Culture and Cancer

Genetic mechanisms, since they broadly involve information transmission, should be translatable into information dynamics formalism. From this perspective we reconsider the adaptive mutator, one possible means of 'second order selection' by which a highly structured 'language' of environment and development writes itself onto the variation upon which evolutionary selection and tumorigenesis operate. Our approach uses recent results in the spirit of the Large Deviations Program of applied probability that permit transfer of phase transition approaches from statistical mechanics to information theory, generating evolutionary and developmental punctuation in what we claim to be a highly natural manner

Learning curve assessment of rule use provides evidence for spared implicit sequence learning in a mouse model of mental retardation

Humans with Fragile X Syndrome (FXS) have a mental retardation of which a notable characteristic is a weakness in recalling sequences of information. A mouse model of the disorder exists which exhibits behavioral and neurologic changes, but cognitive testing has not revealed learning deficits seemingly comparable in magnitude to that seen in the human condition. A working memory task for olfactory sequences was employed to test learning set acquisition in mice, half of which had a disruption of the gene responsible for FXS in humans. The task protected against reward detection artifact and demonstrated stringency-dependent task acquisition. A comparable image-based sequence learning set task was used to test humans. The performances of human subjects who did and did not report consciously acquiring the task rules were used as positive and negative controls to assess the mouse learning curves. Learning curve plateau error fluctuation for individual mice was comparable to that of human subjects who never acquired an explicit rule to perform the task, but different from those of human subjects who could state a rule to solve the problem. Sliding window error plots and nonparametric statistical analysis discriminated between the consciously rule-based human performances and that of the mice and humans who did not explicitly obtain the rule. Based on comparison to the human results, wild-type and FX mouse learning curves with a continuingly variable terminal plateau error rate in sliding epochs were classified as “implicit”. Although a moderately large difference in performance of the olfactory task was observed among mouse strains, there was no significant effect of FX genotype. The wild-type performance of the FX mice in this sequence task suggests that implicit learning may be relatively spared in FXS

Characterization of Fragile X mental retardation antibodies for use in cross-species immunoblotting, immunohistochemistry, and electron microscopy

This information is provided on Cogprints for colleagues in the Fragile X field who have requested it directly in the past. It is also a companion work to the article “Human Fragile X gene locus P1 artificial chromosome transgenic mice” from our group (manuscript to be made available on Cogprints)

In Remembrance of Denis Alan Trevor New

Non

Commentary: Urine chemical content may be a false measure of environmental exposure

No abstrac

Elevated glycogen synthase kinase 3 activity in Fragile X mice: key metabolic regulator with evidence for treatment potential

Significant advances have been made in understanding the underlying defects of and developing potential treatments for Fragile X Syndrome (FXS), the most common heritable mental retardation. It has been shown that neuronal mGluR5-mediated signaling is affected in FX animal models, with consequent alterations in activity-dependent protein translation and synaptic spine functionality. We demonstrate here that a central metabolic regulatory enzyme, glycogen synthase kinase 3 (GSK3) is present in a form indicating elevated activity in several regions of the FX mouse brain. Furthermore, we show that selective GSK3 inhibitors, as well as lithium, are able to revert mutant phenotypes of the FX mouse. Lithium, in particular, remained active with chronic dosing, although its effects were transient even when given from birth. The combination of mGluR5 antagonist and GSK3 inhibitors was not additive. Instead, it was discovered that mGluR5 signaling and GSK3 activation in the FX mouse are coordinately elevated, with inhibition of mGluR5 leading to inhibition of GSK3. These findings raise the possibility that GSK3 is a fundamental and central component of FXS pathology, with a substantial treatment potential

The role of the pediatrican in the effort to prevent congenital malformations

N

NGO\u27s BPA Report Intended to Frighten, Not Enlighten.

Non

A phenotypic and molecular characterization of the fmr1-tm1Cgr Fragile X mouse

Fragile X Syndrome is the most common form of\ud inherited mental retardation. It is also known for having\ud a substantial behavioral morbidity, including autistic features. In humans, Fragile X Syndrome is almost always\ud caused by inactivation of the X-linked FMR1 gene. A\ud single knockout mouse model, fmr1-tm1Cgr, exists. In\ud this report we further characterize the cognitive and\ud behavioral phenotype of the fmr1-tm1Cgr Fragile X\ud mouse through the use of F1 hybrid mice derived from\ud two inbred strains (FVB/NJ and C57BL/6J). Use of F1\ud hybrids allows focus on the effects of the fmr1-tm1Cgr\ud allele with reduced influence from recessive alleles\ud present in the parental inbred strains. We find that the\ud cognitive phenotype of fmr1-tm1Cgr mice, including\ud measures of working memory and learning set formation\ud that are known to be seriously impacted in humans with\ud Fragile X Syndrome, are essentially normal. Further testing of inbred strains supports this conclusion. Thus, any\ud fmr1-tm1Cgr cognitive deficit is surprisingly mild or\ud absent. There is, however, clear support presented for a\ud robust audiogenic seizure phenotype in all strains tested,\ud as well as increased entries into the center of an open\ud field. Finally, a molecular examination of the fmr1-tm1Cgr\ud mouse shows that, contrary to common belief, it is not a\ud molecular null. Implications of this finding for interpretation of the phenotype are discussed.\u