Variation in RTN3 and PPIL2 Genes Does not Influence Platelet Membrane β-Secretase Activity or Susceptibility to Alzheimer’s Disease in the Northern Irish Population

beta-site amyloid precursor protein cleaving enzyme (BACE1) is the rate-limiting enzyme for production of beta-amyloid peptides (A beta), which are proposed to drive the pathological changes found in Alzheimer's disease (AD). Reticulon 3 (RTN3) is a negative modulator of BACE1 (beta-secretase) proteolytic activity, while peptidylprolyl isomerase (cyclophilin)-like 2 (PPIL2) positively regulates BACE1 expression. The present study investigated whether there was any association between genetic variation in RTN3 and PPIL2, and either risk for AD, or levels of platelet beta-secretase activity, in a large Northern Irish case-control sample. Four hundred and sixty-nine patients with a diagnosis of probable AD (NINCDS-ADRDA criteria) and 347 control individuals (MMSE > 28/30) were genotyped. SNPs in both genes were selected by downloading genotype data from the International HapMap Project (Phase II) and tags selected using multimarker approach in Haploview, where r (2) > 0.8 and LOD > 3.0. Non-synonymous SNPs of interest were also included. Genotyping was performed by Sequenom iPLEX and TaqMan technologies. Alleles, genotypes and multi-marker haplotypes were tested for association with AD, and platelet beta-secretase activities were measured for a subset of individuals (n = 231). Eight SNPs in RTN3 and 7 in PPIL2 were genotyped. We found no significant associations between allele, genotype or haplotype frequencies and risk of AD. Further, there was no effect of genotype on platelet membrane beta-secretase activity. We conclude that common or potentially functional genetic variation in these BACE1 interacting proteins does not affect platelet membrane beta-secretase activity or contribute to risk of AD in this population.

Crossing borders through cyberspace: a discussion of a social work education electronic exchange pilot project across the Atlantic

This article discusses a trial electronic exchange project developed between social work education departments in the Republic of Ireland and the USA. It outlines the contemporary significance and challenges of integrating global content into national social work curricula, which are often strongly tied to statutory or accreditation requirements. The mechanics of the exchange are explained and critiqued in detail. An illustrative example of how the transnational students discussed two questions is analyzed. The article finds that an international electronic exchange has great potential to make global social work real to students by allowing them to cross borders through cyberspace, however it requires careful planning and attention to cultural and educational system differences.

Peadiatric social admission

The phenomenon of paediatric social admission describes the hospitalisation of children for medicallynon- urgent and/or social reasons. Much of the research in this field has been in relation to avoidable admissions which have been identified, studied and condoned based on strict medical criteria. Such research has tended to mask the significance of social factors and the commonplace practice of Paediatric Social Admission. This paper examines decision making from the perspective of the health professionals at the clinical coal face. It explores how health professionals are influenced by social, organisational and subjective factors which determine their decision to admit or not to admit a child to hospital. The paper reports findings from interviews with 27 health professionals involved in PSA and a document audit of 21 specific cases. In doing so it begins to address the inherent paradox of responding to a child and families social needs in a medical context.

A case study in group learning and supervision

Student units or the group-based field education and supervision of social work students offer many advantages as an efficient field placement model as well as opportunities for students to learn from each other through sharing knowledge, working collaboratively, hearing different perspectives and discussing issues. Despite the enormous potential of student units, they are a largely uncharted territory. There is a scarcity of literature on the topic and very few guidelines as to the provision of student units. The term student unit covers a broad range of student group learning opportunities and activities. This study explores this model of social work field education and its implications for student field work learning in a group context. The discussion is based on a review of the experiences, opinions and impressions of participants of an actual university based social work student unit.

The paradox of peadiatric social admission

The paradox of paediatric social admission involves the hospitalisation of children for medically non- urgent and/or social reasons. Much of the research in this field has been in relation to avoidable admissions which have been identified, studied and condoned based on strict medical criteria. Such research has tended to mask the significance of social influences and the reasons why health professionals make such decisions. This paper explores social, organisational and subjective influences on medical decision making and is based on study involving interviews with 27 health professionals directly involved in paediatric social admissions (PSA). The findings highlight inherent paradoxes as a consequence of responding to social concerns in a medical context.

BACE1 mRNA Expression in Alzheimer's Disease Postmortem Brain Tissue

ß-site AßPP cleaving enzyme 1 (BACE1) catalyses the rate-limiting step for production of amyloid-ß (Aß) peptides, involved in the pathological cascade underlying Alzheimer's disease (AD). Elevated BACE1 protein levels and activity have been reported in AD postmortem brains. Our study explored whether this was due to elevated BACE1 mRNA expression. RNA was prepared from five brain regions in three study groups: controls, individuals with AD, and another neurodegenerative disease group affected by either Parkinson's disease (PD) or dementia with Lewy bodies (DLB). BACE1 mRNA levels were measured using quantitative realtime PCR (qPCR) and analyzed by qbasePLUS using validated stably-expressed reference genes. Expression of glial and neuronal markers (glial fibrillary acidic protein (GFAP) and neuron-specific enolase (NSE), respectively) were also analyzed to quantify the changing activities of these cell populations in the tissue. BACE1 mRNA levels were significantly elevated in medial temporal and superior parietal gyri, compared to the PD/DLB and/or control groups. Superior frontal gryus BACE1 mRNA levels were significantly increased in the PD/DLB group, compared to AD and control groups. For the AD group, BACE1 mRNA changes were analyzed in the context of the reduced NSE mRNA, and strongly increased GFAP mRNA levels apparent as AD progressed (indicated by Braak stage). This analysis suggested that increased BACE1 mRNA expression in remaining neuronal cells may contribute to the increased BACE1 protein levels and activity found in brain regions affected by AD.

Replication of association between schizophrenia and ZNF804A in the Irish Case-Control Study of Schizophrenia sample

A recent genome-wide association study reported association between schizophrenia and the ZNF804A gene on chromosome 2q32.1. We attempted to replicate these findings in our Irish Case-Control Study of Schizophrenia (ICCSS) sample (N=1021 cases, 626 controls). Following consultation with the original investigators, we genotyped three of the most promising single-nucleotide polymorphisms (SNPs) from the Cardiff study. We replicate association with rs1344706 (trend test one-tailed P=0.0113 with the previously associated A allele) in ZNF804A. We detect no evidence of association with rs6490121 in NOS1 (one-tailed P=0.21), and only a trend with rs9922369 in RGRIP1L (one-tailed P=0.0515). On the basis of these results, we completed genotyping of 11 additional linkage disequilibrium-tagging SNPs in ZNF804A. Of 12 SNPs genotyped, 11 pass quality control criteria and 4 are nominally associated, with our most significant evidence of association at rs7597593 (P=0.0013) followed by rs1344706. We observe no evidence of differential association in ZNF804A on the basis of family history or sex of case. The associated SNP rs1344706 lies in approximately 30 bp of conserved mammalian sequence, and the associated A allele is predicted to maintain binding sites for the brain-expressed transcription factors MYT1l and POU3F1/OCT-6. In controls, expression is significantly increased from the A allele of rs1344706 compared with the C allele. Expression is increased in schizophrenic cases compared with controls, but this difference does not achieve statistical significance. This study replicates the original reported association of ZNF804A with schizophrenia and suggests that there is a consistent link between the A allele of rs1344706, increased expression of ZNF804A and risk for schizophrenia.