Characterization of pathogenic germline mutations in human Protein Kinases

Background: Protein Kinases are a superfamily of proteins involved in crucial cellular processes such as cell cycle regulation and signal transduction. Accordingly, they play an important role in cancer biology. To contribute to the study of the relation between kinases and disease we compared pathogenic mutations to neutral mutations as an extension to our previous analysis of cancer somatic mutations. First, we analyzed native and mutant proteins in terms of amino acid composition. Secondly, mutations were characterized according to their potential structural effects and finally, we assessed the location of the different classes of polymorphisms with respect to kinase-relevant positions in terms of subfamily specificity, conservation, accessibility and functional sites.Results: Pathogenic Protein Kinase mutations perturb essential aspects of protein function, including disruption of substrate binding and/or effector recognition at family-specific positions. Interestingly these mutations in Protein Kinases display a tendency to avoid structurally relevant positions, what represents a significant difference with respect to the average distribution of pathogenic mutations in other protein families.Conclusions: Disease-associated mutations display sound differences with respect to neutral mutations: several amino acids are specific of each mutation type, different structural properties characterize each class and the distribution of pathogenic mutations within the consensus structure of the Protein Kinase domain is substantially different to that for non-pathogenic mutations. This preferential distribution confirms previous observations about the functional and structural distribution of the controversial cancer driver and passenger somatic mutations and their use as a proxy for the study of the involvement of somatic mutations in cancer development. © 2011 Izarzugaza et al; licensee BioMed Central Ltd

An integrated approach to the interpretation of Single Amino Acid Polymorphisms within the framework of CATH and Gene3D

Background: The phenotypic effects of sequence variations in protein-coding regions come about primarily via their effects on the resulting structures, for example by disrupting active sites or affecting structural stability. In order better to understand the mechanisms behind known mutant phenotypes, and predict the effects of novel variations, biologists need tools to gauge the impacts of DNA mutations in terms of their structural manifestation. Although many mutations occur within domains whose structure has been solved, many more occur within genes whose protein products have not been structurally characterized.Results: Here we present 3DSim (3D Structural Implication of Mutations), a database and web application facilitating the localization and visualization of single amino acid polymorphisms (SAAPs) mapped to protein structures even where the structure of the protein of interest is unknown. The server displays information on 6514 point mutations, 4865 of them known to be associated with disease. These polymorphisms are drawn from SAAPdb, which aggregates data from various sources including dbSNP and several pathogenic mutation databases. While the SAAPdb interface displays mutations on known structures, 3DSim projects mutations onto known sequence domains in Gene3D. This resource contains sequences annotated with domains predicted to belong to structural families in the CATH database. Mappings between domain sequences in Gene3D and known structures in CATH are obtained using a MUSCLE alignment. 1210 three-dimensional structures corresponding to CATH structural domains are currently included in 3DSim; these domains are distributed across 396 CATH superfamilies, and provide a comprehensive overview of the distribution of mutations in structural space.Conclusion: The server is publicly available at http://3DSim.bioinfo.cnio.es/. In addition, the database containing the mapping between SAAPdb, Gene3D and CATH is available on request and most of the functionality is available through programmatic web service access

Theeffectivenessofginger compress on non-specific low back pain

The purpose of this study was to identify the effectiveness of ginger compress in relief non-specific low back pain and reduce functional disability due to low back pain. After screening, 15 participants were randomly allocated into two groups: experimental group (n=8) received ginger compress treatment for 20 minutes per session, three sessions per week for a total of ten sessions and control group (n=7) did not received any treatment. Numeric Rating Scale for pain and OswetryDisability Questionnaire were used to measure pain and functional disability before and after the intervention. This study revealed the experimental group indicated significantly pain relief (p=0.000) and disability reduced (p=0.000) after three weeks intervention. This study concludesthat ginger compress is effective in pain relief and reduces functional disability in patients with non-specific low back pain.Keywords: ginger compress, non-specific low back pain, Oswetry Disability Questionnair

Results of Skylab medical experiment M171: Metabolic activity

The experiment was conducted to establish whether man's ability to perform mechanical work would be progressively altered as a result of exposure to the weightless environment of space flight. The Skylab crewmen exercised on a bicycle ergometer at workloads approximating 25, 50, and 75 percent of their maximum aerobic capacity. The physiological parameters monitored were respiratory gas exchange, blood pressure, and vectorcardiogram/heart rate. The results of these tests indicate that the crewmen had no significant decrement in their responses to exercise during their exposure to zero gravity. The results of the third manned Skylab mission (Skylab 4) are presented and a comparison is made of the overall results obtained from the three successively longer Skylab manned missions. The Skylab 4 crewmembers' 84-day in-flight responses to exercise were no worse and were probably better than the responses of the crewmen on the first two Skylab missions. Indications that exercise was an important contributing factor in maintaining this response are discussed

A clinical study comparing corneal thickness changes bteween Paraperm O2 and Optacryl K lenses

A clinical evaluation was made comparing the amount of corneal edema indicated by pachometric changes in corneal thickness wlith the wearing of two rigid gas permeable lenses, Optacryl K and Paraperm o2 . Each of the nine subjects selected wore an Optacryl K lens on one eye and a Paraperm o2 lens on the other . This study encompassed a one-month period following the dispensing of the lenses. The average corneal thickness increase of the Paraperm o2 eyes was slightly less than that of the Optacryl K eyes in all three trials. However, the difference in corneal thickness changes was not found to be clinically significant. It was concluded that both lenses perform equally well in their abilities to limit the amount of corneal edema produced

Kinetics of charge carrier recombination in β- Ga2 O3 crystals

© 2018 American Physical Society. Cathodoluminescence (CL) spectra were measured to determine the characteristics of luminescence bands and carrier dynamics in β-Ga2O3 bulk single crystals. The CL emission was found to be dominated by a broad UV emission peaked at 3.40 eV, which exhibits strong quenching with increasing temperature; however, its spectral shape and energy position remain virtually unchanged. We observed a superlinear increase of CL intensity with excitation density; this kinetics of carrier recombination can be explained in terms of carrier trapping and charge transfer at Fe impurity centers. The temperature-dependent properties of this UV band are consistent with weakly bound electrons in self-trapped excitons with an activation energy of 48±10meV. In addition to the self-trapped exciton emission, a blue luminescence (BL) band is shown to be related to a donor-like defect, which increases significantly in concentration after hydrogen plasma annealing. The point defect responsible for the BL, likely an oxygen vacancy, is strongly coupled to the lattice exhibiting a Huang-Rhys factor of ∼7.3

Field Monitoring of the Compressibility of Municipal Solid Waste and Soft Alluvium

The paper presents the results of a settlement-monitoring program for a preloaded roadway embankment over a closed landfill underlain by three compressible units: municipal solid waste, alluvial peat, and organic silt. To monitor the progression of embankment settlement and assess the effectiveness of the preload treatment, a field instrumentation system was installed within the embankment footprint. The field instrumentation system, consisting of settlement plates, and vertical extensometer and vibrating wire piezometer stations, was monitored prior to construction, during construction, and for approximately 18 months thereafter. The extensometer and piezometer stations provided information on the individual response characteristics of the compressible units to load application. The paper discusses the field settlement and piezometric data, and provides time-settlement relationships for the compressible units. Backcalculated compressibility parameters for landfill refuse are compared with those reported by other researchers for such materials. Application of hyperbolic methods for consolidation analysis is evaluated with respect to reliability as a tool for settlement predictions for similar preload procedures

Photonic crystals of coated metallic spheres

It is shown that simple face-centered-cubic (fcc) structures of both metallic and coated metallic spheres are ideal candidates to achieve a tunable complete photonic bandgap (CPBG) for optical wavelengths using currently available experimental techniques. For coated microspheres with the coating width to plasma wavelength ratio $l_c/\lambda_p \leq 10$ and the coating and host refractive indices $n_c$ and $n_h$, respectively, between 1 and 1.47, one can always find a sphere radius $r_s$ such that the relative gap width $g_w$ (gap width to the midgap frequency ratio) is larger than 5% and, in some cases, $g_w$ can exceed 9%. Using different coatings and supporting liquids, the width and midgap frequency of a CPBG can be tuned considerably.Comment: 14 pages, plain latex, 3 ps figures, to appear in Europhys. Lett. For more info on this subject see http://www.amolf.nl/research/photonic_materials_theory/moroz/moroz.htm