Up-regulation of the levels of expression and function of a constitutively active mutant of the hamster alpha1B-adrenoceptor by ligands that act as inverse agonists.

The alpha1-adrenergic agonist phenylephrine stimulated phospholipase D (PLD) activity in Rat 1 fibroblasts transfected to express either the wild-type hamster alpha1B-adrenoceptor or a constitutively active mutant (CAM) form of this receptor. The EC50 for agonist stimulation of PLD activity was substantially lower at the CAM receptor than at the wild-type receptor as previously noted for phenylephrine stimulation of phosphoinositidase C activity. Sustained treatment of cells expressing the CAM alpha1B-adrenoceptor with phentolamine resulted in a marked up-regulation in levels of this receptor with half-maximal effects produced within 24 h and with an EC50 of approx. 40 nM. Such an up-regulation could be produced with a range of other ligands generally viewed as alpha1-adrenoceptor antagonists but equivalent treatment of cells expressing the wild-type alpha1B-adrenoceptor was unable to mimic these effects. After sustained treatment of the CAM alpha1B-adrenoceptor expressing cells with phentolamine, basal PLD activity was increased and phenylephrine was now able to stimulate PLD activity to greater levels than in vehicle-treated CAM alpha1B-adrenoceptor-expressing cells. The EC50 for phenylephrine stimulation of PLD activity was not altered, however, by phentolamine pretreatment and the associated up-regulation of the receptor. After phentolamine-induced up-regulation of basal PLD activity, a range of alpha1-antagonists were shown to possess the characteristics of inverse agonists of the CAM alpha1B-adrenoceptor as they were able to substantially decrease the elevated basal PLD activity.

Impact of antiretroviral therapy (ART), immunosuppression and viraemia on lipid levels: the D:A:D study

Purpose of the study: To investigate the impact of ART, HIV viremia and immunosuppression on triglyceride (TG), total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) levels. Methods: We considered the cross-sectional associations between TG, TC and HDL-C (mmol/l; first available measurement on/after enrolment in the D:A:D study) and use of ART, HIV viral load (VL; copies/ml), and CD4 count (cells/mm3) measured at the same time. TG was log10 transformed to ensure normality. Analyses were performed using linear regression and adjusted for other factors known to impact lipid levels (table footnote). ART and VL status were combined (off ART&VL _100,000, off ART&VL B100,000, on ART&VL B500, on ART&VL _500), current and nadir CD4 count were categorised as B200, 200_349, 350_499 and _500. Summary of results: 44,322/49,734 participants in the D:A:D Study (89.1%) contributed a TG measurement (median; IQR 1.52; 1.00_ 2.45), 45,169 (90.8%) a TC measurement (4.80; 4.00_5.70) and 38,604 (77.6%) a HDL-C measurement (1.12; 0.90_1.40). Most participants were male (74%), of white ethnicity (51%), without AIDS (78%), were not receiving lipid-lowering drugs (4%) and were ART experienced (61%) with 47% previously exposed to PIs, 61% previously exposed to NRTIs and 29% previously exposed to NNRTIs. The median (IQR) age, current CD4 count and CD4 nadir were 38 (36_45) years, 400 (242_590) cells/ml and 240 (100_410) cells/ml respectively. Compared to those on ART with a suppressed VL, all lipids were lower for those off ART (Table); non-suppressive ART was also associated with lower TC and HDL-C levels (no impact on TG). A low current CD4 count was associated with lower lipid levels, whereas a low nadir CD4 count was associated with higher TC and TG levels. Prior AIDS diagnosis was associated with higher TG and TC, but lower HDL-C levels. Conclusion: Although specific drug classes were not considered, lipid levels are considerably higher in those on a suppressive ART regimen. The higher TC/TG and lower HDL-C levels seen among those with low nadir CD4 count and with a prior AIDS diagnosis suggests severe immunosuppression may be associated with dyslipidaemia over the long-term.

The persistence of abnormal returns at industry and firm levels

The present paper proposes a model for the persistence of abnormal returnsboth at firm and industry levels, when longitudinal data for the profitsof firms classiffied as industries are available. The model produces a two-way variance decomposition of abnormal returns: (a) at firm versus industrylevels, and (b) for permanent versus transitory components. This variancedecomposition supplies information on the relative importance of thefundamental components of abnormal returns that have been discussed in theliterature. The model is applied to a Spanish sample of firms, obtainingresults such as: (a) there are significant and permanent differences betweenprofit rates both at industry and firm levels; (b) variation of abnormal returnsat firm level is greater than at industry level; and (c) firm and industry levelsdo not differ significantly regarding rates of convergence of abnormal returns.

Evolution at Two Levels in Fire Ants: The Relationship between Patterns of Gene Expression and Protein Sequence Evolution.

Variation in protein sequence and gene expression each contribute to phenotypic diversity, and may be subject to similar selective pressures. Eusocial insects are particularly useful for investigating the evolutionary link between protein sequence and condition-dependent patterns of gene expression because gene expression plays a central role in determining differences between eusocial insect sexes and castes. We investigated the relationship between protein coding sequence evolution and gene expression patterns in the fire ants Solenopsis invicta, S. richteri, and their hybrids to gain greater insight into how selection jointly operates on gene expression and coding sequence. We found that genes with high expression variability within castes and sexes were frequently differentially expressed between castes and sexes, as well as between species and hybrids. These results indicate that genes showing high variation in expression in one context also tend to show high variation in expression in other contexts. Our analyses further revealed that variation in both intra- and interspecific gene expression was positively associated with rate of protein sequence evolution in Solenopsis. This suggests that selective constraints on a gene operate both at the level of protein sequence and at the level of gene expression regulation. Overall, our study provides one of the strongest demonstrations that selective constraints mediate both protein sequence evolution and gene expression variability across different biological contexts and timescales.

The rise and decline of children's labour participation levels during the early stages of industrialisation. Catalonia (1850-1925)

This article aims to analyse the reasons for the intensive use of childlabour in the 19th century and its subsequent decline in the first thirdof the 20th century in the context of an economy with a highly flexiblelabour supply like that of Catalonia. During the second half of the 19thcentury,factors relating to family economies, such as numerous familiesand low wages for adults, along with the technologies of the time thatrequired manual labour resources, would appear to explain the intensiveuse of child labour to the detriment of schooling. The technologicalchanges that occurred during the first third of the 20th century, thedemographic transition and adult wage increase (for both men and women)explain the schooling of children up to the age of 15 and theconsequent practical abolition of child labour in that new era ofeconomic modernisation.

Elevated endocannabinoid plasma levels are associated with coronary circulatory dysfunction in obesity.

AIMS: Aim of this study was to evaluate a possible association between endocannabinoid (EC) plasma levels, such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG), and coronary circulatory function in obesity. METHODS AND RESULTS: Myocardial blood flow (MBF) responses to cold pressor test (CPT) and during pharmacological vasodilation with dipyridamole were measured with (13)N-ammonia PET/CT. Study participants (n = 77) were divided into three groups based on their body mass index (BMI, kg/m(2)): control group 20 ≤ BMI <25 (n = 21); overweight group, 25 ≤ BMI <30 (n = 26); and obese group, BMI ≥ 30 (n = 30). Anandamide plasma levels, but not 2-AG plasma levels, were significantly elevated in obesity as compared with controls, respectively [0.68 (0.53, 0.78) vs. 0.56 (0.47, 0.66) ng/mL, P = 0.020, and 2.2 (1.21, 4.59) vs. 2.0 (0.80, 5.90) ng/mL, P = 0.806)]. The endothelium-related change in MBF during CPT from rest (ΔMBF) progressively declined in overweight and obese when compared with control group [0.21 (0.10, 0.27) and 0.09 (-0.01, 0.15) vs. 0.26 (0.23, 0.39) mL/g/min; P = 0.010 and P = 0.0001, respectively). Compared with controls, hyperaemic MBFs were significantly lower in overweight and obese individuals [2.39 (1.97, 2.62) vs. 1.98 (1.69, 2.26) and 2.10 (1.76, 2.36); P = 0.007 and P = 0.042, respectively)]. In obese individuals, AEA and 2-AG plasma levels were inversely correlated with ΔMBF to CPT (r = -0.37, P = 0.046 and r = -0.48, P = 0.008) and hyperaemic MBFs (r = -0.38, P = 0.052 and r = -0.45, P = 0.017), respectively. CONCLUSIONS: Increased EC plasma levels of AEA and 2-AG are associated with coronary circulatory dysfunction in obese individuals. This observation might suggest increases in EC plasma levels as a novel endogenous cardiovascular risk factor in obesity, but needing further investigations.

Adiponectin isoform distribution in serum and in follicular fluid of women undergoing treatment by ICSI.

Adiponectin is an adipokine, present in the circulation in comparatively high concentrations and different molecular weight isoforms. For the first time, the distribution of these isoforms in serum and follicular fluid (FF) and their usefulness as biological markers for infertility investigations was studied. In vitro study. University based hospital. Fifty-four women undergoing intracytoplasmic sperm injection (ICSI). Oocytes were retrieved, fertilized in vitro using ICSI, and the resulting embryos transferred. Serum was collected immediately prior to oocyte retrieval. Adiponectin isoforms (high molecular weight (HMW), medium and low molecular weight) were determined in serum and FF. Total adiponectin and the different isoform levels were compared with leptin and ovarian steroid concentrations. Adiponectin isoforms in serum and FF. Adiponectin isoform distribution differed between serum and FF; the HMW fraction made up half of all adiponectin in the serum but only 23.3% in the FF. Total and HMW adiponectin in both serum and FF correlated negatively with the body mass index and the concentration of leptin. No correlations were observed for total adiponectin or its isoforms with estradiol, progesterone, anti-Mullerian hormone, inhibin B, or the total follicle stimulating hormone (FSH) dose administered during the ovarian stimulation phase. This study shows for the first time that adiponectin isoform distribution varies between the serum and FF compartments in gonadotropin stimulated patients. A trend towards higher HMW adiponectin serum levels in successful ICSI cycles compared to implantation failures was observed; studies with larger patient groups are required to confirm this observation.

Sexual behaviour of men that consulted in medical outpatient clinics in Western Switzerland from 2005-2006: risk levels unknown to doctors?

BACKGROUND: To determine male outpatient attenders' sexual behaviours, expectations and experience of talking about their sexuality and sexual health needs with a doctor. METHODS: A survey was conducted among all male patients aged 18-70, recruited from the two main medical outpatient clinics in Lausanne, Switzerland, in 2005-2006. The anonymous self-administered questionnaire included questions on sexual behaviour, HIV/STI information needs, expectations and experiences regarding discussion of sexual matters with a doctor. RESULTS: The response rate was 53.0% (N = 1452). The mean age was 37.7 years. Overall, 13.4% of patients were defined as at STI risk--i.e. having not consistently used condoms with casual partners in the last 6 months, or with a paid partner during the last intercourse--regarding their sexual behaviour in the last year. 90.9% would have liked their physician to ask them questions concerning their sexual life; only 61.4% had ever had such a discussion. The multivariate analysis showed that patients at risk tended to have the following characteristics: recruited from the HIV testing clinic, lived alone, declared no religion, had a low level of education, felt uninformed about HIV/AIDS, were younger, had had concurrent sexual partners in the last 12 months. However they were not more likely to have discussed sexual matters with their doctor than patients not at risk. CONCLUSION: Recording the sexual history and advice on the prevention of the risks of STI should become routine practice for primary health care doctors.

Sudden weather deterioration but not brood size affects baseline corticosterone levels in nestling Alpine swifts.

While evidence is accumulating that stress-induced glucocorticoid responses help organisms to quickly adjust their physiology and behaviour to life-threatening environmental perturbations, the function and the ecological factors inducing variation in baseline glucocorticoid levels remain poorly understood. In this study we investigated the effects of brood size by experimentally manipulating the number of nestlings per brood and the effect of weather condition on baseline corticosterone levels of nestling Alpine swifts (Apus melba). We also examined the potential negative consequences of an elevation of baseline corticosterone on nestling immunity by correlating corticosterone levels with ectoparasite intensity and the antibody production towards a vaccine. Although nestlings reared in enlarged broods were in poorer condition than nestlings reared in reduced broods, they showed similar baseline corticosterone levels. In contrast, nestling baseline corticosterone levels were higher immediately after cold and rainy episodes with strong winds. Neither nestling infestation rate by ectoparastic flies nor nestling antibody production against a vaccine was correlated with baseline corticosterone levels. Thus, our results suggest that altricial Alpine swift nestlings can quickly modulate baseline corticosterone levels in response to unpredictable variations in meteorological perturbation but not to brood size which may be associated with the degree of sibling competition. Apparently, short-term elevations of baseline corticosterone have no negative effects on nestling immunocompetence.

Egg laying site selection by a host plant specialist leaf miner moth at two intra-plant levels in the northern Chilean Atacama Desert

Egg laying site selection by a host plant specialist leaf miner moth at two intra-plant levels in the northern Chilean Atacama Desert. The spatial distribution of the immature stages of the leaf miner Angelabella tecomae Vargas & Parra, 2005 was determined at two intra-plant levels (shoot and leaflet) on the shrub Tecoma fulva fulva (Cav.) D. Don (Bignoniaceae) in the Azapa valley, northern Chilean Atacama Desert. An aggregated spatial pattern was detected for all the immature stages along the shoot, with an age dependent relative position: eggs and first instar larvae were clumped at apex; second, third and fourth instar larvae were mostly found at intermediate positions; meanwhile the spinning larva and pupa were clumped at basis. This pattern suggests that the females select new, actively growing leaflets for egg laying. At the leaflet level, the immature stages were found more frequently at underside. Furthermore, survivorship was higher for larvae from underside mines. All these results highlight the importance of an accurate selection of egg laying site in the life history of this highly specialized leaf miner. By contrast, eventual wrong choices in the egg laying site selection may be associated with diminished larval survivorship. The importance of the continuous availability of new plant tissue in this highly human modified arid environment is discussed in relation with the observed patterns.

lntergenerational differences in overweight and obesity levels in Switzerland

Background/Introduction: There is little information regarding intergenerational trends in obesity levels in Switzerland. We aimed at assessing generational differences in obesity levels. Methods: Data from MONICA (1984-1986) and CoLaus-(2003-2006) surveys. Analyses were stratified by gender and age groups (35-44, 45-54, 55-64 and 65-74 years). Results: No changes were found for body mass index (BMI) between surveys (26.2±3.4 vs. 26.6±4.0 kg/m2 in men and 24.8±4.3 vs. 25.1±4.8 kg/m2 in women, for MONICA and CoLaus, respectively). ln men, the prevalence of overweight decreased from 48.6% to 46.0% and the prevalence of obesity increased slightly from 12.4% to 16.7% (p=NS). ln women, the prevalence of overweight decreased from 29.4% to 28.4% and the prevalence of obesity increased slightly from 12.9% to 14.5% (p=NS). After multivariate adjustment on age, education and smoking levels, the odds ratio (OR) and (95% confidence interval) of being obese in 2003-6 relative to 1984-6 was 1.36 (1.01-1.83) in men and 1.44 (1.07-1.93) in women, while no significant trend was found for overweight. After stratifying for age, no increase in BMI levels was found for bath genders. Obesity levels increased in participants aged 35-44 years (from 6.2% to 11.5% in men and from 4.9% to 10.0% in women, p<0.001) and 45-54 years (from 6.2% to 14.5% in men and 4.9% to 14.5% in women, p<0.001 ). After multivariate adjustment on age, education and smoking levels, the increase in obesity levels was signifiant in women aged 35-44, OR=2.10 (1.02-4.30), while a similar, albeit nonsignificant trend was obser11ed in men: 1.85 (0.97-3.51 ). Conclusion: BMI levels appear to have levelled off in Switzerland, but the prevalence of obesity is still on the rise. The increase in obesity levels among the youngest generations is of particular concern.