The multiple conformations of a cyclic disaccharide: DI-β-d-glucopyranose 1,6′:1′,6-dianhydride hexaacetate

The conformational behaviour of a cyclic disaccharide, di-β-d-glucopyranose 1,6′:1′,6-dianhydride hexaacetate, has been investigated. Because this molecule can exist only with the glucose rings in the unusual flexible forms, such conformational parameters as pseudorotation phase-angles have been used. Within a given number of approximations, the conformational space available for the whole system can be explored by considering only one two-dimensional map. Detailed investigations have shown that three stable conformations may be proposed. Among these, two correspond to minima found in the solid state. In one form, the six-membered rings adopt a boat conformation, whereas a skew conformation is found for the other form. However, these two conformations cannot be considered to be unique models of the conformation in solution; they both produce sets of proton-proton coupling-constants inconsistent with observed n.m.r.-spectroscopic results. At least the third form, having the six-membered rings in skew conformations, has to be taken into account. Deviations from coupling constants-molecular conformation relationships are thought to originate from ring strain.     

Alcohol Consumption in Midlife and Cognitive Performance Assessed 13 Years Later in the SU.VI.MAX 2 Cohort

Background

Associations between alcohol consumption and cognitive function are discordant and data focusing on midlife exposure are scarce.

Objective

To estimate the association between midlife alcohol consumption and cognitive performance assessed 13 y later while accounting for comorbidities and diet.

Methods

3,088 French middle-aged adults included in the SU.VI.MAX (1994) study with available neuropsychological evaluation 13 y later. Data on alcohol consumption were obtained from repeated 24h dietary records collected in 1994–1996. Cognitive performance was assessed in 2007–2009 via a battery of 6 neuropsychological tests. A composite score was built as the mean of the standardized individual test scores (mean = 50, SD = 10). ANCOVA were performed to estimate mean differences in cognitive performance and 95% confidence intervals (CI).

Results

In women, abstainers displayed lower cognitive scores than did low-to-moderate alcohol drinkers (1 to 2 drinks/day) (mean difference = −1.77; 95% CI: −3.29, −0.25). In men, heavy drinkers (>3 drinks/day) had higher cognitive scores than did low-to-moderate (1 to 3 drinks/day) (mean difference = 1.05; 95% CI: 0.10, 1.99). However, a lower composite cognitive score was detected in male drinkers consuming ≥90 g/d (≈8 drinks/d). A higher proportion of alcohol intake from beer was also associated with lower cognitive scores. These associations remained significant after adjustment for diet, comorbidities and sociodemographic factors.

Conclusion

In men, heavy but not extreme drinking was associated with higher global cognitive scores. Given the known harmful effects of alcohol even in low doses regarding risk of cancer, the study does not provide a basis for modifying current public health messages.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00272428","term_id":"NCT00272428"}}NCT00272428     

La forme scléronodulaire de la maladie de Hodgkin: expérience du CHU de Sherbrooke

Scleronodular type of Hodgkin''s disease: experience at the Centre hospitalier universitaire de SherbrookeThe nodular sclerosis type of Hodgkin''s disease appears to be a distinct clinical entity. However, the incidence, the initial localization of the tumour and the survival of the patients are variable. The present study was carried out on a group of 17 patients, all French Canadians living in the province of Quebec, from a total of 31 with Hodgkin''s disease, an incidence of 55%. There were more males (10) than females (7). The mean age of the group was 37 years, but that of the females was lower than that of the males. The mediastinum was involved at the onset in 47% of the patients. The initial staging (according to the classification of Rye) in 76% of the patients was I or II.Four patients showed disease below the diaphragm. The lungs were infiltrated three times, the spleen six times, and the liver five times. The duration of survival of the 17 patients was twice that of the patients with the three other types of the disease.     

Expedient syntheses of neoglycoproteins using phase transfer catalysis and reductive amination as key reactions

Starting from peracetylated chloro- or bromo-glycosyl donors ofN-acetylneurmainic acid,N-acetylglucosamine, glucose and lactose, the correspondingp-formylphenyl glycosides were synthesized stereospecifically under phase transfer catalysed conditions at room temperature in yields of 38–67%. After Zemplén de-O-acetylation, the formyl groups were directly and chemoselectively coupled to the lysine residues of bovine serum albumin by reductive amination using sodium cyanoborohydride. The conjugation reactions were followed as a function of time and under a series of different molar ratios of the reactants to provide glycoconjugates of varying degree of antigenicities. Thus, carbohydrate protein conjugates were made readily available using essentially two key reactions.Presented in part at the 15th International Carbohydrate Symposium, Yokohama, Japan, August 12–17, 1990.     

Extracellular Events Induced by γ-Hydroxybutyrate in Striatum: A Microdialysis Study

The modification of dopamine release and accumulation induced by gamma-hydroxybutyrate (GHB) was studied using both striatal slices and in vivo microdialysis of caudate-putamen. GHB inhibited dopamine release for approximately 5-10 min in vitro, and this was associated with an accumulation of dopamine in the tissue. Subsequently, there was an increase in dopamine release. In the microdialysis experiments, low doses of GHB inhibited dopamine release, whereas higher doses strongly increased release; the initial decrease seen in slices could not be detected in vivo. Thus, GHB had a biphasic effect on the release of dopamine: An initial decrease in the release of transmitter was followed by an increase. A time-dependent biphasic effect was observed when GHB was added to brain slices, and a dose-dependent biphasic effect was seen in dialysate after systemic administration of GHB. Naloxone blocked GHB-induced dopamine accumulation and release both in vitro and in vivo. GHB also increased the release of opioid-like substances in the striatum. A specific antagonist of GHB receptors completely blocked both the dopamine response and the release of opioid-like substances. These data suggest that GHB increases dopamine release via specific receptors that may modulate the activity of opioid interneurons.     

Individual and Contextual Variation in Thomas Langur Male Loud Calls

Individual and contextual differences in male loud calls of wild Thomas langurs (Presbytis thomasi) were studied in northern Sumatra, Indonesia. Loud calls were given in the following contexts: morning calls, vocal responses to other groups, between‐group encounter calls and alarm calls. Loud call spectrograms were analysed for a large number of variables. With discriminant analyses, 14 variables were found to be important in distinguishing individuals and contexts. Loud calls were assigned to the correct individual in 95.6% of the cases (91.8% with ‘leave‐one‐out’ validation) and to the correct context in 52.2% of the cases (39.0% with ‘leave‐one‐out’ validation). Further analyses with two‐way anova s showed significant differences in both temporal and frequency variables between individuals and contexts. Loud calls seemed to differ between the contexts in functionally meaningful ways, relating to the distance of the intended receivers and to the urgency of the message. Observation showed that females in the caller's group collected infants more often in the between‐group encounter context and in the alarm call context than in the vocal exchange context. These differential responses suggest that the monkeys also perceive the measurable differences in loud call characteristics between the various contexts.     

Chemical synthesis of a 7 kDa insect gonadotropic neurohormone

An original insect neurohormone of 65 residues was synthesized by the solid-phase methodology using t-Boc strategy and Boc-Val-PAM–resin. The purification, conducted by several steps of liquid chromatography having mass, polarity or charge as separative criteria, yielded the product with the correct molecular weight of 6922 Da determined by mass spectrometry. The synthetic peptide had both the same affinity for the antinative neurohormone serum and the same biological activity as the native neurohormone.     

The Matricellular Protein Periostin Is Required for Sost Inhibition and the Anabolic Response to Mechanical Loading and Physical Activity

Periostin (gene Postn) is a secreted extracellular matrix protein involved in cell recruitment and adhesion and plays an important role in odontogenesis. In bone, periostin is preferentially expressed in the periosteum, but its functional significance remains unclear. We investigated Postn^−/− mice and their wild type littermates to elucidate the role of periostin in the skeletal response to moderate physical activity and direct axial compression of the tibia. Furthermore, we administered a sclerostin-blocking antibody to these mice in order to demonstrate the influence of sustained Sost expression in their altered bone phenotypes. Cancellous and cortical bone microarchitecture as well as bending strength were altered in Postn^−/− compared with Postn^+/+ mice. Exercise and axial compression both significantly increased bone mineral density and trabecular and cortical microarchitecture as well as biomechanical properties of the long bones in Postn^+/+ mice by increasing the bone formation activity, particularly at the periosteum. These changes correlated with an increase of periostin expression and a consecutive decrease of Sost in the stimulated bones. In contrast, mechanical stimuli had no effect on the skeletal properties of Postn^−/− mice, where base-line expression of Sost levels were higher than Postn^+/+ and remained unchanged following axial compression. In turn, the concomitant injection of sclerostin-blocking antibody rescued the bone biomechanical response in Postn^−/− mice. Taken together, these results indicate that the matricellular periostin protein is required for Sost inhibition and thereby plays an important role in the determination of bone mass and microstructural in response to loading.