Methods in molecular biology
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The specific causes of prostate cancer are not known. However, multiple etiologic factors, including genetic profile, metabolism of steroid hormones, nutrition, chronic inflammation, family history of prostate cancer, and environmental exposures are thought to play significant roles. Variations in exposure to these risk factors may explain interindividual differences in prostate cancer risk. ⋯ Numerous single nucleotide polymorphisms (SNPs) in DNA repair genes have been found, and studies of these SNPs and prostate cancer risk are critical to understanding the response of prostate cells to DNA damage. A few SNPs in DNA repair genes are associated with significantly increased risk of prostate cancer; however, in most cases, the effects are moderate and often depend upon interactions among the risk alleles of several genes in a pathway or with other environmental risk factors. This report reviews the published epidemiologic literature on the association of SNPs in genes involved in DNA repair pathways and prostate cancer risk.
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Mouse models that mimic human diseases are important tools for investigating underlying mechanisms in many disease states. Although the demand for these models is high, there are few schools or courses available for surgeons to obtain the necessary skills. Researchers are usually exposed to brief descriptions of the procedures in scientific journals, which they then attempt to reproduce by trial and error. ⋯ It guides the reader through the entire procedure, from the preparation of the animal for surgery until its full recovery, and includes a list of all necessary tools and devices. Due consideration has been given to the pitfalls and possible complications in the course of surgery. Adhering to our recommendations should improve reproducibility of the models and bring the number of the animal subjects to the minimum.
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Magnetoencephalography (MEG) encompasses a family of non-contact, non-invasive techniques for detecting the magnetic field generated by the electrical activity of the brain, for analyzing this MEG signal and for using the results to study brain function. The overall purpose of MEG is to extract estimates of the spatiotemporal patterns of electrical activity in the brain from the measured magnetic field outside the head. The electrical activity in the brain is a manifestation of collective neuronal activity and, to a large extent, the currency of brain function. The estimates of brain activity derived from MEG can therefore be used to study mechanisms and processes that support normal brain function in humans and help us understand why, when and how they fail.
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Higher-grade gliomas are distinguished by increased vascular endothelial cell proliferation and peritumoral edema. These are thought to be instigated by vascular endothelial growth factor, which in turn is regulated by cellular oxygen tension. Hypoxia inducible factor-1alpha (HIF-1alpha) is a main responder to intracellular hypoxia and is overexpressed in many human cancers, including gliomas. Here we present methods for investigating the role of HIF-1alpha in glioma growth in vivo and in vitro using RNA interference in U251, U87, and U373 glioma cells.
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Spinal cord injury (SCI) is a major public health problem with no known effective treatment. Traumatic injury to the spinal cord initiates a host of pathophysiological events that are secondary to the initial insult leading to neuronal dysfunction and death; yet, the molecular mechanisms underlying its dysfunction are poorly understood. Furthermore, while use of imaging methods (e.g., computed tomography scans and magnetic resonance imaging) may help define injury severity and location, they do not elucidate biological mechanisms of SCI progression. ⋯ Spinal cord contusion is an extensively used SCI model in rats that best represents the etiology of SCI in humans. In this chapter, we describe a two-dimensional (2D) gel electrophoresis-based proteomic approach to investigate the injury-related differences in the proteome and phosphoproteome of spinal cord lesion epicenter at 24 h after spinal cord contusion in rats. The purpose of this study is to elucidate the mechanisms of acute spinal cord dysfunction, as well as discover novel biomarker candidates to evaluate the biological mechanisms of SCI progression and the injury severity.