Dominant-negative variant in SLC1A4 causes an autosomal dominant epilepsy syndrome.

SLC1A4 is a trimeric neutral amino acid transporter essential for shuttling L-serine from astrocytes into neurons. Individuals with biallelic variants in SLC1A4 are known to have spastic tetraplegia, thin corpus callosum, and progressive microcephaly (SPATCCM) syndrome, but individuals with heterozygous variants are not thought to have disease. We identify an 8-year-old patient with global developmental delay, spasticity, epilepsy, and microcephaly who has a de novo heterozygous three amino acid duplication in SLC1A4 (L86_M88dup). We demonstrate that L86_M88dup causes a dominant-negative N-glycosylation defect of SLC1A4, which in turn reduces the plasma membrane localization of SLC1A4 and the transport rate of SLC1A4 for L-serine

Global Globin Network Consensus Paper: Classification and Stratified Roadmaps for Improved Thalassaemia Care and Prevention in 32 Countries

The Global Globin Network (GGN) is a project-wide initiative of the Human Variome/Global Variome Project (HVP) focusing on haemoglobinopathies to build the capacity for genomic diagnosis, clinical services, and research in low- and middle-income countries. At present, there is no framework to evaluate the improvement of care, treatment, and prevention of thalassaemia and other haemoglobinopathies globally, despite thalassaemia being one of the most common monogenic diseases worldwide. Here, we propose a universally applicable system for evaluating and grouping countries based on qualitative indicators according to the quality of care, treatment, and prevention of haemoglobinopathies. We also apply this system to GGN countries as proof of principle. To this end, qualitative indicators were extracted from the IthaMaps database of the ITHANET portal, which allowed four groups of countries (A, B, C, and D) to be defined based on major qualitative indicators, supported by minor qualitative indicators for countries with limited resource settings and by the overall haemoglobinopathy carrier frequency for the target countries of immigration. The proposed rubrics and accumulative scores will help analyse the performance and improvement of care, treatment, and prevention of haemoglobinopathies in the GGN and beyond. Our proposed criteria complement future data collection from GGN countries to help monitor the quality of services for haemoglobinopathies, provide ongoing estimates for services and epidemiology in GGN countries, and note the contribution of the GGN to a local and global reduction of disease burden

Investigating relationship of talent management and organizational entrepreneurship

Introduction: talent management is a comprehensive strategy and an approach to international human resource practices and a commitment to widespread sharing of the belief that human resource is a priority and a source of competitive advantage. Talent management ensures the organizations that competent individuals with the right skills have taken the right position. The aim of this study was to investigate the relationship between talent management and organizational entrepreneurship. Methodology: The present study is an applied one in terms of its nature and purpose, and it is a descriptive and correlational one in terms of the data collection method to test the hypothesis. The population of this study included experts, officials, supervisors and middle and top managers of Golestan province Gas Company who have at least 7 years’ experience. Accordingly, a total number of 51 participated in the study. A questionnaire was used to collect data. Data analysis was carried out through SPSS software for descriptive data and SMART PLS software for inferential data. Results: This study shows that there is a significant positive relationship between talent management and organizational entrepreneurship, and components of each of the main criteria also have a significant relationship with each other. Conclusion: The findings suggest that managers should improve their organization's talent management system in order to increase innovation and competitiveness. These systems can complete and implement various initiatives by creating opportunities to achieve talent resources and providing transparency in selection criteria

Enhanced expression of gene coding for β-endorphin in human monocytic cells exposed to pulsed radio frequency electric fields through thermal and non-thermal effects

Toshiharu Azma,1,2 Akira Nishioka,1 Saori Ogawa,3 Hiroshi Nagasaka,2 Nobuyuki Matsumoto2 1Department of Anesthesiology and Pain Medicine, Kohnodai Hospital, National Center for Global Health and Medicine, Ichikawa, Chiba 272-8516, Japan; 2Department of Anesthesiology, Saitama Medical University Hospital, Moroyama-cho, Iruma-gun, Saitama 350-0495, Japan; 3Department of Dental Anesthesiology, Matsumoto Dental University, Shiojiri, Nagano 399-0781, Japan Background: The enhanced expression of endogenous opioid peptides, including β-endorphin, has been implicated in the mechanism of action of pulsed radio frequency (PRF) application in pain modulation. Because thermal effects cannot be separated from the physical property of PRF application to biological tissues, we evaluated whether temperatures higher than that of the normal body temperature (37°C) modulate mRNA expression for the precursor of β-endorphin, proopiomelanocortin (POMC) in human monocytic cells THP-1. We also attempted to examine whether mechanisms other than thermal effects also modulate such gene expression. Methods and results: The mRNA for POMC in THP-1 cells increased by a 15-minutes incubation at 42°C, 45°C, or 70°C without PRF application as compared with that in cells incubated at 37°C. On the other hand, gene expression for POMC in cells incubated at 20°C as well as at 37°C with PRF application for 15 minutes increased as compared to that in cells incubated at 37°C without PRF application. Continuous radio frequency at 70°C but not PRF provoked apoptotic cell death at 1–2 hour, and necrotic cell death at 24 hours after the RF application. Conclusion: A simple experimental system using human monocytic cells in culture demonstrated that a 15 minute elevation of temperature above 37°C enhanced gene expression for POMC in THP-1 cells, while a 15 minute application of PRF to these cells incubated at 37°C or lower, also enhanced gene expression, indicating that temperature-independent mechanisms as well as thermal effects may be involved in such gene expression. Keywords: pulsed radio frequency electric field, human monocytic cells, THP-1, proopiomelanocortin, β-endorphin, necrosis, apoptosis, apoptotic vesicl

Individual peer assessment of contribution to group work (IPAC): Key points and recommendations

Individual Peer Assessment of Contribution to group work (IPAC) has been widely reported in the literature as successfully addressing problems that arise when students are asked to perform group work, such as complaints of ‘passengers’, and staff and student concerns about fairness of the marks. However, there are multiple variations on how to implement it, which makes it difficult for current and potential users to have an in-depth view and understanding of this assessment method or what works best. A working group was created at University College London (UCL) to look into this methodology (IPAC Consortium). This paper reports the key points of the IPAC methodology, as well as guidelines and recommendations for practice, e.g. make it more useful for students by sharing the feedback. These are informed in the review of relevant literature, discussion with academics and educators, and own experience. We also introduce the software that is currently in use at UCL to implement this practice easily and time efficiently. This is of interest to anyone organizing and running assessed student group work activities, and that is using or might want to use in the future the IPAC methodology

The potential of pineapple leaf fibre as an acoustic absorber

This study discussed an alternative material known as pineapple leaf fibres (PALF) as a replacement of synthetic fibres in sound absorber production. The samples were fabricated from two different sizes of PALF, with and without binder of different thicknesses and densities to determine their effects on the sound absorption coefficient (SAC). The performance of SAC was measured by using an impedance tube instrument according to ISO 10534-2. The resulting frequency peak value of PALF obtained was in the range of 1–2 kHz. The results demonstrated PALF as a new hope for environmentally-friendly sound absorption material in replacing synthetic fibres. The PALF was capable of achieving SAC of more than 0.9 on average above 1 kHz by keeping the densities and thicknesses of the fibres under control. Additionally, the acoustic performance of PALF specimens was better than that of synthetic absorbers available in the market. Therefore, PALF is a promising natural fibre that can be potentially used as a sound absorber material