Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson's disease

Human pluripotent stem cells (PSCs) are a promising source of cells for applications in regenerative medicine. Directed differentiation of PSCs into specialized cells such as spinal motoneurons or midbrain dopamine (DA) neurons has been achieved. However, the effective use of PSCs for cell therapy has lagged behind. Whereas mouse PSC-derived DA neurons have shown efficacy in models of Parkinson's disease, DA neurons from human PSCs generally show poor in vivo performance. There are also considerable safety concerns for PSCs related to their potential for teratoma formation or neural overgrowth. Here we present a novel floor-plate-based strategy for the derivation of human DA neurons that efficiently engraft in vivo, suggesting that past failures were due to incomplete specification rather than a specific vulnerability of the cells. Midbrain floor-plate precursors are derived from PSCs 11 days after exposure to small molecule activators of sonic hedgehog (SHH) and canonical WNT signalling. Engraftable midbrain DA neurons are obtained by day 25 and can be maintained in vitro for several months. Extensive molecular profiling, biochemical and electrophysiological data define developmental progression and confirm identity of PSC-derived midbrain DA neurons. In vivo survival and function is demonstrated in Parkinson's disease models using three host species. Long-term engraftment in 6-hydroxy-dopamine-lesioned mice and rats demonstrates robust survival of midbrain DA neurons derived from human embryonic stem (ES) cells, complete restoration of amphetamine-induced rotation behaviour and improvements in tests of forelimb use and akinesia. Finally, scalability is demonstrated by transplantation into parkinsonian monkeys. Excellent DA neuron survival, function and lack of neural overgrowth in the three animal models indicate promise for the development of cell-based therapies in Parkinson's disease.     

Transfer of diabetes in mice prevented by blockade of adhesion-promoting receptor on macrophages

Insulin-dependent diabetes mellitus (IDDM) is a disease with an autoimmune aetiology. The non-obese diabetic mouse is a good spontaneous animal model of the human disease, with IDDM developing in 50-80% of female mice by the age of 6 months. The disease can be transferred by splenic T cells from diabetic donors and is prevented by T-cell depletion. The mechanism(s) by which the beta cell is specifically destroyed is not known, but T cells and macrophages have both been implicated, based on the presence of macrophages in the infiltrated islet and the ability of chronic silica treatment to prevent disease. The monoclonal antibody 5C6 is specific for the myelomonocytic adhesion-promoting type-3 complement receptor (CR3 or CD11b/CD18) and does not bind to T cells. Here we show that blockade of macrophage CR3 in vivo prevents intra-islet infiltration by both macrophages and T cells and inhibits development of IDDM. We conclude that both T cells and macrophages have an essential role in the onset of IDDM.     

The human microbiome project

A strategy to understand the microbial components of the human genetic and metabolic landscape and how they contribute to normal physiology and predisposition to disease.     

Bionomics and control of the walnut spanworm, Phigalia plumogeraria (Hulst), on bitterbrush in Utah

In 1979, the walnut spanworm defoliated a 1 ha bitterbrush seed orchard near Nephi, Utah. No seed was produced for two years thereafter due to feeding damage. Life stages were described and illustrated. The female is brachypterous and incapable of flight. First instar larvae readily drop on their silk threads and probably are dispersed by wind. The insect has one annual generation. Moths laid an average of 159 eggs per cluster in April; larvae began to appear in early May and matured by the first week of June. The pupal period extended from June until mid-April. The parasitic bombyliid, Villa faustina (Osten Sacken), was reared from pupae. In April 1980, shrubs contained an estimated average of 1044 eggs each. On 19 May, larvae averaged 1.9 per 7.5 cm of twig and were in the first and second instar. On 20 May the population was controlled by spraying with Sevimol-4. Other potential host plants, as determined from greenhouse tests, are rose, ceanothus, mountain mahogany, serviceberry, and willow.     

Winter food habits of the pine marten in Colorado

Eighteen pine marten ( Martes americana ) stomachs and 29 intestinal tracts, collected between October 1983 and March 1984 from northern Colorado, were examined for food items. Voles ( Microtus spp.) occurred most frequently, followed by shrews ( Sorex spp.), insects, and vegetative matter.