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351.
352.
Richarda M. de Voer Marc-Manuel Hahn Robbert D. A. Weren Arjen R. Mensenkamp Christian Gilissen Wendy A. van Zelst-Stams Liesbeth Spruijt C. Marleen Kets Junxiao Zhang Hanka Venselaar Lilian Vreede Nil Schubert Marloes Tychon Ronny Derks Hans K. Schackert Ad Geurts van Kessel Nicoline Hoogerbrugge Marjolijn J. L. Ligtenberg Roland P. Kuiper 《PLoS genetics》2016,12(2)
Approximately 25–30% of colorectal cancer (CRC) cases are expected to result from a genetic predisposition, but in only 5–10% of these cases highly penetrant germline mutations are found. The remaining CRC heritability is still unexplained, and may be caused by a hitherto-undefined set of rare variants with a moderately penetrant risk. Here we aimed to identify novel risk factors for early-onset CRC using whole-exome sequencing, which was performed on a cohort of CRC individuals (n = 55) with a disease onset before 45 years of age. We searched for genes that were recurrently affected by rare variants (minor allele frequency ≤0.001) with potentially damaging effects and, subsequently, re-sequenced the candidate genes in a replication cohort of 174 early-onset or familial CRC individuals. Two functionally relevant genes with low frequency variants with potentially damaging effects, PTPN12 and LRP6, were found in at least three individuals. The protein tyrosine phosphatase PTP-PEST, encoded by PTPN12, is a regulator of cell motility and LRP6 is a component of the WNT-FZD-LRP5-LRP6 complex that triggers WNT signaling. All variants in LRP6 were identified in individuals with an extremely early-onset of the disease (≤30 years of age), and two of the three variants showed increased WNT signaling activity in vitro. In conclusion, we present PTPN12 and LRP6 as novel candidates contributing to the heterogeneous susceptibility to CRC. 相似文献
353.
L H Snoeckx H F Abeling J A Lambregts J J Schmitz F T Verstappen R S Reneman 《European journal of applied physiology and occupational physiology》1983,52(1):20-28
The cardiac dimensions of male long-distance runners (LDR) and cycle racers (CR) were determined echocardiographically during four different training seasons, i.e., a preparation, a competitive, a slowing-down and a resting season, and were compared with those of control subjects (CS). Left ventricular hypertrophy (LVH) was also assessed from the electrocardiogram. The maximal aerobic performance was determined on a bicycle ergometer. In the athletes, left ventricular mass was significantly greater in all seasons than the values in the CS. This difference resulted from a thicker interventricular septum and left ventricular posterior wall as well as a larger left ventricular internal diameter. The existence of LVH was confirmed by the electrocardiographic findings. No differences were observed between the four different training seasons, despite considerable changes in the training program for weeks to months. The maximal aerobic performance test in LDR showed a significantly higher workload during the competitive than during the preparation season. The CR reached significantly lower values during the resting season than during the other seasons. The results indicate that the possible adaptation of the cardiac dimensions to variations in the heaviness of the training program is relatively slow. 相似文献
354.
Guillaume Tahon Bjorn Tytgat Liesbeth Lebbe Aurélien Carlier Anne Willems 《Systematic and applied microbiology》2018,41(4):279-290
Most bacterial lineages are known only by molecular sequence data from environmental surveys and represent the uncultivated majority. One of these lineages, candidate phylum FBP, is widespread in extreme environments on Earth, ranging from polar and desert ecosystems to wastewater and contaminated mine sites. Here we report on the characterization of strain LMG 29911T, the first cultivated representative of the FBP lineage. The strain was isolated from a terrestrial surface sample from Utsteinen, Sør Rondane Mountains, East Antarctica and is a Gram-negative, aerobic, oligotrophic chemoheterotrophic bacterium. It displays growth in a very narrow pH range, use of only a limited number of carbon sources, but also a metabolism optimized for survival in low-nutrient habitats. Remarkably, phenotypic and genome analysis indicated an extreme resistance against antibiotics and toxic compounds. We propose the names Abditibacterium utsteinense for this bacterium and Abditibacteriota for the former candidate phylum FBP. Furthermore, inter- and intra-phylum relationships indicate Armatimonadetes, a neighboring lineage to the Abditibacteriota, to be a superphylum. 相似文献
355.
T Arts W C Hunter A Douglas A M Muijtjens R S Reneman 《Journal of biomechanics》1992,25(10):1119-1127
A model of left ventricular (LV) kinematics is essential to identify the fundamental physiological modes of LV deformation during a complete cardiac cycle as observed from the motion of a finite number of markers embedded in the LV wall. Kinematics can be described by a number of modes of motion and deformation in succession. An obvious mode of LV deformation is the ejection of cavity volume while the wall thickens. In the more sophisticated model of LV kinematics developed here, seven time-dependent parameters were used to describe not only volume change but also torsion and shape changes throughout the cardiac cycle. Rigid-body motion required another six parameters. The kinematic model employed a deformation field that had no singularities within the myocardium, and all parameters describing the modes of deformation were dimensionless. Note that torsion, volume and symmetric shape changes all require the definition of a cardiac coordinate system, which has generally been related to the measured cardiac geometry by reference to approximate anatomical landmarks. However, in the present study the coordinate system was positioned objectively by a least-squares fit of the kinematic model to the measured motion of markers. Theoretically, at least five markers are needed to find a unique set of parameters.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
356.
The relation between global left ventricular pumping characteristics and local cardiac muscle fiber mechanics is represented by a mathematical model of left ventricular mechanics in which the mitral valve papillary muscle system is incorporated. The wall of the left ventricle is simulated by a thick-walled cylinder. Transmural differences in fiber orientation are incorporated by changing the direction of material anisotropy across the wall. The cylinder is free to twist. The upper end of the cylinder is covered by a thin, flexible sheet, representing the base of the left ventricle. The mitral valve is incorporated in this sheet. The tips of the mitral leaflets are connected by chordae tendineae to the papillary muscles which are attached to the bottom of the cylinder. Canine cardiac cycles were simulated for various end-diastolic values of left ventricular volume (25-120 ml, control 60 ml), left atrial pressure (0-2.7 kPa, control 0.22 kPa) and aortic pressure (5-11 kPa, control 11 kPa). In this wide range of preload and afterload mechanical loading of the muscle fibers appeared to be distributed quite evenly (SD: +/- 5% of control value) over all muscular structures of the left ventricle, including the papillary muscles. 相似文献