Reversal of β cell de-differentiation by a small molecule inhibitor of the TGFβ pathway

Dysfunction or death of pancreatic β cells underlies both types of diabetes. This functional decline begins with β cell stress and de-differentiation. Current drugs for type 2 diabetes (T2D) lower blood glucose levels but they do not directly alleviate β cell stress nor prevent, let alone reverse, β cell de-differentiation. We show here that Urocortin 3 (Ucn3), a marker for mature β cells, is down-regulated in the early stages of T2D in mice and when β cells are stressed in vitro. Using an insulin expression-coupled lineage tracer, with Ucn3 as a reporter for the mature β cell state, we screen for factors that reverse β cell de-differentiation. We find that a small molecule inhibitor of TGFβ receptor I (Alk5) protects cells from the loss of key β cell transcription factors and restores a mature β cell identity even after exposure to prolonged and severe diabetes. DOI: http://dx.doi.org/10.7554/eLife.02809.00

Genetic Circuitry of Survival Motor Neuron, the Gene Underlying Spinal Muscular Atrophy

The clinical severity of the neurodegenerative disorder spinal muscular atrophy (SMA) is dependent on the levels of functional Survival Motor Neuron (SMN) protein. Consequently, current strategies for developing treatments for SMA generally focus on augmenting SMN levels. To identify additional potential therapeutic avenues and achieve a greater understanding of SMN, we applied in vivo, in vitro, and in silico approaches to identify genetic and biochemical interactors of the Drosophila SMN homolog. We identified more than 300 candidate genes that alter an Smn-dependent phenotype in vivo. Integrating the results from our genetic screens, large-scale protein interaction studies, and bioinformatic analysis, we define a unique interactome for SMN that provides a knowledge base for a better understanding of SMA.Stem Cell and Regenerative Biolog

The Internet as a Small Business E-Commerce Ecosystem.

The purpose of this chapter is to analyse how the ecosystem concept can be applied to small businesses and how the Internet and e-commerce can help SMEs harness the required resources to enhance their competitive performance in the marketplace. The chapter will investigate the wide variety of e-commerce applications that are available to small businesses to help address the issue of limited resources. It will provide an ecosystem map illustrating how each functional area of a small business can utilise Internet e-commerce applications to enhance their resource base. The chapter also explores the opportunities and threats that the e-commerce ecosystem model poses for small, medium-sized enterprises (SMEs). This is based upon empirical research consisting of three focus group interviews undertaken with small and medium-sized retail service firms located in the Herefordshire and Worcestershire regions of the United Kingdom in January–February 2014

Victimisation in the lives of lesbian-identified women in South Africa : implications for clinical assessment and treatment

Few clinical studies have examined victimisation in the lives of lesbian women in South Africa and whether there are distinct implications for psychological treatment. This paper presents the assessment and treatment of a lesbian-identified South African survivor of childhood sexual abuse who, as an adult, was raped and later gang raped. Her victimisation in adulthood represented ‘corrective rape’ motivated by the prejudiced assumption that the sexuality of lesbian women is pathological and should be ‘corrected’ through rape. This paper lends insights into the role of heterosexism in shaping vulnerability to victimisation and the process of recovery. It provides recommendations for work with sexual minority clients and highlights the implications when there is an absence of safety and support in the external environment

The Intentional Use of Service Recovery Strategies to Influence Consumer Emotion, Cognition and Behaviour

Service recovery strategies have been identified as a critical factor in the success of. service organizations. This study develops a conceptual frame work to investigate how specific service recovery strategies influence the emotional, cognitive and negative behavioural responses of . consumers., as well as how emotion and cognition influence negative behavior. Understanding the impact of specific service recovery strategies will allow service providers' to more deliberately and intentionally engage in strategies that result in positive organizational outcomes. This study was conducted using a 2 x 2 between-subjects quasi-experimental design. The results suggest that service recovery has a significant impact on emotion, cognition and negative behavior. Similarly, satisfaction, negative emotion and positive emotion all influence negative behavior but distributive justice has no effect

The impacts of Information and Communications Technology (ICT) and E-commerce on bilateral trade flows

This study examines the impact of Internet and e-commerce adoption on bilateral trade flows using a panel of 21 developing- and least-developed countries and 30 OECD countries. Given the commitment of East African Community (EAC) to become the frontrunner in export-led economy across the African continent, special attention is dedicated to analyse the role of ICT and e-commerce on EAC’s export performance. The empirical results indicate that better access to the modern ICT and adoption of e-commerce applications stimulate bilateral trade flows at various levels. The study notes that the efficient use of ICT equipped with high speed internet and secured servers is a crucial milestone for unlocking the e-trade potentials for developing- and least-developed counties

Suitability and managerial implications of a Master Surgical Scheduling approach

Abstract: Operating room (OR) planning and scheduling is a popular and challenging subject within the operational research applied to health services research (ORAHS). However, the impact in practice is very limited. The organization and culture of a hospital and the inherent characteristics of its processes impose specific implementation issues that affect the success of planning approaches. Current tactical OR planning approaches often fail to account for these issues.Master surgical scheduling (MSS) is a promising approach for hospitals to optimize resource utilization and patient flows. We discuss the pros and cons of MSS and compare MSS with centralized and decentralized planning approaches. Finally, we address various implementation issues of MSS and discuss its suitability for hospitals with different organizational foci and culture

DISPLACE study shows poor quality of transcranial Doppler ultrasound for stroke risk screening in sickle cell anemia

Children with sickle cell anemia (SCA) are at increased risk of stroke when compared with their age-based counterparts. The Stroke Prevention Trial in Sickle Cell Anemia (STOP) previously demonstrated that with the use of transcranial Doppler ultrasound (TCD; Sickle Stroke Screen) and chronic red cell transfusion, the risk of stroke is reduced by over 90%. The STOP criteria detailed the type and method of measurement required; the time-averaged mean maximum velocity (TAMMV). Unfortunately, it has been difficult to adhere to the appropriate TAMMV measurements. The objectives of this study were to assess the quality of TCD and transcranial Doppler imaging (TCDi) reports to determine the report quality and accuracy. This is a subanalysis of the DISPLACE (Dissemination and Implementation of Stroke Prevention Looking at the Care Environment) study. Over 12 000 TCD/TCDi reports were collected during this study from 28 institutions; 391 TCDs were reviewed for this subanalysis. There were significant variations in the vessels being assessed, the velocities used to define abnormal results, and who was interpreting the scans. In 52% of reports, it was impossible to identify whether the TAMMV was what was measured. Similarly, it was only clear in 42% of reports that the TAMMV was used to interpret the examination as normal/abnormal. Given this inconsistency, we strongly recommend standardization of TCD/TCDi reporting, specialized training for those performing and interpreting the scans in the use of TCD/TCDi in patients with SCA, internal quality assurance, and institutional quality improvement work to ensure appropriate use of this potentially lifesaving technology