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Frommer's Prague day by day
\"Frommer's Day-by-Day Guide to Prague\" is the complete up-to-date reference for visitors who want to maximize their stay in the smartest, most time-efficient way. With full-color throughout with hundreds of evocative photos, this invaluable guide offers reviews on a wide array of sightseeing, lodging, shopping, dining and entertainment options in all price ranges, and also includes thematic and walking tours of the city's best-loved neighborhoods with Frommer's trademark candid and accessible expertise.
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Oxidative stress and male reproductive health
One of the major causes of defective sperm function is oxidative stress, which not only disrupts the integrity of sperm DNA but also limits the fertilizing potential of these cells as a result of collateral damage to proteins and lipids in the sperm plasma membrane. The origins of such oxidative stress appear to involve the sperm mitochondria, which have a tendency to generate high leve｜s of superoxide anion as a prelude to entering the intrinsic apoptotic cascade. Unfortunately, these cells have very little capacity to respond to such an attack because they only possess the first enzyme in the base excision repair （BER） pathway, 8-oxoguanine glycosylase 1 （OGG1）. The latter successfully creates an abasic site, but the spermatozoa cannot process the oxidative lesion further because they lack the downstream proteins （APE1, XRCC1） needed to complete the repair process. It is the responsibility of the oocyte to continue the BER pathway prior to initiation of S-phase of the first mitotic division. If a mistake is made by the oocyte at this stage of development, a mutation will be created that will be represented in every cell in the body. Such mechanisms may explain the increase in childhood cancers and other diseases observed in the offspring of males who have suffered oxidative stress in their germ line as a consequence of age, environmental or lifestyle factors. The high prevalence of oxidative DNA damage in the spermatozoa of male infertility patients may have implications for the health of children conceived in vitro and serves as a driver for current research into the origins of free radical generation in the germ line.
Journal Article
Are sperm capacitation and apoptosis the opposite ends of a continuum driven by oxidative stress
This chapter explores the possibility that capacitation and apoptosis are linked processes joined by their common dependence on the continued generation of reactive oxygen species （ROS）. According to this model capacitation is initiated in spematozoa following their release into the female reproductive tract as a consequence of intracellular ROS generation, which stimulates intracellular cAMP generation, inhibits tyrosine phosphatase activity and enhances the formation of oxysterols prior to their removal from the sperm surface by albumin. The continued generation of ROS by capacitating populations of spermatozoa eventually overwhelms the limited capacity of these cells to protect themselves from oxidative stress. As a result the over-capacitation of spermatozoa leads to a state of senescence and the activation of a truncated intrinsic apoptotic cascade characterized by enhanced mitochondrial RO$ generation, lipid peroxidation, motility loss, caspase activation and phosphatidylserine externalization. The latter may be particularly important in instructing phagocytic leukocytes that the removal of senescent, moribund spermatozoa should be a silent process unaccompanied by the generation of proinflammatory cytokines. These observations reveal the central role played by redox chemistry in defining the life and death of spermatozoa. A knowledge of these mechanisms may help us to engineer novel solutions to both support and preserve the functionality of these highly specialized cells.
Journal Article
Botulinum Toxin: An Update on Pharmacology and Newer Products in Development
Since its introduction as a treatment for strabismus, botulinum toxin (BoNT) has had a phenomenal journey and is now recommended as first-line treatment for focal dystonia, despite short-term clinical benefits and the risks of adverse effects. To cater for the high demand across various medical specialties, at least six US Food and Drug Administration (FDA)-approved formulations of BoNT are currently available for diverse labelled indications. The toxo-pharmacological properties of these formulations are not uniform and thus should not be used interchangeably. Synthetic BoNTs and BoNTs from non-clostridial sources are not far from clinical use. Moreover, the study of mutations in naturally occurring toxins has led to modulation in the toxo-pharmacokinetic properties of BoNTs, including the duration and potency. We present an overview of the toxo-pharmacology of conventional and novel BoNT preparations, including those awaiting imminent translation from the laboratory to the clinic.
Journal Article
Giant vortex clusters in a two-dimensional quantum fluid
Adding energy to a system through transient stirring usually leads to more disorder. In contrast, point-like vortices in a bounded two-dimensional fluid are predicted to reorder above a certain energy, forming persistent vortex clusters. In this study, we experimentally realize these vortex clusters in a planar superfluid: a 87Rb Bose-Einstein condensate confined to an elliptical geometry. We demonstrate that the clusters persist for long time periods, maintaining the superfluid system in a high-energy state far from global equilibrium. Our experiments explore a regime of vortex matter at negative absolute temperatures and have relevance for the dynamics of topological defects, two-dimensional turbulence, and systems such as helium films, nonlinear optical materials, fermion superfluids, and quark-gluon plasmas.
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