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Hereditary channelopathies, that is, mutations in channel genes that alter channel function
and are causal for the pathogenesis of the disease, have been described for several members
of the transient receptor potential channel family. Mutations in the TRPV4 gene,
encoding a polymodal Ca2+ permeable channel, are causative for several human
diseases, which affect the skeletal system and the peripheral nervous system, with highly
variable phenotypes. In this review, we describe the phenotypes of TRPV4 channelopathies and
overlapping symptoms. Putative mechanisms to explain the puzzle, and how mutations in the
same region of the channel cause different diseases, are discussed and experimental
approaches to tackle this surprising problem are suggested. 相似文献
74.
Christina R?hr Martin Kerick Axel Fischer Alexander Kühn Karl Kashofer Bernd Timmermann Andriani Daskalaki Thomas Meinel Dmitriy Drichel Stefan T. B?rno Anja Nowka Sylvia Krobitsch Alice C. McHardy Christina Kratsch Tim Becker Andrea Wunderlich Christian Barmeyer Christian Viertler Kurt Zatloukal Christoph Wierling Hans Lehrach Michal R. Schweiger 《PloS one》2013,8(7)
MiRNAs are discussed as diagnostic and therapeutic molecules. However, effective miRNA drug treatments with miRNAs are, so far, hampered by the complexity of the miRNA networks. To identify potential miRNA drugs in colorectal cancer, we profiled miRNA and mRNA expression in matching normal, tumor and metastasis tissues of eight patients by Illumina sequencing. We validated six miRNAs in a large tissue screen containing 16 additional tumor entities and identified miRNA-1, miRNA-129, miRNA-497 and miRNA-215 as constantly de-regulated within the majority of cancers. Of these, we investigated miRNA-1 as representative in a systems-biology simulation of cellular cancer models implemented in PyBioS and assessed the effects of depletion as well as overexpression in terms of miRNA-1 as a potential treatment option. In this system, miRNA-1 treatment reverted the disease phenotype with different effectiveness among the patients. Scoring the gene expression changes obtained through mRNA-Seq from the same patients we show that the combination of deep sequencing and systems biological modeling can help to identify patient-specific responses to miRNA treatments. We present this data as guideline for future pre-clinical assessments of new and personalized therapeutic options. 相似文献
75.
Anaerobic Co-Culture of Mesenchymal Stem Cells and Anaerobic Pathogens - A New In Vitro Model System
Background
Human mesenchymal stem cells (hMSCs) are multipotent by nature and are originally isolated from bone marrow. In light of a future application of hMSCs in the oral cavity, a body compartment with varying oxygen partial pressures and an omnipresence of different bacterial species i.e. periodontitis pathogens, we performed this study to gain information about the behavior of hMSC in an anaerobic system and the response in interaction with oral bacterial pathogens.Methodology/Principal Findings
We established a model system with oral pathogenic bacterial species and eukaryotic cells cultured in anaerobic conditions. The facultative anaerobe bacteria Fusobacterium nucleatum, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans were studied. Their effects on hMSCs and primary as well as permanent gingival epithelial cells (Ca9-22, HGPEC) were comparatively analyzed. We show that hMSCs cope with anoxic conditions, since 40% vital cells remain after 72 h of anaerobic culture. The Ca9-22 and HGPEC cells are significantly more sensitive to lack of oxygen. All bacterial species reveal a comparatively low adherence to and internalization into hMSCs (0.2% and 0.01% of the initial inoculum, respectively). In comparison, the Ca9-22 and HGPEC cells present better targets for bacterial adherence and internalization. The production of the pro-inflammatory chemokine IL-8 is higher in both gingival epithelial cell lines compared to hMSCs and Fusobacterium nucleatum induce a time-dependent cytokine secretion in both cell lines. Porphyromonas gingivalis is less effective in stimulating secretion of IL-8 in the co-cultivation experiments.Conclusions/significance
HMSCs are suitable for use in anoxic regions of the oral cavity. The interaction with local pathogenic bacteria does not result in massive pro-inflammatory cytokine responses. The test system established in this study allowed further investigation of parameters prior to set up of oral hMSC in vivo studies. 相似文献76.
77.
Christine Rauch Michael Trieb Fajar R. Wibowo Bernd Wellenzohn Erwin Mayer Klaus R. Liedl 《Journal of biomolecular structure & dynamics》2013,31(6):695-706
Abstract CpG methylation determines a variety of biological functions of DNA. The methylation signal is interpreted by proteins containing a methyl-CpG binding domain (MBDs). Based on the NMR structure of MBD1 complexed with methylated DNA we analysed the recognition mode by means of molecular dynamics simulations. As the protein is monomeric and recognizes a symmetrically methylated CpG step, the recognition mode is an asymmetric one. We find that the two methyl groups do not contribute equally to the binding energy. One methyl group is associated with the major part of the binding energy and the other one nearly does not contribute at all. The contribution of the two cytosine methyl groups to binding energy is calculated to be ?3.6 kcal/mol. This implies a contribution of greater than two orders of magnitude to the binding constant. The conserved amino acid Asp32 is known to be essential for DNA binding by MBD1, but so far no direct contact with DNA has been observed. We detected a direct DNA base contact to Asp32. This could be the main reason for the importance of this amino acid. MBD contacts DNA exclusively in the major groove, the minor groove is reserved for histone contacts. We found a deformation of the minor groove shape due to complexation by MBD1, which indicates an information transfer between the major and the minor groove. 相似文献
78.
Chanjuan Guo Judy Simon Rainer Gasche Pascale Sarah Naumann Carolin Bimüller Rodica Pena Andrea Polle Ingrid Kögel-Knabner Bernd Zeller Heinz Rennenberg Michael Dannenmann 《Plant and Soil》2013,369(1-2):657-668
Aims
Our aims were to characterize the fate of leaf-litter-derived nitrogen in the plant-soil-microbe system of a temperate beech forest of Southern Germany and to identify its importance for N nutrition of beech seedlings.Methods
15N-labelled leaf litter was traced in situ into abiotic and biotic N pools in mineral soil as well as into beech seedlings and mycorrhizal root tips over three growing seasons.Results
There was a rapid transfer of 15N into the mineral soil already 21 days after tracer application with soil microbial biomass initially representing the dominant litter-N sink. However, 15N recovery in non-extractable soil N pools strongly increased over time and subsequently became the dominant 15N sink. Recovery in plant biomass accounted for only 0.025 % of 15N excess after 876 days. After three growing seasons, 15N excess recovery was characterized by the following sequence: non-extractable soil N?>>?extractable soil N including microbial biomass?>>?plant biomass?>?ectomycorrhizal root tips.Conclusions
After quick vertical dislocation and cycling through microbial N pools, there was a rapid stabilization of leaf-litter-derived N in non-extractable N pools of the mineral soil. Very low 15N recovery in beech seedlings suggests a high importance of other N sources such as root litter for N nutrition of beech understorey. 相似文献79.
Katja M. Boldt-Burisch Horst H. Gerke Seth Nii-Annang Bernd Uwe Schneider Reinhard F. Hüttl 《Plant and Soil》2013,368(1-2):281-296
Background and aims
In post mining landscapes as in the Lusatian region (Brandenburg, Germany), Pleistocene coarse-textured, sandy sediments are used for soil rehabilitation and land reclamation. The homogeneously-appearing initial soils are characterized by finer-textured soil clumps (fragments) of different sizes that are embedded in a sandy matrix. These soils with typical local-scale heterogeneity may serve as a model for studying how spatially-distributed soil fragments may be utilized by pioneering plant species. The aim of this study was to gain insight into the physical and chemical properties of sandy matrix and fragments that could possibly explain why embedded fragment may act as hot spots for root growth.Methods
In 2009, three soil monoliths of dimension 50 cm?×?50 cm?×?50 cm that were exclusively vegetated by Lotus corniculatus L. planted in 2008 were studied. Each layer of 10 cm was sampled successively using a cubic metal frame with 10 cm edge length (25 samples per layer each with a volume of 1 l). The samples were analyzed for root biomass, root lengths and diameter, and for chemical and physical properties of sandy matrix and fragments.Results
Bulk density, water contents, total carbon, total nitrogen, and plant available calcium contents were higher for the fragments compared to the sandy matrix. The roots of L. corniculatus were heterogeneously distributed in the monoliths. The root density distributions for the 1 L samples indicated a positive influence of fragments on directed root growth. Fragments embedded in the sandy matrix were found to be strongly penetrated by roots despite their relatively high bulk density. The presence of fragments also led to an increased root biomass in the sandy matrix in the direct vicinity of fragments. Such direct effects on root development were accompanied by more indirect effects by locally-elevated moisture and nutrient contents.Conclusion
The results suggest that finer-textured fragments embedded in coarser-textured sediments, can have favorable effect on plant and root development during the initial stages of establishment of vegetation cover. The fragments can act as water and nutrient hot spots to improve supply of pioneering plants especially in coarse-textured soil. The existence of small-scale heterogeneities owing to incomplete sediment mixing e.g., in soil reclamation, could be generally important for controlling the speed and direction of early plants-establishment, for instance, in the succession of post-mining areas. 相似文献80.
Sébastien Besseau Franziska Kellner Arnaud Lanoue Antje M.K. Thamm Vonny Salim Bernd Schneider Fernando Geu-Flores René H?fer Grégory Guirimand Anthony Guihur Audrey Oudin Ga?lle Glevarec Emilien Foureau Nicolas Papon Marc Clastre Nathalie Giglioli-Guivarc’h Benoit St-Pierre Danièle Werck-Reichhart Vincent Burlat Vincenzo De Luca Sarah E. O’Connor Vincent Courdavault 《Plant physiology》2013,163(4):1792-1803