The oDGal Mouse: A Novel, Physiologically Relevant Rodent Model of Sporadic Alzheimer's Disease.

Sporadic Alzheimer's disease (sAD) represents a serious and growing worldwide economic and healthcare burden. Almost 95% of current AD patients are associated with sAD as opposed to patients presenting with well-characterized genetic mutations that lead to AD predisposition, i.e.

Selective FFA2 Agonism Appears to Act via Intestinal PYY to Reduce Transit and Food Intake but Does Not Improve Glucose Tolerance in Mouse Models.

Free fatty acid receptor 2 (FFA2) is expressed on enteroendocrine L cells that release glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) when activated by short-chain fatty acids (SCFAs). Functionally GLP-1 and PYY inhibit gut transit, increase glucose tolerance, and suppress appetite; thus, FFA2 has therapeutic potential for type 2 diabetes and obesity. However, FFA2-selective agonists have not been characterized in vivo.

Characterization of the heterozygous glucokinase knockout mouse as a translational disease model for glucose control in type 2 diabetes.

Background And Purpose: The global heterozygous glucokinase (GK) knockout (gk(wt/del)) male mouse, fed on a high-fat (60% by energy) diet, has provided a robust and reproducible model of hyperglycaemia. This model could be highly relevant to some facets of human type 2 diabetes (T2D). We aimed to investigate the ability of standard therapeutic agents to lower blood glucose at translational doses, and to explore the glucose-lowering potential of novel glucokinase activators (GKAs) in this model.

Early Pleistocene human occupation at the edge of the boreal zone in northwest Europe.

The dispersal of early humans from Africa by 1.75 Myr ago led to a marked expansion of their range, from the island of Flores in the east to the Iberian peninsula in the west. This range encompassed tropical forest, savannah and Mediterranean habitats, but has hitherto not been demonstrated beyond 45 degrees N.

Differentiation of MIS 9 and MIS 11 in the continental record: vegetational, faunal, aminostratigraphic and sea-level evidence from coastal sites in Essex, UK.

Multidisciplinary investigations of the vegetational, faunal and sea-level history inferred from the infills of buried channels on the coast of eastern Essex have a direct bearing on the differentiation of MIS 11 and MIS 9 in continental records. New data are presented from Cudmore Grove, an important site on Mersea Island that can be linked to the terrace sequence of the River Thames. The vegetational history has been reconstructed from a pollen sequence covering much of the interglacial represented.

Predictive blood glucose lowering efficacy by Glucokinase activators in high fat fed female Zucker rats.

Background And Purpose: Glucokinase (GK) is the rate-limiting enzyme of hepatic glucose metabolism and acts as a sensor for glucose-stimulated insulin release in beta-cells. Here we examine whether the lowering of blood glucose levels in the rat by small molecule glucokinase activators (GKAs) can be predicted from in vitro enzyme potencies and plasma compound exposure.

Experimental Approach: We developed an insulin resistant and hyperinsulinemic animal model, the high fat fed female Zucker (fa/fa) rat (HFFZ), and measured the acute in vivo glucose-lowering efficacy of a number of GKAs in an oral glucose tolerance test.

Juvenile laryngeal papillomatosis.

Always ask about hoarseness and quality of voice in a history of any child presenting with cough or asthma-like symptoms. Children presenting with what appears to be an acute onset of hoarseness, without any physical signs of airways obstruction, should be reviewed after two weeks. If there is chronic hoarseness, referral to an ENT specialist should be considered with a view to laryngoscopy.

The earliest record of human activity in northern Europe.

The colonization of Eurasia by early humans is a key event after their spread out of Africa, but the nature, timing and ecological context of the earliest human occupation of northwest Europe is uncertain and has been the subject of intense debate. The southern Caucasus was occupied about 1.8 million years (Myr) ago, whereas human remains from Atapuerca-TD6, Spain (more than 780 kyr ago) and Ceprano, Italy (about 800 kyr ago) show that early Homo had dispersed to the Mediterranean hinterland before the Brunhes-Matuyama magnetic polarity reversal (780 kyr ago).

Several million years of stability among insect species because of, or in spite of, Ice Age climatic instability?

There is a curious paradox in the evolutionary legacy of Ice Ages. Studies of modern species suggest that they are currently evolving in response to changing environments. If extrapolated into the context of Quaternary Ice Ages, this evidence would suggest that the frequent climatic changes should have stimulated the evolutionary process and thus increased the rates of change within species and the number of speciation events.

Evidence of two temperate episodes in late Pleistocene deposits at Marsworth, UK.

In the British Quaternary, two post-Cromerian interglacials, the Hoxnian and the Ipswichian, are recognized. Evidence of additional interglacials in this interval is widely accepted in the oceanic record of Quaternary events, and the possibility that at least one additional interglacial of this age is represented in Britain has been discussed. However, in the absence of datable interglacial deposits which are seen to overlie one another, the issue has remained controversial.