710 research outputs found

    Transforming Library Services for and with Teens through Continuing Education

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    Together with the Chief Officers of State Library Agencies (COSLA), the Young Adult Library Services Association (YALSA) embarked on a year-long exploration of the continuing education (CE) needs of staff at state library agencies (SLA) and libraries to identify challenges and opportunities and recommend ways for improving the CE landscape as a strategy to transforming serving teens through libraries.  This project was funded through a National Forum grant from the Institute of Museum and Library Services

    Detection and Characterisation of Lactobacillus spp. in the Bovine Uterus and Their Influence on Bovine Endometrial Epithelial Cells In Vitro

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    Bacterial infections and inflammation of the uterus are common in dairy cattle after parturition. In particular, pathogenic bacteria that cause endometritis have been the focus of research in cattle reproduction in the last ten years. The aim of the present study was to identify commensal lactobacilli in the bovine uterus and to examine their influence on the synthesis of pro- inflammatory factors in bovine endometrial epithelial cells in vitro. Lactobacillus species were isolated from healthy bovine uteri and further characterised. Bovine endometrial epithelial cells in the second passage (n = 5 animals) were co-cultured with the autochthonous isolates L. buchneri, L. ruminis and L. amylovorus as well as with a commercially available L. vaginalis in different multiplicities of infection (MOI = 1, 5 and 10, respectively). Endometrial epithelial cells cultured without bacteria served as controls. At distinct points in time (2, 4 and 6 h) total RNA was extracted from co-cultured epithelial cells and subjected to reverse transcription quantitative PCR of pro-inflammatory factors. Furthermore, the release of such factors by co-cultured epithelial cells was measured by ELISA or EIA after 24 and 48 h. L. ruminis and L. amylovorus induced increased interleukin (IL) IL1A, IL6, IL8 and prostaglandin-endoperoxide synthase 2 mRNA levels and the release of IL8 and prostaglandin F2α in endometrial epithelial cells compared with control cells. In contrast, L. buchneri did not significantly influence the expression and release of these factors. Toll-like receptors 2 and 6 transcripts were found unchanged in co-cultured and untreated epithelial cells in vitro. However, endometrial epithelial cells of each animal showed individual differences in the response to bacterial load. These results suggest that Lactobacillus species are present in the bovine uterus, revealing immunomodulatory properties

    Delineating endogenous Cushing's syndrome by GC-MS urinary steroid metabotyping

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    BACKGROUND Diagnosing Cushing's syndrome (CS) is highly complex. As the diagnostic potential of urinary steroid metabolome analysis by gas chromatography-mass spectrometry (GC-MS) in combination with systems biology has not yet been fully exploited, we studied a large cohort of patients with CS. METHODS We quantified daily urinary excretion rates of 36 steroid hormone metabolites. Applying cluster analysis, we investigated a control group and 168 patients: 44 with Cushing's disease (CD) (70% female), 18 with unilateral cortisol-producing adrenal adenoma (83% female), 13 with primary bilateral macronodular adrenal hyperplasia (PBMAH) (77% female), and 93 ruled-out CS (73% female). FINDINGS Cluster-Analysis delineated five urinary steroid metabotypes in CS. Metabotypes 1, 2 and 3 revealing average levels of cortisol and adrenal androgen metabolites included patients with exclusion of CS or and healthy controls. Metabotype 4 reflecting moderately elevated cortisol metabolites but decreased DHEA metabolites characterized the patients with unilateral adrenal CS and PBMAH. Metabotype 5 showing strong increases both in cortisol and DHEA metabolites, as well as overloaded enzymes of cortisol inactivation, was characteristic of CD patients. 11-oxygenated androgens were elevated in all patients with CS. The biomarkers THS, F, THF/THE, and (An + Et)/(11β-OH-An + 11β-OH-Et) correctly classified 97% of patients with CS and 95% of those without CS. An inverse relationship between 11-deoxygenated and 11-oxygenated androgens was typical for the ACTH independent (adrenal) forms of CS with an accuracy of 95%. INTERPRETATION GC-MS based urinary steroid metabotyping allows excellent identification of patients with endogenous CS and differentiation of its subtypes. FUNDING The study was funded by the Else Kröner-Fresenius-Stiftung and the Eva-Luise-und-Horst-Köhler-Stiftung

    Probing the SELEX Process with Next-Generation Sequencing

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    Background SELEX is an iterative process in which highly diverse synthetic nucleic acid libraries are selected over many rounds to finally identify aptamers with desired properties. However, little is understood as how binders are enriched during the selection course. Next-generation sequencing offers the opportunity to open the black box and observe a large part of the population dynamics during the selection process. Methodology We have performed a semi-automated SELEX procedure on the model target streptavidin starting with a synthetic DNA oligonucleotide library and compared results obtained by the conventional analysis via cloning and Sanger sequencing with next-generation sequencing. In order to follow the population dynamics during the selection, pools from all selection rounds were barcoded and sequenced in parallel. Conclusions High affinity aptamers can be readily identified simply by copy number enrichment in the first selection rounds. Based on our results, we suggest a new selection scheme that avoids a high number of iterative selection rounds while reducing time, PCR bias, and artifacts

    The Prethalamus Is Established during Gastrulation and Influences Diencephalic Regionalization

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    The vertebrate neural plate contains distinct domains of gene expression, prefiguring the future brain areas. In this study, we draw an extended expression map of the rostral neural plate that reveals discrete domains inside the presumptive posterior forebrain. We show, by fate mapping, that these well-defined cell populations will develop into specific diencephalic regions. To address whether these early subterritories are already committed to restricted identities, we began to analyse the consequences of ablation and transplantation of these specific cell populations. We found that precursors of the prethalamus are already specified and irreplaceable at late gastrula stage, because ablation of these cells results in loss of prethalamic markers. Moreover, when transplanted into the ectopic environment of the presumptive hindbrain, these cells still pursue their prethalamic differentiation program. Finally, transplantation of these precursors, in the rostral-most neural epithelium, induces changes in cell identity in the surrounding host forebrain. This cell–non-autonomous property led us to propose that these committed prethalamic precursors may play an instructive role in the regionalization of the developing diencephalon

    Correction to: EGFR/Ras-induced CCL20 production modulates the tumour microenvironment

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    The article ‘EGFR/Ras-induced CCL20 production modulates the tumour microenvironment’, written by Andreas Hippe, Stephan Alexander Braun, Péter Oláh, Peter Arne Gerber, Anne Schorr, Stephan Seeliger, Stephanie Holtz, Katharina Jannasch, Andor Pivarcsi, Bettina Buhren, Holger Schrumpf, Andreas Kislat, Erich Bünemann, Martin Steinhoff, Jens Fischer, Sérgio A. Lira, Petra Boukamp, Peter Hevezi, Nikolas Hendrik Stoecklein, Thomas Hoffmann, Frauke Alves, Jonathan Sleeman, Thomas Bauer, Jörg Klufa, Nicole Amberg, Maria Sibilia, Albert Zlotnik, Anja Müller- Homey and Bernhard Homey, was originally published electronically on the publisher’s internet portal on 30 June 2020 without open access. With the author(s)’ decision to opt for Open Choice the copyright of the article changed on 16 September 2021 to © The Author(s) 2021 and the article is forthwith distributed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/ licenses/by/4.0/. Open Access funding enabled and organized by Projekt DEAL

    A Novel Task for the Investigation of Action Acquisition

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    We present a behavioural task designed for the investigation of how novel instrumental actions are discovered and learnt. The task consists of free movement with a manipulandum, during which the full range of possible movements can be explored by the participant and recorded. A subset of these movements, the ‘target’, is set to trigger a reinforcing signal. The task is to discover what movements of the manipulandum evoke the reinforcement signal. Targets can be defined in spatial, temporal, or kinematic terms, can be a combination of these aspects, or can represent the concatenation of actions into a larger gesture. The task allows the study of how the specific elements of behaviour which cause the reinforcing signal are identified, refined and stored by the participant. The task provides a paradigm where the exploratory motive drives learning and as such we view it as in the tradition of Thorndike [1]. Most importantly it allows for repeated measures, since when a novel action is acquired the criterion for triggering reinforcement can be changed requiring a new action to be discovered. Here, we present data using both humans and rats as subjects, showing that our task is easily scalable in difficulty, adaptable across species, and produces a rich set of behavioural measures offering new and valuable insight into the action learning process

    Development of Measure Yourself Concerns and Wellbeing for informal caregivers of people with cancer – a multicentred study

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    Purpose: Measure Yourself Concerns and Wellbeing (MYCaW) is a validated person-centred measure of the concerns and wellbeing of people affected by cancer. Research suggests that the concerns of informal caregivers (ICs) are as complex and severely rated as people with cancer, yet MYCaW has only been used to represent cancer patients’ concerns and wellbeing. This paper reports on the development of a new qualitative coding framework for MYCaW to capture the concerns of ICs, to better understand the needs of this group. Methods: This multicentred study involved collection of data from ICs receiving support from two UK cancer support charities (Penny Brohn UK and Cavendish Cancer Care). Qualitative codes were developed through a detailed thematic analysis of ICs’ stated concerns. Results: Thematic analysis of IC questionnaire data identified key themes which were translated into a coding framework with two overarching sections; 1. ‘informal caregiver concerns for self’ and 2. ‘informal caregiver concerns for the person with cancer’. Supercategories with specific accompanying codes were developed for each section. Two further rounds of framework testing across different cohorts allowed for iterative development and refinement of the framework content. Conclusions: This is the first person-centred tool specifically designed for capturing IC’s concerns through their own words. This coding framework will allow for IC data to be analysed using a rigorous and reproducible method, and therefore reported in a standardised way. This may also be of interest to those exploring the needs of ICs of people in other situations
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