Deciphering a transcriptional regulatory code: modeling short-range repression in the Drosophila embryo

A well-defined set of transcriptional regulatory modules was created and analyzed in the Drosophila embryo.Fractional occupancy-based models were developed to explain the interaction of short range transcriptional repressors with endogenous activators by using quantitative data from these modules.Our fractional occupancy-based modeling uncovered specific quantitative features of short-range repressors; a complex nonlinear quenching relationship, similar quenching efficiencies for different activators, and modest levels of cooperativityThe extension of the study to endogenous enhancers highlighted several features of enhancer architecture design in Drosophila embryos

Is self-report sleepiness associated with cognitive performance in temporal lobe epilepsy?

Vascouto HD, Rodrigues de Oliveira Thais ME, Osorio CM, et al. Is self-report sleepiness associated with cognitive performance in temporal lobe epilepsy? ARQUIVOS DE NEURO-PSIQUIATRIA. 2018;76(9):575-581.Sleepiness and cognitive impairment are common symptoms observed in patients with epilepsy. We investigate whether self-reported sleepiness is associated with cognitive performance in patients with refractory mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). Seventy-one consecutive patients with MTLE-HS were evaluated with the Stanford Sleepiness Scale (SSS) before neuropsychological evaluation. Their mean SSS scores were compared with controls. Each cognitive test was compared between patients with (SSS >= 3) or without sleepiness (SSS < 3). Imbalances were controlled by regression analysis. Patients reported a significantly higher degree of sleepiness than controls (p < 0.0001). After multiple linear regression analysis, only one test (RAVLT total) remained associated with self-reported sleepiness. Conclusion: Self-reported sleepiness was significantly higher in MTLE-HS patients than controls, but did not affect their cognitive performance. If confirmed in other populations, our results may have implications for decision making about sleepiness screening in neuropsychological settings

Influence of the balanced scorecard on the science and innovation performance of Latin American universities

This is an Accepted Manuscript of an article published by Taylor & Francis in Knowledge Management Research & Practice on 2019, available online: http://www.tandfonline.com/10.1080/14778238.2019.1569488[EN] Pressure on the education system to meet society's needs has led some universities to adopt organisational performance measurement systems as strategic control tools. One of the most commonly used systems in business is the balanced scorecard (BSC). For Latin American universities, the urgent task of increasing the quantity and quality of research and innovation has led these universities to update their essential processes. A suitable control system is necessary to ensure the effectiveness of these new policies. Based on strategic management theory, this study focuses on the implementation of a BSC method in Latin American public universities. The aim of this study is to determine the influence of BSC implementation on universities? research and innovation performance. The results reveal similar patterns of indicators to measure performance in public universities. Furthermore, these indicators develop favourably following implementation of the BSC.Peris-Ortiz, M.; García-Hurtado, D.; Devece Carañana, CA. (2019). Influence of the balanced scorecard on the science and innovation performance of Latin American universities. Knowledge Management Research & Practice. 17(4):373-383. https://doi.org/10.1080/14778238.2019.1569488S373383174Agostino, D., & Arnaboldi, M. (2012). Design issues in Balanced Scorecards: The «what» and «how» of control. European Management Journal, 30(4), 327-339. doi:10.1016/j.emj.2012.02.001Al-Ashaab, A., Flores, M., Doultsinou, A., & Magyar, A. (2011). A balanced scorecard for measuring the impact of industry–university collaboration. Production Planning & Control, 22(5-6), 554-570. doi:10.1080/09537287.2010.536626Ankrah, S., & AL-Tabbaa, O. (2015). Universities–industry collaboration: A systematic review. Scandinavian Journal of Management, 31(3), 387-408. doi:10.1016/j.scaman.2015.02.003Broadbent, J., & Laughlin, R. (2009). Performance management systems: A conceptual model. Management Accounting Research, 20(4), 283-295. doi:10.1016/j.mar.2009.07.004Chen, S., Yang, C., & Shiau, J. (2006). The application of balanced scorecard in the performance evaluation of higher education. The TQM Magazine, 18(2), 190-205. doi:10.1108/09544780610647892Ferreira, A., & Otley, D. (2009). The design and use of performance management systems: An extended framework for analysis. Management Accounting Research, 20(4), 263-282. doi:10.1016/j.mar.2009.07.003Franceschini, F., & Turina, E. (2011). Quality improvement and redesign of performance measurement systems: an application to the academic field. Quality & Quantity, 47(1), 465-483. doi:10.1007/s11135-011-9530-1Gibbert, M., Ruigrok, W., & Wicki, B. (2008). What passes as a rigorous case study? Strategic Management Journal, 29(13), 1465-1474. doi:10.1002/smj.722Ittner, C. D., Larcker, D. F., & Randall, T. (2003). Performance implications of strategic performance measurement in financial services firms. Accounting, Organizations and Society, 28(7-8), 715-741. doi:10.1016/s0361-3682(03)00033-3Kaplan, R. S., & Norton, D. P. (2001). Transforming the Balanced Scorecard from Performance Measurement to Strategic Management: Part II. Accounting Horizons, 15(2), 147-160. doi:10.2308/acch.2001.15.2.147Khalid, S., Knouzi, N., Tanane, O., & Talbi, M. (2014). Balanced Scoreboard, the Performance Tool in Higher Education: Establishment of Performance Indicators. Procedia - Social and Behavioral Sciences, 116, 4552-4558. doi:10.1016/j.sbspro.2014.01.984Kraus, K., & Lind, J. (2010). The impact of the corporate balanced scorecard on corporate control—A research note. Management Accounting Research, 21(4), 265-277. doi:10.1016/j.mar.2010.08.001Langfield-Smith, K. (1997). Management control systems and strategy: A critical review. Accounting, Organizations and Society, 22(2), 207-232. doi:10.1016/s0361-3682(95)00040-2Lawrence, S., & Sharma, U. (2002). Commodification of Education and Academic LABOUR—Using the Balanced Scorecard in a University Setting. Critical Perspectives on Accounting, 13(5-6), 661-677. doi:10.1006/cpac.2002.0562Lee, B., Collier, P. M., & Cullen, J. (2007). Reflections on the use of case studies in the accounting, management and organizational disciplines. Qualitative Research in Organizations and Management: An International Journal, 2(3), 169-178. doi:10.1108/17465640710835337Neely, A., Gregory, M., & Platts, K. (1995). Performance measurement system design. International Journal of Operations & Production Management, 15(4), 80-116. doi:10.1108/01443579510083622Philbin, S. (2008). Process model for university‐industry research collaboration. European Journal of Innovation Management, 11(4), 488-521. doi:10.1108/14601060810911138Pritchard, R. D., Roth, P. L., Jones, S. D., & Roth, P. G. (1990). Implementing feedback systems to enhance productivity: A practical guide. National Productivity Review, 10(1), 57-67. doi:10.1002/npr.4040100107Ridwan, R., Harun, H., An, Y., & Fahmid, I. M. (2013). The Impact of the Balanced Scorecard on Corporate Performance: The Case of an Australian Public Sector Enterprise. International Business Research, 6(10). doi:10.5539/ibr.v6n10p103Sayed, N. (2013). Ratify, reject or revise: balanced scorecard and universities. International Journal of Educational Management, 27(3), 203-220. doi:10.1108/09513541311306440Spender, J.-C. (2014). Business Strategy. doi:10.1093/acprof:oso/9780199686544.001.0001Tangen, S. (2005). Analysing the requirements of performance measurement systems. 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The Unconserved Groucho Central Region Is Essential for Viability and Modulates Target Gene Specificity

Groucho (Gro) is a Drosophila corepressor required by numerous DNA-binding repressors, many of which are distributed in gradients and provide positional information during development. Gro contains well-conserved domains at its N- and C-termini, and a poorly conserved central region that includes the GP, CcN, and SP domains. All lethal point mutations in gro map to the conserved regions, leading to speculation that the unconserved central domains are dispensable. However, our sequence analysis suggests that the central domains are disordered leading us to suspect that the lack of lethal mutations in this region reflects a lack of order rather than an absence of essential functions. In support of this conclusion, genomic rescue experiments with Gro deletion variants demonstrate that the GP and CcN domains are required for viability. Misexpression assays using these same deletion variants show that the SP domain prevents unrestrained and promiscuous repression by Gro, while the GP and CcN domains are indispensable for repression. Deletion of the GP domain leads to loss of nuclear import, while deletion of the CcN domain leads to complete loss of repression. Changes in Gro activity levels reset the threshold concentrations at which graded repressors silence target gene expression. We conclude that co-regulators such as Gro are not simply permissive components of the repression machinery, but cooperate with graded DNA-binding factors in setting borders of gene expression. We suspect that disorder in the Gro central domains may provide the flexibility that allows this region to mediate multiple interactions required for repression

Induction of antigen-specific tolerance through hematopoietic stem cell-mediated gene therapy: the future for therapy of autoimmune disease?

Based on the principle that immune ablation followed by HSC-mediated recovery purges disease-causing leukocytes to interrupt autoimmune disease progression, hematopoietic stem cell transplantation (HSCT) has been increasingly used as a treatment for severe autoimmune diseases. Despite clinically-relevant outcomes, HSCT is associated with serious iatrogenic risks and is suitable only for the most serious and intractable diseases. A further limitation of autologous HSCT is that relapse rates can be high, suggesting disease-causing leukocytes are incompletely purged or the environmental and genetic determinants that drive disease remain active. Incorporation of antigen-specific tolerance approaches that synergise with autologous HSCT could reduce or prevent relapse. Further, by reducing the requirement for highly toxic immune-ablation and instead relying on antigen-specific tolerance, the clinical utility of HSCT could be significantly diversified. Substantial progress has been made exploring HSCT-mediated induction of antigen-specific tolerance in animal models but studies have focussed on primarily on prevention of autoimmune diseases. However, as diagnosis of autoimmune disease is often not made until autoimmune disease is well developed and populations of autoantigen-specific pathogenic effector and memory T cells have become well established, immunotherapies must be developed to address effector and memory T-cell responses which have traditionally been considered the key impediment to immunotherapy. Here, focusing on T-cell mediated autoimmune diseases we review progress made in antigen-specific immunotherapy using HSCT-mediated approaches, induction of tolerance in effector and memory T cells and the challenges for progression and clinical application of antigen-specific ‘tolerogenic’ HSCT therapy