742 research outputs found

    Investigation of catalytic combustion of impurities in air Final report, 24 Mar. - 28 Dec. 1966

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    Catalytic coil to oxidize carbon monoxide, hydrogen, and methane present as impurities in ai

    Inhibition of CaMKK2 reverses age-associated decline in bone mass

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    Decline in bone formation is a major contributing factor to the loss of bone mass associated with aging. We previously showed that the genetic ablation of the tissue-restricted and multifunctional Ca(2+)/calmodulin (CaM)-dependent protein kinase kinase 2 (CaMKK2) stimulates trabecular bone mass accrual, mainly by promoting anabolic pathways and inhibiting catabolic pathways of bone remodeling. In this study, we investigated whether inhibition of this kinase using its selective cell-permeable inhibitor STO-609 will stimulate bone formation in 32 week old male WT mice and reverse age-associated of decline in bone volume and strength. Tri-weekly intraperitoneal injections of saline or STO-609 (10 μM) were performed for six weeks followed by metabolic labeling with calcein and alizarin red. New bone formation was assessed by dynamic histomorphometry whereas micro-computed tomography was employed to measure trabecular bone volume, microarchitecture and femoral mid-shaft geometry. Cortical and trabecular bone biomechanical properties were assessed using three-point bending and punch compression methods respectively. Our results reveal that as they progress from 12 to 32 weeks of age, WT mice sustain a significant decline in trabecular bone volume, microarchitecture and strength as well as cortical bone strength. However, treatment of the 32 week old WT mice with STO-609 stimulated apposition of new bone and completely reversed the age-associated decrease in bone volume, quality, as well as trabecular and cortical bone strength. We also observed that regardless of age, male Camkk2(-/-) mice possessed significantly elevated trabecular bone volume, microarchitecture and compressive strength as well as cortical bone strength compared to age-matched WT mice, implying that the chronic loss of this kinase attenuates age-associated decline in bone mass. Further, whereas STO-609 treatment and/or the absence of CaMKK2 significantly enhanced the femoral mid-shaft geometry, the mid-shaft cortical wall thickness and material bending stress remained similar among the cohorts, implying that regardless of treatment, the material properties of the bone remain similar. Thus, our cumulative results provide evidence for the pharmacological inhibition of CaMKK2 as a bone anabolic strategy in combating age-associated osteoporosis

    Investigating Skeletal Muscle Metabolic Adaptations underlying Aerobic Fitness Gains Following High Intensity Interval Training in a Rat Model of Pulmonary Arterial Hypertension

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    poster abstractRationale: In patients with pulmonary arterial hypertension (PAH) a shift from oxidative to a less efficient non-oxidative (glycolytic) metabolism in skeletal muscle is believed to contribute to the reduced exercise tolerance hallmark of the disease. As seen for other cardiopulmonary diseases, exercise training (ExT) may ameliorate this “glycolytic switch” in PAH and improve exercise capacity. Previous studies in this lab showed an improved metabolic profile of skeletal muscle in PAH rats following an ExT protocol of continuous running at moderate relative intensity, 60 minutes at 75% of maximal aerobic capacity (VO2Max). High intensity interval training (HIIT) has been shown in healthy individuals as well as in patients with cardiovascular disease to promote favorable cardiac and skeletal muscle adaptations and greater improvements in aerobic capacity versus customary continuous training. This study tests the hypothesis in a PAH rat model that HIIT will result in preserved aerobic capacity and a greater attenuation of skeletal muscle glycolytic shift than that observed with continuous moderate intensity exercise. Methods: Male Sprague-Dawley rats received either monocrotaline (MCT, 40 mg/kg, s.q.) to induce PAH (n= 8), or saline, for healthy controls (n=4). After 2 wks, with MCT-induced PAH wellestablished, 6 wks of treadmill HIIT was initiated for a subset of PAH animals (PAH-ExT, n= 6) and healthy controls (CON-ExT, n=2). The HIIT runs were alternated between 2 to 3 minutes of high intensity exercise (85% VO2max reserve) and active recovery intervals between 2 to 3 minutes (10 m/min, 0 incline) VO2max was assessed at baseline, and in pre-training and post-training via analysis of expired gases during incremental treadmill running. Preliminary results: MCT-induced decrement in VO2max was attenuated by HIIT. Abundance of membrane glucose transporter Glut-1, a marker of glycolytic metabolism, is currently being evaluated in soleus cryosections with immunofluorescent staining. Findings are being compared to historical data for PAH and healthy rats from a study protocol that differed only by training approach-continuous instead of HIIT

    LMWH in the prevention of preeclampsia and fetal growth restriction in women without thrombophilia. A systematic review and meta-analysis.

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    SummaryPlacental mediated pregnancy complications such as preeclampsia and fetal growth restriction (FGR) are common, serious, and associated with increased morbidity and mortality. We conducted a systematic review and meta-analysis to determine the effect of treatment with low-molecular-weight heparins (LMWHs) for secondary prevention of these complications in non thrombophilic women. We searched the electronic databases PubMed, Scopus, and Cochrane Library for randomised controlled trials addressing this question. Five studies including 403 patients met the inclusion criteria, 68 developed preeclampsia and 118 FGR. The studies were very heterogeneous in terms of inclusion criteria, LMWH preparation, and dosage. Meta-analyses were performed using random-effect models. The overall use of LMWHs was associated with a risk reduction for preeclampsia (Relative risk (RR) 0.366; 95 % confidence interval (CI), 0.219–0.614) and FGR (RR 0.409; 95 % CI, 0.195–0.932) vs. no treatment. From the data available for analysis it appears that the use of Dalteparin is associated with a risk reduction for preeclampsia (p=0.002) and FGR (p&lt;0.001); while Enoxaparin is associated with risk reduction for preeclampsia (p=0.013) but not for FGR (p=0.3). In spite of the small number of studies addressing the research question, and the high variability among them, our meta-analysis found a modest beneficial effect of LMWH for secondary prevention of preeclampsia and FGR. Further studies are needed to address these questions before a definite conclusion can be reached.Supplementary Material to this article is available online at www.thrombosis-online.com.</jats:p

    Treatment with a Green Tea Polyphenol Corrects Craniofacial Deficits Associated with Down Syndrome

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    poster abstractDown syndrome (DS) is caused by trisomy of human chromosome 21 (HSA21). Individuals with DS present craniofacial abnormalities including an undersized, dismorphic mandible leading to difficulty with eating, breathing, and swallowing. Using the Ts65Dn DS mouse model (three copies of ~50% HSA21 homologs), we have traced the mandibular deficit to a neural crest cell (NCC) deficiency and reduction in first pharyngeal arch (PA1 or mandibular precursor) size at embryonic day 9.5. At E9.5, Dyrk1A, a triplicated DS candidate gene, is overexpressed and may cause the NCC and PA1 deficits. We hypothesize that treatment of pregnant Ts65Dn mothers with Epigallocatechin gallate (EGCG), a known Dyrk1A inhibitor, will correct NCC deficits and rescue the undersized PA1 in trisomic E9.5 embryos. To test our hypothesis, we treated pregnant Ts65Dn mothers with EGCG from either E7-E8 or E0-E9.5. Our preliminary study found an increase in PA1 volume and NCC number in trisomic E9.5 embryos after treatment, but observed differences between treatment regimens. Differential gene expression was also quantified in trisomic treated embryos. This preliminary data suggests EGCG treatment has the potential to rescue the mandibular phenotype caused by trisomy. These findings provide preclinical testing for a potential therapy for craniofacial disorders linked to DS

    The data facility of the Airborne Visible/Infrared Imaging Spectrometer (AVIRIS)

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    AVIRIS operations at the Jet Propulsion Laboratory include a significant data task. The AVIRIS data facility is responsible for data archiving, data calibration, quality monitoring and distribution. Since 1987, the data facility has archived over one terabyte of AVIRIS data and distributed these data to science investigators as requested. In this paper we describe recent improvements in the AVIRIS data facility
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