Inhibition of gastric secretion by a water extract from Baccharis triptera, Mart

Baccharus triptera Mart, is a widespread Compositae used in Brazilian folk medicine to treat gastrointestinal disturbances, rheumatic disease, mild fever, diabetes and as an anti-helminthic. Water extract of small branches of the plant (WE) administered to mice and rats (0.1 to 2 g/Kg, p.o) did not alter spontaneous motor activity, sleeping time induced by barbiturates or the tailflick response in mice. The extract decreased by 40 por cento the number of writhings induced by 0.8 por cento scetic acid, i.p., but did not influence paw edema induced by carrageenan or dextran in rats WE (2g/Kg, p.o.) decreased the intestinal transit of charcoal in mice by 20//. Gastric secretion in pylorus ligated rats was reduced after treatment with WE (1 and 2 g/Kg. i.p. or intraduodenal and the gastric pH was raised. The extract (1 g/Kg, p.o.) prevented gastric ulcers induced in rats by immobilization at 4ºC, but not those induced by indomethacin (10 mg/Kg, s.c.). The results indicate that WE may relieve gastrointestinal disorders by reducing acid secretion and gastrointestinal hiperactivity. Neither analgesic nor anti-inflammatory activities were detectable.

A higher mutational burden in females supports a "female protective model" in neurodevelopmental disorders.

Increased male prevalence has been repeatedly reported in several neurodevelopmental disorders (NDs), leading to the concept of a "female protective model." We investigated the molecular basis of this sex-based difference in liability and demonstrated an excess of deleterious autosomal copy-number variants (CNVs) in females compared to males (odds ratio [OR] = 1.46, p = 8 × 10(-10)) in a cohort of 15,585 probands ascertained for NDs. In an independent autism spectrum disorder (ASD) cohort of 762 families, we found a 3-fold increase in deleterious autosomal CNVs (p = 7 × 10(-4)) and an excess of private deleterious single-nucleotide variants (SNVs) in female compared to male probands (OR = 1.34, p = 0.03). We also showed that the deleteriousness of autosomal SNVs was significantly higher in female probands (p = 0.0006). A similar bias was observed in parents of probands ascertained for NDs. Deleterious CNVs (>400 kb) were maternally inherited more often (up to 64%, p = 10(-15)) than small CNVs < 400 kb (OR = 1.45, p = 0.0003). In the ASD cohort, increased maternal transmission was also observed for deleterious CNVs and SNVs. Although ASD females showed higher mutational burden and lower cognition, the excess mutational burden remained, even after adjustment for those cognitive differences. These results strongly suggest that females have an increased etiological burden unlinked to rare deleterious variants on the X chromosome. Carefully phenotyped and genotyped cohorts will be required for identifying the symptoms, which show gender-specific liability to mutational burden.

Aging and motor programming: differential effects according to the selection of action

There are controversial reports about the effect of aging on movement preparation, and it is unclear to which extent cognitive and/or motor related cerebral processes may be affected. This study examines the age effects on electro-cortical oscillatory patterns during various motor programming tasks, in order to assess potential differences according to the mode of action selection. Twenty elderly (EP, 60-84 years) and 20 young (YP, 20-29 years) participants with normal cognition underwent 3 pre-cued response tasks (S1-S2 paradigm). S1 carried either complete information on response side (Full; stimulus-driven motor preparation), no information (None; general motor alertness), or required free response side selection (Free; internally-driven motor preparation). Electroencephalogram (EEG) was recorded using 64 surface electrodes. Alpha (8-12 Hz) desynchronization (ERD)/synchronization (ERS) and motor-related amplitude asymmetries (MRAA) were analyzed during the S1-S2 interval. Reaction times (RTs) to S2 were slower in EP than YP, and in None than in the other 2 tasks. There was an Age x Task interaction due to increased RTs in Free compared to Full in EP only. Central bilateral and midline activation (alpha ERD) was smaller in EP than YP in None. In Full just before S2, readiness to move was reflected by posterior midline inhibition (alpha ERS) in both groups. In Free, such inhibition was present only in YP. Moreover, MRAA showed motor activity lateralization in both groups in Full, but only in YP in Free. The results indicate reduced recruitment of motor regions for motor alertness in the elderly. They further show less efficient cerebral processes subtending free selection of movement in elders, suggesting reduced capacity for internally-driven action with age.

Are glutamate and lactate increases ubiquitous to physiological activation? A (1)H functional MR spectroscopy study during motor activation in human brain at 7Tesla.

Recent studies at high field (7Tesla) have reported small metabolite changes, in particular lactate and glutamate (below 0.3μmol/g) during visual stimulation. These studies have been limited to the visual cortex because of its high energy metabolism and good magnetic resonance spectroscopy (MRS) sensitivity using surface coil. The aim of this study was to extend functional MRS (fMRS) to investigate for the first time the metabolite changes during motor activation at 7T. Small but sustained increases in lactate (0.17μmol/g±0.05μmol/g, p<0.001) and glutamate (0.17μmol/g±0.09μmol/g, p<0.005) were detected during motor activation followed by a return to the baseline after the end of activation. The present study demonstrates that increases in lactate and glutamate during motor stimulation are small, but similar to those observed during visual stimulation. From the observed glutamate and lactate increase, we inferred that these metabolite changes may be a general manifestation of the increased neuronal activity. In addition, we propose that the measured metabolite concentration increases imply an increase in ΔCMRO2 that is transiently below that of ΔCMRGlc during the first 1 to 2min of the stimulation.

Sleep structure and cardiometabolic disorders in the general population : the Hypnolaus study

Objectives: Previous studies using subjective assessments have reported associations between sleep quantity and quality and cardiometabolic disorders, but little is known regarding the associ-ations with objective sleep characteristics. The purpose of this study was to evaluate the association between objective sleep measure sand metabolic syndrome (MS), hypertension, diabetes and obesity. Methods: 2162 subjects (51.2% women, mean age 58,11.1) from the general population were evaluated for hypertension,diabetes, overweight/obesity and MS, and underwent a full polysom-nography (PSG). PSG measured variables included: Total sleep time(TST), percentage and time spent in slow wave sleep (SWS) and in rapid eye movement (REM) sleep, sleep efficiency and arousal index(ArI) Results: In univariate analyses, MS was associated with decreased TST, SWS, REM sleep, sleep efficiency and increased ArI. After adjustment for age, gender, smoking, alcohol, physical activity, drugsthat affect sleep and depression, the ArI remained significantly higher, but the difference disappeared in subjects without significant sleep disordered breathing (SDB). Differences in sleep structure were also found according to the presence or absence of hypertension, diabetes and overweight/obesity in univariate analysis. However, these differences were attenuated after multivariate adjustment and after excluding subjects with significant SDB. Conclusions: In this population-based sample we found significant associations between sleep structure and MS, hypertension, diabetes and obesity. However, these associations were cancelled after multivariate adjustment. We conclude that normal variations in sleep contribute little if any to MS and associated disorders.

Regulation of the akt signalling in human skeletal muscle atrophy

Abstract : The term "muscle disuse" is often used to refer collectively to reductions in neuromuscular activity as observed with sedentary lifestyles, reduced weight bearing, cancer, chronic obstructive pulmonary disease, chronic heart failure, spinal cord injury, sarcopenia or exposure to microgravity (spaceflight). Muscle disuse atrophy, caused by accelerated proteolysis, is predominantly due to the activation of the ATP-dependent ubiquitin (Ub) proteasome pathway. The current advances in understanding the molecular factors contributing to the Ub-dependent proteolysis process have been made mostly in rodent models of human disease and denervation with few investigations performed directly in humans. Recently, in mice, the genes Atrogin-1 and MuRF1 have been designated as primary candidates in the control of muscle atrophy. Additionally, the decreased activity of the Akt/GSK-3ß and Akt/mTOR pathways has been associated with a reduction in protein synthesis and contributing to skeletal muscle atrophy. Therefore, it is now commonly accepted that skeletal muscle atrophy is the result of a decreased protein synthesis concomitant with an increase in protein degradation (Glass 2003). Atrogin-1 and MuRF1 are genes expressed exclusively in muscle. In mice, their expression has been shown to be directly correlated with the severity of atrophy. KO-mice experiments showed a major protection against atrophy when either of these genes were deleted. Skeletal muscle hypertrophy is an important function in normal postnatal development and in the adaptive response to exercise. It has been shown, in vitro, that the activation of phosphatidylinositol 3-kinase (PI-3K), by insulin growth factor 1 (IGF-1), stimulates myotubes hypertrophy by activating the downstream pathways, Akt/GSK-3ß and Akt/mTOR. It has also been demonstrated in mice, in vivo, that activation of these signalling pathways causes muscle hypertrophy. Moreover, the latter were recently proposed to also reduce muscle atrophy by inhibiting the FKHR mediated transcription of several muscle atrophy genes; Atrogin-1 and MuRF1. Therefore, these targets present new avenues for developing further the understanding of the molecular mechanisms involved in both skeletal muscle atrophy and hypertrophy. The present study proposed to investigate the regulation of the Akt/GSK-3ß and Akt/mTOR signalling pathways, as well as the expression levels of the "atrogenes", Atrogin-1 and MuRF1, in four human models of skeletal muscle atrophy. In the first study, we measured the regulation of the Akt signalling pathway after 8 weeks of both hypertrophy stimulating resistance training and atrophy stimulation de-training. As expected following resistance training, muscle hypertrophy and an increase in the phosphorylation status of the different members of the Akt pathway was observed. This was paralleled by a concomitant decrease in FOXO1 nuclear protein content. Surprisingly, exercise training also induced an increase in the, expression of the atrophy genes and proteins involved in the ATP-dependant ubiquitin-proteasome system. On the opposite, following the de-training period a muscle atrophy, relative to the post-training muscle size, was measured. At the same time, the phosphorylation levels of Akt and GSK-3ß were reduced while the amount of FOXO1 in the nucleus increased. After the atrophy phase, there was also a reduction in Atrogin-1 and MuRF1 contents. In this study, we demonstrate for the first time in healthy human skeletal muscle, that the regulation of Akt and its downstream targets GSK-3ß, mTOR and FOXO1 are associated with both thé skeletal muscle hypertrophy and atrophy processes. Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the loss of both upper and lower motor neurons, which leads to severe muscle weakness and atrophy. All measurements were performed in biopsies from 22 ALS patients and 16 healthy controls. ALS patients displayed an increase in Atrogin-1 mRNA and protein content which was associated with a decrease in Akt activity. However there was no difference in the mRNA and phospho-protein content of FOXO1, FOXO3a, p70S6K and GSK-3ß. The transcriptional regulation of human Atrogin-1 may be controlled by an Akt-mediated transcription factor other than FKHR or via an other signalling pathway. Chronic complete spinal cord injury (SCI) is associated with severe muscle atrophy which is linked to co-morbidity factors such as diabetes, obesity, lipid disorders and cardiovascular diseases. Molecular mechanisms associated with chronic complete SCI-related muscle atrophy are not well understood. The aim of the present study was to determine if there was an increase in catabolic signalling targets such as Atrogin-1, MuRF1, FOXO and myostatin, and decreases in anabolic signalling targets such as IGF, Akt, GSK-3ß, mTOR, 4E-BP1 and p-70S6K in chronic complete SCI patients. All measurements were performed in biopsies taken from 8 complete chronic SCI patients and 7 age matched healthy controls. In SCI patients when compared with controls, there was a significant reduction in mRNA levels of Atrogin1, MuRF1 and Myostatin. Protein levels for Atrogin-1, FOX01 and FOX03a were also reduced. IGF-1 and both phosphorylated GSK-3ß and 4E-BP1 were decreased; the latter two in an Akt and mTOR independent manner, respectively. Reductions in Atrogin-1, MuRF1, FOXO and myostatin suggest the existence of an internal mechanism aimed at reducing further loss of muscle proteins during chronic SCI. The downregulation of signalling proteins regulating anabolism such as IGF, GSK3ß and 4E-BP1 would reduce the ability to increase protein synthesis rates in this chronic state of muscle wasting. The molecular mechanisms controlling age-related skeletal muscle loss in humans are poorly understood. The present study aimed to investigate the regulation of several genes and proteins involved in the activation of key signalling pathways promoting muscle hypertrophy such as GH/STAT5/IGF, IGF/Akt/GSK-3ß/4E-BP1 and muscle atrophy such as TNFα/SOCS3 and Akt/FOXO/Atrogin-1 or MuRF1 in muscle biopsies from 13 young and 16 elderly men. In the older, as compared with the young subjects, TNFα and SOCS-3 were increased while growth hormone receptor protein (GHR) and IGF-1 mRNA were both decreased. Akt protein levels were increased however no change in phosphorylated Akt content was observed. GSK-3ß phosphorylation levels were increased while 4E-BP1 was not changed. Nuclear FKHR and FKHRL1 protein levels were decreased, with no changes in their atrophy target genes, Atrogin-1 and MuRF1. Myostatin mRNA and protein levels were significantly elevated. Human sarcopenia may be linked to a reduction in the activity or sensitivity of anabolic signalling proteins such as GHR, IGF and Akt. TNFα, SOCS-3 and myostatin are potential candidates influencing this anabolic perturbation. In conclusion our results support those obtained in rodent or ín vitro models, and demonstrate Akt plays a pivotal role in the control of muscle mass in humans. However, the Akt phosphorylation status was dependant upon the model of muscle atrophy as Akt phosphorylation was reduced in all atrophy models except for SCI. Additionally, the activity pattern of the downstream targets of Akt appears to be different upon the various human models. It seems that under particular conditions such as spinal cord injury or sarcopenia, .the regulation of GSK-3ß, 4eBP1 and p70S6K might be independent of Akt suggesting alternative signalling pathways in the control of these the anabolic response in human skeletal muscle. The regulation of Atrogin-1 and MuRF1 in some of our studies has been shown to be also independent of the well-described Akt/FOXO signalling pathway suggesting that other transcription factors may regulate human Atrogin-1 and MuRF1. These four different models of skeletal muscle atrophy and hypertrophy have brought a better understanding concerning the molecular mechanisms controlling skeletal muscle mass in humans.

Effects of unilateral motor cortex lesion on ipsilesional hand's reach and grasp performance in monkeys: relationship with recovery in the contralesional hand.

Manual dexterity, a prerogative of primates, is under the control of the corticospinal (CS) tract. Because 90-95% of CS axons decussate, it is assumed that this control is exerted essentially on the contralateral hand. Consistently, unilateral lesion of the hand representation in the motor cortex is followed by a complete loss of dexterity of the contralesional hand. During the months following lesion, spontaneous recovery of manual dexterity takes place to a highly variable extent across subjects, although largely incomplete. In the present study, we tested the hypothesis that after a significant postlesion period, manual performance in the ipsilesional hand is correlated with the extent of functional recovery in the contralesional hand. To this aim, ten adult macaque monkeys were subjected to permanent unilateral motor cortex lesion. Monkeys' manual performance was assessed for each hand during several months postlesion, using our standard behavioral test (modified Brinkman board task) that provides a quantitative measure of reach and grasp ability. The ipsilesional hand's performance was found to be significantly enhanced over the long term (100-300 days postlesion) in six of ten monkeys, with the six exhibiting the best, though incomplete, recovery of the contralesional hand. There was a statistically significant correlation (r = 0.932; P < 0.001) between performance in the ipsilesional hand after significant postlesion period and the extent of recovery of the contralesional hand. This observation is interpreted in terms of different possible mechanisms of recovery, dependent on the recruitment of motor areas in the lesioned and/or intact hemispheres.

Inter-informant agreement and prevalence estimates for substance use disorders: direct interview versus family history method.

OBJECTIVES: Family studies typically use multiple sources of information on each individual including direct interviews and family history information. The aims of the present study were to: (1) assess agreement for diagnoses of specific substance use disorders between direct interviews and the family history method; (2) compare prevalence estimates according to the two methods; (3) test strategies to approximate prevalence estimates according to family history reports to those based on direct interviews; (4) determine covariates of inter-informant agreement; and (5) identify covariates that affect the likelihood of reporting disorders by informants. METHODS: Analyses were based on family study data which included 1621 distinct informant (first-degree relatives and spouses) - index subject pairs. RESULTS: Our main findings were: (1) inter-informant agreement was fair to good for all substance disorders, except for alcohol abuse; (2) the family history method underestimated the prevalence of drug but not alcohol use disorders; (3) lowering diagnostic thresholds for drug disorders and combining multiple family histories increased the accuracy of prevalence estimates for these disorders according to the family history method; (4) female sex of index subjects was associated with higher agreement for nearly all disorders; and (5) informants who themselves had a history of the same substance use disorder were more likely to report this disorder in their relatives, which entails the risk of overestimation of the size of familial aggregation. CONCLUSION: Our findings have important implications for the best-estimate procedure applied in family studies.

A measure of the intensity of response to alcohol to screen for alcohol use disorders in primary care.

Alcohol-dependent subjects tend to report lower level of response to alcohol (LR) in the years before the disorder developed, compared to control subjects. The Self-Rating of the Effects of alcohol (SRE) score is a quick and valid retrospective estimate of LR. This study examined the associations between alcohol abuse or dependence and early experience of alcohol as measured on retrospective SRE score (relating to the first five times alcohol was imbibed), and the presence of alcohol abuse or dependence, in patients attending primary care. Higher Early SRE score (i.e. greater early tolerance of alcohol) was obtained in patients with an alcohol-related diagnosis than in patients without those diagnoses. Using a cut-off of 2 on the Early SRE score, the Early SRE score could discriminate between patients with and without an alcohol diagnosis with moderate to high sensitivity (84%) and modest specificity (57%).

Relationship of aerobic fitness and motor skills with memory and attention in preschoolers (Ballabeina): a cross-sectional and longitudinal study.

BACKGROUND: The debate about a possible relationship between aerobic fitness and motor skills with cognitive development in children has recently re-emerged, because of the decrease in children's aerobic fitness and the concomitant pressure of schools to enhance cognitive performance. As the literature in young children is scarce, we examined the cross-sectional and longitudinal relationship of aerobic fitness and motor skills with spatial working memory and attention in preschool children. METHODS: Data from 245 ethnically diverse preschool children (mean age: 5.2 (0.6) years, girls: 49.4%) analyzed at baseline and 9 months later. Assessments included aerobic fitness (20 m shuttle run) and motor skills with agility (obstacle course) and dynamic balance (balance beam). Cognitive parameters included spatial working memory (IDS) and attention (KHV-VK). All analyses were adjusted for age, sex, BMI, migration status, parental education, native language and linguistic region. Longitudinal analyses were additionally adjusted for the respective baseline value. RESULTS: In the cross-sectional analysis, aerobic fitness was associated with better attention (r=0.16, p=0.03). A shorter time in the agility test was independently associated with a better performance both in working memory (r=-0.17, p=0.01) and in attention (r=-0.20, p=0.01). In the longitudinal analyses, baseline aerobic fitness was independently related to improvements in attention (r=0.16, p=0.03), while baseline dynamic balance was associated with improvements in working memory (r=0.15, p=0.04). CONCLUSIONS: In young children, higher baseline aerobic fitness and motor skills were related to a better spatial working memory and/or attention at baseline, and to some extent also to their future improvements over the following 9 months. TRIAL REGISTRATION: clinicaltrials.gov NCT00674544.

FtsK Is a DNA motor protein that activates chromosome dimer resolution by switching the catalytic state of the XerC and XerD recombinases.

FtsK acts at the bacterial division septum to couple chromosome segregation with cell division. We demonstrate that a truncated FtsK derivative, FtsK(50C), uses ATP hydrolysis to translocate along duplex DNA as a multimer in vitro, consistent with FtsK having an in vivo role in pumping DNA through the closing division septum. FtsK(50C) also promotes a complete Xer recombination reaction between dif sites by switching the state of activity of the XerCD recombinases so that XerD makes the first pair of strand exchanges to form Holliday junctions that are then resolved by XerC. The reaction between directly repeated dif sites in circular DNA leads to the formation of uncatenated circles and is equivalent to the formation of chromosome monomers from dimers.

El turismo, motor fundamental de la economía de Cataluña (1951-2010)

Este trabajo presenta las dimensiones básicas de las actividades productivas asociadas al turismo receptor en Cataluña desde 1951 hasta 2010. Analiza sus características desde una perspectiva macroeconómica y con un enfoque comparativo. Demuestra que se ha ido transformando desde el modelo de sol y playa, que definió la fase de instalación del turismo de masas, hasta convertirse en un destino turístico muy diversificado, con un protagonismo creciente de la conurbación de Barcelona. Esta transformación ha facilitado una positiva adaptación a la segmentación de la demanda turística internacional. El turismo extranjero ha proporcionado a Cataluña el liderazgo español y europeo y se ha convertido en motor fundamental del crecimiento económico.

Externalizing disorders and substance use: empirically derived subtypes in a population-based sample of adults.

PURPOSE: Attention-deficit/hyperactivity disorder (ADHD), conduct disorder (CD), and oppositional defiant disorder (ODD) are common externalizing disorders of childhood. The common effects of these disorders on substance abuse need further investigation. The current study investigated the joint clusters of childhood/adolescence ADHD, CD, and ODD, and their influence on substance abuse/dependence in a population-based sample of adults. METHODS: The data were drawn from the PsyCoLaus study (n = 3,720) conducted in Lausanne, Switzerland. The population-based sample included 238 subjects meeting criteria for ADHD/ODD/CD diagnoses before the age of 15. Latent class analyses (LCA) were performed to derive comorbidity subtypes, which were subsequently characterized with respect to psychosocial correlates and substance use. RESULTS: The best fit in LCAs was achieved with three latent classes: an ADHD subtype (35.7 %); an externalizing multimorbid subtype (33.6 %) involving ODD, ADHD, and CD; and a third subtype with CD (30.7 %). The CD subtype showed the highest association with substance use. Apart from this, the externalizing multimorbid subtype was also significantly linked to substance use. The ADHD subtype had only elevated frequencies for alcohol dependence in comparison with subjects that had no history of ADHD, ODD, and CD during childhood or adolescence. Finally, important interactions between subtypes and sex were observed with regard to substance use. CONCLUSIONS: This study provides evidence showing that subtyping the externalizing disorders, ADHD, ODD and CD, along their comorbidity patterns leads to important differences regarding substance use. This could have implications for the etiology, prevention, and treatment of substance use disorders.