The explosion in population genomic data demands ever more complex modes of analysis, and increasingly these analyses depend on sophisticated simulations. Re-cent advances in population genetic simulation have made it possible to simulate large and complex models, but specifying such models for a particular simulation engine remains a difficult and error-prone task. Computational genetics researchers currently re-implement simulation models independently, leading to inconsistency and duplication of effort. This situation presents a major barrier to empirical researchers seeking to use simulations for power analyses of upcoming studies or sanity checks on existing genomic data. Population genetics, as a field, also lacks standard benchmarks by which new tools for inference might be measured. Here we describe a new resource, stdpopsim, that attempts to rectify this situation. Stdpopsim is a community-driven open source project, which provides easy access to a growing catalog of published simulation models from a range of organisms and supports multiple simulation engine backends. This resource is available as a well-documented python library with a simple command-line interface. We share some examples demonstrating how stdpopsim can be used to systematically compare demographic inference methods, and we encourage a broader community of developers to contribute to this growing resource.
Hyperoxia leads to oxidative modification and damage of macromolecules in the respiratory tract with loss of biological functions. Given the lack of antioxidant gene induction with acute exposure to 100% oxygen, we hypothesized that clearance pathways for oxidatively modified proteins may be induced and serve in the immediate cellular response to preserve the epithelial layer. To test this, airway epithelial cells were obtained from individuals under ambient oxygen conditions and after breathing 100% oxygen for 12 h. Gene expression profiling identified induction of genes in the chaperone and proteasome-ubiquitin-conjugation pathways that together comprise an integrated cellular response to manage and degrade damaged proteins. Analyses also revealed gene expression changes associated with oxidoreductase function, cell cycle regulation, and ATP synthesis. Increased HSP70, protein ubiquitination, and intracellular ATP were validated in cells exposed to hyperoxia in vitro. Inhibition of proteasomal degradation revealed the importance of accelerated protein catabolism for energy production of cells exposed to hyperoxia. Thus, the human airway early response to hyperoxia relies predominantly upon induction of cytoprotective chaperones and the ubiquitin-proteasome-dependent protein degradation system to maintain airway homeostatic integrity.Keywords: airways; gene expression; hyperoxia; proteasome; ubiquitin Oxygen, one of the most abundant elements in our world, is essential for the oxidation of organic compounds to generate the energy needed to sustain life. Under ambient conditions, reactive oxygen species (ROS) are generated at a low level in lung cells during aerobic metabolism. To minimize the oxidant injury that is a consequence of aerobic life, the human lung is endowed with an integrated antioxidant system, which detoxifies reactive products (1-4). However, excessive ROS may overwhelm the antioxidant system and result in damage to major cellular components, including membrane lipids, proteins, carbohydrates, and DNA (1,(5)(6)(7)(8). The pathophysiologic consequences of this injury may include cell death, and tissue inflammation and damage. This is particularly evident during conditions of increased oxygen exposure for medical therapy (4, 9, 10). The bronchial epithelium is particularly vulnerable to the effects of airborne oxidative stress as the moist mucosal surface of the airway is in direct contact with the environment (11). Hyperoxia leads to oxidant injury in the respiratory tract, which is manifest as acute tracheobronchitis with edema and decrease in mucocili-(Received in original form July 8, 2005 and in final form May 4, 2006 ) This study was supported by AI70649, HL60917, and M01 RR018390 from the National Center for Research Resources. A.C. was supported by grants from the Collège des Professeurs de Pneumologie.Correspondence and requests for reprints should be addressed to Serpil C. (12,13). Oxidative damage of proteins and loss of biological function is one defined end-point of hyperoxic inj...
There is increasing evidence to support a genetic basis for the development of SUI, but some of the evidence is contradictory. Several candidate genes have been identified and these may lead to alterations in the composition of the ECM, ultimately predisposing some women to develop SUI. Future studies are needed to identify other candidate genes that may be involved in SUI and to study the influence of estrogen and progesterone on ECM proteins thought to be involved in SUI. The identification of genes involved in the development of SUI could lead to new therapies for the treatment of SUI.
The fields of tissue engineering and regenerative medicine have seen major advances over the span of the past two decades, with biomaterials playing a central role. Although the term "regenerative medicine" has been applied to encompass most fields of medicine, in fact urology has been one of the most progressive. Many urological applications have been investigated over the past decades, with the culmination of these technologies in the introduction of the first laboratory-produced organ to be placed in a human body.1 With the quality of life issues associated with urinary incontinence, there is a strong driver to identify and introduce new technologies and the potential exists for further major advancements from regenerative medicine approaches using biomaterials, cells or a combination of both. A central question is why use biomaterials? The answer rests on the need to make up for inadequate or lack of autologous tissue, to decrease morbidity and to improve long-term efficacy. Thus, the ideal biomaterial needs to meet the following criteria: (1) Provide mechanical and structural support, (2) Maintain compliance and be biocompatible with surrounding tissues, and (3) Be "fit for purpose" by meeting specific application needs ranging from static support to bioactive cell signaling. In essence, this represents a wide range of biomaterials with a spectrum of potential applications, from use as a supportive or bulking implant alone, to implanted biomaterials that promote integration and eventual replacement by infiltrating host cells, or scaffolds pre-seeded with cells prior to implant. In this review we shall discuss the structural versus the integrative uses of biomaterials by referring to two key areas in urology of (1) pelvic organ support for prolapse and stress urinary incontinence, and (2) bladder replacement/augmentation.
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