No net land take policy in practice: Applications and potentials of planning instruments in municipalities; Results of an online survey in North Rhine-Westphalia

In line with the European Commission's target, land take in Germany has to be reduced to net zero by 2050. This not only presupposes greater inner urban development and more efficient development outside existing settlements, but also puts a greater planning and political focus on renaturation. The aim of this paper is to investigate the implementation of no net land take policy using the example of the highly dense and urbanised federal state of North Rhine-Westphalia in Germany. Based on an online survey, the current and potential use of (planning) instruments to implement this policy in all 396 municipalities in North Rhine-Westphalia was investigated. The findings suggest that the municipalities are not yet in a position to consistently implement no net land take. Particularly in the field of renaturation, this is often due to a lack of experience and uncertainties in the use of the existing (planning) instruments, but also to lacking awareness of the problem and a lack of political and social acceptance for higher housing densities. Since the necessary instruments are defined in current legislation and the concepts for implementation are generally known, it is important to support municipalities in using the available instruments and concepts even without direct pressure to act.In Übereinstimmung mit der Europäischen Kommission soll die Flächeninanspruchnahme bis 2050 in Deutschland auf Nettonull reduziert werden. Dies setzt nicht nur eine stärkere Innenentwicklung und eine flächensparende Außenentwicklung voraus, sondern rückt Rückbau- und Renaturierungsmaßnahmen ungleich stärker in den Fokus von Planung und Politik. Ziel dieses Beitrags ist es, den Umsetzungstand derFlächenkreislaufwirtschaft in den Städten und Gemeindendes hochverdichteten Bundeslandes Nordrhein-Westfalen zuuntersuchen. Aufbauend auf einer Online-Befragung werdenhierzu der aktuelle und potenzielle Instrumenteneinsatz zur Umsetzung einer Flächenkreislaufwirtschaft in allen 396 nordrhein-westfälischen Städten und Gemeinden abgefragt. Die Ergebnisse zeigen, dass die Städte und Gemeinden gegenwärtig noch nicht in der Lage sind, eine Flächenkreislaufwirtschaft konsequent umzusetzen. Dies liegt, insbesondere im Bereich Rückbau, mitunter an den geringen Erfahrungswerten und Unsicherheiten im Umgang mit den bestehenden (Planungs-)Instrumenten, muss aber bezüglich aktueller Wohnbauvorhaben auch auf ein generell unzureichendes Problembewusstsein und die fehlende politische und gesellschaftliche Akzeptanz für höhere Bebauungsdichten zurückgeführt werden. Da die erforderlichen Instrumente im geltenden Recht definiert und Umsetzungskonzepte allgemein bekannt sind, ist es wichtig, die Kommunen dabei zu unterstützen, die verfügbaren Instrumente und Konzepte auch ohne direkten Handlungsdruck zunutzen

Wo steht die weltweite Polioeradikation und welche Rolle spielt die Impfung?

Poliomyelitis ist eine fäkal-oral übertragbare Erkrankung, die Kinder und Erwachsenen betrifft und lebenslange gesundheitliche Einschränkungen hervorrufen kann. Seit 2014 erklärt die WHO die Ausbreitung der Polioviren zu einer gesundheitspolitischen Notlage von internationaler Bedeutung. Obwohl durch den Einsatz des oralen Polio-Impfstoffs der Rückgang der Poliofälle weltweit um über 99 % möglich war, gestaltet sich die angestrebte Eradikation der Poliomyelitis deutlich schwieriger als zunächst angenommen. Die Impfviren können mutieren und bei nicht ausreichendendem Impfschutz in der Bevölkerung zirkulieren. Im Vorfeld des diesjährigen Weltpoliotages beschreibt der Bericht im Epidemiologischen Bulletin 41/2022 die Verbreitung von Poliowildviren und zirkulierenden impfstoffabgeleiteten Polioviren sowie die Möglichkeit der Abwassersurveillance als Frühwarnsystem

Myoglobin‐mediated lipid shuttling increases adrenergic activation of brown and white adipocyte metabolism and is as a marker of thermogenic adipocytes in humans

Background: Recruitment and activation of brown adipose tissue (BAT) results in increased energy expenditure (EE) via thermogenesis and represents an intriguing therapeutic approach to combat obesity and treat associated diseases. Thermogenesis requires an increased and efficient supply of energy substrates and oxygen to the BAT. The hemoprotein myoglobin (MB) is primarily expressed in heart and skeletal muscle fibres, where it facilitates oxygen storage and flux to the mitochondria during exercise. In the last years, further contributions of MB have been assigned to the scavenging of reactive oxygen species (ROS), the regulation of cellular nitric oxide (NO) levels and also lipid binding. There is a substantial expression of MB in BAT, which is induced during brown adipocyte differentiation and BAT activation. This suggests MB as a previously unrecognized player in BAT contributing to thermogenesis. Methods and results: This study analyzed the consequences of MB expression in BAT on mitochondrial function and thermogenesis in vitro and in vivo. Using MB overexpressing, knockdown or knockout adipocytes, we show that expression levels of MB control brown adipocyte mitochondrial respiratory capacity and acute response to adrenergic stimulation, signalling and lipolysis. Overexpression in white adipocytes also increases their metabolic activity. Mutation of lipid interacting residues in MB abolished these beneficial effects of MB. In vivo, whole-body MB knockout resulted in impaired thermoregulation and cold- as well as drug-induced BAT activation in mice. In humans, MB is differentially expressed in subcutaneous (SC) and visceral (VIS) adipose tissue (AT) depots, differentially regulated by the state of obesity and higher expressed in AT samples that exhibit higher thermogenic potential. Conclusions: These data demonstrate for the first time a functional relevance of MBs lipid binding properties and establish MB as an important regulatory element of thermogenic capacity in brown and likely beige adipocytes. Keywords: energy expenditure; hemoprotein; metabolism; obesity; oxphos; uncoupling protein

Perspektive netto-null Flächenverbrauch: Innenentwicklung, flächensparendes Bauen, Flächenrückgabe und städtebauliche Qualifizierung als Elemente einer Flächenkreislaufwirtschaft

Das anhaltende Wachstum der Siedlungs- und Verkehrsfläche gehört zu den noch nicht bewältigten Herausforderungen einer nachhaltigen Stadt- und Raumentwicklung. Zu den negativen Effekten der Flächenneuinanspruchnahme zählen der Verlust von offener Landschaft, Landwirtschaftsflächen und ökologischen Habitaten, die Beeinträchtigung von Ökosystemdienstleistungen sowie steigende Folgekosten für Infrastrukturen und Leistungen der Daseinsvorsorge. Vor diesem Hintergrund hat die Bundesregierung das Ziel formuliert, die Flächeninanspruchnahme bis 2030 auf unter 30 Hektar je Tag und bis 2050 in Übereinstimmung mit der Zielsetzung der Europäischen Kommission auf netto-null zu reduzieren. Zwar wurden in den zurückliegenden Jahren durchaus Erfolge im Flächenschutz erzielt. Der Druck auf den Wohnungsmärkten in den wachsenden Großstädten hat jedoch eine gegenläufige Entwicklung ausgelöst. In jedem Fall sollten die Erfolge nicht darüber hinwegtäuschen, dass bislang lediglich eine Begrenzung des Zuwachses erreicht wurde. Ein Flächenverbrauch von netto-null setzt eine Flächenkreislaufwirtschaft voraus, die nicht nur quantitativ, sondern auch qualitativ neue Wege im Flächenschutz beschreitet. Um auf veränderte Anforderungen an die Siedlungsstruktur und Verkehrsinfrastruktur reagieren zu können, wird es auch künftig nötig sein, Flächen neu in Anspruch zu nehmen. Unter den Bedingungen einer Flächenkreislaufwirtschaft ist dies nur möglich, wenn gleichzeitig an anderer Stelle im identischen Umfang Siedlungs- und Verkehrsflächen an Natur und Landschaft zurückgegeben werden. Eine Flächenkreislaufwirtschaft kann zudem nur Erfolg haben, wenn die Innenentwicklung und hier insbesondere die Wiedernutzbarmachung von Flächen weiter massiv gestärkt wird.The continuing growth of settlement and transport areas is one of the challenges of sustainable urban and spatial development yet to be solved. The negative effects of land take-up include the loss of open landscape, agricultural land and ecological habitats, the impairment of ecosystem services and rising follow-up costs for infrastructures and services of general interest. Against this background, the German government has formulated the goal of reducing land take-up to less than 30 hectares per day by 2030 and, in line with the European Commission's target, to net zero by 2050. In recent years, there have been remarkable successes in land protection. However, the pressure on the housing markets in the growing metropolitan areas has triggered a development in the opposite direction. In any case, the successes should not obscure the fact that so far only a limitation of the growth has been achieved. Net zero land consumption presupposes a circular land economy that breaks new ground in land conservation, not only quantitatively but also qualitatively. In order to be able to react to changing demands on settlement structure and transport infrastructure, it will continue to be necessary to use up land in the future. Under the conditions of a circular land economy, this is only possible if, at the same time, settlement and transport areas are returned to nature and landscape in the same size elsewhere. Moreover, a circular land economy can only be successful if brownfield development, and in particular the reuse of land, continues to be massively strengthened

Neutrophils incite and macrophages avert electrical storm after myocardial infarction

Sudden cardiac death, arising from abnormal electrical conduction, occurs frequently in patients with coronary heart disease. Myocardial ischemia simultaneously induces arrhythmia and massive myocardial leukocyte changes. In this study, we optimized a mouse model in which hypokalemia combined with myocardial infarction triggered spontaneous ventricular tachycardia in ambulatory mice, and we showed that major leukocyte subsets have opposing effects on cardiac conduction. Neutrophils increased ventricular tachycardia via lipocalin-2 in mice, whereas neutrophilia associated with ventricular tachycardia in patients. In contrast, macrophages protected against arrhythmia. Depleting recruited macrophages in Ccr2−/− mice or all macrophage subsets with Csf1 receptor inhibition increased both ventricular tachycardia and fibrillation. Higher arrhythmia burden and mortality in Cd36−/− and Mertk−/− mice, viewed together with reduced mitochondrial integrity and accelerated cardiomyocyte death in the absence of macrophages, indicated that receptor-mediated phagocytosis protects against lethal electrical storm. Thus, modulation of leukocyte function provides a potential therapeutic pathway for reducing the risk of sudden cardiac death

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts