16-Kaurene-2,6,15-triol

Efficient Synthesis of 1,9-Substituted Benzo[h][1,6]naphthyridin-2(1H)-ones and Evaluation of their Plasmodium falciparum Gametocytocidal Activities.[Pubmed:29024590]

ACS Comb Sci. 2017 Dec 11;19(12):748-754.

A novel three-component, two-step, one-pot nucleophilic aromatic substitution (SNAr)-intramolecular cyclization-Suzuki coupling reaction was developed for the synthesis of benzo[h][1,6]naphthyridin-2(1H)-ones (Torins). On the basis of the new efficiently convergent synthetic route, a library of Torin analogs was synthesized. The antimalarial activities of these compounds were evaluated against asexual parasites using a growth inhibition assay and gametocytes using a viability assay.

Intelligence and all-cause mortality in the 6-Day Sample of the Scottish Mental Survey 1947 and their siblings: testing the contribution of family background.[Pubmed:29025063]

Int J Epidemiol. 2018 Feb 1;47(1):89-96.

Background: Higher early-life intelligence is associated with a reduced risk of mortality in adulthood, though this association is apparently hardly attenuated when accounting for early-life socio-economic status (SES). However, the use of proxy measures of SES means that residual confounding may underestimate this attenuation. In the present study, the potential confounding effect of early-life SES was instead accounted for by examining the intelligence-mortality association within families. Methods: The association between early-life intelligence and mortality in adulthood was assessed in 727 members of the 6-Day Sample of the Scottish Mental Survey 1947 and, for the first time, 1580 of their younger siblings. These individuals were born between 1936 and 1958, and were followed up into later life, with deaths recorded up to 2015. Cox regression was used to estimate the relative risk of mortality associated with higher IQ scores after adjusting for shared family factors. Results: A standard-deviation advantage in IQ score was associated with a significantly reduced mortality risk [hazard ratio = 0.76, p < 0.001, 95% confidence interval (CI) (0.68-0.84)]. This reduction in hazard was only slightly attenuated by adjusting for sex and shared family factors [hazard ratio = 0.79, p = 0.002, 95% CI (0.68-0.92)]. Conclusions: Although somewhat conservative, adjusting for all variance shared by a family avoids any potential residual confounding of the intelligence-mortality association arising from the use of proxy measures of early-life SES. The present study demonstrates that the longevity associated with higher early-life intelligence cannot be explained by early-life SES or within-family factors.

Functional interleukin-6 receptor-alpha is located in tanycytes at the base of the third ventricle.[Pubmed:29024103]

J Neuroendocrinol. 2017 Dec;29(12).

Interleukin (IL)-6(-) /(-) mice develop mature onset obesity, whereas i.c.v. injection of IL-6 decreases obesity in rodents. Moreover, levels of IL-6 in cerebrospinal fluid (CSF) were reported to be inversely correlated with obesity in humans. Tanycytes lining the base of the third ventricle (3V) in the hypothalamus have recently been reported to be of importance for metabolism. In the present study, we investigated whether tanycytes could respond to IL-6 in the CSF. With immunohistochemistry using a well characterised antibody directed against the ligand binding receptor for IL-6, IL-6 receptor alpha (IL-6Ralpha), it was found that tanycytes, identified by the two markers, vimentin and dopamine- and cAMP-regulated phosphoprotein of 32 kDa, contained IL-6Ralpha. There were fewer IL-6Ralpha on another type of ventricle-lining cells, ependymal cells, as identified by the marker glucose transporter-1. To demonstrate that the immunoreactive IL-6Ralpha were responsive to IL-6, we injected IL-6 i.c.v. This treatment increased immunoreactive phosphorylated signal transducer and activator of transcription-3 (pSTAT3) in tanycytes after 5 minutes and in cells in the medial part of the arcuate nucleus after 5 and 15 minutes. Intracerebroventricular injection of leptin exerted similar effects. As expected, i.p. injection of leptin also induced pSTAT3 staining in the hypothalamus, whereas i.p. IL-6 injection had little effect on this parameter. Intracerebroventricular or i.p. injection of vehicle only had no effect on pSTAT3-immunoreactivity. In summary, there are functional IL-6Ralpha on tanycytes at the bottom of the 3V, in agreement with the possibility that ventricular administration of IL-6 decreases obesity in mice via an effect on this cell type.