Rats were treated twice daily for 2 weeks with 2 mg/kg (+/-) PPX (ie, 1 mg/kg of the active form), a dose that improved lesion-induced motor deficits. In both groups, (+/-) PPX increased discounting; preference for the large reinforcer was enhanced 30-45% at the most uncertain probabilities. Tolerance did not develop with repeated treatments. Increased discounting subsided within 2 weeks of (+/-) PPX cessation, and re-exposure to (+/-) PPX reinstated find more heightened discounting.

Such findings emulate the clinical scenario; therefore, ICSS for discounting assessments in rats exhibited high face validity. This model should prove useful in medication development where assessment of the propensity of a putative therapy to induce risk-taking behaviors is of interest. Neuropsychopharmacology (2012) 37, 1397-1408; doi: 10.1038/npp.2011.325; published online 18 January 2012″
“The receptor tyrosine kinase ErbB2 (HER2/neu) is overexpressed in similar to 30% of breast cancers and is associated with poor prognosis and an increased likelihood Selleckchem THZ1 of metastasis. Clinical treatments such as trastuzumab

are effective in less than 35% of women diagnosed as ErbB2-positive, highlighting the necessity of searching for novel targets and alternative therapies. Herein, a proteomic screening strategy combining quantitative-based gel electrophoresis and MS was used to compare the protein expression of 48 normal human breast and tumour tissues differing in ErbB2 expression and lymph node status. The aim was to identify proteins associated with the aggressive phenotype of ErbB2-positive breast cancer which could be potential biomarkers of the disease as well as therapy targets. In total, 177 protein isoforms (107 gene products) differentially expressed between tissue groups were identified. Immunohistochemical staining of a tissue-microarray was used for validation of selected protein candidates. We found that expression of HSP90 alpha, laminin and GSTP1 significantly correlated with ErbB2 expression, while others such as AGR2, NM23H1 and Annexin 2 were overexpressed in greater than 40% of tumours. Finally, knocking-down the

expression by MTMR9 RNA interference of three candidates, AGR2, Transgelin2 and NM23H1 resulted in an enhanced invasive capacity of MDA-MB435 cells. These data support the involvement of these targets in tumour progression and identify them as novel biomarkers of the disease.”
“Common obesity and inherited lipodystrophies, rare disorders characterized by a partial (familial partial lipodystrophy; FPLD) or complete (congenital generalized lipodystrophy; CGL) lack of adipose tissue, are both associated with metabolic complications such as insulin resistance and type 2 diabetes. Mutations in the transcription factor peroxisome proliferator activated receptor (PPAR)7 and a number of its downstream target genes result in lipodystrophy.