Early dietary exposures epigenetically program mammary cancer susceptibility through Igf1-mediated expansion of the mammary stem cell compartment

This article belongs to the Collection Insulin-Like Growth Factors in Development, Cancers and Aging.Diet is a critical environmental factor affecting breast cancer risk, and recent evidence shows that dietary exposures during early development can affect lifetime mammary cancer susceptibility. To elucidate the underlying mechanisms, we used our established crossover feeding mouse model, where exposure to a high-fat and high-sugar (HFHS) diet during defined developmental windows determines mammary tumor incidence and latency in carcinogen-treated mice. Mammary tumor incidence is significantly increased in mice receiving a HFHS post-weaning diet (high-tumor mice, HT) compared to those receiving a HFHS diet during gestation (low-tumor mice, LT). The current study revealed that the mammary stem cell (MaSC) population was significantly increased in mammary glands from HT compared to LT mice. Igf1 expression was increased in mammary stromal cells from HT mice, where it promoted MaSC self-renewal. The increased Igf1 expression was induced by DNA hypomethylation of the Igf1 Pr1 promoter, mediated by a decrease in Dnmt3b levels. Mammary tissues from HT mice also had reduced levels of Igfbp5, leading to increased bioavailability of tissue Igf1. This study provides novel insights into how early dietary exposures program mammary cancer risk, demonstrating that effective dietary intervention can reduce mammary cancer incidenceThe research was supported by institutional funding from Texas A&M University and the Discovery Foundatio

ORCID in Deutschland – Ergebnisse einer Bestandsaufnahme im Jahr 2016

Die Open Researcher and Contributor ID, kurz ORCID, ist eine eindeutige Kennung für Forscherinnen und Forscher und ermöglicht die Verbindung zwischen Wissenschaftlerinnen und Wissenschaftlern mit ihren Aufsätzen, Forschungsdaten und weiteren Produkten des wissenschaftlichen Schaffens. Im Rahmen des dreijährigen DFG-Projektes „ORCID DE – Förderung der Open Researcher and Contributor ID in Deutschland“ wird die vielerorts erwogene Implementierung der ORCID an Hochschulen und außeruniversitären Forschungseinrichtungen gefördert. Der vorliegende Beitrag bietet einen umfassenden Überblick über die Ergebnisse der im Rahmen des Projekts durchgeführten Umfrage zum Stand der Implementierung von ORCID an wissenschaftlichen Einrichtungen in Deutschland. Die Umfrage wurde im Zeitraum vom 13.07.2016 bis 03.08.2016 durchgeführt und bietet zahlreiche Erkenntnisse sowohl über den Stand der Implementierung von ORCID an wissenschaftlichen Einrichtungen in Deutschland als auch über bestehende technische, rechtliche und organisatorische Hürden bei der Implementierung des Dienstes.The Open Researcher and Contributor ID, ORCID, enables connections between researchers and their articles and research data using a unique ID for researchers. The three-year project „ORCID DE – Promotion of the Open Researcher and Contributor ID in Germany”, funded by the German Research Foundation (DFG), was recently launched in order to foster adoption of ORCID at scientific institutions in Germany. This article offers a comprehensive overview about the results of a survey of the current status of ORCID at scientific institutions accomplished as part of the project. The survey ran from 13 July 2016 until 3 August 2016 and offers numerous findings concerning the current status of the implementation of ORCID at scientific institutions and also with regard to existing technical, legal and organizational barriers which hinder a successful implementation of ORCID

Realizations of Thermal Supersymmetry

We investigate realizations of supersymmetry at finite temperature in terms of thermal superfields, in a thermally constrained superspace: the Grassmann coordinates are promoted to be time-dependent and antiperiodic, with a period given by the inverse temperature. This approach allows to formulate a Kubo-Martin-Schwinger (KMS) condition at the level of thermal superfield propagators. The latter is proven directly in thermal superspace, and is shown to imply the correct (bosonic and fermionic) KMS conditions for the component fields. In thermal superspace, we formulate thermal covariant derivatives and supercharges and derive the thermal super-Poincar\'e algebra. Finally, we briefly investigate field realizations of this thermal supersymmetry algebra, focussing on the Wess-Zumino model. The thermal superspace formalism is used to characterize the breaking of global supersymmetry at finite temperature.Comment: 27 pages, no figures, LaTeX. Typos corrected and references added. To appear in Nucl. Phys.

Dynamic role of the codon 72 p53 single-nucleotide polymorphism in mammary tumorigenesis in a humanized mouse model

Female breast cancer (BrCa) is the most common noncutaneous cancer among women in the United States. Human epidemiological studies reveal that a p53 single-nucleotide polymorphism (SNP) at codon 72, encoding proline (P72) or arginine (R72), is associated with differential risk of several cancers, including BrCa. However, the molecular mechanisms by which these variants affect mammary tumorigenesis remain unresolved. To investigate the effects of this polymorphism on susceptibility to mammary cancer, we used a humanized p53 mouse model, homozygous for either P72 or R72. Our studies revealed that R72 mice had a significantly higher mammary tumor incidence and reduced latency in both DMBAinduced and MMTV-Erbb2/Neu mouse mammary tumor models compared to P72 mice. Analyses showed that susceptible mammary glands from E-R72 (R72 x MMTV-Erbb2/Neu) mice developed a senescence-associated secretory phenotype (SASP) with influx of proinflammatory macrophages, ultimately resulting in chronic, protumorigenic inflammation. Mammary tumors arising in E-R72 mice also had an increased influx of tumor-associated macrophages, contributing to angiogenesis and elevated tumor growth rates. These results demonstrate that the p53 R72 variant increased susceptibility to mammary tumorigenesis through chronic inflammation.This work was funded by the National Institutes of Health grant R01MD006228 (to RF-Y)

Mobilized Peripheral Blood Stem Cells Versus Unstimulated Bone Marrow As a Graft Source for T-Cell-Replete Haploidentical Donor Transplantation Using Post-Transplant Cyclophosphamide.

Purpose T-cell-replete HLA-haploidentical donor hematopoietic transplantation using post-transplant cyclophosphamide was originally described using bone marrow (BM). With increasing use of mobilized peripheral blood (PB), we compared transplant outcomes after PB and BM transplants. Patients and Methods A total of 681 patients with hematologic malignancy who underwent transplantation in the United States between 2009 and 2014 received BM (n = 481) or PB (n = 190) grafts. Cox regression models were built to examine differences in transplant outcomes by graft type, adjusting for patient, disease, and transplant characteristics. Results Hematopoietic recovery was similar after transplantation of BM and PB (28-day neutrophil recovery, 88% v 93%, P = .07; 100-day platelet recovery, 88% v 85%, P = .33). Risks of grade 2 to 4 acute (hazard ratio [HR], 0.45; P \u3c .001) and chronic (HR, 0.35; P \u3c .001) graft-versus-host disease were lower with transplantation of BM compared with PB. There were no significant differences in overall survival by graft type (HR, 0.99; P = .98), with rates of 54% and 57% at 2 years after transplantation of BM and PB, respectively. There were no differences in nonrelapse mortality risks (HR, 0.92; P = .74) but relapse risks were higher after transplantation of BM (HR, 1.49; P = .009). Additional exploration confirmed that the higher relapse risks after transplantation of BM were limited to patients with leukemia (HR, 1.73; P = .002) and not lymphoma (HR, 0.87; P = .64). Conclusion PB and BM grafts are suitable for haploidentical transplantation with the post-transplant cyclophosphamide approach but with differing patterns of treatment failure. Although, to our knowledge, this is the most comprehensive comparison, these findings must be validated in a randomized prospective comparison with adequate follow-up

Growing spatial correlations of particle displacements in a simulated liquid on cooling toward the glass transition

We define a correlation function that quantifies the spatial correlation of single-particle displacements in liquids and amorphous materials. We show for an equilibrium liquid that this function is related to fluctuations in a bulk dynamical variable. We evaluate this function using computer simulations of an equilibrium glass-forming liquid, and show that long range spatial correlations of displacements emerge and grow on cooling toward the mode coupling critical temperature

Editorial

The nine articles in the special issue highlight two main issues related to the pandemic- induced experimentation in teaching and learning: As indicated by the diversity of the authors’ physical locations, COVID and emergency-remote teaching affected HEIs at a nearly global scale. Authors in this issue come from European countries (Switzerland, Germany), North America (the USA) as well as the southern hemisphere (South Africa). Given the breadth of COVID-related (change) experiences, the insights presented in this issue can be relevant to many HEIs across the globe, notwithstanding their cultural and institutional specificities. In addition, and of high relevance to us, the articles collected here focus both on different positions or roles (students, faculty, management) as well as on different levels of teaching and learning in higher education (teaching and learning, curricular or institutional levels). While most contributions focus on the student experience during COVID, others investigate faculty/instructors’ perspectives including faculty development. Yet another group takes a more systemic, institutional point of view. It could be argued that higher-education research takes up a multi-level perspective when exploring change and the new normal

Umsetzung der Energiestrategie 2050 - Band II : Neue Ansätze für Staat und Wirtschaft

In diesem, dem zweiten Band von "Energy Governance" befassen sich die Autoren aus vielfältiger Perspektive mit zahlreichen Fragen zur Umsetzung der Energiestrategie 2050. Sie identifizieren jene Fälle von Solaranlagen, bei denen der Ersatz einer Baubewilligung zu Rechtsunsicherheit führt. Sie untersuchen die Wirkung moderner Finanzberichterstattung auf die Politik der kantonalen Beteiligungen an Energieversorgungsunternehmen in einer Marktumgebung tiefer Strompreis. Analysiert wird weiter die staatliche Förderung der erneuerbaren Stromproduktion im Hinblick auf ihre Wirkung. Eine kritische Analyse der "Smart City"-Projekte in der Schweiz und in den Nachbarländern Deutschland und Österreich führt zu Empfehlungen, wie solche Projekte effizienter geplant und umgesetzt werden können. Auch die Beziehung öffentlicher Organisationen zu ihrer "Stakeholder-Umwelt" wird behandelt

Group Testing for SARS-CoV-2 Allows for Up to 10-Fold Efficiency Increase Across Realistic Scenarios and Testing Strategies

Background: Due to the ongoing COVID-19 pandemic, demand for diagnostic testing has increased drastically, resulting in shortages of necessary materials to conduct the tests and overwhelming the capacity of testing laboratories. The supply scarcity and capacity limits affect test administration: priority must be given to hospitalized patients and symptomatic individuals, which can prevent the identification of asymptomatic and presymptomatic individuals and hence effective tracking and tracing policies. We describe optimized group testing strategies applicable to SARS-CoV-2 tests in scenarios tailored to the current COVID-19 pandemic and assess significant gains compared to individual testing. Methods: We account for biochemically realistic scenarios in the context of dilution effects on SARS-CoV-2 samples and consider evidence on specificity and sensitivity of PCR-based tests for the novel coronavirus. Because of the current uncertainty and the temporal and spatial changes in the prevalence regime, we provide analysis for several realistic scenarios and propose fast and reliable strategies for massive testing procedures. Key Findings: We find significant efficiency gaps between different group testing strategies in realistic scenarios for SARS-CoV-2 testing, highlighting the need for an informed decision of the pooling protocol depending on estimated prevalence, target specificity, and high- vs. low-risk population. For example, using one of the presented methods, all 1.47 million inhabitants of Munich, Germany, could be tested using only around 141 thousand tests if the infection rate is below 0.4% is assumed. Using 1 million tests, the 6.69 million inhabitants from the city of Rio de Janeiro, Brazil, could be tested as long as the infection rate does not exceed 1%. Moreover, we provide an interactive web application, available at , for visualizing the different strategies and designing pooling schemes according to specific prevalence scenarios and test configurations. Interpretation: Altogether, this work may help provide a basis for an efficient upscaling of current testing procedures, which takes the population heterogeneity into account and is fine-grained towards the desired study populations, e.g., mild/asymptomatic individuals vs. symptomatic ones but also mixtures thereof