Developing the repository manager community

This paper describes activities which have taken place within the UK institutional repository (IR) sector focusing on developing a community of practice through the sharing of experiences and best practice. This includes work done by the UK Council of Research Repositories (UKCoRR) and other bodies, together with informal activities, such as sharing the experience of organising Open Access Week events. The paper also considers future work to be undertaken by UKCoRR to continue developing the community

USP4 is regulated by Akt phosphorylation and deubiquitylates TGF-beta type I receptor

Stability and membrane localization of Transforming growth factor-β (TGF-β) type I receptor (TβRI) is essential for controlling TGF-β signaling. TβRI is targeted for ubiquitination-mediated degradation by Smad7/Smurf2 complex. However, it is unclear whether polyubiquitin modified TβRI can be reversed. Here we performed a genome-wide gain of function screen and identified ubiquitin-specific protease (USP) 4 as a strong inducer of TGF-β signaling. Putative oncogenic USP4 was found to interact with TβRI as deubiquitinating enzyme thus maintains TβR1 levels at the plasma membrane. Depletion of USP4 mitigates TGF-β-induced breast cancer cell migration, epithelial to mesenchymal transition and metastasis. Importantly, Akt/Protein kinase B (PKB), which has been associated with poor prognosis in breast cancer, associates with and phosphorylates USP4. Akt mediated phosphorylation relocates USP4 to cytoplasm and membrane and is required for maintaining its protein stability. Moreover, Akt-induced breast cancer cell migration was inhibited by USP4 depletion and TβRI kinase inhibition. Our results identified USP4 as an important determinant for crosstalk between TGF-β and Akt, which provides new opportunities for cancer treatment

Minimally Invasive Access to the Pericardium for the Active and Adjustable Cardiac Support Device

According to the American Heart Association, congestive heart failure affected 5.7 million Americans age 20 and older in 2006, and had an estimated direct and indirect cost of $37.2 billion in 2009. Heart assist devices are proving useful in a population where the demand for donor hearts is much greater than the supply. These technologies have successfully improved heart function, but current devices bypass heart pathways, and require invasive surgical methods for placement. Dr. Criscione proposed the Active and Adjustable Cardiac Support Device (AACSD) that allows the heart to maintain some intrinsic motion to restore normal function in the myocytes of a failing heart. Ventricular recovery follows the uniform application of pressure, working on the principle that mechanical stimuli are the key to repairing a mechanical organ. There is a need for a less invasive surgical technique to place the AACSD into the pericardial space. The Pericardial Access and Support System (PASS) is designed to gain access to the pericardium through a 1-2 inch sub-xiphoid incision in ovine models, reducing recovery time, trauma, and costs of the surgery. The design process followed FDA design controls intended to produce a safe and effective device. This includes forming user needs and product function into design input requirements and translating requirements into detailed design specifications. Verification plans were made to confirm that the specifications are consistent with the requirements. Once a physical device is manufactured, validation will ensure that the product satisfies user needs

Executive functions and the ω-6-to-ω-3 fatty acid ratio: a cross-sectional study

BACKGROUND: The ω-6 (n-6) to ω-3 (n-3) fatty acid (FA) ratio (n-6:n-3 ratio) was previously shown to be a predictor of executive function performance in children aged 7-9 y. OBJECTIVE: We aimed to replicate and extend previous findings by exploring the role of the n-6:n-3 ratio in executive function performance. We hypothesized that there would be an interaction between n-3 and the n-6:n-3 ratio, with children with low n-3 performing best with a low ratio, and those with high n-3 performing best with a high ratio. DESIGN: Children were recruited on the basis of their consumption of n-6 and n-3 FAs. The executive function performance of 78 children aged 7-12 y was tested with the use of the Cambridge Neuropsychological Test Automated Battery and a planning task. Participants provided blood for plasma FA quantification, and the caregiver completed demographic and activity questionnaires. We investigated the role of the n-6:n-3 ratio in the entire sample and separately in children aged 7-9 y (n = 41) and 10-12 y (n = 37). RESULTS: Dietary and plasma n-6:n-3 ratio and n-3 predicted performance on working memory and planning tasks in children 7-12 y old. The interaction between dietary n-6:n-3 ratio and n-3 predicted the number of moves required to solve the most difficult planning problems in children aged 7-9 y and those aged 10-12 y, similar to results from the previous study. There was also an interaction between the plasma n-6:n-3 ratio and n-3 predicting time spent thinking through the difficult 5-move planning problems. The n-6:n-3 ratio and n-3 predicted executive function performance differently in children aged 7-9 y and in those aged 10-12 y, indicating different optimal FA balances across development. CONCLUSIONS: The n-6:n-3 ratio is an important consideration in the role of FAs in cognitive function, and the optimal balance of n-6 and n-3 FAs depends on the cognitive function and developmental period studied. This trial was registered at clinicaltrials.gov as NCT02199808

The archaeal transamidosome for RNA-dependent glutamine biosynthesis

Archaea make glutaminyl-tRNA (Gln-tRNAGln) in a two-step process; a non-discriminating glutamyl-tRNA synthetase (ND-GluRS) forms Glu-tRNAGln, while the heterodimeric amidotransferase GatDE converts this mischarged tRNA to Gln-tRNAGln. Many prokaryotes synthesize asparaginyl-tRNA (Asn-tRNAAsn) in a similar manner using a non-discriminating aspartyl-tRNA synthetase (ND-AspRS) and the heterotrimeric amidotransferase GatCAB. The transamidosome, a complex of tRNA synthetase, amidotransferase and tRNA, was first described for the latter system in Thermus thermophilus [Bailly, M., Blaise, M., Lorber, B., Becker, H.D. and Kern, D. (2007) The transamidosome: a dynamic ribonucleoprotein particle dedicated to prokaryotic tRNA-dependent asparagine biosynthesis. Mol. Cell, 28, 228–239.]. Here, we show a similar complex for Gln-tRNAGln formation in Methanothermobacter thermautotrophicus that allows the mischarged Glu-tRNAGln made by the tRNA synthetase to be channeled to the amidotransferase. The association of archaeal ND-GluRS with GatDE (KD = 100 ± 22 nM) sequesters the tRNA synthetase for Gln-tRNAGln formation, with GatDE reducing the affinity of ND-GluRS for tRNAGlu by at least 13-fold. Unlike the T. thermophilus transamidosome, the archaeal complex does not require tRNA for its formation, is not stable through product (Gln-tRNAGln) formation, and has no major effect on the kinetics of tRNAGln glutamylation nor transamidation. The differences between the two transamidosomes may be a consequence of the fact that ND-GluRS is a class I aminoacyl-tRNA synthetase, while ND-AspRS belongs to the class II family

Fatty Acids and Executive Functions: Behavioral Performance and Cortical Activation Across the Lifespan

An imbalance in the omega-6 to omega-3 fatty acid ratio may be a preventable contributor to cognitive deficits across the lifespan. Omega-6 and omega-3 fatty acids are integral to neuronal growth and communication in the hippocampus and frontal cortex, brain areas that subserve executive functions (EF). EF are higher order cognitive functions that control thoughts, behaviors, and emotions. The present study focused on how the balance of omega-6 and omega-3 fatty acids contributes to EF in children 7 to 12 years old and older adults 65 to 79 years old. One hundred fifty-two children were screened for their omega-6 and omega-3 fatty acid intake using three 24-hour diet recalls, and 78 children representing equal recruitment of nine fatty acid intake patterns completed standardized measures of memory, working memory, and planning and one novel planning task, the Electric Maze Task (EMT). Near-infrared spectroscopy (NIRS) data were also collected. Eighty-eight older adults recruited for a study of cognitive decline also completed standardized measures of memory, working memory, and visual processing. The omega-6 to omega-3 ratio predicted performance on EF tasks among the children and older adults. The younger children (7- to 9-year-olds) and oldest adults (75- to 79-year-olds) benefitted from balanced ratios (e.g., low omega-3 and low omega-6). The older children (10- to 12-year-olds) and youngest adults (65- to 69-year-olds) benefitted from imbalanced ratios (e.g., high omega-3 and low omega-6). The ratio also predicted brain activity in the right and central prefrontal cortex associated with better performance on the EMT and planning problems. The balance of fatty acids likely supports the flexible use of prefrontal cortical resources necessary for complex EF. Different balances of omega-6 and omega-3 fatty acids are optimal at different points in development, and additional work with the omega-6 to omega-3 ratio will help elucidate the optimal diet for cognitive function across the lifespan.Doctor of Philosoph

Sibling placement in foster care: exploring the context and possibility of sibling separation

Sibling placement in foster care has long been a contentious topic of discussion. The decision or desire to place siblings together when they must enter foster care has been based on policies, procedures, and strong preferences of child welfare agencies. There is much literature and research supporting the practice of placing siblings together; however little empirical research examining the context and possibility of sibling separation as it relates to foster parent and social worker perceptions has been conducted. Research based primarily on mixed methods of quantitative and quantitative aspects was undertaken and a small online survey conducted exploring: the experiences of foster parents caring for sibling groups in Newfoundland and Labrador (NL); the conditions under which separating siblings support the development of each child in the sibling group; and what foster parents and social workers think about separating siblings who are in care in the same home

Developing 11-13 year old students’ conceptual understanding of rational numbers : a case study investigating effective teacher pedagogical actions in a mathematics classroom : a thesis presented in partial fulfilment of the requirements for the degree of Master of Education in Mathematics Education at Massey University, Albany, New Zealand

Rational numbers, encompassing fractions, percentages, and decimals, are challenging for many students to understand. Research often focuses on the teaching and learning of these topics in isolation, rather than as part of the broader concept of rational numbers. However, there is limited research on the teaching practices that effectively support students’ overall understanding of rational numbers. This study explores the teacher actions that help students develop a conceptual understanding of rational numbers and examines how students demonstrate their growing understanding. A case study and qualitative methods were chosen for this research. The study involved one teacher and a class of 24 Year 7 and 8 students from an urban school in New Zealand. The teacher facilitated eight lessons focused on rational numbers, which included collaborative mathematical discussions. A variety of data were collected and analysed, including interviews, video recorded classroom observations, and examples of student work. The findings revealed that when teachers design lessons around real-world mathematical tasks, promote collaborative discourse, and encourage the use of mathematical practices, students develop a deeper understanding of rational numbers. Additionally, using visual representations and explicitly connecting different forms of rational number representations helped enhance students’ mathematical understanding. This study contributes to the literature on how primary school teachers can effectively support students in developing a strong understanding of rational number concepts. It highlights that teacher content knowledge, combined with purposeful teaching strategies, can provide greater opportunities for students to develop a deeper understanding of rational numbers

Participatory arts and affective engagement with climate change: the missing link in achieving climate compatible behaviour change?

Despite a growing number of arts based climate change interventions and the importance emphasised in the social psychology literature of achieving affective (emotional) engagement with climate change before climate compatible behaviour change is likely (exactly the kind of engagement the arts and humanities are arguably best at), to date there has been no systematic application of interpretive social science techniques to understand the ways in which these arts based interventions do, or do not, achieve affective public engagement with climate change and hence might hold the key to unlocking broader climate compatible behaviour change. This article makes three key contributions. First, it analyses the literature across social psychology and participatory arts to demonstrate why participatory, climate change based arts interventions could hold the key to more effective approaches to engaging multiple publics in climate compatible behaviour change. Second, using a small sample of participants in an arts based climate change intervention in the Inner Hebrides, Scotland, it demonstrates the potential value of combining social science techniques (in this case Q Methodology) with participatory arts interventions to better understand and learn from the ways in which climate based arts interventions achieve affective public engagement with climate change. Thirdly, it extends its analysis to engage explicitly with the under-researched issue of the role of place attachment and local, situated knowledge in mediating the influence of climate change communication. These contributions provide the basis for a significant new research and policy agenda looking forward

Comparative analysis of the lambda-interferons IL-28A and IL-29 regarding their transcriptome and their antiviral properties against hepatitis C virus.

Specific differences in signaling and antiviral properties between the different Lambda-interferons, a novel group of interferons composed of IL-28A, IL-28B and IL-29, are currently unknown. This is the first study comparatively investigating the transcriptome and the antiviral properties of the Lambda-interferons IL-28A and IL-29. Expression studies were performed by microarray analysis, quantitative PCR (qPCR), reporter gene assays and immunoluminometric assays. Signaling was analyzed by Western blot. HCV replication was measured in Huh-7 cells expressing subgenomic HCV replicon. All hepatic cell lines investigated as well as primary hepatocytes expressed both IFN-λ receptor subunits IL-10R2 and IFN-λR1. Both, IL-28A and IL-29 activated STAT1 signaling. As revealed by microarray analysis, similar genes were induced by both cytokines in Huh-7 cells (IL-28A: 117 genes; IL-29: 111 genes), many of them playing a role in antiviral immunity. However, only IL-28A was able to significantly down-regulate gene expression (n = 272 down-regulated genes). Both cytokines significantly decreased HCV replication in Huh-7 cells. In comparison to liver biopsies of patients with non-viral liver disease, liver biopsies of patients with HCV showed significantly increased mRNA expression of IL-28A and IL-29. Moreover, IL-28A serum protein levels were elevated in HCV patients. In a murine model of viral hepatitis, IL-28 expression was significantly increased. IL-28A and IL-29 are up-regulated in HCV patients and are similarly effective in inducing antiviral genes and inhibiting HCV replication. In contrast to IL-29, IL-28A is a potent gene repressor. Both IFN-λs may have therapeutic potential in the treatment of chronic HCV