Unexpected mode of engagement between enterovirus 71 and its receptor SCARB2

Enterovirus 71 (EV71) is a common cause of hand, foot and mouth disease—a disease endemic especially in the Asia-Pacific region1. Scavenger receptor class B member 2 (SCARB2) is the major receptor of EV71, as well as several other enteroviruses responsible for hand, foot and mouth disease, and plays a key role in cell entry2. The isolated structures of EV71 and SCARB2 are known3,4,5,6, but how they interact to initiate infection is not. Here, we report the EV71–SCARB2 complex structure determined at 3.4 Å resolution using cryo-electron microscopy. This reveals that SCARB2 binds EV71 on the southern rim of the canyon, rather than across the canyon, as predicted3,7,8. Helices 152–163 (α5) and 183–193 (α7) of SCARB2 and the viral protein 1 (VP1) GH and VP2 EF loops of EV71 dominate the interaction, suggesting an allosteric mechanism by which receptor binding might facilitate the low-pH uncoating of the virus in the endosome/lysosome. Remarkably, many residues within the binding footprint are not conserved across SCARB2-dependent enteroviruses; however, a conserved proline and glycine seem to be key residues. Thus, although the virus maintains antigenic variability even within the receptor-binding footprint, the identification of binding ‘hot spots’ may facilitate the design of receptor mimic therapeutics less likely to quickly generate resistance

Comparison of tonic spinal cord stimulation, high-frequency and burst stimulation in patients with complex regional pain syndrome: a double-blind, randomised placebo controlled trial

BACKGROUND: Complex Regional Pain Syndrome (CRPS) is a disabling disease that is sometimes difficult to treat. Although spinal cord stimulation (SCS) can reduce pain in most patients with CRPS, some do not achieve the desired reduction in pain. Moreover, the pain reduction can diminish over time even after an initially successful period of SCS. Pain reduction can be regained by increasing the SCS frequency, but this has not been investigated in a prospective trial. This study compares pain reduction using five SCS frequencies (standard 40 Hz, 500 Hz, 1200 Hz, burst and placebo stimulation) in patients with CRPS to determine which of the modalities is most effective. DESIGN: All patients with a confirmed CRPS diagnosis that have unsuccessfully tried all other therapies and are eligible for SCS, can enroll in this trial (primary implantation group). CRPS patients that already receive SCS therapy, or those previously treated with SCS but with loss of therapeutic effect over time, can also participate (re-implantation group). Once all inclusion criteria are met and written informed consent obtained, patients will undergo a baseline assessment (T0). A 2-week trial with SCS is performed and, if successful, a rechargeable internal pulse generator (IPG) is implanted. For the following 3 months the patient will have standard 40 Hz stimulation therapy before a follow-up assessment (T1) is performed. Those who have completed the T1 assessment will enroll in a 10-week crossover period in which the five SCS frequencies are tested in five periods, each frequency lasting for 2 weeks. At the end of the crossover period, the patient will choose which frequency is to be used for stimulation for an additional 3 months, until the T2 assessment. DISCUSSION: Currently no trials are available that systematically investigate the importance of variation in frequency during SCS in patients with CRPS. Data from this trial will provide better insight as to whether SCS with a higher frequency, or with burst stimulation, results in more effective pain relief. TRIAL REGISTRATION: Current Controlled Trials ISRCTN3665525

Entrepreneurial literacy and skills

Entrepreneurial literacy and skills (ELS) empower European citizens to act on economic opportunities and enable them to adequately respond to ongoing impactful changes, such as the green transition, the ageing workforce and the digitalisation. This research paper analyses relevant empirical indicators of ELS, highlights the role of underrepresented groups in entrepreneurship and discusses EU-funded mechanisms in relation to ELS. The research paper concludes with recommendations on policy-making in order to more effectively foster ELS among EU citizens.This document was provided by the Policy Department for Economic, Scientific and Quality of Life Policies at the request of the committee on Employment and Social Affairs (EMPL)

Towards more synergy in entrepreneurial competence research in entrepreneurship education

To move forward as researchers interested in contributing to the (European) political debate on entrepreneurial competence, on the one hand, and conducting sound scientific research, on the other, we argue that it is time for researchers to move to the next level of entrepreneurial competence research. Therefore, this chapter discusses two important aspects associated with the concept of entrepreneurial competence, namely the ‘what’ and the ‘how’ question. Both questions seem to be common sense, but interestingly the fundaments behind these two questions receive limited attention in the entrepreneurship education (EE) literature. Concerning the ‘what’ question, to prevent the generation of endless lists of competencies we propose to cluster entrepreneurial competencies in four competence domains, including a cognition-orientated, function-oriented, social-oriented and meta-oriented domain. To illustrate the power of using this framework we discuss specific research that has been done on opportunity identification competence, social competence and moral competence. Concerning the ‘how’ question we invite EE research to embrace modern educational design principles that will help to develop targeted theoretical frameworks that direct empirical intervention studies in EE. Examples of pedagogical approaches discussed in this chapter that incorporate modern education principles come from problem-based learning, project-based learning, student-centred learning environments and boundary crossing theory