Uncoupling Protein 2 (UCP2) Function in the Brain as Revealed by the Cerebral Metabolism of (1–<Superscript>13</Superscript>C)-Glucose

The mitochondrial aspartate/glutamate transporter Aralar/AGC1/Slc25a12 is critically involved in brain aspartate synthesis, and AGC1 deficiency results in a drastic fall of brain aspartate levels in humans and mice. It has recently been described that the uncoupling protein UCP2 transports four carbon metabolites including aspartate. Since UCP2 is expressed in several brain cell types and AGC1 is mainly neuronal, we set to test whether UCP2 could be a mitochondrial aspartate carrier in the brain glial compartment. The study of the cerebral metabolism of (1–¹³C)-glucose in vivo in wild type and UCP2-knockout mice showed no differences in C3 or C2 labeling of aspartate, suggesting that UCP2 does not function as a mitochondrial aspartate carrier in brain. However, surprisingly, a clear decrease (of about 30–35?%) in the fractional enrichment of glutamate, glutamine and GABA was observed in the brains of UCP2-KO mice which was not associated with differences in either glucose or lactate enrichments. The results suggest that the dilution in the labeling of glutamate and its downstream metabolites could originate from the uptake of an unlabeled substrate that could not leave the matrix via UCP2 becoming trapped in the matrix. Understanding the nature of the unlabeled substrate and its precursor(s) as alternative substrates to glucose is of interest in the context of neurological diseases associated with UCP2.     

Selenium Status in Patients with Turner Syndrome: a Biochemical Assessment Related with Body Composition

Studies about selenium status in patients with Turner syndrome (TS) are non-existent in the literature. The aim of this study was to evaluate selenium status in patients with TS, while considering the different ages of the studied population and the relation with body composition. In total, 33 patients with TS were evaluated and grouped according to their developmental stages (children, adolescents, and adults). Selenium concentrations in their plasma, erythrocytes, urine, and nails were determined by using hydride generation atomic absorption spectrometry and erythrocyte glutathione peroxidase activity were measured by using Randox commercial kits. Additionally, height, weight, body fat percentage, waist circumference, and waist-height ratio were measured to characterize the patients. No differences in the selenium concentrations in the plasma, erythrocyte, urine, and nails or in the glutathione peroxidase activity were observed among the age groups (p > 0.05). The evaluated selenium levels were less than the established normal ones. The patients with larger waist circumference, body fat percentage, body mass index, and waist-height ratio showed lower glutathione peroxidase enzyme activity (p = 0.023). The present study shows that most patients with TS are deficient in selenium and that those with a greater accumulation of body fat have a lower GPx activity.     

Spectral attenuation of brain and retina tissues in the near‐infrared range measured using a fiber‐based supercontinuum device

A novel setup for the efficient constant optical measurements of biological tissues in the near infrared is presented. The system combines the use of a fiber‐based supercontinuum source with a simple optics fiber collimator. This configuration allows a wide spectral range of measurement and, at the same time, can efficiently filter the straightforward transmitted light while avoiding scattered light. As a performance example, the optical characterization of rat brain and retina tissues are shown. The attenuation coefficient for both tissues in the near infrared region is also obtained. This technique could be applied in clinical research as a noninvasive method with several potential practical applications.     

Differential expression of osteoblast and osteoclast chemmoatractants in compression and tension sides during orthodontic movement

Orthodontic tooth movement is achieved by the remodeling of alveolar bone in response to mechanical loading, and is supposed to be mediated by several host mediators, such as chemokines. In this study we investigated the pattern of mRNAs expression encoding for osteoblast and osteoclast related chemokines, and further correlated them with the profile of bone remodeling markers in palatal and buccal sides of tooth under orthodontic force, where tensile (T) and compressive (C) forces, respectively, predominate. Real-time PCR was performed with periodontal ligament mRNA from samples of T and C sides of human teeth submitted to rapid maxillary expansion, while periodontal ligament of normal teeth were used as controls. Results showed that both T and C sides exhibited significant higher expression of all targets when compared to controls. Comparing C and T sides, C side exhibited higher expression of MCP-1/CCL2, MIP-1α/CCL3 and RANKL, while T side presented higher expression of OCN. The expression of RANTES/CCL5 and SDF-1/CXCL12 was similar in C and T sides. Our data demonstrate a differential expression of chemokines in compressed and stretched PDL during orthodontic tooth movement, suggesting that chemokines pattern may contribute to the differential bone remodeling in response to orthodontic force through the establishment of distinct microenvironments in compression and tension sides.     

Effects of training exercises for the development of strength and endurance in soccer

A training program designed to increase strength and aerobic endurance in 1 season was tested on 16 professional soccer players from Spain with a mean age of 28 +/- 3.37 years. The schedule comprised 4 macrocycles of 12 weeks of aerobic endurance and strength training. As much for the strength training as for the aerobic endurance, the program used a sequence of general, special, and specific exercises. Assessments were made with routine tests (i.e., squat jumps [SJs], countermovement jumps [CMJs], and countermovement jumps with arm swing [CMJas]) at the end of each macrocycle, and the Probst test was used to assess aerobic endurance as a function of running speed and distance, at the start and end of the training schedule and at the start of the third macrocycle. Jumps were performed on an infrared platform fitted to the MuscleLab system. The Probst test showed differences between the first evaluation and the second and third evaluations: 3,550 +/- 411.59 m vs. 2,006 +/- 207.20 m (P < 0.01). For 2 of the 3 jumps analyzed, the results were better in the last 2 than in the first 2 evaluations (SJ, 43.13 +/- 3.77 vs. 39.47 +/- 3.4 [P < 0.05]; CMJ, 49.80 +/- 3.77 vs. 46.67 +/- 3.76 [P < 0.05]; CMJas, 56.24 +/- 5.2 vs. 52.98 +/- 4.54 [P > 0.05]). Improvement of aerobic endurance was produced on the first phase of the season as a consequence of the training. To increase strength, it is necessary to augment the number of training sessions of this type. It is convenient to separate aerobic endurance and strength training to create more ample blocks during the last 2 macrocycles.     

Presenilin-1 280Glu-->Ala mutation alters C-terminal APP processing yielding longer abeta peptides: implications for Alzheimer's disease

Presenilin (PS) mutations enhance the production of the Abeta42 peptide that is derived from the amyloid precursor protein (APP). The pathway(s) by which the Abeta42 species is preferentially produced has not been elucidated, nor is the mechanism by which PS mutations produce early-onset dementia established. Using a combination of histological, immunohistochemical, biochemical, and mass spectrometric methods, we examined the structural and morphological nature of the amyloid species produced in a patient expressing the PS1 280Glu-->Ala familial Alzheimer's disease mutation. Abundant diffuse plaques were observed that exhibited a staining pattern and morphology distinct from previously described PS cases, as well as discreet amyloid plaques within the white matter. In addition to finding increased amounts of CT99 and Abeta42 peptides, our investigation revealed the presence of a complex array of Abeta peptides substantially longer than 42/43 amino acid residue species. The increased hydrophobic nature of longer Abeta species retained within the membrane walls could impact the structure and function of plasma membrane and organelles. These C-terminally longer peptides may, through steric effects, dampen the rate of turnover by critical amyloid degrading enzymes such as neprilysin and insulin degrading enzyme. A complete understanding of the deleterious side effects of membrane bound Abeta as a consequence of gamma-secretase alterations is needed to understand Alzheimer's disease pathophysiology and will aid in the design of therapeutic interventions.     

Exon creation and establishment in human genes

Background

A large proportion of species-specific exons are alternatively spliced. In primates, Alu elements play a crucial role in the process of exon creation but many new exons have appeared through other mechanisms. Despite many recent studies, it is still unclear which are the splicing regulatory requirements for de novo exonization and how splicing regulation changes throughout an exon's lifespan.

Results

Using comparative genomics, we have defined sets of exons with different evolutionary ages. Younger exons have weaker splice-sites and lower absolute values for the relative abundance of putative splicing regulators between exonic and adjacent intronic regions, indicating a less consolidated splicing regulation. This relative abundance is shown to increase with exon age, leading to higher exon inclusion. We show that this local difference in the density of regulators might be of biological significance, as it outperforms other measures in real exon versus pseudo-exon classification. We apply this new measure to the specific case of the exonization of anti-sense Alu elements and show that they are characterized by a general lack of exonic splicing silencers.

Conclusions

Our results suggest that specific sequence environments are required for exonization and that these can change with time. We propose a model of exon creation and establishment in human genes, in which splicing decisions depend on the relative local abundance of regulatory motifs. Using this model, we provide further explanation as to why Alu elements serve as a major substrate for exon creation in primates. Finally, we discuss the benefits of integrating such information in gene prediction.     

Estrogen regulation of proteins in the rat ventromedial nucleus of the hypothalamus

The effects of estradiol (E2) on the expression of proteins in the pars lateralis of the ventromedial nucleus of the hypothalamus (VMNpl) in ovariectomized rats was studied using 2-dimensional gel electrophoresis followed by RPLC-nanoESI-MS/MS. E2 treatment resulted in the up-regulation of 29 identified proteins. Many of these proteins are implicated in the promotion of neuronal plasticity and signaling.