8 research outputs found
Warum sprechen momentan eigentlich alle über's Meer?
Das Meer ist in aller Munde. Nicht nur, aber sicher auch der Tagespresse wegen, die uns regelmäßig mit neuen furchtbaren Bildern von humanitären Katastrophen oder von besorgniserregenden Interventionen in der Golfregion versorgen. Das Meer hat Historiker*innen schon lange fasziniert. Fernand Braudels großem Klassiker über die Méditerranée (1949) haben sich gerade in den letzten Jahrzehnten zahlreiche große und unüberschaubar viele kleine Studien an die Seite gesellt. Die Mediterranistik ist mittlerweile im deutschen Sprachraum ein etabliertes Fach, die Ozeane dagegen noch immer eher ein Feld, das von der anglo- und frankophonen Forschung dominiert wird. Im Feature dieser Ausgabe haben wir Expert*innen, die sich in unterschiedlichen Kontexten mit den historischen Dimensionen des Meeres beschäftigen, die Frage gestellt, warum das Meer eigentlich momentan so ein großes Thema ist
Exploring deep microbial life in coal-bearing sediment down to ~2.5 km below the ocean floor
Peer reviewedPostprin
Erratum : Methylglyoxal modification of Na v 1.8 facilitates nociceptive neuron firing and causes hyperalgesia in diabetic neuropathy (Nature Medicine (2012) 18 (926-933))
publishersversio
The First Scube3 Mutant Mouse Line with Pleiotropic Phenotypic Alterations
The vertebrate Scube (Signal peptide, CUB, and EGF-like domain-containing protein) family consists of three independent members, Scube1–3, which encode secreted cell surface-associated membrane glycoproteins. Limited information about the general function of this gene family is available, and their roles during adulthood. Here, we present the first Scube3 mutant mouse line (Scube3N294K/N294K), which clearly shows phenotypic alterations by carrying a missense mutation in exon 8, and thus contributes to our understanding of SCUBE3 functions. We performed a detailed phenotypic characterization in the German Mouse Clinic (GMC). Scube3N294K/N294K mutants showed morphological abnormalities of the skeleton, alterations of parameters relevant for bone metabolism, changes in renal function, and hearing impairments. These findings correlate with characteristics of the rare metabolic bone disorder Paget disease of bone (PDB), associated with the chromosomal region of human SCUBE3. In addition, alterations in energy metabolism, behavior, and neurological functions were detected in Scube3N294K/N294K mice. The Scube3N294K/N294K mutant mouse line may serve as a new model for further studying the effect of impaired SCUBE3 gene function
Methylglyoxal modification of Nav1.8 facilitates nociceptive neuron firing and causes hyperalgesia in diabetic neuropathy
This study establishes a mechanism for metabolic hyperalgesia based on the glycolytic metabolite methylglyoxal. We found that concentrations of plasma methylglyoxal above 600 nM discriminate between diabetes-affected individuals with pain and those without pain. Methylglyoxal depolarizes sensory neurons and induces post-translational modifications of the voltage-gated sodium channel Nav1.8, which are associated with increased electrical excitability and facilitated firing of nociceptive neurons, whereas it promotes the slow inactivation of Nav1.7. In mice, treatment with methylglyoxal reduces nerve conduction velocity, facilitates neurosecretion of calcitonin gene-related peptide, increases cyclooxygenase-2 (COX-2) expression and evokes thermal and mechanical hyperalgesia. This hyperalgesia is reflected by increased blood flow in brain regions that are involved in pain processing. We also found similar changes in streptozotocin-induced and genetic mouse models of diabetes but not in Nav1.8 knockout (Scn10−/−) mice. Several strategies that include a methylglyoxal scavenger are effective in reducing methylglyoxal- and diabetes-induced hyperalgesia. This previously undescribed concept of metabolically driven hyperalgesia provides a new basis for the design of therapeutic interventions for painful diabetic neuropathy