FoxP1 marks medium spiny neurons from precursors to maturity and is required for their differentiation

Identifying the steps involved in striatal development is important both for understanding the striatum in health and disease, and for generating protocols to differentiate striatal neurons for regenerative medicine. The most prominent neuronal subtype in the adult striatum is the medium spiny projection neuron (MSN), which constitutes more than 85% of all striatal neurons and classically expresses DARPP-32. Through a microarray study of genes expressed in the whole ganglionic eminence (WGE: the developing striatum) in the mouse, we identified the gene encoding the transcription factor Forkhead box protein P1 (FoxP1) as the most highly up-regulated gene, thus providing unbiased evidence for the association of FoxP1 with MSN development. We also describe the expression of FoxP1 in the human fetal brain over equivalent gestational stages. FoxP1 expression persisted through into adulthood in the mouse brain, where it co-localised with all striatal DARPP-32 positive projection neurons and a small population of DARPP-32 negative cells. There was no co-localisation of FoxP1 with any interneuron markers. FoxP1 was detectable in primary fetal striatal cells following dissection, culture, and transplantation into the adult lesioned striatum, demonstrating its utility as an MSN marker for transplantation studies. Furthermore, DARPP-32 expression was absent from FoxP1 knock-out mouse WGE differentiated in vitro, suggesting that FoxP1 is important for the development of DARPP-32-positive MSNs. In summary, we show that FoxP1 labels MSN precursors prior to the expression of DARPP-32 during normal development, and in addition suggest that FoxP1 labels a sub-population of MSNs that are not co-labelled by DARPP-32. We demonstrate the utility of FoxP1 to label MSNs in vitro and following neural transplantation, and show that FoxP1 is required for DARPP-32 positive MSN differentiation in vitro

The nature and culture of social work with children and families in long-term casework:Findings from a qualitative longitudinal study

Social work in the United Kingdom is preoccupied with what social workers cannot do due to having limited time to spend with service users. Yet remarkably little research has examined what social workers actually do, especially in long-term relationships. This paper draws from an ethnographic study of two social work departments in England that spent 15 months observing practice and organizational life. Our findings show that social work some of the time has a significant amount of involvement with some service users and the dominant view that relationship-based practice is rarely achieved is in need of some revision. However, families at one research site received a much more substantial, reliable overall service due to the additional input of family support workers and having a stable workforce who had their own desks and were co-located with managers in small team offices. This generated a much more supportive, reflective culture for social workers and service users than at the second site, a large open plan "hot-desking" office. Drawing on relational, systemic, and complexity theories, the paper shows how the nature of what social workers do and culture of practice are shaped by the interaction between available services, office designs, and practitioners', managers', and service users' experiences of relating together

Lack of transketolase-like (TKTL) 1 aggravates murine experimental colitis

Background: Transketolase-like (TKTL) 1 indirectly replenishes NADPH preventing damage induced by reactive oxygen species (ROS) formed upon intestinal inflammation. We investigated the function of TKTL1 during murine colitis and ROS detoxification for prevention of tissue damage. Methods: Mucosal damage in TKTL1(-/-) and wild type (WT) mice was assessed by miniendoscopy and histology during DSS colitis. mRNA levels of IFN-γ, iNOS, IL-6, TNF, transketolase (TKT) and TKTL2 were determined by PCR and/or Western blotting. To assess oxidative and nitrosative stress nitrosylation, carbonylation and anti-oxidative enzymes catalase (Cat), superoxide dismutase (SOD) 1 and 2 as well as glutathione (GSH) were determined. Myeloperoxidase (MPO) was determined for assessment of tissue neutrophils. Results: TKTL1 knock out or DSS treatment did not influence TKT and TKTL2 mRNA or protein expression. Mucosal damage was significantly increased in TKTL1(-/-) mice indicated by miniendoscopy as well as a significant shorter colon and more severe histological scores compared to WT mice during DSS colitis. This was associated with higher mRNA levels of IFN-γ, iNOS, IL-6 and TNF. In addition, iNOS protein expression was significantly enhanced in TKTL1(-/-) mice as well as MPO activity. Protein modification by NO (N-Tyr) was induced in TKTL1(-/-) mice. However, introduction of carbonylgroups by ROS was not induced in these mice. The expression of SOD1, SOD2, Cat as well as GSH content were not significantly changed in TKTL1(-/-) mice. Conclusion: Induced colitis in TKTL1(-/-) mice was more severe as compared to WT. This indicates a role of TKTL1 during mucosal repair and restoration