Search

Emotional content is known to enhance memory in a content-dependent manner in healthy populations. In middle-aged and older adults, a reduced preference for negative material, or even an enhanced preference for positive material has been observed. This preference seems to be modulated by the emotional arousal that the material evokes. The neuroanatomical basis for emotional memory processes is, however, not well understood in middle-aged and older healthy people. Previous research on local gray matter correlates of emotional memory in older populations has mainly been conducted with patients suffering from various neurodegenerative diseases. To our knowledge, this is the first study to examine regional gray matter correlates of immediate free recall and recognition memory of intentionally encoded positive, negative, and emotionally neutral words using voxel-based morphometry (VBM) in a sample of 50-to-79-year-old cognitively intact normal adults. The behavioral analyses yielded a positivity bias in recognition memory, but not in immediate free recall. No associations with memory performance emerged from the region-of-interest (ROI) analyses using amygdalar and hippocampal volumes. Controlling for total intracranial volume, age, and gender, the whole-brain VBM analyses showed statistically significant associations between immediate free recall of negative words and volumes in various frontal regions, between immediate free recall of positive words and cerebellar volume, and between recognition memory of positive words and primary visual cortex volume. The findings indicate that the neural areas subserving memory for emotion-laden information encompass posterior brain areas, including the cerebellum, and that memory for emotion-laden information may be driven by cognitive control functions. [ABSTRACT FROM AUTHOR]

STAT3 mediates signalling downstream of cytokine and growth factor receptors where it acts as a transcription factor for its target genes, including oncogenes and cell survival regulating genes. STAT3 has been found to be persistently activated in many types of cancers, primarily through its tyrosine phosphorylation (Y705). Here, we show that constitutive STAT3 activation protects cells from cytotoxic drug responses of several drug classes. To find novel and potentially targetable STAT3 regulators we performed a kinase and phosphatase siRNA screen with cells expressing either a hyperactive STAT3 mutant or IL6-induced wild type STAT3. The screen identified cell division cycle 7-related protein kinase (CDC7), casein kinase 2, alpha 1 (CSNK2), discoidin domain-containing receptor 2 (DDR2), cyclin-dependent kinase 8 (CDK8), phosphatidylinositol 4-kinase 2-alpha (PI4KII), C-terminal Src kinase (CSK) and receptor-type tyrosine-protein phosphatase H (PTPRH) as potential STAT3 regulators. Using small molecule inhibitors targeting these proteins, we confirmed dose and time dependent inhibition of STAT3-mediated transcription, suggesting that inhibition of these kinases may provide strategies for dampening STAT3 activity in cancers. [ABSTRACT FROM AUTHOR]

The AGA gene is mutated in patients with aspartylglucosaminuria (AGU), a lysosomal storage disease enriched in the Finnish population. The disease mechanism of AGU and the biochemistry and cell biology of the lysosomal aspartylglucosaminidase (AGA) enzyme are well characterized. Here, we have investigated a novel AGU mutation found in a Finnish patient. The mutation was detected as a compound heterozygote with the Finnish major mutation in the other allele. The novel point mutation, c.44T>G, causes the L15R amino acid substitution in the signal sequence of the AGA enzyme. The mutated AGA enzyme was here analyzed by over expression in BHK and COS-1 cells. The L15R AGA protein was only faintly detectable by immunofluorescence analysis and observed in the endoplasmic reticulum. Metabolic labeling and immunoprecipitation revealed only a small amount of AGA polypeptides but the specific activity of the mutant enzyme was surprisingly high, 37% of the wild type. The amino acid substitution probably affects translocation of AGA polypeptides by altering a critical hydrophobic core structure of the signal sequence. It appears that the small amounts of active enzyme are not able to reach the lysosomes thus explaining the development of AGU disease in the patient. © 2004 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]