Impact of Sleep on Monocytes and Infection

Sleep has been linked to several vital body functions from memory and metabolism to immunity. The results in this work – showing that sleep in mice has a profound effect on innate immune cells and their ability to fight bacterial infection – support these findings. For the experiments two mice groups were used, sleep mice with 6 h of normal sleep were compared to mice with 6 h of enhanced wakefulness. 6 h of sleep increases the overall cellularity in the blood and spleen of WT mice, in particular the number and frequency of monocytes. This is described in this work as the sleep phenotype, a strong increase in frequency and count of monocytes due to sleep. This phenotype was found for classical monocytes and non-classical monocytes. The increase of monocytes is not due to stress or the progression into macrophages or DCs. Furthermore, no effect of sleep was found on monocytes precursors or their release from the BM. Interestingly, the increase of monocytes in blood and spleen did not lead to a reduction of monocytes in Lymph Nodes, the LP, or the lung. On the contrary, monocyte numbers as well increase in the lung after 6 h of sleep. Furthermore, the sleep phenotype is independent of the ICAM-1-LFA-1 axis and just partially dependent on CCR2. Both are very important factors for the migration of classical monocytes and their contribution to the marginal pool. However, it could be shown that for non-classical monocytes Cx3CR1 is involved in the sleep phenotype. Beyond this, it was demonstrated that the sleep phenotype for classical monocytes is dependent on the Clock gene Arntl, indicating a strong connection between the circadian system and sleep. With regards to immune cell function, sleep increases the ROS production of PMNs and classical monocytes. Consequential this leads to better bacterial clearance and improved survival time upon infection. Taken together sleep is imperative for immune functions and monocyte numbers are highly affected by sleep as well as their ability to fight a bacterial infection. Even though the exact mechanism is not yet fully understood there are strong indications for a connection to the circadian system

Responsible research and innovation: a global perspective

Based on the paper presented at the Doctorate Conference on Technologogy Assessment in July 2013 at the University Nova Lisboa, Caparica campusResponsible Research and Innovation (RRI) is a normative concept that has captured considerable attention on the Science and Technology (S&T) policy level, but also in academic discourses. It represents a new approach to how science, innovation and research can be shaped in accordance with societal values that builds directly on the concepts and methodologies of Technology Assessment (TA). The definition and operationalization aspects of RRI remain still unclear although key ingredients such as ethical acceptability are well-established in S&T debates and embrace a spectrum of standard methodological approaches. In this paper we review the conceptual debate on RRI with a focus on its constituent parts. We then present a functional comparison between RRI and TA that proves the considerable conceptual overlap in the two approaches. We argue that TA methodologies and precepts should be employed as key operationalisational features in RRI. Finally we argue for a global perspective on RRI by describing a case study on global ethics in S&T that introduces an analytical framework for ethics debates

How Targeted Are Federal Expenditures on Children? A Kids' Share Analysis of Expenditures by Income in 2009

Analyzes the distribution of government spending on children by family income; category, such as health, social services, and education; and program, such as Medicaid; and the extent to which it is targeted to low-income children. Considers implications

Technology Assessment in a Globalized World

The interaction between science and policy is affected by increasingly dissolving boundaries whereby a number of issues arise, such as, what should political advice for national parliaments consist of in the face of global socio-technical developments? The Internet of Things in relation to Big Data resulting in enormously fast analysis of huge amounts of data, accelerates the dissolution of boundaries between science, society and policy at global level. This type of “globalization” raises questions that concern very diverse and intimate areas of life, ranging from food to health to work automation. How can access to science and technology in very different societal settings can be enabled, while also accounting for global developments? The article deals with the assumption that global effects of science and technology as well as global challenges lead to an urgent need to develop methodologies for analyzing and also shaping these developments. Under the umbrella term “Global Technology Assessment” (Global TA) it is argued that the problem-oriented, interdisciplinary methodology of technology assessment offers a promising frame to deal with cultural and ethical questions in relation to emerging technologies. This framework is needed in order to be able to develop meaningful national comparisons, but also in order to be able to approach the analysis of common future challenges on equal footing

Responsibility versus sustainability, ethics, and societal engagement: The German Science, Technology, Innovation context

We examine the concept of responsible research and innovation (RRI) in Germany in the context of national science, technology and innovation (STI) as well as its legal and normative framework in relation to ethics and societal engagement and compare the results to similar international research. Our analysis shows that responsibility plays a central role in research practice guided by research ethics standards and societal grand challenges. Consequently, there is a significant increase in demands for inclusion and engagement of a wider stakeholder spectrum in STI. Compared to other countries, the concept of RRI in Germany is increasingly superseded by that of sustainability. We argue that responsibility and sustainability are conceptually close and highly interchangeable in the German national debate. We conclude with basic recommendations for greater clarity in research on responsibility and sustainability and the aims of ethics and societal engagement.Im Folgenden wird das Konzept "Responsible Research and Innovation" (RRI) im Kontext nationaler Forschung, Technologie und Innovation (FTI) sowie seiner rechtlichen und normativen Rahmen in Bezug auf Ethik und gesellschaftliche Partizipation untersucht und mit Erkenntnissen internationaler Forschung verglichen. Die Ergebnisse zeigen, dass Verantwortung eine zentrale Rolle in einer Forschungspraxis einnimmt, die auf forschungsethische Standards und große gesellschaftliche Herausforderungen ausgerichtet ist. Forderungen nach Einbeziehung und Partizipation eines breiteren Stakeholder-Spektrums in FTI nehmen daher deutlich zu. Im Vergleich zu anderen Ländern zeigt sich, dass das RRI-Konzept in Deutschland jedoch zunehmend durch das der Nachhaltigkeit verdrängt wird. Wir argumentieren, dass Verantwortung und Nachhaltigkeit in der deutschen Debatte konzeptionell nahe beieinander liegen und häufig austauschbar sind. Der Beitrag schließt mit grundlegenden Handlungsempfehlungen für mehr Klarheit in der Forschung zu Verantwortung und Nachhaltigkeit sowie den Zielen von Ethik und gesellschaftlicher Partizipation

The Assembly and Evaluation of Antisense Oligonucleotides Applied in Exon Skipping for Titin-based Mutations in Dilated Cardiomyopathy

Die dilatative Kardiomyopathie (DCM) ist eine multifaktorielle Erkrankung; ca. 15-20% der familiären und 18% der sporadischen Formen lassen sich allerdings auf Mutationen im Titin, einem Sarkomerprotein mit wichtigen Funktionen für den kontraktilen Apparat, zurückführen. Im Moment steht keine spezifische Therapie für Patienten mit fortgeschrittener DCM zur Verfügung, sodass neben symptomatischen Maßnahmen mit Behandlung der Herzinsuffizienz lediglich die Option einer Herztransplantation existiert (Hahn et al.,2019). Ein potentieller Ansatz einer genotyp-spezifischen Therapie ist das sogenannte „Exon skipping“. Hierfür werden RNA-basierte Antisense-Oligonucleotide (AON) verwendet, um ein mutiertes Titin-Exon gezielt zu überspringen. Durch Wiederherstellung des Leserahmens entsteht ein verkürztes, aber funktionell intaktes Titin-Protein. In einer vorausgegangenen Machbarkeitsstudie haben wir das Prinzip des Exon-skippings an Zellkultur- und Mausmodell demonstrieren können. Das TTN-Gen besteht jedoch aus 363 Exonen und ist somit massiv; alle AON Sequenzen müssen deshalb für jedes einzelne Exon spezifisch entwickelt werden(Gramlich et al., 2015). Diese Arbeit beschreibt ein Protokoll, welches für das Design und die Evaluierung von AONs für ein effizientes Exon-Skipping spezifischer TTN-Exone angewandt werden kann. Zunächst werden verschiedene in silico Algorithmen beschrieben, die putative AON Sequenzen zum Überspringen eines Titin-Exons erstellen. Anschließend werden diese AONs in transfizierten HL-1 Zellen, einer murinen Kardiomyozytenlinie, getestet. Neben dem Nachweis eines korrekten Überspringens des Target- Exons mittels RT- PCR und Sanger-Sequenzierung werden die funktionellen Auswirkungen des skippings durch Immunhistochemie, Store-Operate-Calcium-Entry (SOCE) und Kontraktilitätsmessungen untersucht(Hahn et al.,2019). Diese Arbeit ist somit das erste systematische Protokoll zum AON-Design und deren Evaluation, um spezifische TTN Exons durch Antisense-Therapie zu überspringen. Dies ist ein erster Schritt in Richtung einer individualisierten Therapie für die titin-basierten dilatativen Kardiomyopathie(Hahn et al.,2019)