Measurements of urinary leptin and capillary leptin: alternative tools for the assessment of the leptin status?

OBJECTIVES: The aim of this study was to check whether leptin is reliably measurable in urine samples of children, adolescents, and adults and to examine whether capillary leptin measurements can be utilized as an alternative tool to assess the leptin status. METHODS: Two studies were performed. In both studies, leptin was quantified by an ultrasensitive and highly specific enzyme immunoassay (ELISA; R & D Systems). Anthropometric measures were taken from all study subjects, and body fat was calculated using skinfold thickness measurements. In study 1, leptin was analyzed in 24-hour urine samples of 155 healthy children and adolescents and 26 healthy adults after a methodological modification of the assay necessary for urine analysis. In study 2, venous and capillary blood samples were collected in 26 healthy adults within 10 min on the same day. RESULTS: After adapting the assay system to urine matrix, the detection range was 20-160 pg/ml. Only in 2 of 181 urine samples reproducibly measurable urinary leptin concentrations in the lowest detection range were found. In study 2, a close correlation was found between log capillary and log venous leptin concentrations (r = 0.98, p < 0.001) and between log capillary as well as log venous leptin levels and percent body fat (r = 0.86, p < 0.001). CONCLUSIONS: Our results based on one of the most specific and sensitive ELISAs currently available show that leptin is generally undetectable in the urine from healthy children, adolescents and adults. Thus, urinary leptin excretion cannot be used as a noninvasive marker of the leptin status. Our findings in healthy adults show that the merely moderately invasive determination of capillary leptin allows a reliable assessment of the individual leptin status and may be used instead of venous leptin as a biochemical indicator of body fatness.     

NK recognition of target structures: is the transferrin receptor the NK target structure?

That the transferrin receptor acts as a target antigen for human NK cells has previously been suggested. In this study we used two models to examine the hypothesis that the transferrin receptor is recognized by NK cells. In the first model, we employed mouse cloned NK cells in conjunction with the species-specific monoclonal antibody R17 217, which binds to the murine transferrin receptor. We show that there is no correlation between the amount of transferrin receptor expressed on targets and the susceptibility of these targets to NK lysis or NK binding in cold target competition assays. In the second model, we used human NK cells and transferrin receptor-positive transformants as targets. These transformants were derived from mouse L cells transfected with human DNA and selected for the presence of human transferrin receptor. Results show that, in contrast to the mouse system, there is a correlation between the expression of the human transferrin receptor on targets and the ability of these targets to competitively inhibit the lysis of K562 by NK cells. However, because inhibition is not complete, other cell surface antigens probably play a role in human NK-target interactions.     

NMR structure of the transmembrane domain of the n-acetylcholine receptor β2 subunit

Nicotinic acetylcholine receptors (nAChRs) are involved in fast synaptic transmission in the central and peripheral nervous system. Among the many different types of subunits in nAChRs, the β2 subunit often combines with the α4 subunit to form α4β2 pentameric channels, the most abundant subtype of nAChRs in the brain. Besides computational predictions, there is limited experimental data available on the structure of the β2 subunit. Using high-resolution NMR spectroscopy, we solved the structure of the entire transmembrane domain (TM1234) of the β2 subunit. We found that TM1234 formed a four-helix bundle in the absence of the extracellular and intracellular domains. The structure exhibited many similarities to those previously determined for the Torpedo nAChR and the bacterial ion channel GLIC. We also assessed the influence of the fourth transmembrane helix (TM4) on the rest of the domain. Although secondary structures and tertiary arrangements were similar, the addition of TM4 caused dramatic changes in TM3 dynamics and subtle changes in TM1 and TM2. Taken together, this study suggests that the structures of the transmembrane domains of these proteins are largely shaped by determinants inherent in their sequence, but their dynamics may be sensitive to modulation by tertiary and quaternary contacts.     

Effect of ConA—receptor interaction on the structure of cell membrane

Recently,the effect of ligand receptor interaction on the membrane structure of liposomes has been studied extensively,However,little is known about how it exists on biological membranes,In this paper,the effect of Concanavalin A(ConA) receptorinteratcion on the structure of cell membranes was studied by Circular DIchrosim(CD) and 31P Nuclear Magnetic Resonance(NMR).CD results of both the purified macrophage membranes and human erythrocyte hgosts(EG) showed that the conformation of membrane proteins changed after ConA binding.For further research,31P-NMR was used to detect the orgainzation of phosp[holipid molecules on macrophage membranes.After ConA binding,the tendercy to form non bilayer structure increased with the amount of ConA.The changes of 31P-NMR spectra of living macrophages might be partly due to the above stated reason too.In addition,ConA-receptor interaction also induced similar results of 31P-NMR spectra in EG.In contrast,wheat germ agglutinin (WGA),another kind of lectin,rarely showed the same influence.     

Loss of μ-crystallin causes PPARγ activation and obesity in high-fat diet-fed mice

The thyroid hormone-binding protein μ-crystallin (CRYM) mediates thyroid hormone action by sequestering triiodothyronine in the cytoplasm and regulating the intracellular concentration of thyroid hormone. As thyroid hormone action is closely associated with glycolipid metabolism, it has been proposed that CRYM may contribute to this process by reserving or releasing triiodothyronine in the cytoplasm. We aimed to clarify the relationship between CRYM and glycolipid metabolism by comparing wild-type and CRYM knockout mice fed a high-fat diet. Each group was provided a high-fat diet for 10 weeks, and then their body weight and fasting blood glucose levels were measured. Although no difference in body weight was observed between the two groups with normal diet, the treatment with a high-fat diet was found to induce obesity in the knockout mice. The knockout group displayed increased dietary intake, white adipose tissue, fat cell hypertrophy, and hyperglycemia in the intraperitoneal glucose tolerance test. In CRYM knockout mice, liver fat deposits were more pronounced than in the control group. Enhanced levels of PPARγ, which is known to cause fatty liver, and ACC1, which is a target gene for thyroid hormone and is involved in the fat synthesis, were also detected in the livers of CRYM knockout mice. These observations suggest that CRYM deficiency leads to obesity and lipogenesis, possibly in part through increasing the food intake of mice fed a high-fat diet.     

Drug-Related Disorders and the Criminal and Clinical Background of the Prison Population of S?o Paulo State,Brazil

Objective

To analyze the association between drug (DAD) and alcohol (AAD) abuse and dependency and criminal and clinical background by gender of prisoners in São Paulo, Brazil.

Method

Cross-sectional study, random sample stratified by administrative district, from which prisons and prisoners were selected via random, multistage sampling. Psychiatric diagnoses were made with the CIDI 2.1. Lifetime prevalence and 95% CI were calculated and adjusted via analysis of complex samples. Multinomial logistic regression analysis was carried out with four categories of dependent variables: presence AAD; presence DAD; presence of another mental disorder; no mental disorders. For female alcohol and drug abuse and dependency (ADAD) were combined into a single category.

Results

The sample was composed by 1809 interviewed prisoners (1192 men and 617 women). Prevalence of DAD and AAD was 25.2% and 15.6%, respectively, among female prisoners, and 26.5% and 18.5% among males. Male prisoners with DAD were more likely to have a criminal record as an adolescent (OR 2.17), to be a repeat offender (OR 2.85), and to have committed a property crime (OR 2.18). Prisoners with AAD were repeat offenders (OR 2.18). Among female prisoners, ADAD was associated with repeat offenses (OR 3.39), a criminal record as an adolescent (OR 9.24), a clinical or infectious condition (OR 5.09), another health problem (OR 3.04), and violent crime (OR 2.5).

Conclusion

The study confirmed an association between drug-use disorders and the criminal and clinical background in the study population. Prisoners with such disorders were more likely to be repeat offenders and to have a criminal record as adolescents. Among female prisoners disorders were also associated with violent crime and health problems, while among males they were associated with property crime. These patterns in clinical and criminal backgrounds illustrate the need for social rehabilitation programs and specific medical treatment for prison populations.     

Does the impact of nutrients on the biological structure and function of brackish and freshwater lakes differ?

The effects of nutrients on the biological structure of brackish and freshwater lakes were compared. Quantitative analysis of late summer fish, zooplankton, mysid and macrophyte populations was undertaken in 20–36 shallow brackish lakes of various trophic states and the findings compared with a similar analysis of shallow freshwater lakes based on either sampling (fish) or existing data (zooplankton, mysids and macrophytes). Special emphasis was placed on differences in pelagic top-down control. Whereas the fish biomass (CPUE, multiple mesh-size gill nets) rose with increasing P-concentration in freshwater lakes, that of brackish lakes was markedly reduced at P-concentrations above ca. 0.4 mg P l^-1 and there was a concomitant shift to exclusive dominance by the small sticklebacks (Gasterosteus aculeatus and Pungitius pungitius); as a result, fish density remained relatively high. Mysids (Neomysis integer) were found at a salinity greater than 0.5 and increased substantially with increasing P-concentration, reaching levels as high as 13 ind. l^-1. This is in contrast to the carnivorous zooplankton of freshwater lakes, which are most abundant at intermediate P levels. The efficient algal controller, Daphnia was only found at a salinity below 2 and N. integer in lakes with a salinity above 0.5. Above 2 the filter-feeding zooplankton were usually dominated by the less efficient algal controllers Eurytemora and Acartia. In contrast to freshwater lakes, no shift to a clearwater state was found in eutrophic brackish lakes when submerged macrophytes became abundant. We conclude that predation pressure on zooplankton is higher and algal grazing capacity lower in brackish eutrophic-hypertrophic lakes than in comparable freshwater lakes, and that the differences in trophic structure of brackish and freshwater lakes have major implications for the measures available to reduce the recovery period following a reduction in nutrient loading. From the point of view of top-down control, the salinity threshold dividing freshwater and brackish lakes is much lower than the conventionally defined 5.     

Hormonal and neuroendocrine regulation of energy balance‐the role of leptin

A new dimension to the regulation of energy balance has come from the identification of the ob (obese) gene and its protein product, leptin. Leptin is produced primarily in white adipose tissue, but synthesis also occurs in brown fat and the placenta. Several physiological functions have been described for leptin‐the inhibition of food intake, the stimulation/maintenance of energy expenditure, as a signal of energy reserves to the reproductive system, and as a factor in haematopoiesis. The production of leptin by white fat is influenced by a number of factors, including insulin and glucocorticoids (which are stimulatory), and fasting, cold exposure and ß‐adrenoceptor agonists (which are inhibitory). A key role in the regulation of leptin production is envisaged for the sympathetic nervous system, operating through ß3‐adreno‐ceptors. The leptin receptor gene is expressed in a wide range of tissues, and several splice variants are evident. A long form variant (Ob‐Rb) with an intracellular signalling domain is found particularly in the hypothalamus. Leptin exerts its central effects through neuropeptide Y, and through the glucagon‐like peptide‐1 and melanocortin systems, but it may also interact with other neuroendocrine pathways. The role and function of the leptin system in agricultural animals has not been established, but it offers a potential new target for the manipulation of body fat.     

Synthesis and structure–activity relationship of non-peptidic antagonists of neuropilin-1 receptor

Neuropilins (NRPs) are VEGF-A₁₆₅ co-receptors over-expressed in tumor cells, and considered as targets in angiogenic-related pathologies. We previously identified compound 1, the first non-peptidic antagonist of the VEGF-A₁₆₅/NRP binding, which exhibits in vivo anti-angiogenic and anti-tumor activities. We report here the synthesis and biological evaluations of new antagonists structurally-related to compound 1. Among these molecules, 4a, 4c and 4d show cytotoxic effects on HUVEC and MDA-MB-31 cells, and antagonize VEGF-A₁₆₅/NRP-1 binding. This study confirmed our key structure–activity relationships hypothesis and paved the way to compound 1 ‘hit to lead’ optimization.     

What is the function of receptor and membrane endocytosis at the postsynaptic neuron?

This paper explores the implications of certain new developments in cell biology upon neuroscience. Until recently it was thought that neurotransmitters and neuromodulators had only one function, which was to stimulate their specific receptors at the cell surface. From here on, all activity was supposed to be effected by postsynaptic cascades. The discovery that membrane components, particularly G-protein-linked receptors, are not static but are subject to a massive and complex process of continual endocytosis, processing in the endosome system and recycling back to the external membrane, raises the question of its functional significance. In addition, it has been found that many neuromodulators such as polypeptides have their main locus of action inside the postsynaptic neuron. This review covers the role of the endocytic mechanism on receptor desensitization and resensitization, synaptic reorganization and plasticity synaptic scaling and the possible repair of oxidative damage. The possible involvement of this system in Alzheimer's disease is discussed.     

Preassembly and ligand-induced restructuring of the chains of the IFN-γ receptor complex： the roles of Jak kinases, Statl and the receptor chains

We previously demonstrated using noninvasive technologies that the interferon-gamma （IFN-γ） receptor complex is preassembled [ 1 ]. In this report we determined how the receptor complex is preassembled and how the ligand-mediated conformational changes occur. The interaction of Statl with IFN-γR1 results in a conformational change localized to IFN- γR1. Jakl but not Jak2 is required for the two chains of the IFN-γ receptor complex （IFN-γR1 and IFN-γR2） to interact; however, the presence of both Jakl and Jak2 is required to see any ligand-dependant conformational change. Two IFN- γR2 chains interact through species-specific determinants in their extracellular domains. Finally, these determinants also participate in the interaction of IFN-γR2 with IFN-γR1. These results agree with a detailed model of the IFN-γ receptor that requires the receptor chains to be pre-associated constitutively for the receptor to be active.     

René Girard and the Mimetic Nature of Eating Disorders

French historian and literary critic René Girard (1923–2015), most widely known for the concepts of mimetic desire and scapegoating, also engaged in the discussion of the surge of eating disorders in his 1996 essay Eating Disorders and Mimetic Desire. This article explores Girard’s ideas on the mimetic nature and origin of eating disorders from a clinical psychiatric perspective and contextualizes them within the field of eating disorders research as well as in relation to broader psychological, sociological and anthropological models of social comparison and non-consumption. Three main themes in Girard’s thinking on the topic of eating disorders are identified and explored: the ‘end of prohibitions’ as a driving force in the emergence of eating disorders, eating disorders as a phenomenon specific to modernity, and the significance of ‘conspicuous non-consumption’ in the emergence of eating disorders.     

Heme oxygenase, a novel target for the treatment of hypertension and obesity?

Heme oxygenase (HO) is the rate-limiting enzyme in the metabolism of heme-releasing bioactive molecules carbon monoxide (CO), biliverdin, and iron, each with beneficial cardiovascular actions. Biliverdin is rapidly reduced to bilirubin, a potent antioxidant, by the enzyme biliverdin reductase, and iron is rapidly sequestered by ferritin in the cell. Several studies have demonstrated that HO-1 induction can attenuate the development of hypertension as well as lower blood pressure in established hypertension in both genetic and experimental models. HO-1 induction can also reduce target organ injury and can be beneficial in cardiovascular diseases, such as heart attack and stroke. Recent studies have also identified a beneficial role for HO-1 in the regulation of body weight and metabolism in diabetes and obesity. Chronic HO-1 induction lowers body weight and corrects hyperglycemia and hyperinsulinemia. Chronic HO-1 induction also modifies the phenotype of adipocytes in obesity from one of large, cytokine producing to smaller, adiponectin producing. Finally, chronic induction of HO-1 increases oxygen consumption, CO(2), and heat production and activity in obese mice. This review will discuss the current understanding of the actions of the HO system to lower blood pressure and body weight and how HO or its metabolites may be ideal candidates for the development of drugs that can both reduce blood pressure and lower body weight.     

Age–size structure of common bivalve mollusc populations in the White Sea: the causes of instability

Inter-annual fluctuations in the recruitment rate and size–age structure are typical for marine bivalve beds. Until now there is no common opinion about the causes of this variability. One of them may be related to the adult–larval interactions in mollusk populations. To test this suggestion and to reveal the possible causes of inter-annual instability in bed recruitment level we analyzed the long-term (9–30 years) dynamics of the size–age structure of 22 populations of 9 bivalve species in the White Sea. Inter-annual variability in the successful recruitment was typical of most studied bivalve beds. This phenomenon was apparently caused, on the one hand, by the intensity of molluscs’ intraspecific interactions, and on the other (no less), by the juvenile survival in their first winter. The bivalve stationary beds in the White Sea are likely the exception from the general rule. They can be formed in case of a relatively stable level of annual recruitment with a decrease in intensity of intraspecific competition. However, in this case, the stability of the bed size–age structure can be easily disrupted under unfavourable conditions for spat survival in their first winter.     

Are human progestagens among the causes of amphibian extinction?

We hypothesised that massive elimination of human and animal progestagens through wastewater can be toxic for reproduction of amphibians. Several medical test using amphibian bioassays (i.e. Hogben test) have demonstrated that human chorionic gonadotropin is toxic for amphibians. Nowadays, a huge amount of sexual hormones from women, animal farms and aquaculture arrive to inland water systems and could be a cause of amphibians extinction.