86 research outputs found

    A history of public school finance and educational trends within the state of Nevada: Summary and conclusions

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    Funding public education has long been debated by policymakers and educators throughout history. This dissertation presents a systematic, structured, historical analysis of Nevada school funding and educational trends; This study provides a foundation for assessing the funding of public schools in Nevada. In addition, this work examines the social, economic, and legislative events influencing the funding of public education in Nevada. The social, economic, and legislative events were chosen because of their importance to Nevada Governors and Superintendents of Public Instruction, as described in Biennial Reports and Legislative Addresses, from statehood to present times. This study also provides information for those interested in the evolution of the current funding formula and educational trends, documenting the history of public school funding in Nevada for future reference

    Two-photon time-lapse microscopy of BODIPY-cholesterol reveals anomalous sterol diffusion in chinese hamster ovary cells

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    Background Cholesterol is an important membrane component, but our knowledge about its transport in cells is sparse. Previous imaging studies using dehydroergosterol (DHE), an intrinsically fluorescent sterol from yeast, have established that vesicular and non-vesicular transport modes contribute to sterol trafficking from the plasma membrane. Significant photobleaching, however, limits the possibilities for in-depth analysis of sterol dynamics using DHE. Co-trafficking studies with DHE and the recently introduced fluorescent cholesterol analog BODIPY-cholesterol (BChol) suggested that the latter probe has utility for prolonged live-cell imaging of sterol transport. Results We found that BChol is very photostable under two-photon (2P)-excitation allowing the acquisition of several hundred frames without significant photobleaching. Therefore, long-term tracking and diffusion measurements are possible. Two-photon temporal image correlation spectroscopy (2P-TICS) provided evidence for spatially heterogeneous diffusion constants of BChol varying over two orders of magnitude from the cell interior towards the plasma membrane, where D ~ 1.3 μm2/s. Number and brightness (N&B) analysis together with stochastic simulations suggest that transient partitioning of BChol into convoluted membranes slows local sterol diffusion. We observed sterol endocytosis as well as fusion and fission of sterol-containing endocytic vesicles. The mobility of endocytic vesicles, as studied by particle tracking, is well described by a model for anomalous subdiffusion on short time scales with an anomalous exponent α ~ 0.63 and an anomalous diffusion constant of Dα = 1.95 x 10-3 μm2/sα. On a longer time scale (t \u3e ~5 s), a transition to superdiffusion consistent with slow directed transport with an average velocity of v ~ 6 x 10-3 μm/s was observed. We present an analytical model that bridges the two regimes and fit this model to vesicle trajectories from control cells and cells with disrupted microtubule or actin filaments. Both treatments reduced the anomalous diffusion constant and the velocity by ~40-50%. Conclusions The mobility of sterol-containing vesicles on the short time scale could reflect dynamic rearrangements of the cytoskeleton, while directed transport of sterol vesicles occurs likely along both, microtubules and actin filaments. Spatially varying anomalous diffusion could contribute to fine-tuning and local regulation of intracellular sterol transport

    Lymphatic vasculature mediates macrophage reverse cholesterol transport in mice

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    Reverse cholesterol transport (RCT) refers to the mobilization of cholesterol on HDL particles (HDL-C) from extravascular tissues to plasma, ultimately for fecal excretion. Little is known about how HDL-C leaves peripheral tissues to reach plasma. We first used 2 models of disrupted lymphatic drainage from skin — 1 surgical and the other genetic — to quantitatively track RCT following injection of [3H]-cholesterol–loaded macrophages upstream of blocked or absent lymphatic vessels. Macrophage RCT was markedly impaired in both models, even at sites with a leaky vasculature. Inhibited RCT was downstream of cholesterol efflux from macrophages, since macrophage efflux of a fluorescent cholesterol analog (BODIPY-cholesterol) was not altered by impaired lymphatic drainage. We next addressed whether RCT was mediated by lymphatic vessels from the aortic wall by loading the aortae of donor atherosclerotic Apoe-deficient mice with [2H]6-labeled cholesterol and surgically transplanting these aortae into recipient Apoe-deficient mice that were treated with anti-VEGFR3 antibody to block lymphatic regrowth or with control antibody to allow such regrowth. [2H]-Cholesterol was retained in aortae of anti–VEGFR3-treated mice. Thus, the lymphatic vessel route is critical for RCT from multiple tissues, including the aortic wall. These results suggest that supporting lymphatic transport function may facilitate cholesterol clearance in therapies aimed at reversing atherosclerosis

    Lysophosphatidic Acid Induces Neointima Formation Through PPARγ Activation

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    Neointimal lesions are characterized by accumulation of cells within the arterial wall and are a prelude to atherosclerotic disease. Here we report that a brief exposure to either alkyl ether analogs of the growth factor–like phospholipid lysophosphatidic acid (LPA), products generated during the oxidative modification of low density lipoprotein, or to unsaturated acyl forms of LPA induce progressive formation of neointima in vivo in a rat carotid artery model. This effect is completely inhibited by the peroxisome proliferator-activated receptor (PPAR)γ antagonist GW9662 and mimicked by PPARγ agonists Rosiglitazone and 1-O-hexadecyl-2-azeleoyl-phosphatidylcholine. In contrast, stearoyl-oxovaleryl phosphatidylcholine, a PPARα agonist and polypeptide epidermal growth factor, platelet-derived growth factor, and vascular endothelial growth factor failed to elicit neointima. The structure-activity relationship for neointima induction by LPA analogs in vivo is identical to that of PPARγ activation in vitro and disparate from that of LPA G protein–coupled receptor activation. Neointima-inducing LPA analogs up-regulated the CD36 scavenger receptor in vitro and in vivo and elicited dedifferentiation of cultured vascular smooth muscle cells that was prevented by GW9662. These results suggest that selected LPA analogs are important novel endogenous PPARγ ligands capable of mediating vascular remodeling and that activation of the nuclear transcription factor PPARγ is both necessary and sufficient for neointima formation by components of oxidized low density lipoprotein

    Survey of hormone activities in municipal biosolids and animal manures.

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    ABSTRACT: The potential exists for natural or synthetic hormonal chemicals present in agricultural fertilizers to be transferred to adjacent aquatic environments in order to alter endocrine function in exposed wildlife. Recombinant yeast and mammalian cell line (BG1Luc4E 2 ) assays were used to screen crude organic extracts of municipal biosolids and animal manures for estrogen-, androgen-, and progesterone receptor gene transcription activities. Of the biosolid extracts, those samples that had undergone aerobic digestion had no or minimal estrogen-and no androgen receptor gene transcription activities. In contrast, those biosolid samples that had undergone anaerobic digestion had much higher estrogen-and, for all but one site, androgen receptor gene transcription activities. Extracts prepared from animal manure samples had variable levels of androgen-and estrogen receptor gene transcription activities, which may be related to the type, sex, age, and reproductive status of the animals. The diet and treatment of animals with hormone implants also appeared to be factors influencing hormone activity in animal manure. Progesterone receptor gene transcription activity was observed for only one chicken litter sample. Overall, results of this study suggest that in vitro bioassays can be used to survey and detect hormone activity in municipal biosolids and animal manures. Furthermore, results of these assays can be used to develop 216 practices that will minimize the potential environmental endocrine-disrupting effects of these substances

    Designing Data Structures to Minimize Bit Flips on NVM

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