A highly diastereoselective chloride-mediated dynamic kinetic resolution at phosphorus on-route to a key intermediate in the synthesis of GSK2248761A

A highly diastereoselective chloride-mediated dynamic kinetic resolution at phosphorus has been developed to access a key intermediate in the synthesis of GSK2248761A. This procedure utilises a soluble chloride source and a cheap readily available chiral auxiliary. The practicality of this transformation is demonstrated on a multi-gram scale

Crude Ethanol Extract of Pithecellobium ellipticum

If left untreated, hypercholesterolaemia can lead to atherosclerosis, given time. Plants from the Fabaceae family have shown the ability to significantly suppress atherosclerosis progression. We selected four extracts from Pithecellobium ellipticum, from the Fabaceae family, to be screened in a 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) assay. The ethanol extract, at a concentration of 500 μg/mL, exhibited superior inhibition properties over the other extracts by demonstrating 80.9% inhibition, while 0.223 μg/mL of pravastatin (control) showed 78.1% inhibition towards enzymatic activity. These findings led to the fractionation of the ethanol extract using ethyl acetate : methanol (95 : 5), gradually increasing polarity and produced seven fractions (1A to 7A). Fraction 7A at 150 μg/mL emerged as being the most promising bioactive fraction with 78.7% inhibition. FRAP, beta carotene, and DPPH assays supported the findings from the ethanol extract as it exhibited good overall antioxidant activity. The antioxidant properties have been said to reduce free radicals that are able to oxidize lipoproteins which are the cause of atherosclerosis. Phytochemical screenings revealed the presence of terpenoid, steroid, flavonoid, and phenolic compounds as the responsible group of compound(s), working individually or synergistically, within the extract to prevent binding of HMG-CoA to HMG-CoA reductase

Cardiac glycoside cerberin exerts anticancer activity through PI3K/AKT/mTOR signal transduction inhibition

Natural products possess a significant role in anticancer therapy and many currently-used anticancer drugs are of natural origin. Cerberin (CR), a cardenolide isolated from the fruit kernel of Cerbera odollam, was found to potently inhibit cancer cell growth (GI 50 values 60% bioavailability and rapid absorption; doses of 1–10 mg/kg CR were predicted to maintain efficacious unbound plasma concentrations (>GI 50 value). CR's potent and selective anti-tumour activity, and its targeting of key signalling mechanisms pertinent to tumourigenesis support further preclinical evaluation of this cardiac glycoside

Scaling up: material culture as scaffold for the social brain

Many other species besides Homo sapiens are tool-users and even tool-makers, but one aspect of material culture still sets modern humans apart: our emotional and social engagement with objects. Here I argue that this engagement acted as a crucial scaffold for the scaling-up of human social networks beyond those of our closest relatives the chimpanzees to the global ‘small world’ of modern humans. Material culture plays a crucial role in conveying social information about relationships between people, places and things that extend geographically and temporally beyond the here and now – a role which allowed our ancestors to off-load some of the cognitive demands of maintaining such extensive social networks, and thereby surpass the limits to sociality imposed by neurology alone. Broad-scale developments in the archaeological record of the Lower Palaeolithic through to the early Neolithic are used to trace the process by which hominins and humans slowly scaled up their social worlds

CD134L expression on dendritic cells in the mesenteric lymph nodes drives colitis in T cell-restored SCID mice

Transfer of CD45RBhigh CD4+ T cells to immune-deficient mice in the absence of regulatory T cells leads to a Th1-mediated colitis. In this study, we show that intestinal inflammation is characterized by a 15-fold increase in the number of CD134L+ (OX40L+)-activated DC in the mesenteric lymph nodes (MLNs) compared with BALB/c mice. This was important functionally, as administration of an anti-CD134L mAb inhibited the proliferation of T cells in the MLNs as well as their expression of the gut-homing integrin ?4?7. Most importantly, the anti-CD134L mAb completely blocked development of colitis. Surprisingly, CD134L was found to be expressed by a proportion of dendritic cells (DC) in the MLNs of unreconstituted SCID mice, suggesting that CD134L can be induced on DC in the absence of T cell-derived signals. These results indicate that some DC in the MLNs of SCID mice express an activated phenotype and that CD134L expression by these cells is involved in the development of colitis induced by T cell transfer. Accumulation of CD134L+ DC was inhibited by cotransfer of regulatory T cells, suggesting that inhibition of the accumulation of activated DC is one mechanism by which these cells prevent immune pathology