Individual and cumulative measures of knee joint load associate with T2 relaxation times of knee cartilage in young, uninjured individuals: A pilot study

Background: Articular cartilage structure and chondrocyte health are sensitive and reliant on dynamic joint loading during activities. The purpose of this pilot study was to determine the association between measures of individual and cumulative knee joint loading with T2 relaxation times in the knee cartilage of young individuals without knee injury. Methods: Twelve participants (17–30 years old) without history of knee injury or surgery completed MRI, physical activity (PA), and biomechanical gait testing. T2 relaxation times were calculated in the cartilage within the patella and lateral and medial compartments. Accelerometry was used to measure mean daily step counts, minutes of PA, and % sedentary time over 7 days. Vertical ground reaction force, external knee joint moments and peak knee flexion angle were measured during stance phase of gait using three-dimensional motion capture. Cumulative knee joint loading was calculated as daily step count by external knee joint moment impulse. The relationship between measures of knee joint loading and T2 relaxation times was assessed using Pearson correlations. Results: Higher T2 relaxation times in the femoral and tibial cartilage were consistently correlated to greater body mass, daily step counts, moderate and vigorous PA, and peak knee joint moments (r = 0.10–0.84). Greater cumulative knee flexion and adduction loading was associated with higher T2 relaxation times in the femoral and tibial cartilage (r = 0.16–0.65). Conclusion: Preliminary findings suggest that individual loading factors and cumulative knee joint loading are associated with higher T2 relaxation times in the articular cartilage of young, healthy knees

Growth Based Morphogenesis of Vertebrate Limb Bud

Many genes and their regulatory relationships are involved in developmental phenomena. However, by chemical information alone, we cannot fully understand changing organ morphologies through tissue growth because deformation and growth of the organ are essentially mechanical processes. Here, we develop a mathematical model to describe the change of organ morphologies through cell proliferation. Our basic idea is that the proper specification of localized volume source (e.g., cell proliferation) is able to guide organ morphogenesis, and that the specification is given by chemical gradients. We call this idea “growth-based morphogenesis.” We find that this morphogenetic mechanism works if the tissue is elastic for small deformation and plastic for large deformation. To illustrate our concept, we study the development of vertebrate limb buds, in which a limb bud protrudes from a flat lateral plate and extends distally in a self-organized manner. We show how the proportion of limb bud shape depends on different parameters and also show the conditions needed for normal morphogenesis, which can explain abnormal morphology of some mutants. We believe that the ideas shown in the present paper are useful for the morphogenesis of other organs

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

An Isoprene Mechanism Intercomparison

Annual; Electronic coverage as of Dec. 15, 2005: 2000-; Description based on: 2000; title from cover of PDF document (viewed Dec. 15, 2005).; Report year runs from Jan. 1-Dec. 31.; Harvested from the web on 6/16/06Annual program and geographic summaries of contractual agreements for loans and grants managed by the Dept. of Development.Annual program and geographic summaries of contractual agreements for loans and grants managed by the Dept. of Development