Different Mechanisms Confer Gradual Control and Memory at Nutrient- and Stress-Regulated Genes in Yeast.

Cells respond to environmental stimuli by fine-tuned regulation of gene expression. Here we investigated the dose-dependent modulation of gene expression at high temporal resolution in response to nutrient and stress signals in yeast. The GAL1 activity in cell populations is modulated in a well-defined range of galactose concentrations, correlating with a dynamic change of histone remodeling and RNA polymerase II (RNAPII) association. This behavior is the result of a heterogeneous induction delay caused by decreasing inducer concentrations across the population. Chromatin remodeling appears to be the basis for the dynamic GAL1 expression, because mutants with impaired histone dynamics show severely truncated dose-response profiles. In contrast, the GRE2 promoter operates like a rapid off/on switch in response to increasing osmotic stress, with almost constant expression rates and exclusively temporal regulation of histone remodeling and RNAPII occupancy. The Gal3 inducer and the Hog1 mitogen-activated protein (MAP) kinase seem to determine the different dose-response strategies at the two promoters. Accordingly, GAL1 becomes highly sensitive and dose independent if previously stimulated because of residual Gal3 levels, whereas GRE2 expression diminishes upon repeated stimulation due to acquired stress resistance. Our analysis reveals important differences in the way dynamic signals create dose-sensitive gene expression outputs.

Errorless learning and memory performance in schizophrenia

There is evidence that patients with schizophrenia have impaired explicit memory and intact implicit memory. The present study sought to replicate and extend that of O'Carroll et al. [O'Carroll, R.E., Russell, H.H., Lawrie, S.M. and Johnstone, E.C., 1999. Errorless learning and the cognitive rehabilitation of memory-impaired schizophrenic patients. Psychological Medicine 29, 105-112.] which reported that for memory-impaired patients with schizophrenia performance on a (cued) word recall task is enhanced using errorless learning techniques (in which errors are prevented during learning) compared to errorful learning (the traditional trial-and-error approach). Thirty patients with a DSM-IV diagnosis of schizophrenia and fifteen healthy controls (HC) participated. The Rivermead Behavioural Memory Test was administered and from their scores, the schizophrenic patients were classified as either memory-impaired (MIS), or memory-unimpaired (MUS). During the training phase two lists of words were learned separately, one using the errorless learning approach and the other using an errorful approach. Subjects were then tested for their recall of the words using cued recall. After errorful learning training, performance on word recall for the MIS group was impaired compared to the MUS and HC groups. However, after errorless learning training, no significant differences in performance were found between the three groups. Errorless learning may play an important role in remediation of cognitive deficits for patients with schizophrenia. (c) 2007 Elsevier Ireland Ltd. All rights reserved.

The Association Between Childhood Trauma and Memory Functioning in Schizophrenia

Objective: Both neurocognitive impairments and a history of childhood abuse are highly prevalent in patients with schizophrenia. Childhood trauma has been associated with memory impairment as well as hippocampal volume reduction in adult survivors. The aim of the following study was to examine the contribution of childhood adversity to verbal memory functioning in people with schizophrenia. Methods: Eighty-five outpatients with a Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) diagnosis of chronic schizophrenia were separated into 2 groups on the basis of self-reports of childhood trauma. Performance on measures of episodic narrative memory, list learning, and working memory was then compared using multivariate analysis of covariance. Results: Thirty-eight (45%) participants reported moderate to severe levels of childhood adversity, while 47 (55%) reported no or low levels of childhood adversity. After controlling for premorbid IQ and current depressive symptoms, the childhood trauma group had significantly poorer working memory and episodic narrative memory. However, list learning was similar between groups. Conclusion: Childhood trauma is an important variable that can contribute to specific ongoing memory impairments in schizophrenia.