Open practice in science and education – a discussion with researchers and educators who tested to be open

How can we make the shift from closed to open practice in research and education? What are incentives for researchers to apply open science and open educational practices, and what hinders them to do so? The OPER study (Open Practices of Educational Researchers), funded by the Leibniz Research Alliance Open Science, investigates those questions. Study participants chose open scenarios for their daily research or teaching practices and tested them for six to 12 month. They wrote down their experiences with and opinions on open practices in dairies. The starting workshop was held in April 2019 with the first round of participants. First discussions on relevant topics were collected in Wikiversity and online pads.Wie können offene Praktiken im Lehr- und Forschungsalltag umgesetzt werden? Was sind die Anreize, offene Wissenschaft und offene Lehre zu praktizieren, und was hält uns davon ab? Die vom Leibniz-Forschungsverbund Open Science geförderte OPER-Studie (Open Practices of Educational Researchers) wollte dies herausfinden und ließ Bildungsforscher*innen offene Praktiken während eines Zeitraums von 6 bis 12 Monaten in unterschiedlichen Anwendungsfällen testen. Ihre Erfahrungen und Meinungen hielten sie in Tagebucheinträgen fest

LIFE-SHARE Project: Developing a Digitisation Strategy Toolkit

This poster will outline the Digitisation Strategy Toolkit created as part of the LIFE-SHARE project. The toolkit is based on the lifecycle model created by the LIFE project and explores the creation, acquisition, ingest, preservation (bit-stream and content) and access requirements for a digitisation strategy. This covers the policies and infrastructure required in libraries to establish successful practices. The toolkit also provides both internal and external resources to support the service. This poster will illustrate how the toolkit works effectively to support digitisation with examples from three case studies at the Universities of Leeds, Sheffield and York

Doppler cooling of a Coulomb crystal

We study theoretically Doppler laser-cooling of a cluster of 2-level atoms confined in a linear ion trap. Using several consecutive steps of averaging we derive, from the full quantum mechanical master equation, an equation for the total mechanical energy of the one dimensional crystal, defined on a coarse-grained energy scale whose grid size is smaller than the linewidth of the electronic transition. This equation describes the cooling dynamics for an arbitrary number of ions and in the quantum regime. We discuss the validity of the ergodic assumption (i.e. that the phase space distribution is only a function of energy). From our equation we derive the semiclassical limit (i.e. when the mechanical motion can be treated classically) and the Lamb-Dicke limit (i.e. when the size of the mechanical wave function is much smaller than the laser wavelength). We find a Fokker-Planck equation for the total mechanical energy of the system, whose solution is in agreement with previous analytical calculations which were based on different assumptions and valid only in their specific regimes. Finally, in the classical limit we derive an analytic expression for the average coupling, by light scattering, between motional states at different energies.Comment: 19 pages, 3 figure

Molecular characterization of hematopoietic stem cells after in vitro amplification on biomimetic 3D PDMS cell culture scaffolds

Hematopoietic stem cell (HSC) transplantation is successfully applied since the late 1950s. However, its efficacy can be impaired by insufficient numbers of donor HSCs. A promising strategy to overcome this hurdle is the use of an advanced ex vivo culture system that supports the proliferation and, at the same time, maintains the pluripotency of HSCs. Therefore, we have developed artificial 3D bone marrow-like scaffolds made of polydimethylsiloxane (PDMS) that model the natural HSC niche in vitro. These 3D PDMS scaffolds in combination with an optimized HSC culture medium allow the amplification of high numbers of undifferentiated HSCs. After 14 days in vitro cell culture, we performed transcriptome and proteome analysis. Ingenuity pathway analysis indicated that the 3D PDMS cell culture scaffolds altered PI3K/AKT/mTOR pathways and activated SREBP, HIF1α and FOXO signaling, leading to metabolic adaptations, as judged by ELISA, Western blot and metabolic flux analysis. These molecular signaling pathways can promote the expansion of HSCs and are involved in the maintenance of their pluripotency. Thus, we have shown that the 3D PDMS scaffolds activate key molecular signaling pathways to amplify the numbers of undifferentiated HSCs ex vivo effectively

Central Acting Hsp10 Regulates Mitochondrial Function, Fatty Acid Metabolism, and Insulin Sensitivity in the Hypothalamus

Mitochondria are critical for hypothalamic function and regulators of metabolism. Hypothalamic mitochondrial dysfunction with decreased mitochondrial chaperone expression is present in type 2 diabetes (T2D). Recently, we demonstrated that a dysregulated mitochondrial stress response (MSR) with reduced chaperone expression in the hypothalamus is an early event in obesity development due to insufficient insulin signaling. Although insulin activates this response and improves metabolism, the metabolic impact of one of its members, the mitochondrial chaperone heat shock protein 10 (Hsp10), is unknown. Thus, we hypothesized that a reduction of Hsp10 in hypothalamic neurons will impair mitochondrial function and impact brain insulin action. Therefore, we investigated the role of chaperone Hsp10 by introducing a lentiviral-mediated Hsp10 knockdown (KD) in the hypothalamic cell line CLU-183 and in the arcuate nucleus (ARC) of C57BL/6N male mice. We analyzed mitochondrial function and insulin signaling utilizing qPCR, Western blot, XF96 Analyzer, immunohistochemistry, and microscopy techniques. We show that Hsp10 expression is reduced in T2D mice brains and regulated by leptin in vitro. Hsp10 KD in hypothalamic cells induced mitochondrial dysfunction with altered fatty acid metabolism and increased mitochondria-specific oxidative stress resulting in neuronal insulin resistance. Consequently, the reduction of Hsp10 in the ARC of C57BL/6N mice caused hypothalamic insulin resistance with acute liver insulin resistance

<i>Staphylococcus aureus</i> enterotoxins induce FOXP3 in neoplastic T cells in Sézary syndrome

Sezary syndrome (SS) is a heterogeneous leukemic subtype of cutaneous T-cell lymphoma (CTCL) with generalized erythroderma, lymphadenopathy, and a poor prognosis. Advanced disease is invariably associated with severe immune dysregulation and the majority of patients die from infectious complications caused by microorganisms such as, Staphylococcus aureus, rather than from the lymphoma per se. Here, we examined if staphylococcal enterotoxins (SE) may shape the phenotype of malignant SS cells, including expression of the regulatory T-cell-associated marker FOXP3. Our studies with primary and cultured malignant cells show that SE induce expression of FOXP3 in malignant cells when exposed to nonmalignant cells. Mutations in the MHC class II binding domain of SE-A (SEA) largely block the effect indicating that the response relies at least in part on the MHC class II-mediated antigen presentation. Transwell experiments show that the effect is induced by soluble factors, partly blocked by anti-IL-2 antibody, and depends on STAT5 activation in malignant cells. Collectively, these findings show that SE stimulate nonmalignant cells to induce FOXP3 expression in malignant cells. Thus, differences in exposure to environmental factors, such as bacterial toxins may explain the heterogeneous FOXP3 expression in malignant cells in SS.Dermatology-oncolog

Combined analysis of data from two granddaughter designs: A simple strategy for QTL confirmation and increasing experimental power in dairy cattle

A joint analysis of five paternal half-sib Holstein families that were part of two different granddaughter designs (ADR- or Inra-design) was carried out for five milk production traits and somatic cell score in order to conduct a QTL confirmation study and to increase the experimental power. Data were exchanged in a coded and standardised form. The combined data set (JOINT-design) consisted of on average 231 sires per grandsire. Genetic maps were calculated for 133 markers distributed over nine chromosomes. QTL analyses were performed separately for each design and each trait. The results revealed QTL for milk production on chromosome 14, for milk yield on chromosome 5, and for fat content on chromosome 19 in both the ADR- and the Inra-design (confirmed within this study). Some QTL could only be mapped in either the ADR- or in the Inra-design (not confirmed within this study). Additional QTL previously undetected in the single designs were mapped in the JOINT-design for fat yield (chromosome 19 and 26), protein yield (chromosome 26), protein content (chromosome 5), and somatic cell score (chromosome 2 and 19) with genomewide significance. This study demonstrated the potential benefits of a combined analysis of data from different granddaughter designs

Mechanistic insights into p53‐regulated cytotoxicity of combined entinostat and irinotecan against colorectal cancer cells

Late‐stage colorectal cancer (CRC) is still a clinically challenging problem. The activity of the tumor suppressor p53 is regulated via post‐translational modifications (PTMs). While the relevance of p53 C‐terminal acetylation for transcriptional regulation is well defined, it is unknown whether this PTM controls mitochondrially mediated apoptosis directly. We used wild‐type p53 or p53‐negative human CRC cells, cells with acetylation‐defective p53, transformation assays, CRC organoids, and xenograft mouse models to assess how p53 acetylation determines cellular stress responses. The topoisomerase‐1 inhibitor irinotecan induces acetylation of several lysine residues within p53. Inhibition of histone deacetylases (HDACs) with the class I HDAC inhibitor entinostat synergistically triggers mitochondrial damage and apoptosis in irinotecan‐treated p53‐positive CRC cells. This specifically relies on the C‐terminal acetylation of p53 by CREB‐binding protein/p300 and the presence of C‐terminally acetylated p53 in complex with the proapoptotic BCL2 antagonist/killer protein. This control of C‐terminal acetylation by HDACs can mechanistically explain why combinations of irinotecan and entinostat represent clinically tractable agents for the therapy of p53‐proficient CRC