365 research outputs found

    Identification and characterization of early photoreceptor cis-regulatory elements and their relation to Onecut1

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    Background: Cone and rod photoreceptors are two of the primary cell types affected in human retinal disease. Potential strategies to combat these diseases are the use of gene therapy to rescue compromised photoreceptors or to generate new functional photoreceptors to replace those lost in the diseased retina. Cis-regulatory elements specific to cones, rods, or both types of photoreceptors are critical components of successful implementation of these two strategies. The purpose of this study was to identify and characterize the cell type specificity and activity of cis-regulatory elements active in developing photoreceptors. Methods: Cis-regulatory elements were introduced into the developing chicken and mouse retina by electroporation. Characterization of reporter activity in relation with cell type markers was determined using confocal microscopy. In addition, two high-throughput flow cytometry assay were developed to assess whether these elements were downstream of Onecut1 in the photoreceptor specification network. Results: The majority of cis-regulatory elements were active in both cone and rod photoreceptors and were largely uninfluenced by a Onecut1 dominant-negative construct. Elements associated with the Thrb, Nr2e3, and Rhodopsin genes showed highly enriched activity in cones or rods, and were affected by interference in Onecut1 signaling. Rhodopsin promoter activity was the most highly influenced by Onecut1 activity and its induction could be modulated by the Maf family transcription factor L-Maf. Nr2e3 elements were observed to have activity in cone photoreceptors and Nr2e3 protein was expressed in developing cone photoreceptors, suggesting a role for this predominant rod gene in cone photoreceptor development. Conclusions: The analysis presented here provides an experimental framework to determine the specificity and strength of photoreceptor elements within specific genetic networks during development. The Onecut1 transcription factor is one such factor that influences the gene regulatory networks specific to cones and rods, but not those that are common to both

    Evaluation of the ALMA Prototype Antennas

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    The ALMA North American and European prototype antennas have been evaluated by a variety of measurement systems to quantify the major performance specifications. Nearfield holography was used to set the reflector surfaces to 17 microns RMS. Pointing and fast switching performance was determined with an optical telescope and by millimeter wavelength radiometry, yielding 2 arcsec absolute and 0.6 arcsec offset pointing accuracies. Path length stability was measured to be less than or approximately equal to 20 microns over 10 minute time periods using optical measurement devices. Dynamical performance was studied with a set of accelerometers, providing data on wind induced tracking errors and structural deformation. Considering all measurements made during this evaluation, both prototype antennas meet the major ALMA antenna performance specifications.Comment: 83 pages, 36 figures, AASTex format, to appear in PASP September 2006 issu

    Quantitative analysis of the ThrbCRM1-centered gene regulatory network

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    Enhancer activity is determined by both the activity and occupancy of transcription factors as well as the specific sequences they bind. Experimental investigation of this dynamic requires the ability to manipulate components of the system, ideally in as close to an in vivo context as possible. Here we use electroporation of plasmid reporters to define critical parameters of a specific cis-regulatory element, ThrbCRM1, during retinal development. ThrbCRM1 is associated with cone photoreceptor genesis and activated in a subset of developing retinal cells that co-express the Otx2 and Onecut1 (OC1) transcription factors. Variation of reporter plasmid concentration was used to generate dose response curves and revealed an effect of binding site availability on the number and strength of cells with reporter activity. Critical sequence elements of the ThrbCRM1 element were defined using both mutagenesis and misexpression of the Otx2 and OC1 transcription factors in the developing retina. Additionally, these experiments suggest that the ThrbCRM1 element is co-regulated by Otx2 and OC1 even under conditions of sub-optimal binding of OC1

    A 24 hour naproxen dose on gastrointestinal distress and performance during cycling in the heat

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    Using a double-blind, randomized and counterbalanced, cross-over design, we assessed naproxen's effects on gastrointestinal (GI) distress and performance in eleven volunteers (6 male, 5 female). Participants completed 4 trials: 1) placebo and ambient); 2) placebo and heat; 3) naproxen and ambient; and 4) naproxen and heat. Independent variables were one placebo or 220 mg naproxen pill every 8 h (h) for 24 h and ambient (22.7 ± 1.8°C) or thermal environment (35.7 ± 1.3°C). Participants cycled 80 min at a steady heart rate then 10 min for maximum distance. Perceived exertion was measured throughout cycling. Gastrointestinal distress was assessed pre-, during, post-, 3 h post-, and 24 h post-cycling using a GI index for upper, lower, and systemic symptoms. No statistically significant differences occurred between conditions at any time for GI symptoms or perceived exertion, distance, or heart rate during maximum effort. A 24 h naproxen dose did not significantly affect performance or cause more frequent or serious GI distress when participants were euhydrated and cycling at moderate intensity in a thermal environment

    Examination of the Prevalence of Female Athlete Triad Components among Competitive Cheerleaders

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    The purpose of this study was to examine individual and combined Female Athlete Triad components within collegiate cheerleaders, an at-risk group. Cheerleaders ( = 19; age: 20.3 ± 1.2 years) completed anthropometric measurements, health history questionnaires, resting metabolic rate, the eating disorder inventory-3 and symptom checklist, blood sample, and DXA scan. Participants completed dietary and exercise logs for 7 days and used heart rate monitors to track daily and exercise energy expenditure. Proportions were calculated for low energy availability (LEA) risk, disordered eating risk, and pathogenic behaviors. Chi-square analysis was used to determine the difference between cheerleaders who experience low EA with or without disordered eating risk. All cheerleaders demonstrated LEA for the days they participated in cheerleading practice, 52.6% demonstrated LEA with eating disorder risk and 47.4% demonstrated LEA without eating disorder risk, 52.6% self-reported menstrual dysfunction, 14% experienced menstrual dysfunction via hormonal assessment, and 0% demonstrated low bone mineral density. Overall, 47.7% presented with one Triad component, 52.6% demonstrated two Triad components using self-reported menstrual data, and 10.5% demonstrated two Triad components using hormonal assessments. All cheerleaders displayed LEA. These findings support the need for increased education on the individual components of the Triad and their potential consequences by qualified personal

    An acute naproxen dose does not affect core temperature or Interleukin-6 during cycling in a hot environment

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    Non-steroidal anti-inflammatory drugs’ anti-pyretic and anti-inflammatory effects has led some individuals to theorize these medications may blunt core body temperature (Tc) increases during exercise. We utilized a double-blind, randomized, and counterbalanced cross-over design to examine the effects of a 24-h naproxen dose (3–220 ​mg naproxen pills) and placebo (0 ​mg naproxen) on Tc and plasma interleukin-6 (IL-6) concentrations during cycling in a hot or ambient environment. Participants (n ​= ​11; 6 male, 5 female; age ​= ​27.8 ​± ​6.5 years, weight ​= ​79.1 ​± ​17.9 ​kg, height ​= ​177 ​± ​9.5 ​cm) completed 4 conditions: 1) placebo and ambient (Control); 2) placebo and heat (Heat); 3) naproxen and ambient (Npx); and 4) naproxen and heat (NpxHeat). Dependent measures were taken before, during, and immediately after 90 ​min of cycling and then 3 ​h after cycling. Overall, Tc significantly increased pre- (37.1 ​± ​0.4 ​°C) to post-cycling (38.2 ​± ​0.3 ​°C, F1.7,67.3 ​= ​150.5, p ​< ​0.001) and decreased during rest (37.0 ​± ​0.3 ​°C, F2.0,81.5 ​= ​201.6, p ​< ​0.001). Rate of change or maximum Tc were not significantly different between conditions. IL-6 increased pre- (0.54 ​± ​0.06 ​pg/ml) to post-exercise (2.46 ​± ​0.28 ​pg/ml, p ​< ​0.001) and remained significantly higher than pre-at 3 ​h post- (1.17 ​± ​0.14 ​pg/ml, 95% CI ​= ​−1.01 to −0.23, p ​= ​0.001). No significant IL-6 differences occurred between conditions. A 24-h, over-the-counter naproxen dose did not significantly affect Tc or IL-6 among males and females cycling in hot or ambient environments

    Gastrointestinal Cell Injury and Percieved Symptoms after Running the Boston Marathon

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    Gastrointestinal (GI) disturbances are a prevalent cause of marathon related complaints, and in extreme cases can promote life-threatening conditions such as exertional heat stroke. PURPOSE: Our aim was to study intestinal cell injury (via intestinal fatty acid binding protein [I-FABP]) and perceived GI distress symptoms among marathon runners. Potential risk factors (e.g., inadequate sleep) that could exacerbate GI disturbances in healthy, trained endurance runners were also examined. METHODS: A parallel mixed-methods study design was utilized. 2019 Boston Marathon participants were recruited via email. Before the race subjects completed surveys describing demographics and training history. Immediately pre-race, post-race, and 24-hours post-race participants completed a GI questionnaire to assess presence and severity of symptoms, a survey regarding risk factors (e.g., recent illness, medications) that could promote GI disturbances, and provided a urine sample. Due to weather, blood samples were only collected immediately and 24-hours post-race. RESULTS: A total of 40 runners (males: n = 19, age = 44.9 ± 10.8 years; females: n = 21, age = 44.8 ± 10.6 years) completed this study. I-FABP significantly decreased from post-race (3367.5 ± 2633.5 pg/ml) to 24-hours post-race (1657.3 ± 950.7 pg/ml, t(39) = -4.228, p \u3c .001, d = -.669). A significant difference in overall GI symptom scores across the three time points occurred (F(2, 39) = 41.37, p \u3c .001). Compared to pre-race (.09 ± .12) and 24-hour post-race (.44 ± .28), the highest average score occurred post-race (.84 ± .68). Post-race I-FABP (r = .31, p = .048) and post-race urine specific gravity (r = .33, p = .041) were significantly correlated with post-race GI symptom scores. CONCLUSION: Our study further supports the individualized presentation of GI disturbances, with participants experiencing a wide range of risk factors that can influence the extent of GI damage and perceived symptoms during and after exercise

    Blueberry Progress Reports

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    The 1981 edition of the Blueberry Progress Reports was prepared for the Maine Blueberry Commission and the University of Maine Blueberry Advisory Committee by researchers with the Maine Life Sciences and Agriculture Experiment Station and Maine Cooperative Extension Service at the University of Maine, Orono. Projects in this report include: 1. Weed Control in Lowbush Blueberry Fields 2. Pruning of Blueberries 3. 1982 Blueberry Fruit Fly Monitoring IPM Program 4. Physiology and Culture of the Lowbush Blueberry 5. Blueberry Diseases: Incidence and Control 6. Control, biology, and ecology of insects affecting lowbush blueberries 7. Blueberry Extension Progress Report 8. Plan of Work - 1982 - Blueberry Extensio
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