Differential distribution of MAP1A isoforms in the adult mouse barrel cortex and comparison with the serotonin 5-HT2A receptor.

Microtubule-associated protein 1A (MAP1A) is essential during the late differentiation phase of neuronal development. Here, we demonstrated the presence of two MAP1A isoforms with a differential spatial distribution in the adult mouse barrel cortex. Antibody A stained MAP1A in pyramidal and stellate cells, including dendrites that crossed layer IV in the septa between barrels. The other antibody, BW6 recognized a MAP1A isoform that was mainly confined to the barrel hollow and identified smaller caliber dendrites. Previously, an interaction of MAP1A and the serotonin 5-hydroxytryptamine 2A (5-HT(2A)) receptor was shown in the rat cortex. Here, we identified, by double-immunofluorescent labeling, MAP1A isoform and serotonin 5-HT(2A) receptor distribution. MAP1A co-localized mainly with 5-HT(2A) receptor in larger apical dendrites situated in septa. This differential staining of MAP1A and a serotonin receptor in defined barrel compartments may be due to changes in the expression or processing of MAP1A during dendritic transport as a consequence of functional differences in processing of whisker-related sensory input.

Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial.

BACKGROUND: In 2004, a randomised phase III trial by the European Organisation for Research and Treatment of Cancer (EORTC) and National Cancer Institute of Canada Clinical Trials Group (NCIC) reported improved median and 2-year survival for patients with glioblastoma treated with concomitant and adjuvant temozolomide and radiotherapy. We report the final results with a median follow-up of more than 5 years. METHODS: Adult patients with newly diagnosed glioblastoma were randomly assigned to receive either standard radiotherapy or identical radiotherapy with concomitant temozolomide followed by up to six cycles of adjuvant temozolomide. The methylation status of the methyl-guanine methyl transferase gene, MGMT, was determined retrospectively from the tumour tissue of 206 patients. The primary endpoint was overall survival. Analyses were by intention to treat. This trial is registered with Clinicaltrials.gov, number NCT00006353. FINDINGS: Between Aug 17, 2000, and March 22, 2002, 573 patients were assigned to treatment. 278 (97%) of 286 patients in the radiotherapy alone group and 254 (89%) of 287 in the combined-treatment group died during 5 years of follow-up. Overall survival was 27.2% (95% CI 22.2-32.5) at 2 years, 16.0% (12.0-20.6) at 3 years, 12.1% (8.5-16.4) at 4 years, and 9.8% (6.4-14.0) at 5 years with temozolomide, versus 10.9% (7.6-14.8), 4.4% (2.4-7.2), 3.0% (1.4-5.7), and 1.9% (0.6-4.4) with radiotherapy alone (hazard ratio 0.6, 95% CI 0.5-0.7; p<0.0001). A benefit of combined therapy was recorded in all clinical prognostic subgroups, including patients aged 60-70 years. Methylation of the MGMT promoter was the strongest predictor for outcome and benefit from temozolomide chemotherapy. INTERPRETATION: Benefits of adjuvant temozolomide with radiotherapy lasted throughout 5 years of follow-up. A few patients in favourable prognostic categories survive longer than 5 years. MGMT methylation status identifies patients most likely to benefit from the addition of temozolomide. FUNDING: EORTC, NCIC, Nélia and Amadeo Barletta Foundation, Schering-Plough.

n=1/4 domain-growth universality class: Crossover to the n=1/2 class

The kinetic domain-growth exponent is studied by Monte Carlo simulation as a function of temperature for a nonconserved order-parameter model. In the limit of zero temperature, the model belongs to the n=(1/4 slow-growth unversality class. This is indicative of a temporal pinning in the domain-boundary network of mixed-, zero-, and finite-curvature boundaries. At finite temperature the growth kinetics is found to cross over to the Allen-Cahn exponent n=(1/2. We obtain that the pinning time of the zero-curvature boundary decreases rapidly with increasing temperature.

Missouri River Flood Recovery, January 27, 2012 Vol. 1, no. 5

The Missouri River Flood Recovery newsletter is published by the Iowa Homeland Security and Emergency Management Division in cooperation with members of the Missouri River Recovery Coordination Task Force.

Physiology of GLP-1--lessons from glucoincretin receptor knockout mice.

GLP-1 has both peripheral and central actions, as this hormone is secreted by gut endocrine cells and brainstem neurons projecting into the hypothalamus and other brain regions. GLP-1 has multiple regulatory functions participating in the control of glucose homeostasis, beta-cell proliferation and differentiation, food intake, heart rate and even learning. GLP-1 action depends on binding to a specific G-coupled receptor linked to activation of the adenylyl cyclase pathway. Analysis of mice with inactivation of the GLP-1 receptor gene has provided evidence that absence of GLP-1 action in the mouse, despite this hormone potent physiological effects when administered in vivo, only leads to mild abnormalities in glucose homeostasis without any change in body weight. However, a critical role for this hormone and its receptor was demonstrated in the function of the hepatoportal vein glucose sensor, in contrast to that of the pancreatic beta-cells, although absence of both GLP-1 and GIP receptors leads to a more severe phenotype characterized by a beta-cell-autonomous defect in glucose-stimulated insulin secretion. Together, the studies of these glucoincretin receptor knockout mice provide evidence that these hormones are part of complex regulatory systems where multiple redundant signals are involved.

Acreage Answers, December 2000-January 2001, Vol. 1, no. 5

Newsletter for those who reside on acreages in Iowa. Produced by the Iowa State University Extension Office.

Influence of the diketonato ligand on the cytotoxicities of [Ru(eta(6)-p-cymene)-(R(2)acac)(PTA)](+) complexes (PTA=1,3,5-triaza-7-phosphaadamantane)

A series of compounds of general formula [Ru(eta(6)-p-cymene) (R(2)acac)(PTA)][X] (R(2)acac = Me(2)acac, tBu(2)acac, Ph(2)acac, Me(2)acac-Cl; PTA = 1,3,5-triaza-7-phosphaadamantane; X = BPh4, BF4), and the precursor to the Me2acac-Cl derivative [Ru(eta(6)-p-cymene)(Me(2)acac-Cl)Cl], have been prepared and characterised spectroscopically. Five of the compounds have also been characterised in the solid state by X-ray crystallography. The tetrafluoroborate salts are water-soluble, quite resistant to hydrolysis, and have been evaluated for cytotoxicity against A549 lung carcinoma and A2780 human ovarian cancer cells. The compounds are cytotoxic towards the latter cell line, and relative activities are discussed in terms of hydrolysis (less important) and lipophilicity, which appears to exert the dominating influence.

Pauson-Khand Adducts of N-Boc-propargylamine: A New Approach to 4,5-Disubstituted Cyclopentenones

A new approach to the synthesis of 4,5-disubstituted cyclopentenones is described. The strategy is based on the Pauson-Khand (PK) reaction of norbornadiene and N-Boc-propargylamine as alkyne with a masked leaving group, which can be eliminated at will. This approach to the synthesis of 4,5-disubstituted cyclopentenones overcomes the problem of using the alkylation to introduce the alpha-side-chain. As an example, prostane 13-epi-12-oxo-phytodienoic acid (13-epi-12-oxo-PDA) methyl ester was synthesized.

Endeavors Update, Iowa Medicaid Enterprise, Vol. 1, Issue 5, January 27, 2011

The Iowa Medicaid Enterprise (IME) is an endeavor, started in 2005, to unite State staff with “best of breed” contractors into a performance-based model for administration of the Medicaid program.