Zentralität von Kleinstädten in ländlichen Räumen - Mythos und Realität

Als wichtige Funktion von Kleinstädten in ländlichen Räumen wird deren Zentralität angesehen. In der raumwissenschaftlichen Theorie und der raumpolitischen Praxis wird der Zentralitätsfrage für die Entwicklung der ländlichen Räume und der dortigen Kleinstädte eine entsprechend hohe Bedeutung zugemessen. Der Beitrag behandelt die Zentralitätsfrage aus einer interdisziplinären Perspektive und setzt sich kritisch mit der starken normativen Prägung in der Diskussion um Zentralitäten auseinander.Centrality is viewed as one of the most important functions of small towns in rural areas. In spatial scientific theory and spatial policy practice, the question of centrality is granted correspondingly great significance for the development of rural areas and the small towns located in such areas. The article addresses centrality from an interdisciplinary perspective and critically considers the strongly normative nature of the discussion about centralities

Small town research in Germany - status quo and recommendations

Urban studies in Germany are traditionally oriented towards large cities. The structures, meanings and functions of small towns are not sufficiently perceived and differentiated in scientific or political debates. Adequate research on small towns requires systematic, comparative, inter- and transdisciplinary approaches. Traditional attributions should be questioned critically and small towns should be examined empirically in their diversity and differentiation. This involves paying attention to external influences and heterogeneous internal structures as well as to regional functions and interdependencies. The availability and generation of statistical data, which also make small-scale analyses possible, are just as necessary as more comprehensive studies, which go beyond limited case studies. Finally, also research funding and academic teaching should address small towns more systematically than it has been the case in the past. This position paper presents recommendations for research, university teaching, official statistics and research funding in the field of small town research. The Ad-hoc Working Group focused on small town research in Germany and German-language literature, respectively

Kleinstadtforschung

Stadtforschung ist in Deutschland traditionell großstadtorientiert. Kleinstädte werden weder in wissenschaftlichen noch in politischen Auseinandersetzungen in ihren Strukturen, Bedeutungen und Funktionen hinreichend wahrgenommen und differenziert betrachtet. Eine adäquate Erforschung von Kleinstädten erfordert systematische, vergleichende sowie inter- und transdisziplinäre Ansätze. Traditionelle Zuschreibungen sollten kritisch hinterfragt und Kleinstädte in ihrer Vielfalt und Differenziertheit empirisch untersucht werden. Dabei geht es sowohl um die äußeren Prägungen und heterogenen inneren Strukturen als auch um regionale Funktionen und Verflechtungen. Die Verfügbarkeit bzw. Generierung von statistischen Daten, die auch kleinräumige Analysen ermöglichen, sind dabei ebenso notwendig wie umfassendere Studien, die über begrenzte und anlassbezogene Einzelfalluntersuchungen hinausgehen. Schließlich sollten auch die Forschungsförderung und die akademische Lehre Kleinstädte systematischer als bislang adressieren. Dieses Positionspapier enthält Empfehlungen für Wissenschaft, Lehre, amtliche Statistik und Forschungsförderung aus der Perspektive der Kleinstadtforschung.Urban studies in Germany are traditionally oriented towards large cities. The structures, meanings and functions of small towns are not sufficiently perceived and differentiated in scientific or political debates. Adequate research on small towns requires systematic, comparative, inter- and transdisciplinary approaches. Traditional attributions should be questioned critically and small towns should be examined empirically in their diversity and differentiation. This involves paying attention to external influences and heterogeneous internal structures as well as to regional functions and interdependencies. The availability and generation of statistical data, which also make small-scale analyses possible, are just as necessary as more comprehensive studies, which go beyond bounded and case studies. Finally, research funding and academic teaching should address small towns more systematically than has been the case in the past. This position paper presents recommendations for research, university teaching, official statistics and research funding in the field of small town research

Biallelic ADAM22 pathogenic variants cause progressive encephalopathy and infantile-onset refractory epilepsy

Pathogenic variants in A Disintegrin And Metalloproteinase (ADAM) 22, the postsynaptic cell membrane receptor for the glycoprotein leucine-rich repeat glioma-inactivated protein 1 (LGI1), have been recently associated with recessive developmental and epileptic encephalopathy. However, so far, only two affected individuals have been described and many features of this disorder are unknown. We refine the phenotype and report 19 additional individuals harboring compound heterozygous or homozygous inactivating ADAM22 variants, of whom 18 had clinical data available. Additionally, we provide follow-up data from two previously reported cases. All affected individuals exhibited infantile-onset, treatment-resistant epilepsy. Additional clinical features included moderate to profound global developmental delay/intellectual disability (20/20), hypotonia (12/20), delayed motor development (19/20). Brain MRI findings included cerebral atrophy (13/20), supported by post-mortem histological examination in patient-derived brain tissue, cerebellar vermis atrophy (5/20), and callosal hypoplasia (4/20). Functional studies in transfected cell lines confirmed the deleteriousness of all identified variants and indicated at least three distinct pathological mechanisms: defective cell membrane expression (1), impaired LGI1-binding (2), and/or impaired interaction with the postsynaptic density protein PSD-95 (3). We reveal novel clinical and molecular hallmarks of ADAM22 deficiency and provide knowledge that might inform clinical management and early diagnostics

Biallelic ADAM22 pathogenic variants cause progressive encephalopathy and infantile-onset refractory epilepsy

Pathogenic variants in A Disintegrin And Metalloproteinase (ADAM) 22, the postsynaptic cell membrane receptor for the glycoprotein leucine-rich repeat glioma-inactivated protein 1 (LGI1), have been recently associated with recessive developmental and epileptic encephalopathy. However, so far, only two affected individuals have been described and many features of this disorder are unknown. We refine the phenotype and report 19 additional individuals harbouring compound heterozygous or homozygous inactivating ADAM22 variants, of whom 18 had clinical data available. Additionally, we provide follow-up data from two previously reported cases. All affected individuals exhibited infantile-onset, treatment-resistant epilepsy. Additional clinical features included moderate to profound global developmental delay/intellectual disability (20/20), hypotonia (12/20) and delayed motor development (19/20). Brain MRI findings included cerebral atrophy (13/20), supported by post-mortem histological examination in patient-derived brain tissue, cerebellar vermis atrophy (5/20), and callosal hypoplasia (4/20). Functional studies in transfected cell lines confirmed the deleteriousness of all identified variants and indicated at least three distinct pathological mechanisms: (i) defective cell membrane expression; (ii) impaired LGI1-binding; and/or (iii) impaired interaction with the postsynaptic density protein PSD-95. We reveal novel clinical and molecular hallmarks of ADAM22 deficiency and provide knowledge that might inform clinical management and early diagnostics. Van der Knoop et al. describe the clinical features of 21 individuals with biallelic pathogenic variants in ADAM22 and confirm the deleteriousness of the variants with functional studies. Clinical hallmarks of this rare disorder comprise progressive encephalopathy and infantile-onset refractory epilepsy.Peer reviewe

Measures for the mitigation of greenhouse gas release from peatlands in Central Mecklenburg

Abstract: In Central Mecklenburg (NE Germany), various measures are taken to reduce greenhouse gas emissions on a variety of peatland types. In a laboratory experiment we examined methane release of plant litter from fresh and brackish water species. In addition, we measured in-situ-methane fluxes in mono-dominant vegetation stands in a coastal fen before and after rewetting. Finally, we determined nitrous oxide exchange in high and low intensity grasslands on shallow histosols. Our results show that flooding with Baltic Sea water would at least in the short-term decrease methane release substantially, independent of vegetation composition. In contrast, flooding with fresh water leads to a vegetation-specific hundredfold increase of methane emissions of about 1 t CH4 ha-1 yr-1 on average. On the grassland sites we detected no significant net nitrous oxide release on either the high or the low intensity grassland. Our examinations highlight the necessity of long-term investigations to assess the effectiveness of peatland rewetting as a climate mitigation measure.Zusammenfassung: In der Region Mittleres Mecklenburg existiert eine Vielzahl von Moortypen, an denen unterschiedliche Maßnahmen zur Absenkung von Treibhausgasemissionen erprobt werden. Wir untersuchten in einem Laborexperiment die Methanfreisetzung der Streu unterschiedlicher Bestandsbildner in Süß- und Salzwasser und die in-situ-Methanemission von Dominanzbeständen in einem Küstenversumpfungsmoor vor und nach der Wiedervernässung mit Süßwasser. Weiterhin haben wir Lachgasflüsse von Intensivgrünland und Extensivgrünland über Anmoor gemessen. Die Laborergebnisse zeigen, dass die Überflutung mit Ostseewasser die Methanfreisetzung der Streu unabhängig von der Ausprägung der Pflanzenbestände zumindest kurzfristig stark herabsetzen würde. Die Überflutung mit Süßwasser dagegen führt in situ zunächst zu einer vegetationsabhängigen Verhundertfachung der Methanfreisetzung auf im Mittel ca. 0,75 t CH4–C ha-1 a-1. Im ersten Jahr der Extensivierung von Wirtschaftsgrünland stellten wir weder auf der intensiv bewirtschafteten Variante noch auf der Extensivierungsvariante nennenswerte Lachgasflüsse fest. Unsere Untersuchungen belegen die Notwendigkeit von Langzeituntersuchungen, um Maßnahmen zum Moorschutz auf Basis tragfähiger Daten hinsichtlich ihrer Klimawirkung besser abschätzen zu können.DFG, SUB Göttingen, DGMTresearc

Doublet-Mediated DNA Rearrangement-A Novel and Potentially Underestimated Mechanism for the Formation of Recurrent Pathogenic Deletions

Deletions and duplications of genomic DNA contribute to evolution, phenotypic diversity, and human disease. The underlying mechanisms are incompletely understood. We identified deletions of exon 10 of the SPAST gene in two unrelated families with hereditary spastic paraplegia. We excluded a founder event, but observed that the breakpoints map to identical repeat regions. These regions likely represent an intragenic doublet, that is, an enigmatic class of local duplications. The fusion sequences for both deletions are compatible with recombination-based as well as with replication-based mechanisms. Searching the literature, we identified a partial SLC24A4 deletion that involved two copies of another doublet, and was likely formed in an analogous way. Comparing the SPAST and the SLC24A4 doublets with doublets identified previously suggested that many additional doublets have a high potential for triggering rearrangements. Considering that doublets are still being formed in the human genome, and that they likely create high local instability, we suggest that a two-step mechanism consisting of doublet generation and subsequent doublet-mediated deletion/duplication may underlie certain copy-number changes for which other mechanisms are currently assumed. Further studies are necessary to delineate the significance of the thus-far understudied doublets for the formation of copy-number variation. (c) 2016 Wiley Periodicals, Inc

Late-onset manifestation of antenatal Bartter syndrome as a result of residual function of the mutated renal Na+-K+-2Cl- co-transporter

Genetic defects of the Na+-K+-2Cl- (NKCC2) sodium potassium chloride co-transporter result in severe, prenatal-onset renal salt wasting accompanied by polyhydramnios, prematurity, and life-threatening hypovolemia of the neonate (antenatal Bartter syndrome or hyperprostaglandin E syndrome). Herein are described two brothers who presented with hyperuricemia, mild metabolic alkalosis, low serum potassium levels, and bilateral medullary nephrocalcinosis at the ages of 13 and 15 yr. Impaired function of sodium chloride reabsorption along the thick ascending limb of Henle's loop was deduced from a reduced increase in diuresis and urinary chloride excretion upon application of furosemide. Molecular genetic analysis revealed that the brothers were compound heterozygotes for mutations in the SLC12A1 gene coding for the NKCC2 co-transporter. Functional analysis of the mutated rat NKCC2 protein by tracer-flux assays after heterologous expression in Xenopus oocytes revealed significant residual transport activity of the NKCC2 p.F177Y mutant construct in contrast to no activity of the NKCC2-D918fs frameshift mutant construct. However, coexpression of the two mutants was not significantly different from that of NKCC2-F177Y alone or wild type. Membrane expression of NKCC2-F177Y as determined by luminometric surface quantification was not significantly different from wild-type protein, pointing to an intrinsic partial transport defect caused by the p.F177Y mutation. The partial function of NKCC2-F177Y, which is not negatively affected by NKCC2-D918fs, therefore explains a mild and late-onset phenotype and for the first time establishes a mild phenotype-associated SLC12A1 gene mutation