242 research outputs found

    A new, fast algorithm for detecting protein coevolution using maximum compatible cliques

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    <p>Abstract</p> <p>Background</p> <p>The MatrixMatchMaker algorithm was recently introduced to detect the similarity between phylogenetic trees and thus the coevolution between proteins. MMM finds the largest common submatrices between pairs of phylogenetic distance matrices, and has numerous advantages over existing methods of coevolution detection. However, these advantages came at the cost of a very long execution time.</p> <p>Results</p> <p>In this paper, we show that the problem of finding the maximum submatrix reduces to a multiple maximum clique subproblem on a graph of protein pairs. This allowed us to develop a new algorithm and program implementation, MMMvII, which achieved more than 600× speedup with comparable accuracy to the original MMM.</p> <p>Conclusions</p> <p>MMMvII will thus allow for more more extensive and intricate analyses of coevolution.</p> <p>Availability</p> <p>An implementation of the MMMvII algorithm is available at: <url>http://www.uhnresearch.ca/labs/tillier/MMMWEBvII/MMMWEBvII.php</url></p

    Оцінка якості життя у вікових першовагітних та вагітних з великим інтергенетичним інтервалом

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    Проведено изучение показателей качества жизни у 120 возрастных первобеременных и 240 беременных с большим интергенетическим интервалом с использованием опросника SF-36 Health Status Survey, разработанного The Health Institute, New England Medical Center, Boston, USA. Исследование показало, что пациентки обеих групп имеют низкие показатели качества жизни. При сравнении большинство изучаемых параметров оценки качества жизни в обследованных группах не отличались, однако у пациенток с большим интергенетическим интервалом – достоверно выше оценка социальной роли и энергетичности. Оценка качества жизни у возрастных первобеременных и беременных с большим интергенетическим интервалом является важным сегментом наблюдения во время беременности, который оценивает перспективы развития беременности в психологическом, физическом и социальном аспектах.A study of the life quality of 120 over-age primigravidas and of 240 women with a large intergenetic interval has been carried out using the questionnaire SF-36 Health Status Survey developed by The Health Institute, New England Medical Center, Boston, USA. This research has shown that the patients in the both groups have a low quality of life. The major part of the life quality parameters were the same in the both groups, however, in patients with a large interval between births the values of the social role and the energy level were significantly higher. The life quality of over-age primigravidas and pregnant women with a large interval between successive births is an important sector of observation during pregnancy, which allows assessing the prospects of pregnancy in the psychological, physical, and social aspects

    Elements Discrimination in the Study of Super-Heavy Elements using an Ionization Chamber

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    Dedicated ionization chamber was built and installed to measure the energy loss of very heavy nuclei at 2.7 MeV/u produced in fusion reactions in inverse kinematics (beam of 208Pb). After going through the ionization chamber, products of reactions on 12C, 18O targets are implanted in a Si detector. Their identification through their alpha decay chain is ambiguous when their half-life is short. After calibration with Pb and Th nuclei, the ionization chamber signal allowed us to resolve these ambiguities. In the search for rare super-heavy nuclei produced in fusion reactions in inverse or symmetric kinematics, such a chamber will provide direct information on the nuclear charge of each implanted nucleus.Comment: submitted to NIMA, 10 pages+4 figures, Latex, uses elsart.cls and grahpic

    Evolutionary rates vary among rRNA structural elements

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    Understanding patterns of rRNA evolution is critical for a number of fields, including structure prediction and phylogeny. The standard model of RNA evolution is that compensatory mutations in stems make up the bulk of the changes between homologous sequences, while unpaired regions are relatively homogeneous. We show that considerable heterogeneity exists in the relative rates of evolution of different secondary structure categories (stems, loops, bulges, etc.) within the rRNA, and that in eukaryotes, loops actually evolve much faster than stems. Both rates of evolution and abundance of different structural categories vary with distance from functionally important parts of the ribosome such as the tRNA path and the peptidyl transferase center. For example, fast-evolving residues are mainly found at the surface; stems are enriched at the subunit interface, and junctions near the peptidyl transferase center. However, different secondary structure categories evolve at different rates even when these effects are accounted for. The results demonstrate that relative rates and patterns of evolution are lineage specific, suggesting that phylogenetically and structurally specific models will improve evolutionary and structural predictions

    Membranous urethral length measurement on preoperative MRI to predict incontinence after radical prostatectomy:a literature review towards a proposal for measurement standardization

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    Objectives: To investigate the membranous urethral length (MUL) measurement and its interobserver agreement, and propose literature-based recommendations to standardize MUL measurement for increasing interobserver agreement. MUL measurements based on prostate MRI scans, for urinary incontinence risk assessment before radical prostatectomy (RP), may influence treatment decision-making in men with localised prostate cancer. Before implementation in clinical practise, MRI-based MUL measurements need standardization to improve observer agreement. Methods: Online libraries were searched up to August 5, 2022, on MUL measurements. Two reviewers performed article selection and critical appraisal. Papers reporting on preoperative MUL measurements and urinary continence correlation were selected. Extracted information included measuring procedures, MRI sequences, population mean/median values, and observer agreement. Results: Fifty papers were included. Studies that specified the MRI sequence used T2-weighted images and used either coronal images (n = 13), sagittal images (n = 18), or both (n = 12) for MUL measurements. ‘Prostatic apex’ was the most common description of the proximal membranous urethra landmark and ‘level/entry of the urethra into the penile bulb’ was the most common description of the distal landmark. Population mean (median) MUL value range was 10.4–17.1 mm (7.3–17.3 mm), suggesting either population or measurement differences. Detailed measurement technique descriptions for reproducibility were lacking. Recommendations on MRI-based MUL measurement were formulated by using anatomical landmarks and detailed descriptions and illustrations. Conclusions: In order to improve on measurement variability, a literature-based measuring method of the MUL was proposed, supported by several illustrative case studies, in an attempt to standardize MRI-based MUL measurements for appropriate urinary incontinence risk preoperatively. Clinical relevance statement: Implementation of MUL measurements into clinical practise for personalized post-prostatectomy continence prediction is hampered by lack of standardization and suboptimal interobserver agreement. Our proposed standardized MUL measurement aims to facilitate standardization and to improve the interobserver agreement. Key Points: • Variable approaches for membranous urethral length measurement are being used, without detailed description and with substantial differences in length of the membranous urethra, hampering standardization. • Limited interobserver agreement for membranous urethral length measurement was observed in several studies, while preoperative incontinence risk assessment necessitates high interobserver agreement. • Literature-based recommendations are proposed to standardize MRI-based membranous urethral length measurement for increasing interobserver agreement and improving preoperative incontinence risk assessment, using anatomical landmarks on sagittal T2-weighted images.</p

    MSH3 polymorphisms and protein levels affect CAG repeat instability in huntington's disease mice

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    Expansions of trinucleotide CAG/CTG repeats in somatic tissues are thought to contribute to ongoing disease progression through an affected individual's life with Huntington's disease or myotonic dystrophy. Broad ranges of repeat instability arise between individuals with expanded repeats, suggesting the existence of modifiers of repeat instability. Mice with expanded CAG/CTG repeats show variable levels of instability depending upon mouse strain. However, to date the genetic modifiers underlying these differences have not been identified. We show that in liver and striatum the R6/1 Huntington's disease (HD) (CAG)~100 transgene, when present in a congenic C57BL/6J (B6) background, incurred expansion-biased repeat mutations, whereas the repeat was stable in a congenic BALB/cByJ (CBy) background. Reciprocal congenic mice revealed the Msh3 gene as the determinant for the differences in repeat instability. Expansion bias was observed in congenic mice homozygous for the B6 Msh3 gene on a CBy background, while the CAG tract was stabilized in congenics homozygous for the CBy Msh3 gene on a B6 background. The CAG stabilization was as dramatic as genetic deficiency of Msh2. The B6 and CBy Msh3 genes had identical promoters but differed in coding regions and showed strikingly different protein levels. B6 MSH3 variant protein is highly expressed and associated with CAG expansions, while the CBy MSH3 variant protein is expressed at barely detectable levels, associating with CAG stability. The DHFR protein, which is divergently transcribed from a promoter shared by the Msh3 gene, did not show varied levels between mouse strains. Thus, naturally occurring MSH3 protein polymorphisms are modifiers of CAG repeat instability, likely through variable MSH3 protein stability. Since evidence supports that somatic CAG instability is a modifier and predictor of disease, our data are consistent with the hypothesis that variable levels of CAG instability associated with polymorphisms of DNA repair genes may have prognostic implications for various repeat-associated diseases

    New Implications on Genomic Adaptation Derived from the Helicobacter pylori Genome Comparison

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    BACKGROUND: Helicobacter pylori has a reduced genome and lives in a tough environment for long-term persistence. It evolved with its particular characteristics for biological adaptation. Because several H. pylori genome sequences are available, comparative analysis could help to better understand genomic adaptation of this particular bacterium. PRINCIPAL FINDINGS: We analyzed nine H. pylori genomes with emphasis on microevolution from a different perspective. Inversion was an important factor to shape the genome structure. Illegitimate recombination not only led to genomic inversion but also inverted fragment duplication, both of which contributed to the creation of new genes and gene family, and further, homological recombination contributed to events of inversion. Based on the information of genomic rearrangement, the first genome scaffold structure of H. pylori last common ancestor was produced. The core genome consists of 1186 genes, of which 22 genes could particularly adapt to human stomach niche. H. pylori contains high proportion of pseudogenes whose genesis was principally caused by homopolynucleotide (HPN) mutations. Such mutations are reversible and facilitate the control of gene expression through the change of DNA structure. The reversible mutations and a quasi-panmictic feature could allow such genes or gene fragments frequently transferred within or between populations. Hence, pseudogenes could be a reservoir of adaptation materials and the HPN mutations could be favorable to H. pylori adaptation, leading to HPN accumulation on the genomes, which corresponds to a special feature of Helicobacter species: extremely high HPN composition of genome. CONCLUSION: Our research demonstrated that both genome content and structure of H. pylori have been highly adapted to its particular life style
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