Einfluss der Korrosion auf die Schirmdämpfung versilberter Gestricke und Gewebe

Zur Abschirmung elektromagnetischer Strahlung werden unter anderem metallisierte Gestricke eingesetzt, die versilbertes Polyamid enthalten. <br><br> Solche Materialien finden beispielsweise Anwendungen als flexible Verpackungen oder als Strumpfmaterialien im medizinischen Bereich, z.B. bei der Therapie des Phantomschmerzes. <br><br> Versilbertes Polyamid ist dem korrosiven Angriff schwefelhaltiger Verbindungen ausgesetzt, welche die Schirmdämpfungswirkung aufgrund der Ausbildung von Silbersulfidschichten herabsetzen. <br><br> Untersucht wurde, inwieweit Silbersulfidbildung die Schirmdämpfung beeinträchtigt und ob die Silbersulfidbildung durch Schutzschichten aus Titandioxid (TiO<sub>2</sub>) verhindert werden kann. <br><br> Die Silbersulfidschichten wurden mit Hilfe einer alkalischen Natriumsulfid-Lösung (Tuccillo-Nielsen-Lösung) hergestellt. Titandioxid-Schichten wurden durch ein Sol-Gel-Verfahren abgeschieden. <br><br> Die untersuchten versilberten Gestricke zeigten im Bereich von 300 MHz bis 4 GHz eine weitgehend konstante Schirmdämpfung von ca. 40 dB, abhängig von der Strickart. Durch Belegung der Oberfläche mit Silbersulfid nahm die Schirmdämpfung auf ca. 5–10 dB ab. Dünne, durch Sol-Gel-Verfahren abgeschiedene TiO<sub>2</sub> -Schichten verhinderten nicht die Ausbildung von Silbersulfidschichten. <br><br> Durch Reduktion des Silbersulfids mit Aluminium in Natriumchlorid-Lösung konnte die Schirmdämpfung teilweise wiederhergestellt werden, was sich an einem Anstieg der Schirmdämpfung auf ca. 25 dB zeigte

Failure of lamin A/C to functionally assemble in R482L mutated familial partial lipodystrophy fibroblasts: altered intermolecular interaction with emerin and implications for gene transcription

Familial partial lipodystrophy is an autosomal dominant disease caused by mutations of the LMNA gene encoding alternatively spliced lamins A and C. Abnormal distribution of body fat and insulin resistance characterize the clinical phenotype. In this study, we analyzed primary fibroblast cultures from a patient carrying an R482L lamin A/C mutation by a morphological and biochemical approach. Abnormalities were observed consisting of nuclear lamin A/C aggregates mostly localized close to the nuclear lamina. These aggregates were not bound to either DNA-containing structures or RNA splicing intranuclear compartments. In addition, emerin did not colocalize with nuclear lamin A/C aggregates. Interestingly, emerin failed to interact with lamin A in R482L mutated fibroblasts in vivo, while the interaction with lamin C was preserved in vitro, as determined by coimmunoprecipitation experiments. The presence of lamin A/C nuclear aggregates was restricted to actively transcribing cells, and it was increased in insulin-treated fibroblasts. In fibroblasts carrying lamin A/C nuclear aggregates, a reduced incorporation of bromouridine was observed, demonstrating that mutated lamin A/C in FPLD cells interferes with RNA transcription

A multistage sequencing strategy pinpoints novel candidate alleles for Emery-Dreifuss muscular dystrophy and supports gene misregulation as its pathomechanism

BACKGROUND: As genome-wide approaches prove difficult with genetically heterogeneous orphan diseases, we developed a new approach to identify candidate genes. We applied this to Emery-Dreifuss muscular dystrophy (EDMD), characterised by early onset contractures, slowly progressive muscular wasting, and life-threatening heart conduction disturbances with wide intra- and inter-familial clinical variability. Roughly half of EDMD patients are linked to six genes encoding nuclear envelope proteins, but the disease mechanism remains unclear because the affected proteins function in both cell mechanics and genome regulation. METHODS: A primer library was generated to test for mutations in 301 genes from four categories: (I) all known EDMD-linked genes; (II) genes mutated in related muscular dystrophies; (III) candidates generated by exome sequencing in five families; (IV) functional candidates - other muscle nuclear envelope proteins functioning in mechanical/genome processes affected in EDMD. This was used to sequence 56 unlinked patients with EDMD-like phenotype. FINDINGS: Twenty-one patients could be clearly assigned: 18 with mutations in genes of similar muscular dystrophies; 3 with previously missed mutations in EDMD-linked genes. The other categories yielded novel candidate genes, most encoding nuclear envelope proteins with functions in gene regulation. INTERPRETATION: Our multi-pronged approach identified new disease alleles and many new candidate EDMD genes. Their known functions strongly argue the EDMD pathomechanism is from altered gene regulation and mechanotransduction due to connectivity of candidates from the nuclear envelope to the plasma membrane. This approach highlights the value of testing for related diseases using primer libraries and may be applied for other genetically heterogeneous orphan diseases. FUNDING: The Wellcome Trust, Muscular Dystrophy UK, Medical Research Council, European Community's Seventh Framework Programme "Integrated European -omics research project for diagnosis and therapy in rare neuromuscular and neurodegenerative diseases (NEUROMICS)"

Estimation of the genetic contribution of presenilin-1 and -2 mutations in a population-based study of presenile Alzheimer disease

Two closely related genes, the presenilins ( PS ), located at chromosomes 14q24.3 and 1q42.1, have been identified for autosomal dominant Alzheimer disease (AD) with onset age below 65 years (presenile AD). We performed a systematic mutation analysis of all coding and 5'-non-coding exons of PS -1 and PS -2 in a population-based epidemiological series of 101 unrelated familial and sporadic presenile AD cases. The familial cases included 10 patients of autosomal dominant AD families sampled for linkage analysis studies. In all pat

Engineering antibody heavy chain CDR3 to create a phage display Fab library rich in antibodies that bind charged carbohydrates.

peer reviewedA number of small charged carbohydrate moieties have been associated with inflammation and cancer. However, the development of therapeutic Abs targeting these moieties has been hampered by their low immunogenicity and their structural relationship to self-Ag. We report the design of an Ab repertoire enriched in Abs binding to small charged carbohydrates and the construction of a human Fab phagemid library, "FAB-CCHO." This library combines L chain Ig sequences from human donors and H chain synthetic diversity constructed in key Ag contact sites in CDRs 1, 2, and 3 of the human framework V(H)3-23. The H chain CDR3 has been engineered to enrich the library in Abs that bind charged carbohydrates by the introduction of basic residues at specific amino acid locations. These residues were selected on the basis of anti-carbohydrate Ab sequence alignment. The success of this design is demonstrated by the isolation of phage Abs against charged carbohydrate therapeutic target Ags such as sulfated sialyl-Lewis X glycan and heparan sulfate