Molecular basis of altered excitability in Shaker mutants of Drosophila melanogaster.

Mutations in the Shaker (Sh) locus of Drosophila melanogaster have differing effects on action potential duration and repolarization in neurons as well as on A-type K+ channels (I(A)) in muscle. The molecular basis of three exemplary Sh alleles (Sh(KS133), Sh(E62) and Sh5) has been identified. They are point mutation in the Sh transcription unit expressing aberrant voltage-gated A-type K+ channels. Replicas of each mutation have been introduced by in vitro mutagenesis into Sh cDNA. The expression of in vitro transcribed mutant Sh cRNA in Xenopus laevis oocytes reproduced the specific phenotypic traits of each Sh allele. The lack of I(A) in Sh(KS133) is due to a missense mutation within a sequence motif occurring in all hitherto characterized voltage-gated K+ channel forming proteins. The reduction of I(A) in Sh(E62) is due to a mutation in an AG acceptor site. The intervening sequence between exon 19 and 20 is not spliced in Sh(E62) RNA. As a consequence Sh(E62) flies do not contain the full complement of Sh K+ forming proteins. Finally, the Sh5 mutation leads to an altered voltage dependence of K+ channel activation and inactivation as well as to an accelerated rate of recovery from inactivation. This is due to a missense mutation altering the amino acid sequence of the proposed transmembrane segment S5 of the Sh K+ channels. Segment S5 is located adjacently to the presumed voltage sensor of voltage-gated ion channels. The results explain the altered properties of excitable cells in Sh mutants and provide a general model for the possible role of A-type K+ channels in modulation action potential profiles

Alternative job search strategies in remote rural and peri-urban labour markets: the role of social networks

This paper examines the importance of informal methods (especially social networking) to the job search strategies used by unemployed people. It compares three areas: a small rural town; a larger, more sparsely populated, remote rural area; and a centrally-located, peri-urban labour market. The analysis is based first on survey research undertaken with 490 job seekers across the study areas. Emerging issues were then followed up during a series of twelve focus groups. The survey research showed that job seekers in the rural study areas were significantly more likely to use social networks to look for work. However, those who had experienced repeated or long-term periods out of work, the unskilled and young people were significantly less likely to use such networks. Focus groups confirmed the perceived importance of social networking to the job search process in rural areas, in contrast to the more marginal role such methods appear to play in peri-urban settings. For many rural job seekers, formal job search activities conducted through Jobcentres were seen as largely symbolic, lacking the practical value of social networking. These results suggest that service providers seeking to assist unemployed people in rural areas need to address the problems faced by many disadvantaged job seekers who are currently caught between their lack of social network relations and the absence of local public employment service facilities in more remote communities

Ototoxicity of cisplatin plus standard radiation therapy vs. accelerated radiation therapy in glioblastoma patients

Purpose : To assess the effect of cisplatin (CDDP) plus concurrent radiation therapy on hearing loss. Methods : 451 patients with glioblastoma multiforme (GBM) were randomly assigned after surgery to: Arm A: Carmustine (BCNU) + standard radiation therapy (SRT); Arm B: BCNU + accelerated radiation therapy (ART: 160 cGy twice daily for 15 days); Arm C: CDDP + BCNU + SRT; or Arm D: CDDP + BCNU + ART. Patients on arms C and D received audiograms at baseline, and prior to the start of RT, and prior to cycles 3 and 6. Otologic toxicities were recorded at each visit. Results : 56% of patients had hearing loss at baseline. 13% and 50% of patients experienced worsening ototoxicity after 1 year of treatment in arms A and B vs. C and D, respectively, with 13% of those on arms C and D experiencing significant ototoxicity (≥ grade 3) at 6 months. Increasing age was associated with an increased risk of ototoxicity. Conclusions : Increased exposure to CDDP increases the risk of ototoxicity over time. Older patients are more susceptible to hearing loss with CDDP. The low proportion of patients with clinically significant ototoxicity suggests that baseline screening is unnecessary in GBM patients.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43476/1/11060_2005_Article_9049.pd

Residential mobility, housing tenure and the labour market in Britain

SIGLEAvailable from British Library Document Supply Centre-DSC:3597.9735(99/35) / BLDSC - British Library Document Supply CentreGBUnited Kingdo

An alternative method of estimating the worker's reservation wage

This study follows the standard bivariate decision theory of employment and proposes an alternative technique to estimate reservation wages of employed, unemployed and out-of-labor-force (OLF) workers. The validity of this approach is demonstrated by testing several reservation wage hypotheses recommended in earlier studies. Using reservation wages estimated under this new approach, the study further examines the determinants of this important variable.Reservation wages, bivariate probit, selection bias, participation decision,