42 research outputs found

    A Validated Age-Related Normative Model for Male Total Testosterone Shows Increasing Variance but No Decline after Age 40 Years

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    The diagnosis of hypogonadism in human males includes identification of low serum testosterone levels, and hence there is an underlying assumption that normal ranges of testosterone for the healthy population are known for all ages. However, to our knowledge, no such reference model exists in the literature, and hence the availability of an applicable biochemical reference range would be helpful for the clinical assessment of hypogonadal men. In this study, using model selection and validation analysis of data identified and extracted from thirteen studies, we derive and validate a normative model of total testosterone across the lifespan in healthy men. We show that total testosterone peaks [mean (2.5-97.5 percentile)] at 15.4 (7.2-31.1) nmol/L at an average age of 19 years, and falls in the average case [mean (2.5-97.5 percentile)] to 13.0 (6.6-25.3) nmol/L by age 40 years, but we find no evidence for a further fall in mean total testosterone with increasing age through to old age. However we do show that there is an increased variation in total testosterone levels with advancing age after age 40 years. This model provides the age related reference ranges needed to support research and clinical decision making in males who have symptoms that may be due to hypogonadism.Publisher PDFPeer reviewe

    Finishing the euchromatic sequence of the human genome

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    The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

    Among-individual diet variation within a lake trout ecotype: lack of stability of niche use

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    In a polyphenic species, differences in resource use are expected among ecotypes, and homogeneity in resource use is expected within an ecotype. Yet, using a broad resource spectrum has been identified as a strategy for fishes living in unproductive northern environments, where food is patchily distributed and ephemeral. We investigated whether specialization of trophic resources by individuals occurred within the generalist piscivore ecotype of lake trout from Great Bear Lake, Canada, reflective of a form of diversity. Four distinct dietary patterns of resource use within this lake trout ecotype were detected from fatty acid composition, with some variation linked to spatial patterns within Great Bear Lake. Feeding habits of different groups within the ecotype were not associated with detectable morphological or genetic differentiation, suggesting that behavioral plasticity caused the trophic differences. A low level of genetic differentiation was detected between exceptionally large‐sized individuals and other piscivore individuals. We demonstrated that individual trophic specialization can occur within an ecotype inhabiting a geologically young system (8,000–10,000 yr BP), a lake that sustains high levels of phenotypic diversity of lake trout overall. The characterization of niche use among individuals, as done in this study, is necessary to understand the role that individual variation can play at the beginning of differentiation processes

    Potential therapeutic approaches for modulating expression and accumulation of defective lamin A in laminopathies and age-related diseases

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