Deletion of ERK2 mitogen-activated protein kinase identifies its key roles in cortical neurogenesis and cognitive function.

The mitogen-activated protein (MAP) kinases ERK1 and ERK2 are critical intracellular signaling intermediates; however, little is known about their isoform-specific functions in vivo. We have examined the role of ERK2 in neural development by conditional inactivation of the murine mapk1/ERK2 gene in neural progenitor cells of the developing cortex. ERK MAP kinase (MAPK) activity in neural progenitor cells is required for neuronal cell fate determination. Loss of ERK2 resulted in a reduction in cortical thickness attributable to impaired proliferation of neural progenitors during the neurogenic period and the generation of fewer neurons. Mutant neural progenitor cells remained in an undifferentiated state until gliogenic stimuli induced their differentiation, resulting in the generation of more astrocytes. The mutant mice displayed profound deficits in associative learning. Importantly, we have identified patients with a 1 Mb microdeletion on chromosome 22q11.2 encompassing the MAPK1/ERK2 gene. These children, who have reduced ERK2 levels, exhibit microcephaly, impaired cognition, and developmental delay. These findings demonstrate an important role for ERK2 in cellular proliferation and differentiation during neural development as well as in cognition and memory formation.

Exercise for ankylosing spondylitis: An evidence-based consensus statement.

OBJECTIVE: Despite Level 1b evidence and international consensus that exercise is beneficial in ankylosing spondylitis (AS), there is a paucity of detailed information to guide exercise prescription, including the type and dosage of exercise required for the most benefit. This collaborative project, combining evidence with clinical expertise, was established to develop practical recommendations to guide sustainable exercise prescription for individuals with AS. METHODS: Using a modified Delphi technique, 10 clinical questions were generated and a systematic literature review was conducted for each. Draft recommendations were developed at a 2-day meeting, based on the integration of evidence summaries and expert opinion. Feedback was obtained from patient and health professional groups prior to finalisation. RESULTS: Recommendations and practice points were developed for the following areas: assessment; monitoring; safety; disease management; AS-specific exercise; physical activity; dosage, adherence and setting. A framework was developed that could also be adapted for exercise in other chronic musculoskeletal conditions. Feedback suggests that the final consensus statement provides useful information for those seeking to provide best practice exercise prescription for people with AS. CONCLUSION: The recommendations provide an up-to-date, evidence-based approach to the full range of issues related to the use of exercise in AS, as well as identifying evidence gaps for further research. Most importantly, this includes investigation of aspects of exercise programme design required to produce the largest effect, long-term adherence with exercise programs and the specific exercise requirements of sub-groups of people with AS. Widespread dissemination and implementation of the guidelines will be required to optimise exercise outcomes.

Detection and effects of a homeologous reciprocal transposition in Brassica napus.

A reciprocal chromosomal transposition was identified in several annual oilseed Brassica napus genotypes used as parents in crosses to biennial genotypes for genetic mapping studies. The transposition involved an exchange of interstitial homeologous regions on linkage groups N7 and N16, and its detection was made possible by the use of segregating populations of doubled haploid lines and codominant RFLP markers. RFLP probes detected pairs of homeologous loci on N7 and N16 for which the annual and biennial parents had identical alleles in regions expected to be homeologous. The existence of an interstitial reciprocal transposition was confirmed by cytological analysis of synaptonemal complexes of annual x biennial F1 hybrids. Although it included approximately one-third of the physical length of the N7 and N16 chromosomes, few recombination events within the region were recovered in the progenies of the hybrids. Significantly higher seed yields were associated with the parental configurations of the rearrangement in segregating progenies. These progenies contained complete complements of homeologous chromosomes from the diploid progenitors of B. napus, and thus their higher seed yields provide evidence for the selective advantage of allopolyploidy through the fixation of intergenomic heterozygosity.