Astrocytic metabolic and inflammatory changes as a function of age

This study examines age‐dependent metabolic‐inflammatory axis in primary astrocytes isolated from brain cortices of 7‐, 13‐, and 18‐month‐old Sprague–Dawley male rats. Astrocytes showed an age‐dependent increase in mitochondrial oxidative metabolism respiring on glucose and/or pyruvate substrates; this increase in mitochondrial oxidative metabolism was accompanied by increases in COX3/18SrDNA values, thus suggesting an enhanced mitochondrial biogenesis. Enhanced mitochondrial respiration in astrocytes limits the substrate supply from astrocytes to neurons; this may be viewed as an adaptive mechanism to altered cellular inflammatory–redox environment with age. These metabolic changes were associated with an age‐dependent increase in hydrogen peroxide generation (largely ascribed to an enhanced expression of NOX2) and NFκB signaling in the cytosol as well as its translocation to the nucleus. Astrocytes also displayed augmented responses with age to inflammatory cytokines, IL‐1β, and TNFα. Activation of NFκB signaling resulted in increased expression of nitric oxide synthase 2 (inducible nitric oxide synthase), leading to elevated nitric oxide production. IL‐1β and TNFα treatment stimulated mitochondrial oxidative metabolism and mitochondrial biogenesis in astrocytes. It may be surmised that increased mitochondrial aerobic metabolism and inflammatory responses are interconnected and support the functionality switch of astrocytes, from neurotrophic to neurotoxic with age.     

Estradiol-17beta-D-glucuronide induces endocytic internalization of Bsep in rats

Endocytic internalization of the multidrug resistance-associated protein 2 (Mrp2) was previously suggested to be involved in estradiol-17beta-D-glucuronide (E217G)-induced cholestasis. Here we evaluated in the rat whether a similar phenomenon occurs with the bile salt export pump (Bsep) and the ability of DBcAMP to prevent it. E217G (15 micromol/kg i.v.) impaired bile salt (BS) output and induced Bsep internalization, as assessed by confocal microscopy and Western blotting. Neither cholestasis nor Bsep internalization occurred in TR- rats lacking Mrp2. DBcAMP (20 micromol/kg i.v.) partially prevented the decrease in bile flow and BS output and substantially prevented E217G-induced Bsep internalization. In hepatocyte couplets, E217G (50 microM) diminished canalicular accumulation of a fluorescent BS and decreased Bsep-associated fluorescence in the canalicular membrane; DBcAMP (10 microM) fully prevented both effects. In conclusion, our results suggest that changes in Bsep localization are involved in E217G-induced impairment of bile flow and BS transport and that DBcAMP prevents this effect by stimulating insertion of canalicular transporter-containing vesicles. Mrp2 is required for E217G to induce its harmful effect.     

Immunohistochemical determination of estrogen receptor-α in canine vaginal biopsies throughout proestrus,estrus, and early diestrus

The aim of this study was to describe the presence of estrogen receptor-α (ERα) in several vaginal histological compartments in healthy adult bitches throughout three estrous cycle stages (proestrus, estrus, and early diestrus) and to relate ERα presence with serum progesterone and estradiol-17β concentrations. For this purpose, serial blood samples and vaginal biopsies were taken from five bitches every 48 hours, starting at the clinical onset of proestrus, marked by the beginning of serosanguineous vaginal secretion. Serum progesterone and estradiol-17β concentrations were determined by RIA, whereas detection of steroid receptors was carried out through immunohistochemistry. Subjective image analysis was conducted by two independent observers in the following histological compartments: superficial, intermediate, and deep epithelia and superficial (loose) and deep (dense) stroma (connective tissue). Nuclear ERα immunoreactivity was detected in every histological compartment and estrous cycle stage studied. ERα expression varied among histological compartments and during stages of the cycle. Receptor expression was associated with estradiol-17β and progesterone serum profiles. Most relevant cyclic changes were detected in the superficial and deep epithelia and in the dense connective tissue. The highest ERα expression was detected during diestrus, although each compartment had a different pattern throughout the other cycle stages. Thus, vaginal ERα expression in the bitch varied throughout proestrus, estrus, and early diestrus according to the histological compartment involved.     

Cellular Differentiation and Leaf Morphogenesis in Arabdopsis

A focused approach that exploits a single plant species, namely, Arabidopsis thaliana, as a means to understand how leaf cells differentiate and the factors that govern overall leaf morphogenesis has begun to generate a significant body of knowledge in this model plant. Although many studies have concentrated on specific cell types and factors that control their differentiation, some degree of consensus is starting to be reached. However, an understanding of specific mechanisms by which cells differentiate in relation to their position, that appears to be an overriding factor in this process, is not yet in place for cell types in the Arabidopsis leaf. It is clear that perturbations in cellular development within the leaf do not necessarily have a general effect on morphogenesis. Environmental factors, particularly light, have been known to affect leaf cell differentiation and expansion, and endogenous hormones also appear to play an important role, through mechanisms that are beginning to be uncovered. It is likely that continued identification of genes involved in leaf development and their regulation in relation to positional information or other cues will lead to a clearer understanding of the control of differentiation and morphogenesis in the Arabidopsis leaf.     

Sex differences in antipredator tail-waving displays of the diurnal yellow-headed gecko Gonatodes albogularis from tropical forests of Colombia

Many vertebrate species show display behaviors when predators are in their vicinity. Some of these displays may inform the predator of the improbability of capturing the prey (i.e., pursuit-deterrent displays) and are potentially advantageous to both predator and prey. Here we present data on a tail display performed by Gonatodes albogularis, a diurnal tropical gecko. We performed transect surveys in three habitats near Bogotá in Colombia. Geckos detected during transects were approached by the observer in a standardized way, and details of their tail-waving displays were recorded. In control recordings animals were watched from a distant site without approaching them. Results showed sexual differences in tail-waving display: when approached by the observer, males performed this behavior more frequently than females. We found no significant differences between males and females in flight-initiation distances and height above the substratum when they were initially located. Results also showed that males displayed more frequently when approached than when the simulated predator remained stationary. We interpret these results as evidence that the display functions as a pursuit-deterrent signal to potential predators. However, as some tail displays were performed in the presence of conspecifics, the display may also have a social function.     

A genomewide admixture mapping panel for Hispanic/Latino populations

Admixture mapping (AM) is a promising method for the identification of genetic risk factors for complex traits and diseases showing prevalence differences among populations. Efficient application of this method requires the use of a genomewide panel of ancestry-informative markers (AIMs) to infer the population of origin of chromosomal regions in admixed individuals. Genomewide AM panels with markers showing high frequency differences between West African and European populations are already available for disease-gene discovery in African Americans. However, no such a map is yet available for Hispanic/Latino populations, which are the result of two-way admixture between Native American and European populations or of three-way admixture of Native American, European, and West African populations. Here, we report a genomewide AM panel with 2,120 AIMs showing high frequency differences between Native American and European populations. The average intermarker genetic distance is ~1.7 cM. The panel was identified by genotyping, with the Affymetrix GeneChip Human Mapping 500K array, a population sample with European ancestry, a Mesoamerican sample comprising Maya and Nahua from Mexico, and a South American sample comprising Aymara/Quechua from Bolivia and Quechua from Peru. The main criteria for marker selection were both high information content for Native American/European ancestry (measured as the standardized variance of the allele frequencies, also known as "f value") and small frequency differences between the Mesoamerican and South American samples. This genomewide AM panel will make it possible to apply AM approaches in many admixed populations throughout the Americas.