Hypoxia inducible factor‐2α importance for migration, proliferation, and self‐renewal of trunk neural crest cells

Background: The neural crest is a transient embryonic stem cell population. Hypoxia inducible factor (HIF)‐2α is associated with neural crest stem cell appearance and aggressiveness in tumors. However, little is known about its role in normal neural crest development. Results: Here, we show that HIF‐2α is expressed in trunk neural crest cells of human, murine, and avian embryos. Knockdown as well as overexpression of HIF‐2α in vivo causes developmental delays, induces proliferation, and self‐renewal capacity of neural crest cells while decreasing the proportion of neural crest cells that migrate ventrally to sympathoadrenal sites. Reflecting the in vivo phenotype, transcriptome changes after loss of HIF‐2α reveal enrichment of genes associated with cancer, invasion, epithelial‐to‐mesenchymal transition, and growth arrest. Conclusions: Taken together, these results suggest that expression levels of HIF‐2α must be strictly controlled during normal trunk neural crest development and that dysregulated levels affects several important features connected to stemness, migration, and development

Countering Terrorism on Tomorrow’s Battlefield: Critical Infrastructure Security and Resiliency (NATO COE-DAT Handbook 2)

Every day, malicious actors target emerging technologies and medical resilience or seek to wreak havoc in the wake of disasters brought on by climate change, energy insecurity, and supply-chain disruptions. Countering Terrorism on Tomorrow’s Battlefield is a handbook on how to strengthen critical infrastructure resilience in an era of emerging threats. The counterterrorism research produced for this volume is in alignment with NATO’s Warfighting Capstone Concept, which details how NATO Allies can transform and maintain their advantage despite new threats for the next two decades. The topics are rooted in NATO’s Seven Baseline requirements, which set the standard for enhancing resilience in every aspect of critical infrastructure and civil society. As terrorists hone their skills to operate lethal drones, use biometric data to target innocents, and take advantage of the chaos left by pandemics and natural disasters for nefarious purposes, NATO forces must be prepared to respond and prevent terrorist events before they happen. Big-data analytics provides potential for NATO states to receive early warning to prevent pandemics, cyberattacks, and kinetic attacks. NATO is perfecting drone operations through interoperability exercises, and space is being exploited by adversaries. Hypersonic weapons are actively being used on the battlefield, and satellites have been targeted to take down wind farms and control navigation. This handbook is a guide for the future, providing actionable information and recommendations to keep our democracies safe today and in the years to come.https://press.armywarcollege.edu/monographs/1953/thumbnail.jp

In vitro evaluation of iron oxide nanoparticle-induced thromboinflammatory response using a combined human whole blood and endothelial cell model

Iron oxide nanoparticles (IONPs) are widely used in diagnostic and therapeutic settings. Upon systemic administration, however, they are rapidly recognized by components of innate immunity, which limit their therapeutic capacity and can potentially lead to adverse side effects. IONPs were previously found to induce the inflammatory response in human whole blood, including activation of the complement system and increased secretion of cytokines. Here, we investigated the thromboinflammatory response of 10-30 nm IONPs in lepirudin anticoagulated whole blood in interplay with endothelial cells and evaluated the therapeutic effect of applying complement inhibitors to limit adverse effects related to thromboinflammation. We found that IONPs induced complement activation, primarily at the C3-level, in whole blood incubated for up to four hours at 37°C with and without human microvascular endothelial cells. Furthermore, IONPs mediated a strong thromboinflammatory response, as seen by the significantly increased release of 21 of the 27 analyzed cytokines (p<0.05). IONPs also significantly increased cell-activation markers of endothelial cells [ICAM-1 (p<0.0001), P/E-selectin (p<0.05)], monocytes, and granulocytes [CD11b (p<0.001)], and platelets [CD62P (p<0.05), CD63 (p<0.05), NAP-2 (p<0.01), PF4 (p<0.05)], and showed cytotoxic effects, as seen by increased LDH (p<0.001) and heme (p<0.0001) levels. We found that inflammation and endothelial cell activation were partly complement-dependent and inhibition of complement at the level of C3 by compstatin Cp40 significantly attenuated expression of ICAM-1 (p<0.01) and selectins (p<0.05). We show that complement activation plays an important role in the IONPs-induced thromboinflammatory response and that complement inhibition is promising in improving IONPs biocompatibility

The underlying causes of military outsourcing in the USA and UK: bridging the persistent gap between ends, ways and means since the beginning of the Cold War

This article reappraises the two most-studied country cases of military outsourcing: the USA and the UK. It argues that the contemporary wave of military contracting stretches back to the beginning of the cold war and not only to the demobilisation of armies in the 1990s or the neoliberal reforms introduced since the 1980s. It traces the political, technological and ideational developments that laid the groundwork for these reforms and practices since the early cold war and account for its endurance today. Importantly, it argues that a persistent gap between strategic objectives and resources, i.e. the challenge to reconcile ends and means, is an underlying driver of military contracting in both countries. Contemporary contracting is thus most closely tied to military support functions in support of wider foreign and defence political objectives. Security services in either state may not have been outsourced so swiftly, if at all, without decades of experience in outsourcing military logistics functions and the resultant vehicles, processes and familiarities with public-private partnerships. The article thus provides a wider and deeper understanding of the drivers of contractualisation, thereby improving our understanding of both its historical trajectory and the determinants of its present and potential futures

Limbic Justice—Amygdala Involvement in Immediate Rejection in the Ultimatum Game

Imaging studies have revealed a putative neural account of emotional bias in decision making. However, it has been difficult in previous studies to identify the causal role of the different sub-regions involved in decision making. The Ultimatum Game (UG) is a game to study the punishment of norm-violating behavior. In a previous influential paper on UG it was suggested that frontal insular cortex has a pivotal role in the rejection response. This view has not been reconciled with a vast literature that attributes a crucial role in emotional decision making to a subcortical structure (i.e., amygdala). In this study we propose an anatomy-informed model that may join these views. We also present a design that detects the functional anatomical response to unfair proposals in a subcortical network that mediates rapid reactive responses. We used a functional MRI paradigm to study the early components of decision making and challenged our paradigm with the introduction of a pharmacological intervention to perturb the elicited behavioral and neural response. Benzodiazepine treatment decreased the rejection rate (from 37.6% to 19.0%) concomitantly with a diminished amygdala response to unfair proposals, and this in spite of an unchanged feeling of unfairness and unchanged insular response. In the control group, rejection was directly linked to an increase in amygdala activity. These results allow a functional anatomical detection of the early neural components of rejection associated with the initial reactive emotional response. Thus, the act of immediate rejection seems to be mediated by the limbic system and is not solely driven by cortical processes, as previously suggested. Our results also prompt an ethical discussion as we demonstrated that a commonly used drug influences core functions in the human brain that underlie individual autonomy and economic decision making

Human mandibular shape is associated with masticatory muscle force

Understanding how and to what extent forces applied to the mandible by the masticatory muscles influence its form, is of considerable importance from clinical, anthropological and evolutionary perspectives. This study investigates these questions. Head CT scans of 382 adults were utilized to measure masseter and temporalis muscle cross-sectional areas (CSA) as a surrogate for muscle force, and 17 mandibular anthropometric measurements. Sixty-two mandibles of young individuals (20-40 years) whose scans were without artefacts (e.g., due to tooth filling) were segmented and landmarked for geometric morphometric analysis. The association between shape and muscle CSA (controlled for size) was assessed using two-block partial least squares analysis. Correlations were computed between mandibular variables and muscle CSAs (all controlled for size). A significant association was found between mandibular shape and muscle CSAs, i.e. larger CSAs are associated with a wider more trapezoidal ramus, more massive coronoid, more rectangular body and a more curved basal arch. Linear measurements yielded low correlations with muscle CSAs. In conclusion, this study demonstrates an association between mandibular muscle force and mandibular shape, which is not as readily identified from linear measurements. Retrodiction of masticatory muscle force and so of mandibular loading is therefore best based on overall mandibular shape

What is the value of orthodontic treatment?

Orthodontic treatment is as popular as ever. Orthodontists frequently have long lists of people wanting treatment and the cost to the NHS in England was £258m in 2010-2011 (approximately 10% of the NHS annual spend on dentistry). It is important that clinicians and healthcare commissioners constantly question the contribution of interventions towards improving the health of the population. In this article, the authors outline some of the evidence for and against the claims that people with a malocclusion are at a disadvantage compared with those without a malocclusion and that orthodontic treatment has significant health benefits. The authors would like to point out that this is not a comprehensive and systematic review of the entire scientific literature. Rather the evidence is presented in order to stimulate discussion and debate

Behavioral aspects of communication in organizations

International audienc