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Core facilities (CFs) provide a centralised access to costly equipment, scientific expertise, experimental design, day-to-day technical support and training of users. CFs have a tremendous impact on research outputs, skills and educational agendas, increasing the competencies of staff, researchers and students. However, the rapid development of new technologies and methodologies for the life sciences requires fast adaptation and development of existing core facilities and their technical and scientific staff. Given the scarcity of well-defined CF career paths, CF staff positions are typically filled by people having followed either academic or technical tracks. Each academic institution follows different policies and often fails to adequately recognize the merits of CF personnel and to support their training efficiently. Thus, the Core Technologies for Life Science association (CTLS), through the Training working group, has conducted an anonymous online survey to assess the training needs of CF personnel, as well as to identify common characteristics and challenges in this relatively new and dynamic career type. 275 individuals, including core managers and directors, technicians, technologists and administrators, participated in the survey. The survey was divided into 2 sections; the first, applied to all respondents, and the second, specifically targeted core management issues. Training needs in technological areas, financial and soft skills, management and administrative issues were surveyed as well. The lack of clarity and consistency regarding established career paths for CF professionals was evident from the second part of the survey, highlighting geographical or cultural differences. Gender balance was achieved and the distribution was always taken into account. The results of this survey highlight a need to develop better training resources for CF staff, to improve their recognition within academic institutions, and to establish a recognized career pathway., (© Association of Biomolecular Resource Facilities.)

Malformations of cortical development are a group of rare disorders commonly manifesting with developmental delay, cerebral palsy or seizures. The neurological outcome is extremely variable depending on the type, extent and severity of the malformation and the involved genetic pathways of brain development. Neuroimaging plays an essential role in the diagnosis of these malformations, but several issues regarding malformations of cortical development definitions and classification remain unclear. The purpose of this consensus statement is to provide standardized malformations of cortical development terminology and classification for neuroradiological pattern interpretation. A committee of international experts in paediatric neuroradiology prepared systematic literature reviews and formulated neuroimaging recommendations in collaboration with geneticists, paediatric neurologists and pathologists during consensus meetings in the context of the European Network Neuro-MIG initiative on Brain Malformations (https://www.neuro-mig.org/). Malformations of cortical development neuroimaging features and practical recommendations are provided to aid both expert and non-expert radiologists and neurologists who may encounter patients with malformations of cortical development in their practice, with the aim of improving malformations of cortical development diagnosis and imaging interpretation worldwide., (© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Transcriptional interference and transcription through regulatory elements (transcriptional read-through) are implicated in gene silencing and the establishment of DNA methylation. Transcriptional read-through is needed to seed DNA methylation at imprinted genes in the germ line and can lead to aberrant gene silencing by DNA methylation in human disease. To enable the study of parameters and factors influencing transcriptional interference and transcriptional read-through at human promoters, we established a somatic cell culture system. At two promoters of imprinted genes ( UBE3A and SNRPN ) and two promoters shown to be silenced by aberrant transcriptional read-through in human disease ( MSH2 and HBA2 ) we tested, if transcriptional read-through is sufficient for gene repression and the acquisition of DNA methylation. Induction of transcriptional read-through from the doxycycline-inducible CMV promoter resulted in consistent repression of all downstream promoters, independent of promoter type and orientation. Repression was dependent on ongoing transcription, since withdrawal of induction resulted in reactivation. DNA methylation was not acquired at any of the promoters. Overexpression of DNMT3A and DNMT3L, factors needed for DNA methylation establishment in oocytes, was still not sufficient for the induction of DNA methylation. This indicates that induction of DNA methylation has more complex requirements than transcriptional read-through and the presence of de novo DNA methyltransferases., (© 2020 Published by Elsevier Ltd.)

Core Facilities (CF) for advanced light microscopy (ALM) have become indispensable support units for research in the life sciences. Their organizational structure and technical characteristics are quite diverse, although the tasks they pursue and the services they offer are similar. Therefore, throughout Europe, scientists from ALM-CFs are forming networks to promote interactions and discuss best practice models. Here, we present recommendations for ALM-CF operations elaborated by the workgroups of the German network of ALM-CFs, German Bio-Imaging (GerBI). We address technical aspects of CF planning and instrument maintainance, give advice on the organization and management of an ALM-CF, propose a scheme for the training of CF users, and provide an overview of current resources for image processing and analysis. Further, we elaborate on the new challenges and opportunities for professional development and careers created by CFs. While some information specifically refers to the German academic system, most of the content of this article is of general interest for CFs in the life sciences. Microsc. Res. Tech. 79:463-479, 2016. © 2016 THE AUTHORS MICROSCOPY RESEARCH AND TECHNIQUE PUBLISHED BY WILEY PERIODICALS, INC., (© 2016 The Authors Microscopy Research and Technique Published by Wiley Periodicals, Inc.)

We present a fully atomistic Langevin dynamics approach as a method to simulate biopolymers under external forces. In the harmonic regime, this approach permits the computation of the long-term dynamics using only the eigenvalues and eigenvectors of the Hessian matrix of second derivatives. We apply this scheme to identify polymorphs of model proteins by their mechanical response fingerprint, and we relate the averaged dynamics of proteins to their biological functionality, with the ion channel gramicidin A, a phosphorylase, and neuropeptide Y as examples. In an environment akin to dilute solutions, even small proteins show relaxation times up to 50 ns. Atomically resolved Langevin dynamics computations have been performed for the stretched gramicidin A ion channel.

We address the problem of charge transfer (CT) between a nanosized inorganic system and a protein from a theoretical and numerical perspective. The CT process is described on an atomistic level by applying an electronic Hamiltonian that takes into account the chemical bond, vibronic coupling effects, and polarization degrees of freedom. As a structurally well-characterized example, we consider a complex of C60 and its antibody. For this system, we find a novel efficient protein CT mechanism; through-space superexchange is mediated by stacked pi orbital systems. The predicted rates are comparable to those obtained for short-range electron tunneling through covalent bonds, the fastest ground-state CT process known for proteins.