The Release Kinetics of Eosinophil Peroxidase and Mitochondrial DNA Is Different in Association with Eosinophil Extracellular Trap Formation.

Eosinophils are a subset of granulocytes characterized by a high abundance of specific granules in their cytoplasm. To act as effector cells, eosinophils degranulate and form eosinophil extracellular traps (EETs), which contain double-stranded DNA (dsDNA) co-localized with granule proteins. The exact molecular mechanism of EET formation remains unknown. Although the term "EET release" has been used in scientific reports, it is unclear whether EETs are pre-formed in eosinophils and subsequently released. Moreover, although eosinophil degranulation has been extensively studied, a precise time-course of granule protein release has not been reported until now. In this study, we investigated the time-dependent release of eosinophil peroxidase (EPX) and mitochondrial DNA (mtDNA) following activation of both human and mouse eosinophils. Unexpectedly, maximal degranulation was already observed within 1 min with no further change upon complement factor 5 (C5a) stimulation of interleukin-5 (IL-5) or granulocyte/macrophage colony-stimulating factor (GM-CSF)-primed eosinophils. In contrast, bulk mtDNA release in the same eosinophil populations occurred much slower and reached maximal levels between 30 and 60 min. Although no single-cell analyses have been performed, these data suggest that the molecular pathways leading to degranulation and mtDNA release are at least partially different. Moreover, based on these data, it is likely that the association between the mtDNA scaffold and granule proteins in the process of EET formation occurs in the extracellular space

Physiological and Pathophysiological Roles of Metabolic Pathways for NET Formation and Other Neutrophil Functions.

Neutrophils are the most numerous cells in the leukocyte population and essential for innate immunity. To limit their effector functions, neutrophils are able to modulate glycolysis and other cellular metabolic pathways. These metabolic pathways are essential not only for energy usage, but also for specialized effector actions, such as the production of reactive oxygen species (ROS), chemotaxis, phagocytosis, degranulation, and the formation of neutrophil extracellular traps (NETs). It has been demonstrated that activated viable neutrophils can produce NETs, which consists of a DNA scaffold able to bind granule proteins and microorganisms. The formation of NETs requires the availability of increased amounts of adenosine triphosphate (ATP) as it is an active cellular and therefore energy-dependent process. In this article, we discuss the glycolytic and other metabolic routes in association with neutrophil functions focusing on their role for building up NETs in the extracellular space. A better understanding of the requirements of metabolic pathways for neutrophil functions may lead to the discovery of molecular targets suitable to develop novel anti-infectious and/or anti-inflammatory drugs

Developmental perspectives on Europe

The crisis of 2008–2009 has ended, stockmarkets skyrocketed in 2012–2013, while growth of the real sector remained sluggish in Europe. This article attempts to explain the latter puzzle. Analyzing long term factors, the costs of short-termism in crisis management become obvious. The limitations of EU as a growth engine are highlighted

Financial Integration in Emerging Europe: An Enviable Development Opportunity with Tail Risks

This paper draws on the experience of emerging Europe and argues that foreign capital is an enviable development opportunity with tail risks. Financial integration and foreign savings supported growth in the EU12 and EU candidate countries. We argue that this was possible because of EU membership (actual or potential) and its role as an anchor for expectations. In contrast, the eastern partnership states did not benefit from the foreign savings-growth link. But financial integration also led to a buildup of vulnerabilities and now exposes emerging Europe to prolonged uncertainty and financial deleveraging due to eurozone developments. Nonetheless, we believe that external imbalances should not be eradicated-nor should emerging Europe pursue a policy of self-insurance. Instead, what we refer to as an acyclical fiscal policy stance could serve to counterbalance private sector behavior. Going forward, a more proactive macroprudential policy will also be needed to limit financial system vulnerabilities when external imbalances are large

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Transcriptional profile of breast muscle in heat stressed layers is similar to that of broiler chickens at control temperature

Abstract Background In recent years, the commercial importance of changes in muscle function of broiler chickens and of the corresponding effects on meat quality has increased. Furthermore, broilers are more sensitive to heat stress during transport and at high ambient temperatures than smaller egg-laying chickens. We hypothesised that heat stress would amplify muscle damage and expression of genes that are involved in such changes and, thus, lead to the identification of pathways and networks associated with broiler muscle and meat quality traits. Broiler and layer chickens were exposed to control or high ambient temperatures to characterise differences in gene expression between the two genotypes and the two environments. Results Whole-genome expression studies in breast muscles of broiler and layer chickens were conducted before and after heat stress; 2213 differentially-expressed genes were detected based on a significant (P < 0.05) genotype × treatment interaction. This gene set was analysed with the BioLayout Express3D and Ingenuity Pathway Analysis software and relevant biological pathways and networks were identified. Genes involved in functions related to inflammatory reactions, cell death, oxidative stress and tissue damage were upregulated in control broilers compared with control and heat-stressed layers. Expression of these genes was further increased in heat-stressed broilers. Conclusions Differences in gene expression between broiler and layer chickens under control and heat stress conditions suggest that damage of breast muscles in broilers at normal ambient temperatures is similar to that in heat-stressed layers and is amplified when broilers are exposed to heat stress. The patterns of gene expression of the two genotypes under heat stress were almost the polar opposite of each other, which is consistent with the conclusion that broiler chickens were not able to cope with heat stress by dissipating their body heat. The differentially expressed gene networks and pathways were consistent with the pathological changes that are observed in the breast muscle of heat-stressed broilers

Hydrological performance of Sedum species compared to perennial herbaceous species on a full-scale green roof in Italy

Although the ability of green roofs as stormwater source control technologies has been the topic of many recent studies, most conclude that a better understanding of full-scale hydrological performance and of the impact of different plant cover types is still needed. Based on these considerations, this research presents the results of 15 months of monitoring activity in Bologna (Italy) studying the hydrological performance of two adjacent full-scale extensive green roof plots with a different plant cover composition. One of the plots (SR) was planted with Sedum species (CAM) and the other (NR) with native herbaceous perennial species (C3). Continuous rainfall, runoff and weather data were collected and used to compare the effect of changing plant cover type on the green roof retention rate. Over the 15 months of this study, NR presented a 59% retention rate (111 valid events) whereas SR had a 52% retention rate (91 valid events). For 24 common events, with retention lower than 100%, the average difference between the NR and SR plot retention was 10%, confirming the higher water storage capacity, and therefore the higher retention rate, of the NR plot

Hydrological performance of Sedum species compared to perennial herbaceous species on a full-scale green roof in Italy

Although the ability of green roofs as stormwater source control technologies has been the topic of many recent studies, most conclude that a better understanding of full-scale hydrological performance and of the impact of different plant cover types is still needed. Based on these considerations, this research presents the results of 15 months of monitoring activity in Bologna (Italy) studying the hydrological performance of two adjacent full-scale extensive green roof plots with a different plant cover composition. One of the plots (SR) was planted with Sedum species (CAM) and the other (NR) with native herbaceous perennial species (C3). Continuous rainfall, runoff and weather data were collected and used to compare the effect of changing plant cover type on the green roof retention rate. Over the 15 months of this study, NR presented a 59% retention rate (111 valid events) whereas SR had a 52% retention rate (91 valid events). For 24 common events, with retention lower than 100%, the average difference between the NR and SR plot retention was 10%, confirming the higher water storage capacity, and therefore the higher retention rate, of the NR plot

Ergotherapie bei Personen mit kognitiven Einschränkungen

Background: Damage to the central nervous system can occur in adulthood, for example, due to stroke, trauma, tumours, or chronic diseases. After damage to the central nervous system, cognitive impairments occur in addition to physical limitations. Occupational therapy is most often prescribed for neurological diagnoses, including stroke and traumatic brain injury. Methods: The health technology assessment (HTA) report this HTA article is based on investigates the clinical effectiveness, cost-effectiveness, and patient-related, social and ethical aspects of occupational therapy for patients with cognitive impairments compared to no occupational therapy. In addition, the effects of different occupational therapy interventions with and without cognitive components were compared in an explorative overview. Patients with moderate or severe dementia are excluded from the assessment. Systematic overviews, that is, systematic reviews of systematic reviews, were conducted.Results: For the evaluation of clinical effectiveness, a total of nine systematic reviews were included. No systematic review was identified for the assessment of costs or cost-effectiveness. Five systematic reviews were included for the assessment of patient and social aspects.For the assessment of clinical effectiveness compared with no occupational therapy, five systematic reviews comprising 20 randomised controlled trials with a total of 1,316 subjects reported small positive effects for the outcomes "global cognitive function" and "activities of daily living" as well as a non-quantified positive effect on the outcomes "health-related quality of life" and "behavioural control". No effect was found for individual components of cognition and measures of perception. The quality of the evidence for all outcomes is low due to a high risk of bias.In the supplementary presentations, no positive effects could be demonstrated on the basis of the available evidence. The quality of this evidence was not assessed.For the assessment of patient and social aspects, five systematic reviews on patients with a stroke or a traumatic brain injury - without specification regarding cognitive deficits or studies with their relatives - were included.It was reported that patients and family caregivers go through different phases of rehabilitation in which the discharge home is a decisive turning point. The discharge home represents a crucial breaking point. Regaining an active, self-determining role is a process that requires therapists to find the right level of support for patients and relatives.For the assessment of ethical aspects, nine documents were included. We identified ethical problem-solving models for occupational therapy and 16 ethical aspects in occupational therapy for cognitive deficits. The central theme of the analysis is the limited autonomy due to the consequences of the disease as well as the resulting tensions with those treating the patient.Conclusions: Based on this systematic overview, it can neither be proven nor excluded with certainty that occupational therapy for cognitive impairment is an effective therapy for adult patients with central nervous system injuries compared to no occupational therapy. There is a lack of randomised trials with sufficient sample size, well-defined interventions, and comparable concomitant therapies in the control groups, but there is also a lack of well-designed observational studies in routine care and health economic studies.The identified systematic reviews on patient and social aspects provide information on the needs of patients after stroke or traumatic brain injury and their relatives, but there is a lack of studies on this aspect in German-speaking countries.For the ethical assessment, in addition to the identified theoretical models for solving ethical conflicts in occupational therapy, more empirical studies on ethical aspects with patients with cognitive deficits and their relatives as well as occupational therapists are needed.Hintergrund: Schädigungen des zentralen Nervensystems können im Erwachsenenalter zum Beispiel durch Schlaganfall, Trauma, Tumore oder chronische Krankheiten entstehen. Nach Schädigung des zentralen Nervensystems treten neben physischen Einschränkungen auch kognitive Einschränkungen auf. Am häufigsten wird eine Ergotherapie bei neurologischen Diagnosen verordnet, darunter auch Schlaganfall und Schädel-Hirn-Trauma.Methoden: Der diesem Artikel zugrundeliegende Health Technology Assessment (HTA)-Bericht untersucht die medizinische Wirksamkeit, Kosten und Kosteneffektivität, Patienten- und soziale Aspekte sowie ethische Aspekte der Beschäftigungstherapie für Patienten mit kognitiven Beeinträchtigungen aufgrund von Schädigungen des zentralen Nervensystems im Erwachsenenalter im Vergleich zu keiner Ergotherapie. Ergänzend wurden Formen der Ergotherapie mit und ohne kognitive Komponenten verglichen. Personen mit moderater oder schwerer Demenz sind von der Bewertung ausgeschlossen. Es wurden systematische Overviews erstellt, das sind systematische Übersichtsarbeiten von systematischen Übersichtsarbeiten.Ergebnisse: Zur Bewertung der medizinischen Wirksamkeit wurden neun systematische Übersichtsarbeiten eingeschlossen. Zu Kosten und Kosteneffektivität konnte keine systematische Übersichtsarbeit identifiziert werden. Für den Vergleich der medizinischen Wirksamkeit gegenüber keiner Ergotherapie wurden in fünf systematischen Übersichtsarbeiten zu 20 randomisierten Studien mit 1.316 Personen kleine positive Effekte für die Zielgrößen "generelle kognitive Funktion" und "Aktivitäten des täglichen Lebens" und ein nicht-quantifizierter positiver Effekt auf gesundheitsbezogene Lebensqualität und Verhaltenskontrolle berichtet. Für einzelne Komponenten der Kognition und Zielgrößen der Wahrnehmung ließ sich kein Effekt belegen. Die Vertrauenswürdigkeit der Evidenz für alle Zielgrößen ist auf Grund eines hohen Verzerrungsrisikos gering. In der ergänzenden Darstellung ließen sich anhand der verfügbaren Evidenz keine positiven Effekte nachweisen. Die Vertrauenswürdigkeit der Evidenz wurde nicht bewertet.Zu Patienten- und sozialen Aspekten wurden fünf systematische Übersichtsarbeiten zu Patienten mit Schlaganfall oder Schädel-Hirn-Trauma ohne Angaben zu kognitiven Defiziten oder von deren Angehörigen eingeschlossen. Es wurde berichtet, dass Patienten und betreuende Angehörige verschiedene Rehabilitationsphasen durchlaufen, in denen die Entlassung nach Hause einen entscheidenden Einschnitt darstellt. Die Rückgewinnung einer aktiven, selbstbestimmenden Rolle ist ein Prozess, der den Therapeuten abverlangt, das richtige Maß an Unterstützung von Patienten und Angehörigen zu finden.Zur Bewertung ethischer Aspekte wurden neun Dokumente eingeschlossen. Es wurden ethische Problemlösungsmodelle für die Ergotherapie und 16 ethische Aspekte bei Ergotherapie bei kognitiven Defiziten identifiziert. Zentrales Thema der Analyse sind die eingeschränkte Autonomie durch die Krankheitsfolgen sowie daraus resultierende Spannungen mit den Behandelnden.Schlussfolgerungen: Auf Grundlage dieses systematischen Overviews kann weder sicher belegt noch ausgeschlossen werden, dass die Ergotherapie bei kognitiven Einschränkungen für erwachsene Patienten mit Verletzungen des zentralen Nervensystems eine wirksame Therapie im Vergleich zu keiner Ergotherapie darstellt. Es fehlen randomisierte Studien mit ausreichenden Fallzahlen, genau definierten Interventionen und vergleichbaren Begleittherapien in den Kontrollgruppen, aber auch gut geplante Beobachtungsstudien in der Versorgungsroutine sowie gesundheitsökonomische Studien.Die identifizierten Übersichtsarbeiten zu Patienten- und sozialen Aspekten geben Aufschluss über die Bedürfnisse von Patienten nach Schlaganfall oder Schädel-Hirn-Trauma und deren Angehörige, jedoch fehlen hierzu Studien im deutschsprachigen Raum.Für die ethische Bewertung werden neben den identifizierten theoretischen Modellen zur Problemlösung ethischer Konflikte in der Ergotherapie mehr empirische Studien zu ethischen Aspekten mit Patienten mit kognitiven Defiziten und deren Angehörigen sowie Ergotherapeuten benötigt