Developing knowledge and tools for climate change mitigation and adaptation with multi­functional urban green infrastructure – kick-off symposium of the multidisciplinary project “Maximizing the carbon sequestration in urban trees (CliMax)”

Das interdisziplinäre Forschungsprojekt CliMax ist eine Kooperation des Julius Kühn-Instituts und der Technischen Universität Braunschweig. Das Projekt erforscht die Grundlagen für effizientere Entscheidungshilfen für Städte und Kommunen, mit deren Hilfe nicht nur der Status Quo des Beitrages des Stadtgrüns zur Kohlenstoffsequestrierung geschätzt, sondern auch die Klimawirksamkeit des Stadtgrüns maximiert werden kann. Die Berücksichtigung der Multifunktionalität des Stadtgrüns bezieht dessen positive Effekte in eine Entscheidungsmatrix mit ein und unterstützt dadurch die Integration des Klimaschutzaspektes bei Pflanz- oder Pflegeentscheidungen. Zum Anlass des Auftaktsymposiums berichten wir hier von den Projektvorhaben.The interdisciplinary research project CliMax is a cooperation between the Julius Kühn-Institute and the Technische Universität Braunschweig. It provides information on the status quo of the contribution of urban green spaces to carbon sequestration and aims for the development of decision-support tools for maximizing the climate effectiveness of urban green. Considering the multifunctionality of urban green spaces, such tools must incorporate many effects of urban green space into a decision matrix and thereby support the integration of the climate mitigation aspects in planting or maintenance decisions. On the occasion of the kick-off meeting, we report here on our plans for the project

Functional and clinical studies reveal pathophysiological complexity of CLCN4-related neurodevelopmental condition.

Missense and truncating variants in the X-chromosome-linked CLCN4 gene, resulting in reduced or complete loss-of-function (LOF) of the encoded chloride/proton exchanger ClC-4, were recently demonstrated to cause a neurocognitive phenotype in both males and females. Through international clinical matchmaking and interrogation of public variant databases we assembled a database of 90 rare CLCN4 missense variants in 90 families: 41 unique and 18 recurrent variants in 49 families. For 43 families, including 22 males and 33 females, we collated detailed clinical and segregation data. To confirm causality of variants and to obtain insight into disease mechanisms, we investigated the effect on electrophysiological properties of 59 of the variants in Xenopus oocytes using extended voltage and pH ranges. Detailed analyses revealed new pathophysiological mechanisms: 25% (15/59) of variants demonstrated LOF, characterized by a "shift" of the voltage-dependent activation to more positive voltages, and nine variants resulted in a toxic gain-of-function, associated with a disrupted gate allowing inward transport at negative voltages. Functional results were not always in line with in silico pathogenicity scores, highlighting the complexity of pathogenicity assessment for accurate genetic counselling. The complex neurocognitive and psychiatric manifestations of this condition, and hitherto under-recognized impacts on growth, gastrointestinal function, and motor control are discussed. Including published cases, we summarize features in 122 individuals from 67 families with CLCN4-related neurodevelopmental condition and suggest future research directions with the aim of improving the integrated care for individuals with this diagnosis

Functional and clinical studies reveal pathophysiological complexity of CLCN4-related neurodevelopmental condition

Missense and truncating variants in the X-chromosome-linked CLCN4 gene, resulting in reduced or complete loss-of-function (LOF) of the encoded chloride/proton exchanger ClC-4, were recently demonstrated to cause a neurocognitive phenotype in both males and females. Through international clinical matchmaking and interrogation of public variant databases we assembled a database of 90 rare CLCN4 missense variants in 90 families: 41 unique and 18 recurrent variants in 49 families. For 43 families, including 22 males and 33 females, we collated detailed clinical and segregation data. To confirm causality of variants and to obtain insight into disease mechanisms, we investigated the effect on electrophysiological properties of 59 of the variants in Xenopus oocytes using extended voltage and pH ranges. Detailed analyses revealed new pathophysiological mechanisms: 25% (15/59) of variants demonstrated LOF, characterized by a "shift" of the voltage-dependent activation to more positive voltages, and nine variants resulted in a toxic gain-of-function, associated with a disrupted gate allowing inward transport at negative voltages. Functional results were not always in line with in silico pathogenicity scores, highlighting the complexity of pathogenicity assessment for accurate genetic counselling. The complex neurocognitive and psychiatric manifestations of this condition, and hitherto under-recognized impacts on growth, gastrointestinal function, and motor control are discussed. Including published cases, we summarize features in 122 individuals from 67 families with CLCN4-related neurodevelopmental condition and suggest future research directions with the aim of improving the integrated care for individuals with this diagnosis