Inopinatus corneliae sp. nov. gen. nov. isolated from human skin: A newly discovered keratinophilic hyphomycete, order Onygenales.

BACKGROUND: Fungi clinically relevant to human skin comprise prevalent commensals and well-known pathogens. Only rarely human skin harbours fungi that evade identification. OBJECTIVE: To characterise an enigmatic specimen isolated from a skin lesion. METHODS: A comprehensive clinical and mycological workup including conventional methods for phenotypic characterisation and sequencing based on internal transcribed spacer (ITS) and large subunit (LSU) regions to infer a phylogenetic tree. RESULTS: Cultures on common solid media were macroscopically inconspicuous initially until mycelial tufts developed on the surface, notably on potato dextrose agar. Polymorphous chlamydospores were detected but no aleurospores and ascomata. At 26°C, the isolate grew on standard agars, plant materials and garden soil and utilised peptone, keratins, lipids, inulin, erythrocytes and cellulose. It also grew at 5°C and at 37°C. Nucleotide sequences of its ITS region showed 93% similarity to sequences of different Malbranchea species. The closest matches among LSU rRNA sequences were obtained with the genera Amauroascus, Arthroderma, Auxarthronopsis and Malbranchea (93%-95%). A combined phylogenetic analysis placed the fungus in a sister clade to Neogymnomycetaceae, classified as incertae sedis in Onygenales, on a large distance to either Diploospora rosea or 'Amauroascus' aureus. CONCLUSIONS: The genus Inopinatus gen. nov. (MB854685) with the species Inopinatus corneliae sp. nov. (MB854687) is introduced to accommodate our isolate (holotype: DSM 116806; isotypes: CBS 151104, IHEM 29063). Probably Inopinatus corneliae is a geophilic species that, although potentially harmful, was no relevant pathogen in our case. Its ecology, epidemiology and pathogenicity need to be further clarified.

"Indian" strains of Trichophyton mentagrophytes with reduced itraconazole susceptibility in Germany.

We use published reports and three of our own tinea cases as an opportunity to report on "Indian" strains of Trichophyton (T.) mentagrophytes with ITS genotype VIII and reduced susceptibility to itraconazole due to the mutation c.1342G>A in the SQLE gene in Germany. In vitro measurements of resistance revealed normal susceptibility to terbinafine, but markedly reduced susceptibility to itraconazole - although no valid breakpoints are currently defined and minimum inhibitory concentrations (MICs) depend on the methods used. Problems related to the determination and interpretation of MICs are outlined. Our cases show that azole-resistant "Indian" strains of T. mentagrophytes with ITS genotype VIII occurred in Germany as early as 2011, which is earlier than was previously assumed. This variant of the pathogen cannot be phenotypically distinguished from customary strains of T. mentagrophytes; its identification is based on genetics. The taxonomic classification is still under debate. This variant is anthropophilic and causes only mildly inflammatory tinea lesions with many fungal elements. Its further dissemination must therefore be expected. Prerequisites for rapid and valid antimycotic testing against dermatophytes need to be developed.

The role of extracellular regulated kinases I/II in late-phase long-term potentiation.

Extracellular regulated kinases (ERKI/II), members of the mitogen-activated protein kinase family, play a role in long-term memory and long-term potentiation (LTP). ERKI/II is required for the induction of the early phase of LTP, and we show that it is also required for the late phase of LTP in area CA1 in vitro, induced by a protocol of brief, repeated 100 Hz trains. We also show that ERKI/II is necessary for the upregulation of the proteins encoded by the immediate early genes Zif268 and Homer after the induction of LTP in the dentate gyrus by tetanic stimulation of the perforant path in vivo or by BDNF stimulation of primary cortical cultures. To test whether the induction of persistent synaptic plasticity by stimuli such as BDNF is associated with nuclear translocation of ERKI/II, we expressed enhanced green fluorescent protein (EGFP)-ERKII in PC12 cell lines and primary cortical cultures. In both preparations, we observed translocation of EGFP-ERKII from the cytoplasm to the nucleus in cells exposed to neurotrophic factors. Our results suggest that the induction of late LTP involves translocation of ERKI/II to the nucleus in which it activates the transcription of immediate early genes. The ability to visualize the cellular redistribution of ERKII after induction of long-term synaptic plasticity may provide a method for visualizing neuronal circuits underlying information storage in the brain in vivo.

Age-dependent loss of PTP and LTP in the hippocampus of PrP-null mice.

We have investigated synaptic function in the hippocampus in mice of different ages carrying a null mutation in the PrP gene. Experiments carried out in vivo and in vitro in two laboratories revealed no differences in the ability of juvenile and young adult control and PrP-null mice to express long-term potentiation, paired-pulse facilitation, or posttetanic potentiation in either the dentate gyrus or in the CA1 region. However, we found a significant reduction in the level of posttetanic potentiation and long-term potentiation in the CA1 region of aged PrP-null mice. These results are discussed in relationship to reported increased levels of oxidative stress in older PrP-null mice.