Time-Course In Vivo Trafficking Pattern and Effector Function of Donor-Specific Regulatory T Cells in Response to an Allograft.

Background: Experimental data have suggested that adoptive transfer of CD4+CD25+Foxp3+ regulatory T cells (Tregs), capable of controlling immune responses to specifi c auto- or alloantigens, could be used as a therapeutic strategy to promote specifi c tolerance in T-cell mediated diseases and in organ transplantation (Tx). However, before advocating the application of immunotherapy with Tregs in Tx, we need to improve our understanding of their in vivo homeostasis, traffi cking pattern and effector function in response to alloantigens. Methods : Donor-antigen specifi c murine Tregs were generated and characterized in vitro following our described protocols. Using an adoptive transfer and skin allotransplantation model, we have analyzed the in vivo expansion and homing of fl uorescent-labeled effector T cells (Teff) and Tregs, at different time-points after Tx, using fl ow-cytometry as well as fl uorescence microscopy techniques. Results: Tregs expressed CD62L, CCR7 and CD103 allowing their homing into lymphoid and non-lymphoid tissues (gut, skin) after intravenous injection. While hyporesponsive to TCR stimulation in vitro, transferred Tregs survived, migrated to secondary lymphoid organs and preferentially expanded within the allograft draining lymph nodes. Furthermore, Foxp3+ cells could be detected inside the allograft as early as day 3-5 after Tx. At a much later time-point (day 60 after Tx), graft-infi ltrating Foxp3+ cells were also detectable in tolerant recipients. When transferred alone, CD4+CD25- Teff cells expanded within secondary lymphoid organs and infi ltrated the allograft by day 3-5 after Tx. The co-transfer of Tregs limited the expansion of alloreactive Teff cells as well as their recruitment into the allograft. The promotion of graft survival observed in the presence of Tregs was in part mediated by the inhibition of the production of effector cytokines by CD4+CD25- T cells. Conclusion: Taken together, our results suggest that the suppression of allograft rejection and the induction of Tx tolerance are in part dependant on the alloantigendriven homing and expansion of Tregs. Thus, the appropriate localization of Tregs may be critical for their suppressive function in vivo.

Daily pattern of flight activity of Aedes albifasciatus in Central Argentina

Aedes albifasciatus is an important common mosquito in Central Argentina. Its a confirmed vector of the Western Equine Encephalitis and is responsible for loss of milk production in dairy cattle during peak populations. This paper reports the flight activity pattern of Ae. albifasciatus for different seasons, in the southern coast of the Mar Chiquita Lake (Central Argentina). Data were collected by sampling two sites between 1992 and 1993 with CDC traps and human-bait captures. Adult mosquito population density, estimated by CDC trapping and human-bait, were highly correlated. However, when compared to other species, the proportion of Ae. albifasciatus was higher in human-bait collections. Adult female populations were active only when temperature were higher than 6§C. Two daily biting peaks were observed (dusk and dawn) during the spring, summer and autumn, and only one peak during winter (around 15:00 pm). Adult abundance was significantly correlated (R²= 0.71; p<0.01) with temperature and illumination.

V3 peptide binding pattern and HIV-1 transmission route in Rio de Janeiro

To characterize antibody binding to a panel of V3 loop peptides representing diverse HIV-1 neutralization epitopes, 149 HIV-1 infected individuals from Rio de Janeiro (RJ) were investigated. Results were analyzed with respect to risk factors for infection and other epidemiological and clinical data. Peptide reactivity was not associated with sex, clinical status, CD4 counts, antigenemia or ß2-microglobulin serum level. A segregation of peptide reactivity according to route of infection was encountered. This finding suggests that more then one viral strain may be circulating in RJ, in subjects with different risk factors for HIV-1 infection. An investigation of prevalent HIV-1 genotypes, serotypes and immunotypes may be of importance for the design and selection of potential vaccines to be used in Brazil as well as for the selection of populations to be included in future vaccine efficacy trials.

Effect of diets high or low in unavailable and slowly digestible carbohydrates on the pattern of 24-h substrate oxidation and feelings of hunger in humans.

BACKGROUND: The pattern of substrate utilization with diets containing a high or a low proportion of unavailable and slowly digestible carbohydrates may constitute an important factor in the control, time course, and onset of hunger in humans. OBJECTIVE: We tested the hypothesis that isoenergetic diets differing only in their content of unavailable carbohydrates would result in different time courses of total, endogenous, and exogenous carbohydrate oxidation rates. DESIGN: Two diets with either a high (H diet) or a low (L diet) content of unavailable carbohydrates were fed to 14 healthy subjects studied during two 24-h periods in a metabolic chamber. Substrate utilization was assessed by whole-body indirect calorimetry. In a subgroup of 8 subjects, endogenous and exogenous carbohydrate oxidation were assessed by prelabeling the body glycogen stores with [(13)C]carbohydrate. Subjective feelings of hunger were estimated with use of visual analogue scales. RESULTS: Total energy expenditure and substrate oxidation did not differ significantly between the 2 diets. However, there was a significant effect of diet (P: = 0.03) on the carbohydrate oxidation pattern: the H diet elicited a lower and delayed rise of postprandial carbohydrate oxidation and was associated with lower hunger feelings than was the L diet. The differences in hunger scores between the 2 diets were significantly associated with the differences in the pattern of carbohydrate oxidation among diets (r = -0.67, P: = 0. 006). Exogenous and endogenous carbohydrate oxidation were not significantly influenced by diet. CONCLUSIONS: The pattern of carbohydrate utilization is involved in the modulation of hunger feelings. The greater suppression of hunger after the H diet than after the L diet may be helpful, at least over the short term, in individuals attempting to better control their food intake.

New trends in world wine consumption and its impact on the Spanish wineries during the second half of the twentieth century

The main goal of this research is explain the impact of the new trends of wine consumption, and the way these enterprises adapted to the circumstances. The hypothesis is that the Spanish companies had to start a deep and traumatic restructuring process, with the aim of surviving adequately in the changeable wine national and international markets. Heavy technological investments were made, with serious finance problems, during the eighties and nineties. We will see this from two specific cases, the Cooperatives "San Isidro" and "Rosario", located in the Region of Murcia, in the Spanish southeast.

Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption.

Alcohol consumption is a moderately heritable trait, but the genetic basis in humans is largely unknown, despite its clinical and societal importance. We report a genome-wide association study meta-analysis of ∼2.5 million directly genotyped or imputed SNPs with alcohol consumption (gram per day per kilogram body weight) among 12 population-based samples of European ancestry, comprising 26,316 individuals, with replication genotyping in an additional 21,185 individuals. SNP rs6943555 in autism susceptibility candidate 2 gene (AUTS2) was associated with alcohol consumption at genome-wide significance (P = 4 × 10(-8) to P = 4 × 10(-9)). We found a genotype-specific expression of AUTS2 in 96 human prefrontal cortex samples (P = 0.026) and significant (P < 0.017) differences in expression of AUTS2 in whole-brain extracts of mice selected for differences in voluntary alcohol consumption. Down-regulation of an AUTS2 homolog caused reduced alcohol sensitivity in Drosophila (P < 0.001). Our finding of a regulator of alcohol consumption adds knowledge to our understanding of genetic mechanisms influencing alcohol drinking behavior.

Consommation d'alcool à risque dans un collectif de patients de la Policlinique médicale universitaire de Lausanne [High risk alcohol consumption in a sample of patients of the Lausanne University Medical Polyclinic].

OBJECTIVES AND METHODS: This study indicates the prevalence, the characteristics, and the screening methods of patients with at risk alcohol drinking at the University Medical Clinic of Lausanne. RESULTS: The results reported demonstrate that one patient out of six is a drinker at risk without criteria for alcohol-dependance. The questionnaire AUDIT (Alcohol Use Disorders Identification Test) with a cut-off of five points seems to be the best screening test for at risk alcohol consumption. CONCLUSIONS: The high prevalence of at risk drinking in this study, combined with scientific evidence of the efficiency of brief interventions in changing drinking habits, emphasises the importance of alcohol screening for all patients attending outpatient medical settings.

Three Generation Family With Pattern Dystrophy and a Successful Treatment of Subfoveal Cnv Related to Pattern Dystrophy With Anti-vegf Intravitreal Injections

Purpose: To phenotype a large 3 generation Swiss family with pattern dystrophy and to report a successful result of treatment with ranibizumab of a subfoveal choroidal neovascularisation (CNV) associated with pattern dystrophy in 1 patient Patients and methods: 4 affected and 3 unaffected patients (3 female 4 male, age range: 19 - 80 years) were assessed with a complete ophthalmologic examination. AF images were taken using Heidelberg Retina Angiograph and the digital color photos, fluorescein angiogragraphy (FFA) using the same TOPCON 501 camera. Electroretinogram (full-field and multifocal) was performed in 1 affected patient. One 48 years old patient developed a subfoveal CNV, which was treated with 2 injections of ranibizumab, at 3 months interval. Blood sample was taken for molecular analysis (screening of the gene RDS). Results: Two patients had a typical fundoscopic appearance of pattern dystrophy with butterfly shaped deposit at the fovea and some peripheral flecks, as shown with AF imaging.. Two others affected patients had a more unusual appearance with some macular atrophy in one or both eyes, surrounded by flecks. The visual acuity ranged from 1.0 to 0.1 according to Snellen EDTRS chart. The patient with subfoveal CNV presented a drop of vision form 1.0 to 0.6 within 10 days prior to the diagnosis and also reported some metamorphopsia. FFA and optical computerized tomography (OCT) confirmed a classic CNV. After the 1st injection her vision improved to 1.0 but persistent metamorphopsia and fluid on OCT motivated a second injection. One month after the second injection the OCT was flat and the patient had no symptoms. The results of RDS screening will be presented at the meeting. Conclusion: We present a family with pattern dystrophy, with some members having an unusual fundus appearance, which was mistaken for an early onset dry AMD. The AF imaging is a useful tool in diagnosing this condition. A CNV associated with pattern dystrophy a rare. This is the first report of a successful treatment of the CNV with anti-VEGF intravitreal injections.

Inequality across countries in energy intensities: an analysis of the role of energy transformation and final energy consumption

This paper analyzes the role of the energy transformation index and of final energy consumption per GDP unit in the disparities in energy intensity across countries. In that vein, we use a Theil decomposition approach to analyze global primary energy intensity inequality as well as inequality across different regions of the world and inequality within these regions. The paper first demonstrates the pre-eminence of divergence in final energy consumption per GDP unit in explaining global primary energy intensity inequality and its evolution during the 1971-2006 period. Secondly, it shows the lower (albeit non negligible) impact of the transformation index in global primary energy inequality. Thirdly, the relevance of regions as unit of analysis in studying crosscountry energy intensity inequality and their explanatory factors is highlighted. And finally, how regions around the world differ as to the relevance of the energy transformation index in explaining primary energy intensity inequality.

Oxygen consumption in offspring tawny owls Strix aluco is associated with colour morph of foster mother

In several colour polymorphic species, morphs differ in thermoregulation either because dark and pale surfaces absorb solar radiation to a different extent and/or because morphs differ in key metabolic processes. Morph-specific thermoregulation may potentially account for the observation that differently coloured individuals are frequently not randomly distributed among habitats, and differ in many respects, including behaviour, morphology, survival and reproductive success. In a wild population of the colour polymorphic tawny owl Strix aluco, a recent cross-fostering experiment showed that offspring raised and born from red mothers were heavier than those from grey mothers. In the present study, we tested in the same individuals whether these morph-specific offspring growth patterns were associated with a difference in metabolic rate between offspring of red and grey mothers. For this purpose, we measured nestling oxygen consumption under two different temperatures (laboratory measurements: 4 and 20 degrees C), and examined the relationships between these data sets and the colour morph of foster and biological mothers. After controlling for nestling body mass, oxygen consumption at 20 degrees C was greater in foster offspring raised by grey foster mothers. No relationship was found between nestling oxygen consumption and coloration of their biological mother. Therefore, our study indicates that in our experiment offspring raised by grey foster mothers showed not only a lower body mass than offspring raised by red foster mothers, but also consumed more oxygen under warm temperature. This further indicates that rearing conditions in nests of grey mothers were more stressful than in nests of red mothers.

Mepraia spinolai in the Southeastern Pacific Ocean Coast (Chile) - First insular record and feeding pattern on the Pan de Azúcar Island

In a field collection performed at Pan de Azúcar Island in Northern Chile, 95 specimens representing all instars of Mepraia spinolai were collected. The intestinal contents of 55 specimens were examined for Trypanosoma cruzi infection and were found to be negative. This is the first record of an insular habitat for M. spinolai, where the insects had fed mainly on seabirds (78%), some on marine mammals (5%), and some on reptiles (7%).

Alcohol drinking and cardiovascular risk in a population with high mean alcohol consumption.

Moderate alcohol consumption has been associated with lower coronary artery disease (CAD) risk. However, data on the CAD risk associated with high alcohol consumption are conflicting. The aim of this study was to examine the impact of heavier drinking on 10-year CAD risk in a population with high mean alcohol consumption. In a population-based study of 5,769 adults (aged 35 to 75 years) without cardiovascular disease in Switzerland, 1-week alcohol consumption was categorized as 0, 1 to 6, 7 to 13, 14 to 20, 21 to 27, 28 to 34, and > or =35 drinks/week or as nondrinkers (0 drinks/week), moderate (1 to 13 drinks/week), high (14 to 34 drinks/week), and very high (> or =35 drinks/week). Blood pressure and lipids were measured, and 10-year CAD risk was calculated according to the Framingham risk score. Seventy-three percent (n = 4,214) of the participants consumed alcohol; 16% (n = 909) were high drinkers and 2% (n = 119) very high drinkers. In multivariate analysis, increasing alcohol consumption was associated with higher high-density lipoprotein cholesterol (from a mean +/- SE of 1.57 +/- 0.01 mmol/L in nondrinkers to 1.88 +/- 0.03 mmol/L in very high drinkers); triglycerides (1.17 +/- 1.01 to 1.32 +/- 1.05 mmol/L), and systolic and diastolic blood pressure (127.4 +/- 0.4 to 132.2 +/- 1.4 mm Hg and 78.7 +/- 0.3 to 81.7 +/- 0.9 mm Hg, respectively) (all p values for trend <0.001). Ten-year CAD risk increased from 4.31 +/- 0.10% to 4.90 +/- 0.37% (p = 0.03) with alcohol use, with a J-shaped relation. Increasing wine consumption was more related to high-density lipoprotein cholesterol levels, whereas beer and spirits were related to increased triglyceride levels. In conclusion, as measured by 10-year CAD risk, the protective effect of alcohol consumption disappears in very high drinkers, because the beneficial increase in high-density lipoprotein cholesterol is offset by the increases in blood pressure levels.