable tools for dissecting the interactions of DNA-bound domains in other regulatory circuits.

A simple test of the vicarious trial-and-error hypothesis of hippocampal function.

Vicarious trial-and-error (VTE) is a term that Muenzinger and Tolman used to describe the rat's conflict-like behavior before responding to choice. Recently, VTE was proposed as a mechanism alternative to the concept of "cognitive map" in accounts of hippocampal function. That is, many phenomena of impaired learning and memory related to hippocampal interventions may be explained by behavioral first principles: reduced conflicting, incipient, pre-choice tendencies to approach and avoid. The nonspatial black-white discrimination learning and VTE behavior of the rat were investigated. Hippocampal-lesioned and sham-lesioned animals were trained for 25 days (20 trials per day) starting at 60 days of age. Each movement of the head from one discriminative stimulus to the other was counted as a VTE instance. Lesioned rats had fewer VTEs than sham controls, and the former learned much more slowly or never learned. After learning, VTE frequency declined. Male and female rats showed no significant differences in VTE behavior or discrimination learning.

Evidence for a role of pituitary ATP receptors in the regulation of pituitary function.

Despite a rapidly increasing acceptance for a role of ATP as an extracellular mediator in several biological systems, the present report shows that ATP may mediate physiological responses in pituitary cells. We have now been able to demonstrate a specific action of ATP receptors to mediate the release of luteinizing hormone from gonadotropes and have coupled them with further studies that clearly show that ATP can be exocytotically released from cultured rat pituitary cells. Both ATP and UTP (100 microM) caused a > 14-fold increase in the rate of luteinizing hormone release from superfused cells. Adenosine 5'-[alpha, beta-methylene]triphosphate and 5'-[beta,gamma-methylene triphosphate were ineffective, and 2-methylthio-ATP had only a modest stimulatory effect. Homologous and heterologous desensitization occurred with UTP and ATP, and these did not have additive effects. Thus, nucleotides can be effective stimulators of luteinizing hormone release through a single class of ATP receptor (P2U subtype). The calcium ionophore A23187 provoked release of a substantial amount of ATP from pituitary cells in a concentration- and Ca(2+)-dependent manner, which was desensitized by pretreatment with A23187. This implies a possible paracrine and/or autocrine mechanism by which nucleotides may exert their effects on pituitary cells. In conclusion, we have provided strong evidence for a novel role of extracellular nucleotides as mediators in pituitary--in particular, in gonadotrope--function.

Adaptación del BRIEF ("Behavior Rating Inventory of Executive Function") a población española y su utilidad para el diagnóstico del trastorno por déficit de atención-hiperactividad subtipos inatento y combinado

La valoración de las funciones ejecutivas tiene una especial dificultad cuando se intenta llevar a cabo mediante un enfoque tradicional de pruebas neuropsicológicas. Este aspecto es especialmente relevante en la evaluación de funciones ejecutivas en población pediátrica, lo que propició el desarrollo de cuestionarios de conducta como el Behavior Rating Inventory of Executive Function (BRIEF), con el fin de convertirse en una medida ecológica de las alteraciones de funciones ejecutivas. Resulta necesario realizar una adaptación completa de una prueba psicométrica para que ésta pueda ser utilizada en una población diferente para la cual fue diseñada. El BRIEF ha sido utilizado para la valoración de las alteraciones ejecutivas en numerosas patologías, pero destacan los estudios realizados en niños con Trastorno por Déficit de Atención - Hiperactividad (TDAH). El TDAH presenta alteraciones neuropsicológicas que implican especialmente a las funciones ejecutivas, lo que justifica el uso de la prueba en esta patología. Incluso, algunas de las teorías más importantes sobre TDAH apuntan a las alteraciones en inhibición como el síntoma nuclear del trastorno. La existencia de dos subtipos principales en el TDAH (subtipo predominantemente inatento y combinado) podría implicar un patrón diferente de alteraciones ejecutiva en cada tipo. OBJETIVOS: Se presentan dos objetivos principales: 1) Adaptación del BRIEF a población española, y 2) Estudio del perfil diferencial del BRIEF entre los subtipos inatento y combinado del TDAH...

Partial rescue of retinal function in chronically hypoglycemic mice

Purpose. Mice rendered hypoglycemic by a null mutation in the glucagon receptor gene Gcgr display late-onset retinal degeneration and loss of retinal sensitivity. Acute hyperglycemia induced by dextrose ingestion does not restore their retinal function, which is consistent with irreversible loss of vision. The goal of this study was to establish whether long-term administration of high dietary glucose rescues retinal function and circuit connectivity in aged Gcgr−/− mice. Methods. Gcgr−/− mice were administered a carbohydrate-rich diet starting at 12 months of age. After 1 month of treatment, retinal function and structure were evaluated using electroretinographic (ERG) recordings and immunohistochemistry. Results. Treatment with a carbohydrate-rich diet raised blood glucose levels and improved retinal function in Gcgr−/− mice. Blood glucose increased from moderate hypoglycemia to euglycemic levels, whereas ERG b-wave sensitivity improved approximately 10-fold. Because the b-wave reflects the electrical activity of second-order cells, we examined for changes in rod-to-bipolar cell synapses. Gcgr−/− retinas have 20% fewer synaptic pairings than Gcgr+/− retinas. Remarkably, most of the lost synapses were located farthest from the bipolar cell body, near the distal boundary of the outer plexiform layer (OPL), suggesting that apical synapses are most vulnerable to chronic hypoglycemia. Although treatment with the carbohydrate-rich diet restored retinal function, it did not restore these synaptic contacts. Conclusions. Prolonged exposure to diet-induced euglycemia improves retinal function but does not reestablish synaptic contacts lost by chronic hypoglycemia. These results suggest that retinal neurons have a homeostatic mechanism that integrates energetic status over prolonged periods of time and allows them to recover functionality despite synaptic loss.

Impairment of Intrinsically Photosensitive Retinal Ganglion Cells Associated With Late Stages of Retinal Degeneration

Purpose. To evaluate quantitative and qualitative age-related changes in intrinsically photosensitive melanopsin-containing retinal ganglion cells (ipRGCs) in transgenic P23H rats, an animal model of autosomal dominant retinitis pigmentosa (RP) was examined. Methods. ipRGC density, morphology, and integrity were characterized by immunohistochemistry in retinas extracted from P23H and Sprague–Dawley (SD) rats aged 4, 12, and 18 months. Differences between SD and P23H rats throughout the experimental stages, as well as the interactions among them, were morphologically evaluated. Results. In rat retinas, we have identified ipRGCs with dendrites stratifying in either the outer margin (M1) or inner side (M2) of the inner plexiform layer, and in both the outer and inner plexuses (M3). A small group of M1 cells had their somas located in the inner nuclear layer (M1d). In SD rats, ipRGCs showed no significant changes associated with age, in terms of either mean cell density or the morphologic parameters analyzed. However, the mean density of ipRGCs in P23H rats fell by approximately 67% between 4 and 18 months of age. Moreover, ipRGCs in these animals showed a progressive age-dependent decrease in the dendritic area, the number of branch points and terminal neurite tips per cell, and the Sholl area. Conclusions. In the P23H rat model of retinitis pigmentosa, density, wholeness, and dendritic arborization of melanopsin-containing ganglion cells decrease in advanced stages of the degenerative disease.

Gibbs Energy of Mixing Function: Topological Analysis in Azeotropic Systems

ESAT 2014. 27th European Symposium on Applied Thermodynamics, Eindhoven University of Technology, July 6-9, 2014.

Adsorption and first stages of polymerization of aniline on platinum single crystal electrodes

The present communication studies the adsorption of aniline on platinum single crystal electrodes and the electrochemical properties of the first layers of polyaniline(PANI) grown on those platinum surfaces. The adsorption process was studied in aqueous acidic solution (0.1 M HClO4) and the electrochemical properties of thin films of PANI in both aqueous (1 M HClO4) and non-aqueous media (tetrabutyl ammonium hexafluorophosphate (TBAPF6) with additions of methanesulphonic acid in acetonitrile). First of all, it was found that the adsorption of aniline on platinum single crystal surfaces is a surface sensitive process, and even more important that the adsorption features found at low concentrations (5 × 10−5 M) can be directly correlated to the electrochemical properties of thin films of PANI in the very early stages of polymerization. The Pt(1 1 0) surface was found to be more suitable to obtain polymers with more reversible redox transitions when studied in aqueous media (1 M HClO4). This is in good agreement with the higher polymerization rates found on this surface compared to Pt(1 0 0) and Pt(1 1 1). Finally the differences in ionic exchange rate were greatly enhanced when they were studied in organic media. The AC 250 Hz response in the case of the thin films synthesized on Pt(1 1 0) is about twice greater than that obtained in the other basal planes using polymer layers with the same thickness.

Students’ understanding of the function-derivative relationship when learning economic concepts

The aim of this study is to characterise students’ understanding of the function-derivative relationship when learning economic concepts. To this end, we use a fuzzy metric (Chang 1968) to identify the development of economic concept understanding that is defined by the function-derivative relationship. The results indicate that the understanding of these economic concepts is linked to students’ capacity to perform conversions and treatments between the algebraic and graphic registers of the function-derivative relationship when extracting the economic meaning of concavity/convexity in graphs of functions using the second derivative.

Retrieval of phenological stages of onion fields during the first year of growth by means of C-band polarimetric SAR measurements

The phenological stages of onion fields in the first year of growth are estimated using polarimetric observables and single-polarization intensity channels. Experiments are undertaken on a time series of RADARSAT-2 C-band full-polarimetric synthetic aperture radar (SAR) images collected in 2009 over the Barrax region, Spain, where ground truth information about onion growth stages is provided by the European Space Agency (ESA)-funded agricultural bio/geophysical retrieval from frequent repeat pass SAR and optical imaging (AgriSAR) field campaign conducted in that area. The experimental results demonstrate that polarimetric entropy or copolar coherence when used jointly with the cross-polarized intensity allows unambiguously distinguishing three phenological intervals.

The hosiery industry: Report on the cost of production of hosiery in the United States

At head of title: Department of Commerce. Bureau of Foreign and Domestic Commerce. E.E. Pratt, Chief ...

The knit-underwear industry: Report on the cost of production of knit underwear in the United States

At head of title: Department of Commerce. Bureau of Foreign and Domestic Commerce. E.E. Pratt, Chief ...

The women's muslin-underwear industry: report on the cost of production of women's muslin underwear in the United States

Department of Commerce, Bureau of Foreign and Domestic Commerce.