The availability of human neuronal progenitors (hNPs) in high purity would greatly facilitate neuronal drug discovery and developmental studies, as well as cell replacement strategies for neurodegenerative diseases and conditions, such as spinal cord injury, stroke, Parkinson's disease, Alzheimer's disease, and Huntington's disease. Here we describe for the first time a method for producing hNPs in large quantity and high purity from human embryonic stem cells (hESCs) in feeder-free conditions, without the use of exogenous noggin, sonic hedgehog or analogs, rendering the process clinically compliant. The resulting population displays characteristic neuronal-specific markers. When allowed to spontaneously differentiate into neuronal subtypes in vitro, cholinergic, serotonergic, dopaminergic and/or noradrenergic, and medium spiny striatal neurons were observed. When transplanted into the injured spinal cord the hNPs survived, integrated into host tissue, and matured into a variety of neuronal subtypes. Our method of deriving neuronal progenitors from hESCs renders the process amenable to therapeutic and commercial use.

[1] We have developed procedures for deriving land surface temperature and homogenizing 30 years of daily microwave brightness temperatures from the NOAA/ NASA Nimbus 7 scanning multichannel microwave radiometer (SMMR) and Defense Meteorological Satellite Program Special Sensor Microwave/Imager (DMSP SSM/I) Pathfinder EASE-Grid database. Processing includes normalization of variable acquisition overpass time, removing the effects of changing satellite orbits, intercalibration of sensors, and filling gaps between missing data. The derived new database over North America (above 45°N), limited to snow-free periods, provides the first estimate of the trends of consistent mean daily summer land surface temperature over the last three decades. By comparison with near-surface air temperatures derived from the European Centre for Medium-Range Weather Forecasts 40 year Reanalysis (ERA-40), the National Centers for Environmental Prediction North American Regional Reanalysis (NARR), and the exhaustive ground-based meteorological measurements across Canada, we highlighted significant systematic biases in the satellite-derived surface temperatures for the 1983-1991 period, spanning from the second half of Nimbus 7 SMMR lifetime (1983)(1984)(1985)(1986)(1987); mean bias of −0.87°C compared to ERA-40) and the entire period of DMSP-F8 SSM/I lifetime (1987)(1988)(1989)(1990)(1991); mean bias of −1.56°C compared to ERA-40). The biased data were corrected with use of a relative offset derived from ERA-40 and DMSP-F11/F13 mean difference over the 1992-2002 period. The comparison of corrected data from the 9 day overlap between SMMR and DMSP-F8 SSM/I and from ground-based meteorological measurements over the 1983-1991 biased period shows the usefulness of the correction method. The mean difference between corrected satellite-derived surface temperature and in situ meteorological air temperature is +0.05°C ± 1.85°C for the entire period . The NARR data appear, in general, to be too warm by about 1°C. The satellite-derived homogenized database gives new observational evidence for global warming over North American regions (mean summer temperature trend of +0.018°C/a throughout the studied period) with regional variable trends, in agreement with reanalysis and in situ measurement trends. However, over the Canadian Arctic tundra, the increase in observed land surface temperatures appears slightly less than the estimates based on near-surface air temperature.Citation: Royer, A., and S. Poirier (2010), Surface temperature spatial and temporal variations in North America from homogenized satellite SMMR-SSM/I microwave measurements and reanalysis for

myo-Inositol 1,4,5-tris(phosphate) was modified at position 6. The analogues synthesized are reported in this publication are 6-deoxy-myo-inositol 1,4,5-tris(phosphate), 6-fluoro-6-deoxy-myo-inositol 1,4,5-tris(phosphate), epi-inositol 1, 4,5-tris(phosphate), and 6-amino-6-deoxy-myo-inositol 1,4, 5-tris(phosphate). These derivatives showed poor affinity for the Ins(1,4,5)P(3) receptors. The inframolecular acid-base behavior and the cooperative effects between the phosphate groups could help explain the loss of affinity of these 6-modified analogues.

Within all endocrine cells, the inositol 1,4,5-trisphosphate (InsP(3)) receptor plays an important role in regulation of the intracellular Ca(2+) concentration. In the present study we showed that a single short-term treatment with either N-ethylmaleimide (known to decrease InsP(3) receptor activity) or thimerosal (known to increase InsP(3) receptor activity) caused time-dependent biphasic effects on the InsP(3) binding activity of bovine adrenal cortex microsomes. The early potentiating effect of thiol-reactive agents translated into a 2-fold increase in binding affinity and Ca(2+) release efficiency. The late dampening effect of thiol-reactive agents translated into a continuous reduction of the maximal binding capacity of the microsomes with a concomitant decrease in Ca(2+) release efficiency. Under these conditions, Western blot analyses demonstrated that the level of InsP(3) receptor protein was not modified. Sequential treatments with thimerosal and the reducing agent dithiothreitol showed that the InsP(3) receptor can readily oscillate between high and low affinity states that are related to its alkylation state. Our results suggest a common mode of action of thiol-reactive agents on the InsP(3) receptor. These results also support the contention that cellular mechanisms of thiol group modification could play important roles in regulation of the intracellular Ca(2+) concentration.