Effect of weight loss and exercise on angiogenic factors in the circulation and in adipose tissue in obese subjects

Background:

Vascular growth is a prerequisite for adipose tissue (AT) development and expansion. Some AT cytokines and hormones have effects on vascular development, like vascular endothelial growth factor (VEGF‐A), angiopoietin (ANG‐1), ANG‐2 and angiopoietin‐like protein‐4 (ANGPTL‐4).

Methods:

In this study, the independent and combined effects of diet‐induced weight loss and exercise on AT gene expression and proteins levels of those angiogenic factors were investigated. Seventy‐nine obese males and females were randomized to: 1. Exercise‐only (EXO; 12‐weeks exercise without diet‐restriction), 2. Hypocaloric diet (DIO; 8‐weeks very low energy diet (VLED) + 4‐weeks weight maintenance diet) and 3. Hypocaloric diet and exercise (DEX; 8‐weeks VLED + 4‐weeks weight maintenance diet combined with exercise throughout the 12 weeks). Blood samples and fat biopsies were taken before and after the intervention.

Results:

Weight loss was 3.5 kg in the EXO group and 12.3 kg in the DIO and DEX groups. VEGF‐A protein was non‐significantly reduced in the weight loss groups. ANG‐1 protein levels were significantly reduced 22‐25% after all three interventions (P < 0.01). The ANG‐1/ANG‐2 ratio was also decreased in all three groups (P < 0.05) by 27‐38%. ANGPTL‐4 was increased in the EXO group (15%, P < 0.05) and 9% (P < 0.05) in the DIO group. VEGF‐A, ANG‐1, and ANGPTL‐4 were all expressed in human AT, but only ANGPTL‐4 was influenced by the interventions.

Conclusions:

Our data show that serum VEGF‐A, ANG‐1, ANG‐2, and ANGPTL‐4 levels are influenced by weight changes, indicating the involvement of these factors in the obese state. Moreover, it was found that weight loss generally was associated with a reduced angiogenic activity in the circulation.     

Emotion recognition in children and adolescents with attention-deficit/hyperactivity disorder (ADHD)

Children with attention-deficit/hyperactivity disorder (ADHD) are impaired in social adaptation and display deficits in social competence. Deficient emotion recognition has been discussed to underlie these social problems. However, comorbid conduct problems have not been considered in the majority of studies conducted so far, and the influence of medication on emotion recognition has rarely been studied. Here, emotion recognition performance was assessed in children with ADHD without medication compared with children with ADHD under stimulant medication and a matched control group. In order to rule out confounding by externalizing symptoms, children with comorbid conduct problems were excluded. Video clips with neutral faces developing a basic emotion (happiness, sadness, disgust, fear and anger) were presented in order to assess emotion recognition. Results indicated between-group differences neither concerning the number of correctly identified emotions nor concerning reaction times and their standard deviations. Thus, we suggest that ADHD per se is not associated with deficits in emotion recognition.     

Characterization of Arsenate Uptake by Cultured Primary Rat Astrocytes

Arsenate is known to be accumulated by cultured astrocytes and to stimulate astrocytic glutathione export, but the arsenate uptake into astrocytes has not been characterized so far. To address this topic, we have exposed primary rat astrocyte cultures to arsenate and determined the cellular arsenic content by atomic absorption spectroscopy. Viable astrocytes accumulated arsenate in a time- and concentration-dependent manner. Their cellular arsenic content increased almost proportional with time for up to 60 min after application of arsenate. Analysis of the concentration-dependent increase in the specific arsenic content of the cells after 30 min of arsenate exposure revealed that cultured astrocytes take up arsenate with saturable kinetics by a transport process that has apparent K_M- and V_max-values of 1.7 ± 0.2 mM and 28 ± 4 nmol/(mg protein × 30 min), respectively. Arsenate uptake in viable astrocytes was strongly inhibited by the presence of phosphate or by lowering the incubation temperature to 4 °C and was completely abolished in a sodium ion-free medium. These results strongly suggest that the saturable temperature-dependent arsenate uptake into astrocytes is mediated by a sodium-dependent phosphate cotransporter.     

cAMP-dependent Protein Kinase and c-Jun N-terminal Kinase Mediate Stathmin Phosphorylation for the Maintenance of Interphase Microtubules during Osmotic Stress

Dynamic microtubule changes after a cell stress challenge are required for cell survival and adaptation. Stathmin (STMN), a cytoplasmic microtubule-destabilizing phosphoprotein, regulates interphase microtubules during cell stress, but the signaling mechanisms involved are poorly defined. In this study ectopic expression of single alanine-substituted phospho-resistant mutants demonstrated that STMN Ser-38 and Ser-63 phosphorylation were specifically required to maintain interphase microtubules during hyperosmotic stress. STMN was phosphorylated on Ser-38 and Ser-63 in response to hyperosmolarity, heat shock, and arsenite treatment but rapidly dephosphorylated after oxidative stress treatment. Two-dimensional PAGE and Phos-tag gel analysis of stress-stimulated STMN phospho-isoforms revealed rapid STMN Ser-38 phosphorylation followed by subsequent Ser-25 and Ser-63 phosphorylation. Previously, we delineated stress-stimulated JNK targeting of STMN. Here, we identified cAMP-dependent protein kinase (PKA) signaling as responsible for stress-induced STMN Ser-63 phosphorylation. Increased cAMP levels induced by cholera toxin triggered potent STMN Ser-63 phosphorylation. Osmotic stress stimulated an increase in PKA activity and elevated STMN Ser-63 and CREB (cAMP-response element-binding protein) Ser-133 phosphorylation that was substantially attenuated by pretreatment with H-89, a PKA inhibitor. Interestingly, PKA activity and subsequent phosphorylation of STMN were augmented in the absence of JNK activation, indicating JNK and PKA pathway cross-talk during stress regulation of STMN. Taken together our study indicates that JNK- and PKA-mediated STMN Ser-38 and Ser-63 phosphorylation are required to preserve interphase microtubules in response to hyperosmotic stress.     

Morphological delineation and distribution patterns of four newly described species within the Synura petersenii species complex (Chrysophyceae,Stramenopiles)

The Synura petersenii species complex represents a common, cosmopolitan and highly diverse taxon of autotrophic freshwater flagellates. In this paper, we describe and characterize four new species (S. borealis, S. heteropora, S. hibernica and S. laticarina) that have been identified during our extensive sampling of freshwater habitats in 15 European countries. Morphometric analyses of siliceous scales led to the significant phenotypic differentiation of all four newly described species, and their separation from other related species of the S. petersenii complex. Two of these newly described species (S. hibernica and S. borealis) can be clearly distinguished by characteristic large colonies consisting of elongated, lanceolate-shaped cells. Development of strongly elongated, narrow cells in S. hibernica could be explained by the adaptation of this species to oligotrophic conditions. Though morphologically distinct, S. borealis possesses an exceptionally high degree of genetic diversity, possibly indicating recent speciation and evolutionary diversification within this taxon. Three of the four newly described species exhibit restricted biogeographic distribution. The evolutionarily related S. borealis and S. laticarina occur only in Northern Europe, and seem to be adapted to colder areas. The most remarkable distribution pattern was observed for S. hibernica, which has a geographic distribution that is restricted to western Ireland.     

Accuracy of StepWatch? and ActiGraph Accelerometers for Measuring Steps Taken among Persons with Multiple Sclerosis

Introduction

There has been increased interest in the objective monitoring of free-living walking behavior using accelerometers in clinical research involving persons with multiple sclerosis (MS). The current investigation examined and compared the accuracy of the StepWatch activity monitor and ActiGraph model GT3X+ accelerometer for capturing steps taken during various speeds of prolonged, over-ground ambulation in persons with MS who had mild, moderate, and severe disability.

Methods

Sixty-three persons with MS underwent a neurological examination for generation of an EDSS score and undertook two trials of walking on the GAITRite electronic walkway. Participants were fitted with accelerometers, and undertook three modified six-minute walk (6MW) tests that were interspersed with 10–15 minutes of rest. The first 6MW was undertaken at a comfortable walking speed (CWS), and the two remaining 6MW tests were undertaken above (faster walking speed; FWS) or below (slower walking speed; SWS) the participant''s CWS. The actual number of steps taken was counted through direct observation using hand-tally counters.

Results

The StepWatch activity monitor (99.8%–99.9%) and ActiGraph model GT3X+ accelerometer (95.6%–97.4%) both demonstrated highly accurate measurement of steps taken under CWS and FWS conditions. The StepWatch had better accuracy (99.0%) than the ActiGraph (95.5%) in the overall sample under the SWS condition, and this was particularly apparent in those with severe disability (StepWatch: 95.7%; ActiGraph: 87.3%). The inaccuracy in measurement for the ActiGraph was associated with alterations of gait (e.g., slower gait velocity, shorter step length, wider base of support).

Conclusions

This research will help inform the choice of accelerometer to be adopted in clinical trials of MS wherein the monitoring of free-living walking behavior is of particular value.     

Lactate dehydrogenase (LDH) gene duplication during chordate evolution: the cDNA sequence of the LDH of the tunicate Styela plicata

L-Lactate dehydrogenase (L-LDH, E.C. 1.1.1.27) is encoded by two or three loci in all vertebrates examined, with the exception of lampreys, which have a single LDH locus. Biochemical characterizations of LDH proteins have suggested that a gene duplication early in vertebrate evolution gave rise to Ldh-A and Ldh-B and that an additional locus, Ldh-C arose in a number of lineages more recently. Although some phylogenetic studies of LDH protein sequences have supported this pattern of gene duplication, others have contradicted it. In particular, a number of studies have suggested that Ldh-C represents the earliest divergence among vertebrate LDHs and that it may have diverged from the other loci well before the origin of vertebrates. Such hypotheses make explicit statements about the relationship of vertebrate and invertebrate LDHs, but to date, no closely related invertebrate LDH sequences have been available for comparison. We have attempted to provide further data on the timing of gene duplications leading to multiple vertebrate LDHs by determining the cDNA sequence of the LDH of the tunicate Styela plicata. Phylogenetic analyses of this and other LDH sequences provide strong support for the duplications giving rise to multiple vertebrate LDHs having occurred after vertebrates diverged from tunicates. The timing of these LDH duplications is consistent with data from a number of other gene families suggesting widespread gene duplication near the origin of vertebrates. With respect to the relationships among vertebrate LDHs, our data are not consistent with previous claims that Ldh-C represented the earliest divergence. However, the precise relationships among some of the main lineages of vertebrate LDHs were not resolved in our analyses.