Although the basic principles of neocortical development have been known for quite some time, it is only recently that our understanding of the molecular mechanisms that are involved has improved. Such understanding has been facilitated by genetic approaches that have identified key proteins involved in neocortical development, which have been placed into signalling pathways by molecular and cell-biological studies. The challenge of current research is to understand the manner in which these various signalling pathways are interconnected to gain a more comprehensive picture of the molecular intricacies that govern neocortical development.

Disabled-1 regulates laminar organization in the developing mammalian brain. Although mutation of the disabled-1 gene in scrambler mice results in abnormalities in neuronal positioning, migratory behavior linked to Disabled-1 signaling is not completely understood. Here we show that newborn neurons in the scrambler cortex remain attached to the process of their parental radial glia during the entire course of radial migration, whereas wild-type neurons detach from the glial fiber in the later stage of migration. This abnormal neuronal-glial adhesion is highly linked to the positional abnormality of scrambler neurons and depends intrinsically on Disabled-1 Tyr220 and Tyr232, potential phosphorylation sites during corticogenesis. Importantly, phosphorylation at those sites regulates alpha3 integrin levels, which is critical for the timely detachment of migrating neurons from radial glia. Altogether, these results outline the molecular mechanism by which Disabled-1 signaling controls the adhesive property of neurons to radial glia, thereby maintaining proper neuronal positioning during corticogenesis.

The association between p35-Cdk5 and an N-cadherin adhesion complex in cortical neurons and the modulation of N-cadherin-mediated aggregation by p35-Cdk5 suggests that the p35-Cdk5 kinase is involved in the regulation of N-cadherin-mediated adhesion in cortical neurons.

There is no proven neuroprotective or neurorestorative therapy for Parkinson’s disease (PD) to date. Several advances in the genetics of PD have created an opportunity to develop mechanistic based therapies that hold particular promise for identifying agents that slow and even halt the progression of PD as well as restore function. Here we review many of the advances in the last decade regarding the identification of new targets for the treatment of PD based on understanding the molecular mechanisms of how mutations in genes linked to PD cause neurodegeneration.

Several genes essential for neocortical layering have been identified in recent years, but their precise roles in this process remain to be elucidated. Mice deficient in p35--an activator of cyclin-dependent kinase 5 (Cdk5)--are characterized by a neocortex that has inverted layering. To decipher the physiological mechanisms that underlie this defect, we compared time-lapse recordings between p35(-/-) and wild-type cortical slices. In the p35(-/-) neocortex, the classic modes of radial migration--somal translocation and locomotion--were largely replaced by a distinct mode of migration: branched migration. Branched migration is cell-autonomous, associated with impaired neuronal-glial interaction and rare in neurons of scrambler mice, which are deficient in Dab1. Hence, our findings suggest that inside-out layering requires distinct functions of Reelin and p35/Cdk5 signaling, with the latter being important for proper glia-guided migration.

Objectives: To evaluate the differences in hip external rotation (ER) strength and inner, outer, and total hip ER range of motion (ROM) between dancers and non-dancers and between left and right sides in each group. Methods: Seventy one subjects (34 dancers and 37 non-dancers) volunteered for this study. The strength (truncated range average torque (TRAT), work, and angle specific torque (AST)) of the hip external rotator muscle group, through the full available active hip ER ROM, was evaluated using concentric isokinetic (30˚/s) testing on a KinCom dynamometer. Adjustment for lean body mass (LBM) was made for comparison of strength between groups. A two way repeated analysis of covariance was used to compare strength between groups. A two way repeated analysis of variance was used to compare strength between sides and ROM between groups and sides. Bonferroni correction was made for multiple analyses, and significance was accepted at p(0.05. Results: AST at 0˚, 20˚, 30˚, and 40˚of hip ER was greater in the dancers than the non-dancers (p(0.022). TRAT, work, AST 0˚, AST 20˚, and AST 30˚o f hip ER were all greater on the right side than the left (p = 0.007) in both groups. Dancers had greater inner ER ROM (p = 0.013) and less outer ER ROM than non-dancers (p(0.001). There was no difference in total ER ROM between groups (p = 0.133). The right side had greater inner ER (p(0.001) and total ER ROM (p(0.001) than the left in both groups. Conclusions: Ballet dancers have greater inner range, angle specific strength and inner range ER ROM, demonstrated by a shift in the dancers' strength curves. This shift in the strength curve towards the inner range of hip ER may be an adaptive training response.

The cyclin-dependent kinase 5 (Cdk5) plays an important role in the proper establishment of neocortical layers. Over the past several years, key molecular targets of Cdk5 have been identified that show intriguing connections to the adhesional and cytoskeletal components of cell movement. This molecular knowledge about Cdk5 signaling has begun to translate into an understanding of how Cdk5 regulates the cellular physiology of neocortical layer formation. Together with recent progress on the signaling relationship between Cdk5 and Reelin, the other key protein involved in neocortical layer formation, and their relationship to migration modes, research on understanding neocortical layer formation has arrived at a most promising crossroad.

Background Women with pregnancy-related pelvic girdle pain (PPGP) report diminished ability to perform physical activities and experience higher rates of mood disorders, such as anxiety and depression, than pregnant women without PPGP. Despite these physical and psychological impacts, little is known about the lived experiences of PPGP amongst Australian women and the ways in which they cope. Situated within biographical disruption and social support theories, this study sought to gain a conceptual understanding of the experience and impact of PPGP on daily life, and how women cope with this condition during pregnancy. Methods A qualitative research design, situated within a phenomenological framework, using individual, semi-structured interviews consisting of open-ended questions was used with a flexible and responsive approach. Purposive sampling of pregnant women attending a single hospital included 20 participants between 14 and 38 weeks gestation, classified with PPGP as per recommended guidelines, with a mean (SD) age of 31.37 (4.16) years. Thematic analysis was performed where interview data was transcribed, coded, grouped into meaningful categories and then constructed into broad themes. Results Three themes were identified: 1. a transformed biography; 2. coping strategies; and 3. what women want. The pain experienced created a dramatic change in women’s lives, making the pregnancy difficult to endure. Women utilised social support, such as family, to help them cope with pain, and a self-care approach to maintain a positive mindset and reduce stress. Although a few women received support from healthcare professionals, many reported a lack information on PPGP and limited societal recognition of the condition. Women wanted early education, personalised information and prompt referral to help them cope with PPGP. Conclusions Findings from this study highlighted the complexity of living with PPGP as women attempted to deal with the unexpected impact on daily life by seeking support from partners and families, while also struggling with societal expectations. Although women with PPGP used a number of coping strategies, they sought greater support from healthcare professionals to effectively manage PPGP. These findings have important implications for the provision of health care to women living with PPGP. Trial registration Australian New Zealand Clinical Trials Registry: ACTRN12618001423202.