Leptin Predicts a Worsening of the Features of the Metabolic Syndrome Independently of Obesity

Objective: The term metabolic syndrome (MS) describes a cluster of cardiovascular risk factors including dyslipidemia, glucose intolerance, insulin resistance, and hypertension. Obesity increases the risk of MS, but as obesity is neither necessary nor sufficient to cause the syndrome, there is considerable interest in identifying obesity‐independent pathways. One such pathway may involve the actions of the adipokine leptin, which is associated cross‐sectionally with MS and prospectively with coronary heart disease and stroke, independently of obesity. Our goal was to test the hypothesis that leptin predicts the development of the features of MS independently of obesity. Research Methods and Procedures: This study used a prospective population‐based cohort of 748 middle‐aged whites in whom baseline measures of leptin and repeated measurement of the subcomponents of the MS at 5 and 10 years were available. The features of the MS were characterized as five factors (obesity, dyslipidemia, elevated blood pressure, glucose intolerance, and insulin resistance), which were combined to create an MS summary score. Results: Baseline leptin significantly predicted the development of obesity (p = 0.001) and, after adjustment for BMI, development of glucose intolerance (p = 0.016) and insulin resistance (p < 0.0001). Leptin levels did not independently predict a change in lipids or blood pressure. Leptin levels significantly predicted the development of the MS (p = 0.036), independently of baseline BMI. Discussion: Leptin predicts the development of the MS independently of baseline obesity. This association is specifically related to the development of glucose intolerance and insulin resistance. The extent to which these relationships are explained through residual confounding by obesity remains to be determined.     

Relationship between gibberellin and cytokinin activity and flowering in Rosa damascena Mill.

Kinetin at 10 mg l^–1 increased the number of flowers produced on Rosa damascena plants while GA₃ inhibited flowering. In the leaves of non-flowering plants GA-like activity was high while specific cytokinin activity (fraction-II) was significantly higher in flowering plants. A novel compound 10- methyldihydrozeatin riboside and isopentenyl-adenine were identified from TLC fraction-II while TLC fraction-I yielded zeatin and 2-hydroxy-6-methylaminopurine.Abbreviations TLC thin layer chromatography - BA N⁶-benzyladenine - GA₃ gibberellic acid CIMAP communication No. 92-40J     

Associations between lung function and physical and cognitive health in the Canadian Longitudinal Study on Aging (CLSA): A cross-sectional study from a multicenter national cohort

BackgroundLow lung function is associated with high mortality and adverse cardiopulmonary outcomes. Less is known of its association with broader health indices such as self-reported respiratory symptoms, perceived general health, and cognitive and physical performance. The present study seeks to address the association between forced expiratory volume in 1 second (FEV₁), an indicator of lung function, with broad markers of general health, relevant to aging trajectory in the general population.Methods and findingsFrom the Canadian general population, 22,822 adults (58% females, mean age 58.8 years [standard deviation (SD) 9.6]) were enrolled from the community between June 2012 and April 2015 from 11 Canadian cities and 7 provinces. Mixed effects regression was used to assess the cross-sectional relationship between FEV₁ with self-reported respiratory symptoms, perceived poor general health, and cognitive and physical performance. All associations were adjusted for age, sex, body mass index (BMI), education, smoking status, and self-reported comorbidities and expressed as adjusted odds ratios (aORs). Based on the Global Lung Function Initiative (GLI) reference values, 38% (n = 8,626) had normal FEV₁ (z-scores >0), 37% (n = 8,514) mild (z-score 0 to > −1 SD), 19% (n = 4,353) moderate (z-score −1 to > −2 SD), and 6% (n = 1,329) severely low FEV₁ (z-score = < −2 SD). There was a graded association between lower FEV₁ with higher aOR [95% CI] of self-reported moderate to severe respiratory symptoms (mild FEV₁ 1.09 [0.99 to 1.20] p = 0.08, moderate 1.45 [1.28 to 1.63] p < 0.001, and severe 2.67 [2.21 to 3.23] p < 0.001]), perceived poor health (mild 1.07 [0.9 to 1.27] p = 0.45, moderate 1.48 [1.24 to 1.78] p = <0.001, and severe 1.82 [1.42 to 2.33] p < 0.001]), and impaired cognitive performance (mild 1.03 [0.95 to 1.12] p = 0.41, moderate 1.16 [1.04 to 1.28] p < 0.001, and severe 1.40 [1.19 to 1.64] p < 0.001]). Similar graded association was observed between lower FEV₁ with lower physical performance on gait speed, Timed Up and Go (TUG) test, standing balance, and handgrip strength. These associations were consistent across different strata by age, sex, tobacco smoking, obstructive, and nonobstructive impairment on spirometry. A limitation of the current study is the observational nature of these findings and that causality cannot be inferred.ConclusionsWe observed graded associations between lower FEV₁ with higher odds of disabling respiratory symptoms, perceived poor general health, and lower cognitive and physical performance. These findings support the broader implications of measured lung function on general health and aging trajectory.

MyLinh Duong and colleagues investigate associations between lung function and self-reported respiratory symptoms, perceived poor general health, and cognitive and physical performance.     

The Occurrence of Postconflict Skills in Captive Immature Chimpanzees (<Emphasis Type="Italic">Pan troglodytes</Emphasis>)

Conflict management strategies can reduce costs of aggressive competition in group-living animals. Postconflict behaviors such as reconciliation and third-party postconflict affiliation are widely accepted as social skills in primates and have been demonstrated in many species. Although immature primates possess a repertoire of species-specific behaviors, it is thought that they gradually develop appropriate social skills throughout prolonged juvenility to establish and maintain complex social relationships within their group. We examined the occurrence of postconflict skills in five immature chimpanzees (Pan troglodytes) over 15 mo, focusing on interactions that were not with the subject’s mother. We observed reconciliation, with conciliatory tendencies comparable to adults, and provide the first evidence that captive immature chimpanzees commonly reconciled using social play. However, immatures were not more likely to reconcile valuable than nonvaluable relationships. We also observed third party postconflict affiliation although at a lower level than reported for adults. Our results provide evidence for postconflict skills in immature chimpanzees but the lack of higher conciliatory tendency with valuable partners and low occurrence of third-party affiliation indicates extended juvenility may be required refine these skills. Further work is needed to investigate whether these behaviors have the same function and effectiveness as those found in adults.     

Endogenous inhibitors and seasonal changes in abscisic acid in Dioscorea floribunda Mart. & Gal.

In the tubers of medicinal yam (Dioscorea floribunda Mart. & Gal.) abscisic acid (ABA) content was high in all the parts during the dormant condition in the winter, but it decreased to a very low level in the actively growing plants. ABA content of the entire tuber was negatively correlated with temperature and photoperiod. Growth inhibitors including batatasin-I and phthalic acid were identified in the dormant tuber.CIMAP Communication No. 673.     

A POMC variant implicates beta-melanocyte-stimulating hormone in the control of human energy balance

The melanocortin-4 receptor (MC4R) plays a critical role in the control of energy balance. Of its two pro-opiomelanocortin (POMC)-derived ligands, alpha- and beta-MSH, the majority of attention has focused on alpha-MSH, partly reflecting the absence of beta-MSH in rodents. We screened the POMC gene in 538 patients with severe, early-onset obesity and identified five unrelated probands who were heterozygous for a rare missense variant in the region encoding beta-MSH, Tyr221Cys. This frequency was significantly increased (p < 0.001) compared to the general UK Caucasian population and the variant cosegregated with obesity/overweight in affected family members. Compared to wild-type beta-MSH, the variant peptide was impaired in its ability to bind to and activate signaling from the MC4R. Obese children carrying the Tyr221Cys variant were hyperphagic and showed increased linear growth, both of which are features of MC4R deficiency. These studies support a role for beta-MSH in the control of human energy homeostasis.     

Immunoaffinity layering of enzymes

A general procedure for the high yield immobilization of enzymes with the help of specific anti-enzyme antibodies is described. Polyclonal antibodies were raised against Aspergillus niger glucose oxidase and horseradish peroxidase in rabbits and the gamma globulin (IgG) fraction from the immune sera isolated by ammonium sulphate fractionation followed by ion-exchange chromatography. Immobilization of glucose oxidase and horseradish peroxidase was achieved by initially binding the enzymes to a Sepharose matrix coupled with IgG isolated from anti-(glucose oxidase) and anti-(horseradish peroxidase) sera, respectively. This was followed by alternate incubation with the IgG and the enzyme to assemble layers of enzyme and antibody on the support. The immunoaffinity-layered preparations obtained thus were highly active and, after six binding cycles, the amount of enzyme immobilized could be raised about 25 times over that bound initially. It was also possible to assemble layers of glucose oxidase using unfractionated antiserum in place of the IgG. The bioaffinity-layered preparations of glucose oxidase and horseradish peroxidase exhibited good enzyme activities and improved resistance to heat-induced inactivation. The sensitivity of a flow injection analysis system for measuring glucose and hydrogen peroxide could be remarkably improved using immunoaffinity-layered glucose oxidase and horseradish peroxidase. For the detection of glucose, a Clark-type oxygen electrode, constructed as a small flow-through cell integrated with a cartridge bearing immunoaffinity-layered glucose oxidase was employed. The hydrogen peroxide concentration was analysed spectrophotometrically using a flow-through cell and the layered horseradish peroxidase packed into a cartridge. The immunoaffinity-layered enzymes could be conveniently solubilized at acid pH and fresh enzyme loaded onto the support. Immunoaffinity-layered glucose oxidase was successfully used for the on-line monitoring of the glucose concentration during the cultivation of Streptomyces cerevisiae. Received: 16 November 1998 / Received revision: 22 March 1999 / Accepted: 26 March 1999     

Effect of growth retardants on growth and essential oil content in Japanese mint

In field experiments with Japanese mint using different growth retardants, chlormequat chloride (2-chloroethyltrimethylammonium chloride) increased the oil content significantly and inhibited growth to some extent only, whilst ethephon (2-chloroethyl phosphonic acid) at 0.06% concentration significantly decreased growth but had no significant effect on oil content. Among the two oil components studied, menthone content only was significantly increased by 0.06% ethephon whereas the other growth retardants were ineffective. Correlation studies indicated a strong negative relationship of leaf/stem ratio with plant height and herb yield while a strong positive relationship was obtained between the latter two characters. The oil content of the plant was negatively correlated with herb yield and plant height but it was related positively with leaf/stem ratio.CIMAP Communication No. 688.     

miRNA and TMPRSS2-ERG do not mind their own business in prostate cancer cells

Oncogenic fusion proteins belong to an important class that disrupts gene expression networks in a cell. Astonishingly, fusion-positive prostate cancer cells enable the multi-gene regulatory capability of miRNAs to remodel the signal transduction landscape, enhancing or antagonizing the transmission of information to downstream effectors. Accumulating evidence substantiates the fact that miRNAs translate into dose-dependent responsiveness of cells to signaling regulators in transmembrane protease serine 2:ETS-related gene (TMPRSS2-ERG)-positive cells. Wide ranging signaling proteins are the targets for the degree of quantitative fluctuations imposed by miRNAs. miRNA signatures are aberrantly expressed in fusion-positive cancer cells, suggesting that they have a cumulative effect on tumor aggressiveness. It seems attractive to note that TMPRSS2:ERG fusion has a stronger effect as tumors positive for the oncogenic TMPRSS2:ERG have dysregulated oncomirs and tumor suppressor miRNA signature. It is undeniable that a comprehensive analysis of the prostate cancer microRNAome is necessary to uncover novel microRNAs and pathways associated with prostate cancer. Moreover, the identification and validation of miRNA signature in TMPRSS2-ERG-positive prostate cancer cells may help to identify novel molecular targets and pathways for personalized therapy.     

Hepatocellular carcinoma: targeting of oncogenic signaling networks in TRAIL resistant cancer cells

Apoptotic response in hepatocellular carcinoma (HCC) cells is impaired because of interconnectivity of proteins into complexes and signaling networks that are highly divergent in time and space. TNF-related apoptosis-inducing ligand (TRAIL) has emerged as an attractive anticancer agent reported to selectively induce apoptosis in cancer cells. Although diametrically opposed roles of TRAIL are reported both as an inducer of apoptosis and regulator of metastasis, overwhelmingly accumulating experimental evidence highlighting apoptosis inducing activity of TRAIL is directing TRAIL into clinical trials. Insights from TRAIL mediated signaling in HCC research are catalyzing new lines of study that should not only explain molecular mechanisms of disease but also highlight emerging paradigms in restoration of TRAIL mediated apoptosis in resistant cancer cells. It is becoming progressively more understandable that phytochemicals derived from edible plants have shown potential in modelling their interactions with their target proteins. Rapidly accumulating in vitro and in-vivo evidence indicates that phytonutrients have anticancer activity in rodent models of hepatocellular carcinoma. In this review we bring to limelight how phytonutrients restore apoptosis in hepatocellular carcinoma cells by rebalancing pro-apoptotic and anti-apoptotic proteins. Evidence has started to emerge, that reveals how phytonutrients target pharmacologically intractable proteins to suppress cancer. Target-based small-molecule discovery has entered into the mainstream research in the pharmaceutical industry and a better comprehension of the genetics of patients will be essential for identification of responders and non-responders.