Brain tumour diagnostics using a DNA methylation-based classifier as a diagnostic support tool

Aims: Methylation profiling (MP) is increasingly incorporated in the diagnostic process of central nervous system (CNS) tumours at our centres in The Netherlands and Scandinavia. We aimed to identify the benefits and challenges of MP as a support tool for CNS tumour diagnostics. Methods: About 502 CNS tumour samples were analysed using (850 k) MP. Profiles were matched with the DKFZ/Heidelberg CNS Tumour Classifier. For each case, the final pathological diagnosis was compared to the diagnosis before MP. Results: In 54.4% (273/502) of all analysed cases, the suggested methylation class (calibrated score >= 0.9) corresponded with the initial pathological diagnosis. The diagnosis of 24.5% of these cases (67/273) was more refined after incorporation of the MP result. In 9.8% of cases (49/502), the MP result led to a new diagnosis, resulting in an altered WHO grade in 71.4% of these cases (35/49). In 1% of cases (5/502), the suggested class based on MP was initially disregarded/interpreted as misleading, but in retrospect, the MP result predicted the right diagnosis for three of these cases. In six cases, the suggested class was interpreted as 'discrepant but noncontributory'. The remaining 33.7% of cases (169/502) had a calibrated score Conclusions: MP is a powerful tool to confirm and fine-tune the pathological diagnosis of CNS tumours, and to avoid misdiagnoses. However, it is crucial to interpret the results in the context of clinical, radiological, histopathological and other molecular information.</div

Measuring oxytocin and vasopressin:bioassays, immunoassays and random numbers

In this review, we consider the ways in which vasopressin and oxytocin have been measured since their first discovery. Two different ways of measuring oxytocin in widespread use currently give values in human plasma that differ by two orders of magnitude, and the values measured by these two methods in the same samples show no correlation. The notion that we should accept this seems absurd. Either one (or both) methods is not measuring oxytocin, or, by ‘oxytocin’, the scientists that use these different methods mean something very different. If these communities are to talk to each other, it is important to validate one method and invalidate the other, or else to establish exactly what each community understands by ‘oxytocin’. A similar issue concerns vasopressin: again, different ways of measuring vasopressin give values in human plasma that differ by two orders of magnitude, and it appears that the same explanation for discrepant oxytocin measurements applies to discrepant vasopressin measurements. The first assays for oxytocin and vasopressin measured biological activity directly. When immunoassays were introduced, they encountered problems: high molecular weight factors in raw plasma interfered with the binding of antibodies to the hormones, leading to high and erroneous readings. When these interfering factors were removed by extraction of plasma samples, immunoassays gave measurements consistent with bioassays, with measures of turnover and with the sensitivity of target tissues to exogenous hormone. However, many recent papers use an enzyme‐linked immunoassay to measure plasma levels without extracting the samples. Like the first radioimmunassays of unextracted plasma, this generates impossibly high and wholly erroneous measurements

Gene expression patterns in four brain areas associate with quantitative measure of estrous behavior in dairy cows

<p>Abstract</p> <p>Background</p> <p>The decline noticed in several fertility traits of dairy cattle over the past few decades is of major concern. Understanding of the genomic factors underlying fertility, which could have potential applications to improve fertility, is very limited. Here, we aimed to identify and study those genes that associated with a key fertility trait namely estrous behavior, among genes expressed in four bovine brain areas (hippocampus, amygdala, dorsal hypothalamus and ventral hypothalamus), either at the start of estrous cycle, or at mid cycle, or regardless of the phase of cycle.</p> <p>Results</p> <p>An average heat score was calculated for each of 28 primiparous cows in which estrous behavior was recorded for at least two consecutive estrous cycles starting from 30 days post-partum. Gene expression was then measured in brain tissue samples collected from these cows, 14 of which were sacrificed at the start of estrus and 14 around mid cycle. For each brain area, gene expression was modeled as a function of the orthogonally transformed average heat score values using a Bayesian hierarchical mixed model. Genes whose expression patterns showed significant linear or quadratic relationships with heat scores were identified. These included genes expected to be related to estrous behavior as they influence states like socio-sexual behavior, anxiety, stress and feeding motivation (<it>OXT, AVP, POMC, MCHR1</it>), but also genes whose association with estrous behavior is novel and warrants further investigation.</p> <p>Conclusions</p> <p>Several genes were identified whose expression levels in the bovine brain associated with the level of expression of estrous behavior. The genes <it>OXT </it>and <it>AVP </it>play major roles in regulating estrous behavior in dairy cows. Genes related to neurotransmission and neuronal plasticity are also involved in estrous regulation, with several genes and processes expressed in mid-cycle probably contributing to proper expression of estrous behavior in the next estrus. Studying these genes and the processes they control improves our understanding of the genomic regulation of estrous behavior expression.</p

Aberrant Mitochondrial Homeostasis in the Skeletal Muscle of Sedentary Older Adults

The role of mitochondrial dysfunction and oxidative stress has been extensively characterized in the aetiology of sarcopenia (aging-associated loss of muscle mass) and muscle wasting as a result of muscle disuse. What remains less clear is whether the decline in skeletal muscle mitochondrial oxidative capacity is purely a function of the aging process or if the sedentary lifestyle of older adult subjects has confounded previous reports. The objective of the present study was to investigate if a recreationally active lifestyle in older adults can conserve skeletal muscle strength and functionality, chronic systemic inflammation, mitochondrial biogenesis and oxidative capacity, and cellular antioxidant capacity. To that end, muscle biopsies were taken from the vastus lateralis of young and age-matched recreationally active older and sedentary older men and women (N = 10/group; ♀  =  ♂). We show that a physically active lifestyle is associated with the partial compensatory preservation of mitochondrial biogenesis, and cellular oxidative and antioxidant capacity in skeletal muscle of older adults. Conversely a sedentary lifestyle, associated with osteoarthritis-mediated physical inactivity, is associated with reduced mitochondrial function, dysregulation of cellular redox status and chronic systemic inflammation that renders the skeletal muscle intracellular environment prone to reactive oxygen species-mediated toxicity. We propose that an active lifestyle is an important determinant of quality of life and molecular progression of aging in skeletal muscle of the elderly, and is a viable therapy for attenuating and/or reversing skeletal muscle strength declines and mitochondrial abnormalities associated with aging

Electrochemical deposition of hydroxyapatite with vinyl acetate on titanium implants

A novel approach to electrochemical processing of hydroxyapatite (HA) coating was explored. Vinyl acetate was added in the electrolytes of calcium and phosphorous in order to improve the adhesion between HA coating and titanium substrate. X-ray powder diffractometer (XRD) spectra indicated that the vinyl acetate did not interfere with the deposition of HA on the surface of titanium cathodes. X-ray photoelectron spectroscopy (XPS) and scanning electron microscope (SEM) results revealed that both vinyl acetate and HA were deposited on the titanium cathodes. The vinyl acetate changed the HA crystalline morphology in the deposition layer. The shape and growth direction of the HA crystals in the coating with vinyl acetate differed from those of HA deposition along. The addition of vinyl acetate increased the coating strength considerably, even though further improvement is needed for clinical applications. Moreover, a preliminary study of the bioactivity showed that osteoblastic cells exhibited higher cell proliferation potential on the HA/vinyl acetate coating than on that of pure HA. (C) 2003 Wiley Periodicals, Inc

A study on hybrid bioceramic coatings of HA/poly(vinyl acetate) co-deposited electrochemically on Ti-6Al-4V alloy surface

A novel electrochemical co-deposition approach was developed to prepare hybrid bioceramic coating of hydroxyapatite (HA)/poly(vinyl acetate) on the surface of Ti-6Al-4V alloy. The aim is to improve the adhesion between the HA coating and the metal substrate. Surface characterization showed that the composition of inorganic phase in the composite bioceramic coatings was mainly HA and the content of organic phase was more than 4% (W/W). Significant surface morphology changes were observed. The shear-testing experiments indicated that the bonding strength of the hybrid coating to metal substrate was increased by as much as 3 MPa. (C) 2002 Elsevier Science B.V All rights reserved