Magnesium alloys are, due to high specific strength and stiffness, materials suitable for lightweight applications in automotive and aeronautical industries. Very poor corrosion resistance of ...magnesium and magnesium alloys significantly limits their wide utilization. Magnesium alloys are very susceptible to galvanic corrosion that can result in serious pitting corrosion, particularly in wet and salty environment. Magnesium and its alloys can be protected by formation of protective surface layers which can be achieved by plasma spraying capable of preparing metal and/or ceramic coatings. In this work, plasma coatings of NiAl10 and NiAl40 on AZ91 magnesium alloy substrate were prepared by the hybrid plasma spraying system WSP®-H 500. Present results show a significant effect of the preheat temperature of the AZ91 substrate during plasma spraying on development of a diffusion bonding due to the formation of sub-layer composed of Mg3AlNi2, Al12Mg17 phases and of Mg and Al solid solutions. The plasma sprayed coatings were observed by scanning electron microscope with elements point analysis and by X-ray phase analysis. The mechanical properties of prepared coatings were evaluated by adhesion tests. The corrosion resistance of prepared coatings was evaluated using the method of potentiodynamic measurements performed in the 0.5mol·l−1 NaCl solution while the long-term corrosion resistance was assessed in condensation chamber in wet air atmosphere at the temperature of 35°C. Both the tests showed significant effect of present sub-layers on resulting corrosion resistance.
•Coatings NiAl10 and NiAl40, prepared by WSP-H 500, had diffusion bond to AZ91.•Adhesive strength of NiAl10 and NiAl40 coatings was 25MPa and 12MPa, respectively.•Diffusion bond of NiAl40 coating had significant influence on corrosion resistance.•NiAl10 coatings showed up to twelve times higher polarization resistance values (Rp) compared to uncoated AZ91.
Inherited neuromuscular disorder (NMD) is a wide term covering different genetic disorders affecting muscles, nerves, and neuromuscular junctions. Genetic and clinical heterogeneity is the main ...drawback in a routine gene‐by‐gene diagnostics. We present Czech NMD patients with a genetic cause identified using targeted next‐generation sequencing (NGS) and the spectrum of these causes. Overall 167 unrelated patients presenting NMD falling into categories of muscular dystrophies, congenital muscular dystrophies, congenital myopathies, distal myopathies, and other myopathies were tested by targeted NGS of 42 known NMD‐related genes. Pathogenic or probably pathogenic sequence changes were identified in 79 patients (47.3%). In total, 37 novel and 51 known disease‐causing variants were detected in 23 genes. In addition, variants of uncertain significance were suspected in 7 cases (4.2%), and in 81 cases (48.5%) sequence changes associated with NMD were not found. Our results strongly indicate that for molecular diagnostics of heterogeneous disorders such as NMDs, targeted panel testing has a high‐clinical yield and should therefore be the preferred first‐tier approach. Further, we show that in the genetic diagnostic practice of NMDs, it is necessary to take into account different types of inheritance including the occurrence of an autosomal recessive disorder in two generations of one family.
This work presents the preparation of coatings of aluminium and AlCr
Fe
alloy on magnesium alloy AZ91 with metallurgical bonding. Coatings were prepared by plasma spraying system WSP
-H 500. This ...metallurgical bond (sub-layer) is formed by an eutectic structure consisting of the intermetallic phase Mg
Al
and the solid solution of magnesium and aluminium. In this work, the layers were studied using electrochemical impedance spectroscopy (EIS). It was shown that there is a several fold increase of the polarization resistance (R
) of plasma-sprayed coatings of aluminium and AlCr
Fe
alloy, compared with uncoated AZ91 in borate buffer with pH 9.1.
Limb-girdle muscular dystrophy (LGMD) is defined as a muscular dystrophy with predominantly proximal distribution of muscle weakness. It includes a number of disorders with heterogeneous etiology. We ...determined the frequency of recessive LGMD subtypes (LGMD2A, LGMD2D, LGMD2I and LGMD2L) within a cohort of Czech LGMD2 patients using mutation analysis of the calpain3 (CAPN3), fukutin-related protein (FKRP), alpha-sarcoglycan (SGCA), and anoctamin5 (ANO5) genes. Last year we introduced next generation sequencing to accelerate patient diagnosis and to widen spectrum of analysed genes. We designed capture library to target the coding exons of genes responsible for all known types of LGMD and genes responsible for muscular dystrophy with similar phenotype to LGMD. We observed that mutations of the CAPN3 gene are the most common cause of LGMD2. The frequency of particular forms of LGMD2 was 32.6% for LGMD2A, 4.1% for LGMD2I, 2.8% for LGMD2D, and 1.4% for LGMD2L. Using next-generation sequencing, we identified two patients with mutations in the gene encoding dysferlin (DYSF) – LGMD2B and a patient with mutations in the gene encoding beta-sarcoglycan (SGCB) – LGMD2E. In total, we determined mutations in 41% of Czech LGMD2 patients. This work was funded by the project of the Internal Grant Agency of the Czech Ministry of Health (NT/14574-3); the projects of the Czech Ministry of Education “CEITEC – Central European Institute of Technology” (CZ.1.05/1.1.00/02.0068) and SuPReMMe (CZ.1.07/2.3.00/20.0045).
Antitumor cisplatin cis-diamminedichloroplatinum(II) forms on DNA predominantly intrastrand cross-links between neighboring purine residues. Several discoveries suggested that the toxicity of ...cisplatin originated from these lesions. The formation of 1,2-GG intrastrand cross-link of cisplatin leads to marked conformational alterations in DNA including a directional, rigid bend toward the major groove and local unwinding. These altered structures attract various cellular proteins. This phenomenon has been postulated to mediate antitumor properties of cisplatin. Importantly, the binding affinity of several proteins that specifically recognize 1,2-GG intrastrand cross-link to platinated DNA is modulated by the nature of the base pairs that immediately flank the platinated d(GpG) site. However, the influence of sequence context on DNA bending and unwinding due to the formation of the 1,2-GG intrastrand cross-link has not been extensively investigated. In the present study we have employed electrophoretic retardation (phasing) assay to analyze bending and unwinding induced by the single, site-specific 1,2-GG intrastrand cross-link immediately flanked by various bases formed by cisplatin in nine oligodeoxyribonucleotide duplexes. The results indicate that bending and unwinding of DNA as a consequence of the formation of the major adduct of cisplatin is, in the first approximation, independent of the base pairs flanking the platinated d(GpG) site.
Abstract Limb girdle muscular dystrophies (LGMDs) represent a group of clinically and genetically heterogeneous disorders predominantly affecting shoulder and pelvic girdles. To date, 15 forms (2A-N) ...of autosomal recessive (AR) and eight forms (1A-H) of autosomal dominant LGMDs have been described. LGMD2A is the most frequent form of LGMD in many European countries, and is caused by mutations in the CAPN3 gene that encodes a muscle specific protease, calpain-3. Besides LGMD2A, we perform molecular genetic diagnostics of LGMD2I, LGMD2D, and LGMD2L caused by mutations in genes encoding fukutin-related protein (FKRP), alpha-sarcoglycan (SGCA) and anoctamin-5 (ANO5). Based on the results of clinical assessment and histopathological examination of muscle biopsies (including protein analysis using immunohistochemistry and immunoblotting), the mutational analysis of the CAPN3 , FKRP , SGCA , and ANO5 genes was performed at the mRNA level (using reverse transcription-PCR-direct sequencing) and/or at the DNA level (using PCR-direct sequencing) in a cohort of Czech patients with a preliminary diagnosis of LGMD. In total, we screened 230 unrelated patients and mutations associated with the disease were determined in 70 of them (30.4%). Mutations in the CAPN3 gene were found in 55 patients, and LGMD2A was confirmed to represent the most frequent AR LGMD in the Czech Republic. The homozygous occurence of the most common mutation in the FKRP gene (p.Leu276Ile) associated with LGMD2I was determined in eight patients. Mutations in the SGCA and ANO5 genes were detected in 5 LGMD2D and 2 LGMD2L patients, respectively. This work was funded by the project “CEITEC – Central European Institute of Technology” (CZ.1.05/1.1.00/02.0068).
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