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Whilst the majority (~90-95%) of PD cases are sporadic, much of our understanding of the pathophysiological basis of disease can be traced back to the study of rare, monogenic forms of disease. However, in the past decade, the availability of Genome-Wide Association Studies (GWAS) has facilitated a shift in focus, toward identifying common risk variants conferring an increased risk of developing PD across the population. A recently developed mitophagy screening assay of GWAS candidates, has functionally implicated the non-specific lethal (NSL) complex, a chromatin remodeler, in the regulation of PINK1-mitophagy. Here, a bioinformatics approach has been taken to investigate the interactome of the NSL complex, to unpick its relevance to PD progression. The mitochondrial interactome of the NSL complex has been built, mining 3 separate repositories: PINOT, HIPPIE and MIST, for curated, literature-derived protein-protein interaction (PPI) data. A multi-layered approach has been taken to; i) build the ‘mitochondrial’ NSL interactome, applying PD gene-set enrichment analysis to explore the relevance of the NSL mitochondrial interactome to PD and, ii) build the PD-oriented NSL interactome, using functional enrichment, to uncover biological pathways underpinning the NSL /PD association.

Whilst the majority of PD cases are sporadic, much of our understanding of the pathophysiological basis of disease can be traced back to the study of rare, monogenic forms of disease. In the past decade, the availability of Genome-Wide Association Studies (GWAS) has facilitated a shift in focus, toward identifying common risk variants conferring increased risk of developing PD across the population. A recent mitophagy screening assay of GWAS candidates has functionally implicated the non-specific lethal (NSL) complex in the regulation of PINK1-mitophagy. Here, a bioinformatics approach has been taken to investigate the proteome of the NSL complex, to unpick its relevance to PD progression. The mitochondrial NSL interactome has been built, mining 3 separate repositories: PINOT, HIPPIE and MIST, for curated, literature-derived protein-protein interaction (PPI) data. We built; i) the ‘mitochondrial’ interactome, applying gene-set enrichment analysis (GSEA) to explore the relevance of the NSL mitochondrial interactome to PD and, ii) the PD-oriented interactome to uncover biological pathways underpinning the NSL /PD association. In this study, we find the mitochondrial NSL interactome to be significantly enriched for the protein products of PD associated genes, including the Mendelian PD genesLRRK2andVPS35. Additionally, the PD associated interactome is enriched for mitochondrial processes;“mitochondrial cell death”,“mitochondrial protein localisation”, “membrane protein localisation”and“mitochondrial transport”. Our data points to NSL complex members OGT and WDR5 as key drivers of this increased PD association. These findings strengthen a role for mitochondrial quality control in both familial and sporadic disease.

Whilst the majority (~90-95%) of PD cases are sporadic, much of our understanding of the pathophysiological basis of disease can be traced back to the study of rare, monogenic forms of disease. However, in the past decade, the availability of Genome-Wide Association Studies (GWAS) has facilitated a shift in focus, toward identifying common risk variants conferring an increased risk of developing PD across the population. A recently developed mitophagy screening assay of GWAS candidates, has functionally implicated the non-specific lethal (NSL) complex, a chromatin remodeler, in the regulation of PINK1-mitophagy. Here, a bioinformatics approach has been taken to investigate the interactome of the NSL complex, to unpick its relevance to PD progression. The mitochondrial interactome of the NSL complex has been built, mining 3 separate repositories: PINOT, HIPPIE and MIST, for curated, literature-derived protein-protein interaction (PPI) data. A multi-layered approach has been taken to; i) build the ‘mitochondrial’ NSL interactome, applying PD gene-set enrichment analysis to explore the relevance of the NSL mitochondrial interactome to PD and, ii) build the PD-oriented NSL interactome, using functional enrichment, to uncover biological pathways underpinning the NSL /PD association.

The original version of this article contained references to articles and authors that were blinded.

In this chapter, the authors discuss how digital storytelling expands traditional storytelling options to serve as an integrative approach to (1) deepen student understanding of social studies content, (2) learn history through multiple perspectives, and (3) seek social justice through civics engagement. Most stories told about our history tend to focus on the dominant narrative which portrays an inaccurate depiction of events and individuals. When students move beyond the “single story” of the dominant narrative to explore multiple perspectives, voices, and historical accounts through counter narratives, they develop essential critical thinking skills to help them not only deepen their understanding of content in social studies but to encourage them to actively engage as democratic citizens seeking social justice for a better world.

Whilst encounters in psychology are typically experienced relationally, qualitative dyadic research in psychology is relatively rare. This study used qualitative dyadic research to understand psychological therapy assessments, exploring how experiences are actively created through situated, relational encounters. Seven dyads participated in qualitative semi-structured interviews, predominantly from services for trauma survivors. Thematic dyadic analysis explored a third space, distinct from the experiential knowledge of individuals. We found that clients and assessors balance closeness and distance through enacting aspects of their identities impacting on connection, safety, trust and disclosures. Whilst assessors and clients come together as strangers, human beings, experts, collaborators and, at times, survivors, the key determining factor shaping the encounter is how successfully assessors communicate their humanity. We conclude that dyadic qualitative inquiry is a feasible and rich method for understanding the relational in psychological healthcare encounters.

Purpose Psychotherapy assessments are key decision points for both clients and services, carrying considerable weight on both sides. Limited research indicates that assessments have immediate and long-term impacts on clients, particularly where trauma has been experienced, affecting engagement with therapy. Understanding assessments from clients’ perspectives can inform service development and improve client experience. Methods This is a survivor-led exploration of clients’ experiences of undergoing assessment for talking therapies. Interviews were conducted with seven people who had undergone assessment for psychological therapies in third sector and NHS services. Interviews were recorded, transcribed and analysed thematically. Results The core theme was ‘respect for the journey’ reflecting the need expressed by participants for their life experiences prior to the assessment to be given full respect and consideration. Six sub-themes were identified: trauma and desperation, fear of judgement, search for trust and safety, sharing and withholding (a balancing act), feeling deconstructed, and finding hope. Conclusions The findings highlight the heightened emotional power surrounding psychotherapy assessments, reflecting the journey participants had undertaken to reach this point. The dilemma facing clients at the heart of an assessment—how much to share and how much to withhold—demonstrates the importance for services and assessors of treating the journey a client has made to the assessment with care and respect. Findings indicate the value of services and practitioners undertaking a trauma-informed approach to assessment encounters.

As the digital age broadens opportunities for technology use in the classroom, educators must consider how to use technology to create rich and varied learning opportunities for English learners (E...

This chapter examine the role of self-assessment to center elementary learners' participation and ownership in the learning process. Beginning with a literature review to explore the need for more student-centered assessment practices, the chapter then delves into a description and a classroom vignette to demonstrate the use of three approaches (checklists, rubrics, and open-ended responses) to facilitate self-assessment. The chapter concludes with additional suggestions for application to content area connections and recommendations for digital integration.

Hyponatremia is a known but underrecognized presentation of sellar lesions. Herein, we present a series of patients who presented with single or multiple episodes of hyponatremia.Over 5 years, patients undergoing endonasal surgery for a de novo sellar mass with hyponatremia as an initial presentation were included. Pathology, sodium levels, pituitary hormonal status, and treatment course were documented.Of 282 patients, 16 (5.7%) (9 males, 7 females, age 32 to 84 years) presented with severe hyponatremia, with a mean serum sodium level of 115 ± 6 mmol/L (range, 101 to 125 mmol/L), and 3 patients had 2 or more episodes. Severe hyponatremia was a presenting sign in 0, 4.1, 14.3, and 37.5% of patients with craniopharyngiomas (n = 10), pituitary adenomas (n = 243), Rathke's cleft cysts (RCCs) (n = 21), and sellar arachnoid cysts (n = 8), respectively (P.01). Half of the patients presenting with hyponatremia, including 6 of 10 patients with adenomas and 2 of 3 patients with RCCs, had pituitary apoplexy or cyst rupture. All patients had anterior pituitary gland dysfunction, including 81% with hypoadrenalism and 69% with hypothyroidism. Following surgery, hormonal status was unchanged or improved in 15 patients (median follow-up, 14 months). No patient had tumor/cyst recurrence or recurrent hyponatremia.Severe hyponatremia was a presenting sign in 5.7% of patients with sellar pathology, most frequently in patients with arachnoid cysts, RCCs, and pituitary apoplexy. Patients with new-onset severe hyponatremia and no obvious pharmacologic or systemic cause should undergo pituitary hormonal evaluation and brain imaging. Surgical resection and correction of hormonal deficiencies are associated with resolution of recurrent hyponatremic episodes.

This paper draws on a four-year longitudinal ESRC funded project examining learning experiences of disabled students in higher education in four universities. The focus here is on institutional responses to the demands of audit culture and legislation in relation to making reasonable adjustments for students with impairments. The data comes from institutional documents and face-to-face interviews with key informants within the institutions. The findings indicate that quality assurance regimes and legislation have had some positive effect on improving access for disabled students; however, local factors and type of institution also have a major impact on the way that national policies are expressed in particular contexts.

The chromosome 1q23.3 region, which includes the RGS4 gene has been implicated in genetic susceptibility to schizophrenia by two linkage studies with lod scores of 6.35 and 3.20 and with positive lod between 2.00 and 3.00 scores in several other studies. Reduced post mortem RGS4 gene expression in the brain of schizophrenics was reported as well as positive allelic association between markers at the RGS4 gene locus and schizophrenia. We have attempted to replicate the finding of allelic association with schizophrenia in a UK based sample of 450 subjects with schizophrenia and 450 supernormal controls. We genotyped the same SNP marker alleles investigated in the earlier studies and also a di-nucleotide (GT)(14) repeat microsatellite marker, which was 7 kb distal to RGS4. In the new UK sample there was no evidence for allelic or haplotypic association between RGS4 markers and schizophrenia. This might reflect genetic heterogeneity between the population samples, genotyping or other methodological problems. The finding weakens the evidence that mutations or variation in the RGS4 gene have an effect on schizophrenia susceptibility. (c) 2006 Wiley-Liss, Inc.

A survey of students on taught vocational courses finds that the student group is diverse, in terms of prior learning and cultural experiences, and in terms of expectations and priorities. There ar...

Chromosome 5q33 is a region that has previously shown good evidence of linkage to schizophrenia, with four LOD scores >3.00 in independent linkage studies. We studied 450 unrelated white English, Irish, Welsh, and Scottish research subjects with schizophrenia and 450 ancestrally matched supernormal controls. Four adjacent markers at the 5' end of the Epsin 4 gene showed significant evidence of linkage disequilibrium with schizophrenia. These included two microsatellite markers, D5S1403 (P = .01) and AAAT11 (P = .009), and two single-nucleotide-polymorphism markers within the Epsin 4 gene, rs10046055 (P = .007) and rs254664 (P = .01). A series of different two- and three-marker haplotypes were also significantly associated with schizophrenia, as confirmed with a permutation test (HapA, P = .004; HapB, P = .0005; HapC, P = .007; and HapD, P = .01). The Epsin 4 gene encodes the clathrin-associated protein enthoprotin, which has a role in transport and stability of neurotransmitter vesicles at the synapses and within neurons. A genetically determined abnormality in the structure, function, or expression of enthoprotin is likely to be responsible for genetic susceptibility to a subtype of schizophrenia on chromosome 5q33.3.

Background Linkage studies have confirmed that chromosome 1q23.3 is a susceptibility locus for schizophrenia. It was then claimed that markers at the carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase (CAPON) gene showed allelic association with schizophrenia in Canadian families. A second Chinese study found a base pair polymorphism at the CAPON gene also associated with schizophrenia. Methods We attempted replication using eight markers from the Canadian study in a UK based sample of 450 cases and 450 supernormal controls. Results We found no evidence for allelic or haplotypic association with schizophrenia for any of the markers found to be associated in the Canadian sample. Conclusions The negative results might reflect genetic heterogeneity between the Canadian, Chinese and UK samples or be due to methodological problems. The present finding weakens the evidence that mutations or variation in the CAPON gene are causing genetic susceptibility to schizophrenia in European populations.

View From the Chalkboard essays share readers’ reflections on teaching experiences, advice for new teachers, and perspectives on current issues.