Transcriptional regulation of PRPF31 gene expression by MSR1 repeat elements causes incomplete penetrance in retinitis pigmentosa.

PRPF31-associated retinitis pigmentosa presents a fascinating enigma: some mutation carriers are blind, while others are asymptomatic. We identify the major molecular cause of this incomplete penetrance through three cardinal features: (1) there is population variation in the number (3 or 4) of a minisatellite repeat element (MSR1) adjacent to the PRPF31 core promoter; (2) in vitro, 3-copies of the MSR1 element can repress gene transcription by 50 to 115-fold; (3) the higher-expressing 4-copy allele is not observed among symptomatic PRPF31 mutation carriers and correlates with the rate of asymptomatic carriers in different populations. Thus, a linked transcriptional modifier decreases PRPF31 gene expression that leads to haploinsufficiency. This result, taken with other identified risk alleles, allows precise genetic counseling for the first time. We also demonstrate that across the human genome, the presence of MSR1 repeats in the promoters or first introns of genes is associated with greater population variability in gene expression indicating that copy number variation of MSR1s is a generic controller of gene expression and promises to provide new insights into our understanding of gene expression regulation

Transcriptional regulation of PRPF31 gene expression by MSR1 repeat elements causes incomplete penetrance in retinitis pigmentosa.

PRPF31-associated retinitis pigmentosa presents a fascinating enigma: some mutation carriers are blind, while others are asymptomatic. We identify the major molecular cause of this incomplete penetrance through three cardinal features: (1) there is population variation in the number (3 or 4) of a minisatellite repeat element (MSR1) adjacent to the PRPF31 core promoter; (2) in vitro, 3-copies of the MSR1 element can repress gene transcription by 50 to 115-fold; (3) the higher-expressing 4-copy allele is not observed among symptomatic PRPF31 mutation carriers and correlates with the rate of asymptomatic carriers in different populations. Thus, a linked transcriptional modifier decreases PRPF31 gene expression that leads to haploinsufficiency. This result, taken with other identified risk alleles, allows precise genetic counseling for the first time. We also demonstrate that across the human genome, the presence of MSR1 repeats in the promoters or first introns of genes is associated with greater population variability in gene expression indicating that copy number variation of MSR1s is a generic controller of gene expression and promises to provide new insights into our understanding of gene expression regulation

Injectable dual-gelling cell-laden composite hydrogels for bone tissue engineering

The present work investigated the osteogenic potential of injectable, dual thermally and chemically gelable composite hydrogels for mesenchymal stem cell (MSC) delivery in vitro and in vivo. Composite hydrogels comprising copolymer macromers of N-isopropylacrylamide were fabricated through the incorporation of gelatin microparticles (GMPs) as enzymatically digestible porogens and sites for cellular attachment. High and low polymer content hydrogels with and without GMP loading were shown to successfully encapsulate viable MSCs and maintain their survival over 28 days in vitro. GMP incorporation was also shown to modulate alkaline phosphatase production, but enhanced hydrogel mineralization along with higher polymer content even in the absence of cells. Moreover, the regenerative capacity of 2 mm thick hydrogels with GMPs only, MSCs only, or GMPs and MSCs was evaluated in vivo in an 8 mm rat critical size cranial defect for 4 and 12 weeks. GMP incorporation led to enhanced bony bridging and mineralization within the defect at each timepoint, and direct bone-implant contact as determined by microcomputed tomography and histological scoring, respectively. Encapsulation of both GMPs and MSCs enabled hydrogel degradation leading to significant tissue infiltration and osteoid formation. The results suggest that these injectable, dual-gelling cell-laden composite hydrogels can facilitate bone ingrowth and integration, warranting further investigation for bone tissue engineering

Shifting tides: Reflecting on regional aspects of our roles as comparative and international educators

In this paper, we critically interrogate the way in which comparative and international education coursework at two large institutions in Australia and New Zealand embody or challenge teleological, colonial, and Western/Northern-centric perspectives on education and development.  Embedded within a broader and introspective examination of our roles as comparative and international educators in these universities, we deconstruct the intent behind our course objectives, readings, lecture content and assessment tasks, and place them into conversation with our own pedagogical self-reflections, observations of practice and student feedback.  In doing so, we highlight ways in which we believe we are beginning to prepare a new generation of more critically conscious, and regionally-minded set of teachers, development practitioners and researchers.  Specifically, by ’making the familiar strange,’ and encouraging our students to co-construct knowledge, we argue we can begin to create actionable spaces which encourage an alternative reading of the world; something colleagues from across Oceania and further afield have long argued for as part of the decolonizing process.  We also highlight how this process has led us to better recognize our own positionalities and epistemologies as CIE educators, in hopes that it can lead to an ongoing space for dialogue between educators and researchers within and beyond the region.

Cyclohexanedione as the negative electrode reaction for organic redox flow batteries

The electrochemical reduction and oxidation of cyclohexanedione is evaluated for the first time as the negative electrode reaction in an organic redox flow battery. Electrochemical characterization indicates that the redox reaction of cyclohexanedione is a proton-coupled electron transfer process with quasi-reversible behavior in acidic media (pH 2 M) and exhibit reduction process with up to 4 electrons transferred

Medium-chain triglyceride supplementation may increase working memory in older adults: A pilot study

Poster presentatio

Defense spending and economic growth in Asian economies: A panel error-correction approach

Hoping to contribute to the existing pool of literature, this paper examines the relationship between military expenditure and economic growth in selected Asian countries for the period 1989 to 2004. Our panel unit root test suggests that real GDP per capita and military expenditures are I (1) processes, while the Larsson et al. (2001) panel cointegration test indicates that economic growth and military expendirues are cointegrated. Finally, applying the panel error-correction technique proposed by Pesaran et al. (1999), our empirical results show that defense spending and economic growth in the Asian countries under the period of study are not related

Defense spending and economic growth in Asian economies: A panel error-correction approach

Hoping to contribute to the existing pool of literature, this paper examines the relationship between military expenditure and economic growth in selected Asian countries for the period 1989 to 2004. Our panel unit root test suggests that real GDP per capita and military expenditures are I (1) processes, while the Larsson et al. (2001) panel cointegration test indicates that economic growth and military expendirues are cointegrated. Finally, applying the panel error-correction technique proposed by Pesaran et al. (1999), our empirical results show that defense spending and economic growth in the Asian countries under the period of study are not related

Regional Income Disparity In Malaysia: Is Sabah Converging, Catching-Up With Or Falling Behind Other States In Malaysia?

Whether poor economies tend to converge towards rich ones or else to diverge over time is an issue that has attracted the attention of policymakers and academics alike for some decades. Economic convergence or divergence is a topic of considerable interest and debate, not only for validating or otherwise the two leading and competing growth models (the neoclassical and the endogenous growth approaches) but also for its policy-oriented implications. In Malaysia, the issue of economic convergence is also much debated. Despite the various Malaysia Plans for the past three decades, regional disparity between states remains. Thus, the objective of the present paper is to address the question whether the state of Sabah has been converging, catching-up or falling behind the other states in Malaysia. Using annual data for the period 1965 to 2003, our univariate unit root test result suggest that the state of Sabah has been catching-up with other states except with the state of Terengganu. In this respect, the local government has an important role to play in enhancing growth by providing stable economic environment for investment and other productive economic activities. This will ensure convergence can take place in the future