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Find video protocols related to scientific articles indexed in Pubmed.
Synthesis of unsymmetrical N-carboranyl NHCs: directing effect of the carborane anion.
Chem. Commun. (Camb.)
PUBLISHED: 11-13-2014
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The syntheses of unsymmetrical N-heterocyclic carbenes (NHCs) that contain a single N-bound icosahedral carborane anion substituent are reported. Both anionic C-2 and doubly deprotonated dianionic C-2/C-5 NHC lithium complexes are isolated. The latter species is formed selectively, which reveals a surprising directing effect conveyed by icosahedral carborane anion substituents.
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The use of ECMO in HIV/AIDS with Pneumocystis jirovecii Pneumonia: a case report and review of the literature.
ASAIO J.
PUBLISHED: 08-29-2014
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There are few reports of extracorporeal membrane oxygenation (ECMO) therapy for respiratory failure because of Pneumocystis jirovecii pneumonia (PJP) in patients with acquired immunodeficiency syndrome (AIDS). None of the cases reported involvement of immune reconstitution inflammatory syndrome (IRIS), a paradoxical clinical worsening after the initiation of antiretroviral therapy (ART) in ART-naïve patients because of an exaggerated systemic inflammation with cell count recovery. We present a patient with newly diagnosed AIDS and PJP pneumonia that progressed to acute respiratory distress syndrome (ARDS) secondary to probable IRIS for which veno-venous ECMO was initiated. He transitioned to conventional ventilator after 57 days of ECMO therapy. However, he did not survive to hospital discharge. Combined with four previously reported cases of ARDS in human immunodeficiency virus patients secondary to PJP treated with ECMO, three of the five patients survived to ECMO decannulation. Extracorporeal membrane oxygenation is considered an accepted modality for adult patients with respiratory and/or cardiac failure refractory to maximal medical therapy. As ECMO becomes increasingly utilized in clinical practice, there is ongoing controversy regarding the appropriate selection of patients. In the past, contraindications to ECMO included immunocompromised states and conditions with known poor prognosis. The cases herein suggest the indications and contraindications warrant further discussion and research.
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Cerebrospinal fluid pressure in adults.
J Neuroophthalmol
PUBLISHED: 08-19-2014
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Lumbar puncture (LP) is a widely-used investigative procedure. It allows relatively non-invasive measurement of intracranial pressure (ICP) which may have a significant impact on diagnosis and/or patient management. Over the years there has been considerable discussion about various aspects of the procedure, including what constitutes a normal opening pressure, what factors might influence this, and how LP is best performed.
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Metabolite profiling of red and white pitayas (Hylocereus polyrhizus and Hylocereus undatus) for comparing betalain biosynthesis and antioxidant activity.
J. Agric. Food Chem.
PUBLISHED: 08-14-2014
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Metabolite profiling of red and white pitayas (Hylocereus polyrhizus and Hylocereus undatus) was performed using gas chromatography-time-of-flight-mass spectrometry and ultraperformance liquid chromatography-quadrupole-time-of-flight-mass spectrometry with multivariate analysis. Different species and parts of pitayas (red peel, RP; white peel, WP; red flesh, RF; and white flesh, WF) were clearly separated by partial least-squares discriminate analysis. Furthermore, betalain-related metabolites, such as betacyanins and betaxanthins, or their precursors were described on the basis of their metabolites. The results of antioxidant activity tests [1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), and ferric reducing ability of plasma (FRAP)], total phenolic contents (TPC), total flavonoid contents (TFC), and total betacyanin contents (TBC) showed the following: RP ? WP > RF > WF. TPC, TFC, TBC, and betalain-related metabolites were higher in the peel than in the flesh and suggested to be the main contributors to antioxidant activity in pitayas. Therefore, peels as well as pulp of pitaya could beneficially help in the food industry.
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Metabolite Profiling and Antioxidant Activity Comparison of Traditional and Commercial Vinegars.
J. Microbiol. Biotechnol.
PUBLISHED: 08-11-2014
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Metabolite profiles of 7 commercial vinegars and 2 traditional vinegars were performed by gas chromatography time of flight mass spectrometry (GC-TOF-MS) with multivariate statistical analysis. During alcohol fermentation, yeast, nuruk, and koji are used as sugars for nutrients and as fermentation substrates. Commercial and traditional vinegars were significantly separated in the principal component analysis (PCA) and orthogonal partial least square discriminant analysis (OPLS-DA). Six sugars and sugar alcohols, 3 organic acids, and 2 other components were selected as different metabolites. Target analysis by ultra-performance liquid chromatography quadruple-time of flight mass spectrometry (UPLC-Q-TOF-MS) and liquid chromatography-ion trap-mass spectrometry/mass spectrometry (LC-IT-MS/MS) were used to detect several metabolites having antioxidant activity, such as cyanidin-3-xylosylrutinoside, cyanidin-3-rutinoside, and quercetin, which were mainly detected in Rural Korean Black raspberry vinegar (RKB). These metabolites contributed to the highest antioxidant activity measured in RKB among the 9 vinegars. This study revealed that MS-based metabolite profiling was useful in helping to understand the metabolite differences between commercial and traditional vinegars and to evaluate the association between active compounds of vinegar and antioxidant activity.
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Combined mass spectrometry-based metabolite profiling of different pigmented rice (Oryza sativa L.) seeds and correlation with antioxidant activities.
Molecules
PUBLISHED: 08-08-2014
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Nine varieties of pigmented rice (Oryza sativa L.) seeds that were black, red, or white were used to perform metabolite profiling by using ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and gas chromatography (GC) TOF-MS, to measure antioxidant activities. Clear grouping patterns determined by the color of the rice seeds were identified in principle component analysis (PCA) derived from UPLC-Q-TOF-MS. Cyanidin-3-glucoside, peonidin-3-glucoside, proanthocyanidin dimer, proanthocyanidin trimer, apigenin-6-C-glugosyl-8-C-arabiboside, tricin-O-rhamnoside-O-hexoside, and lipids were identified as significantly different secondary metabolites. In PCA score plots derived from GC-TOF-MS, Jakwangdo (JKD) and Ilpoom (IP) species were discriminated from the other rice seeds by PC1 and PC2. Valine, phenylalanine, adenosine, pyruvate, nicotinic acid, succinic acid, maleic acid, malonic acid, gluconic acid, xylose, fructose, glucose, maltose, and myo-inositol were significantly different primary metabolites in JKD species, while GABA, asparagine, xylitol, and sucrose were significantly distributed in IP species. Analysis of antioxidant activities revealed that black and red rice seeds had higher activity than white rice seeds. Cyanidin-3-glucoside, peonidin-3-glucoside, proanthocyanidin dimers, proanthocyanidin trimers, and catechin were highly correlated with antioxidant activities, and were more plentiful in black and red rice seeds. These results are expected to provide valuable information that could help improve and develop rice-breeding techniques.
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Physical Activities of U.S. High School Students, National Youth Physical Activity and Nutrition Survey, 2010.
J Phys Act Health
PUBLISHED: 08-07-2014
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The 2008 Physical Activity Guidelines recommend youth participate in a variety of physical activities; however, few nationally representative studies describe the types and variety of youth activity. This study assessed the most frequently reported types and variety of activities among U.S. high school students, and examined the association between variety and meeting the 2008 Guidelines for aerobic activity (aerobic guideline).
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Associations of school violence with physical activity among U.S. high school students.
J Phys Act Health
PUBLISHED: 08-01-2014
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This study investigated associations of violence-related behaviors with physical activity (PA)-related behaviors among U.S. high school students.
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The Use of Extracorporeal Membrane Oxygenation in HIV/AIDS with Pneumocystis jiroveci Pneumonia: A Case Report and Review of the Literature.
ASAIO J.
PUBLISHED: 07-29-2014
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There are few reports of Extracorporeal Membrane Oxygenation (ECMO) therapy for respiratory failure due to Pneumocystis jirovecii pneumonia (PJP) in patients with Acquired Immunodeficiency Syndrome (AIDS). None of the cases reported involvement of Immune Reconstitution Inflammatory Syndrome (IRIS), a paradoxical clinical worsening after the initiation of antiretroviral therapy (ART) in ART-naïve patients due to an exaggerated systemic inflammation with cell count recovery.We present a patient with newly diagnosed AIDS and PJP pneumonia that progressed to acute respiratory distress syndrome (ARDS) secondary to probable IRIS for which veno-venous (VV) ECMO was initiated.He transitioned to conventional ventilator after 57 days of ECMO therapy. However, he did not survive to hospital discharge. Combined with four previously reported cases of ARDS in HIV patients secondary to PJP treated with ECMO, 3 out of the 5 patients survived to ECMO decannulation.ECMO is considered an accepted modality for adult patients with respiratory and/or cardiac failure refractory to maximal medical therapy. As ECMO becomes increasingly utilized in clinical practice, there is ongoing controversy regarding the appropriate selection of patients. In the past, contraindications to ECMO included immunocompromised states and conditions with known poor prognosis. The cases herein suggest the indications and contraindications warrant further discussion and research.
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Enantioselective nucleophile-catalyzed synthesis of tertiary alkyl fluorides via the ?-fluorination of ketenes: synthetic and mechanistic studies.
J. Am. Chem. Soc.
PUBLISHED: 06-12-2014
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The catalytic asymmetric synthesis of alkyl fluorides, particularly ?-fluorocarbonyl compounds, has been the focus of substantial effort in recent years. While significant progress has been described in the formation of enantioenriched secondary alkyl fluorides, advances in the generation of tertiary alkyl fluorides have been more limited. Here, we describe a method for the catalytic asymmetric coupling of aryl alkyl ketenes with commercially available N-fluorodibenzenesulfonimide (NFSI) and C6F5ONa to furnish tertiary ?-fluoroesters. Mechanistic studies are consistent with the hypothesis that the addition of an external nucleophile (C6F5ONa) is critical for turnover, releasing the catalyst (PPY*) from an N-acylated intermediate. The available data can be explained by a reaction pathway wherein the enantioselectivity is determined in the turnover-limiting transfer of fluorine from NFSI to a chiral enolate derived from the addition of PPY* to the ketene. The structure and the reactivity of the product of this proposed elementary step, an ?-fluoro-N-acylpyridinium salt, have been examined.
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Circulatory Support with Venoarterial ECMO Unsuccessful in Aiding Endogenous Diltiazem Clearance after Overdose.
Case Rep Crit Care
PUBLISHED: 06-06-2014
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Introduction. In cardiovascular collapse from diltiazem poisoning, extracorporeal membrane oxygenation (ECMO) may offer circulatory support sufficient to preserve endogenous hepatic drug clearance. Little is known about patient outcomes and diltiazem toxicokinetics in this setting. Case Report. A 36-year-old woman with a history of myocardial bridging syndrome presented with chest pain for which she self-medicated with 2.4?g of sustained release diltiazem over the course of 8 hours. Hemodynamics and mentation were satisfactory on presentation, but precipitously deteriorated after ICU transfer. She was given fluids, calcium, vasopressors, glucagon, high-dose insulin, and lipid emulsion. Due to circulatory collapse and multiorgan failure including ischemic hepatopathy, she underwent transvenous pacing and emergent initiation of venoarterial ECMO. The peak diltiazem level was 13150?ng/mL (normal 100-200?ng/mL) and it remained elevated at 6340?ng/mL at hour 90. Unfortunately, the patient developed multiple complications which resulted in her death on ICU day 9. Conclusion. This case describes the unsuccessful use of ECMO for diltiazem intoxication. Although past reports suggest that support with ECMO may facilitate endogenous diltiazem clearance, it may be dependent on preserved hepatic function at the time of cannulation, a factor not present in this case.
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Increased fluid administration in the first three hours of sepsis resuscitation is associated with reduced mortality: a retrospective cohort study.
Chest
PUBLISHED: 05-24-2014
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The surviving sepsis guidelines recommend early aggressive fluid resuscitation within 6 h of sepsis onset. Although rapid fluid administration may offer benefit, studies on the timing of resuscitation are lacking. We hypothesized that there is an association between quicker, adequate fluid resuscitation and patient outcome from sepsis onset time.
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Suppression of collagen-induced arthritis with a serine proteinase inhibitor (serpin) derived from myxoma virus.
Clin. Immunol.
PUBLISHED: 04-08-2014
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Many viruses encode virulence factors to facilitate their own survival by modulating a host's inflammatory response. One of these factors, secreted from cells infected with myxoma virus, is the serine proteinase inhibitor (serpin) Serp-1. Because Serp-1 had demonstrated anti-inflammatory properties in arterial injury models and viral infections, it was cloned and evaluated for therapeutic efficacy in collagen-induced arthritis (CIA). Clinical severity was significantly lower in the Serp-1 protocols (p<0.0001) and blinded radiographs indicated that the Serp-1 group had significantly less erosions than the controls (p<0.01). Delayed-type hypersensitivity was lower in the Serp-1 group but antibody titers to type II collagen were not significantly altered. Recipients had minimal histopathologic synovial changes and did not develop neutralizing antibodies to Serp-1. These results indicate that Serp-1 impedes the pathogenesis of CIA and suggests that the therapeutic potential of serine proteinase inhibitors in inflammatory joint diseases, such as rheumatoid arthritis, should be investigated further.
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Tribbles homolog 3 attenuates mammalian target of rapamycin complex-2 signaling and inflammation in the diabetic kidney.
J. Am. Soc. Nephrol.
PUBLISHED: 03-27-2014
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The endoplasmic reticulum (ER) stress response is activated in the diabetic kidney and functions to reduce ER protein accumulation and improve cellular function. We previously showed that tribbles homolog 3 (TRB3), an ER stress-associated protein, is upregulated in the diabetic kidney. Here, we investigated whether absence of TRB3 alters outcomes in diabetic nephropathy. Type 1 diabetes was induced in TRB3 wild-type and knockout ((-/-)) mice by low-dose streptozotocin, and the mice were followed for 12 weeks. Diabetic TRB3(-/-) mice developed higher levels of albuminuria and increased expression of inflammatory cytokine and chemokine mRNA in renal cortices relative to wild-type littermates, despite similar hyperglycemia. Diabetic TRB3(-/-) mice also expressed higher levels of ER stress-associated molecules in both the renal cortices and glomeruli. This change was associated with higher renal cortical phosphorylation of AKT at serine 473 (Ser(473)), which is the AKT site phosphorylated by mammalian target of rapamycin complex-2 (mTORC2). We show in renal tubular cells that TRB3 binds to mTOR and the rapamycin-insensitive companion of mTOR (Rictor), a protein specific to mTORC2. Finally, we demonstrate in murine tubular cells that TRB3 can inhibit secretion of IL-6. Thus, TRB3 reduces albuminuria and inflammatory gene expression in diabetic kidney disease by a mechanism that may involve inhibition of the mTORC2/AKT pathway and may prove to be a novel therapeutic target.
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Correlation between species-specific metabolite profiles and bioactivities of blueberries (Vaccinium spp.).
J. Agric. Food Chem.
PUBLISHED: 02-24-2014
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Metabolite profiling of three blueberry species (Vaccinium bracteatum Thunb., V. oldhamii Miquel., and V. corymbosum L.) was performed using gas chromatography-time-of-flight-mass spectrometry (GC-TOF-MS) and ultraperformance liquid chromatography-quadrupole-time-of-flight-mass spectrometry (UPLC-Q-TOF-MS) combined multivariate analysis. Partial least-squares discriminant analysis clearly showed metabolic differences among species. GC-TOF-MS analysis revealed significant differences in amino acids, organic acids, fatty acids, sugars, and phenolic acids among the three blueberry species. UPLC-Q-TOF-MS analysis indicated that anthocyanins were the major metabolites distinguishing V. bracteatum from V. oldhamii. The contents of anthocyanins such as glycosides of cyanidin were high in V. bracteatum, while glycosides of delphinidin, petunidin, and malvidin were high in V. oldhamii. Antioxidant activities assessed using ABTS and DPPH assays showed the greatest activity in V. oldhamii and revealed the highest correlation with total phenolic, total flavonoid, and total anthocyanin contents and their metabolites.
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Primary and secondary metabolite profiling of doenjang, a fermented soybean paste during industrial processing.
Food Chem
PUBLISHED: 02-11-2014
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In this study, a comprehensive metabolite profile analysis of doenjang, a fermented soybean paste, at various steps of its industrial 5-step production process was conducted, by combining gas and liquid chromatography-mass spectrometry techniques with multivariate analysis. From the partial least squares discriminant analysis of primary and secondary metabolites, the patterns were clearly distinguishable between the various processing steps (step 1: steaming, step 2: drying, step 3: meju fermentation, step 4: brining, step 5: doenjang aging). Of the primary metabolites, most of the monosaccharides, amino acids, and fatty acids increased in steps 3-5. Isoflavone and soyasaponin derivatives were major secondary metabolites identified during the processing of doenjang. Isoflavone glycosides gradually decreased after step 1, while isoflavone aglycones distinctly increased in steps 4-5. Soyasaponins generally decreased during processing after step 2. Increased isoflavone aglycones, such as daidzein, glycitein, and genistein, were observed in steps 4-5 showed the strongest positive correlation with doenjang's antioxidant potential and total phenolic content.
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Histological subclassification of cirrhosis can predict recurrence after curative resection of hepatocellular carcinoma.
Liver Int.
PUBLISHED: 01-26-2014
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Recurrence of hepatocellular carcinoma (HCC) after curative resection continues to be a major cause of death. This prospective study is designed to investigate whether histological subclassification of cirrhosis using the Laennec system could predict recurrence in patients with hepatitis B virus (HBV)-related HCC after curative resection.
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Primary cardiac angiosarcoma - a review.
Med. Sci. Monit.
PUBLISHED: 01-24-2014
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Primary cardiac neoplasms are extremely rare. Angiosarcoma is the most commonly seen histological subtype and is characterized by its permeating and destructive nature. Unfortunately, primary cardiac angiosarcoma is often overlooked as an initial diagnosis because of its rarity. Since the time it was first identified in 1934, little progress has been made in improving survival outcome. Complete or partial surgical resection is still the best option for palliation, with little hope for cure. Improvements have been made in the ability to view and distinguish tumors. Echocardiography is one of the most useful diagnostic tools because of its high sensitivity; therefore, CT and MR images are often used to detect sites of metastatic disease. Immunohistochemistry staining can also be employed as an adjunctive diagnostic tool. CD31, CD34, FLI-1, and von Willebrand factor are the most commonly used markers in detecting tumors of endothelial origin. However, due to the vast heterogeneity within a tumor, immunohistochemistry staining can be quite variable. Surgical resection remains the standard modality of treatment. Primary cardiac angiosarcoma is largely resistant to chemotherapy and/or radiation. However, the exact benefit and its place in a multimodality treatment regimen are still under investigation.
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RNA-seq analysis of Rubus idaeus cv. Nova: transcriptome sequencing and de novo assembly for subsequent functional genomics approaches.
Plant Cell Rep.
PUBLISHED: 01-13-2014
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Using Illumina sequencing technology, we have generated the large-scale transcriptome sequencing data containing abundant information on genes involved in the metabolic pathways in R. idaeus cv. Nova fruits. Rubus idaeus (Red raspberry) is one of the important economical crops that possess numerous nutrients, micronutrients and phytochemicals with essential health benefits to human. The molecular mechanism underlying the ripening process and phytochemical biosynthesis in red raspberry is attributed to the changes in gene expression, but very limited transcriptomic and genomic information in public databases is available. To address this issue, we generated more than 51 million sequencing reads from R. idaeus cv. Nova fruit using Illumina RNA-Seq technology. After de novo assembly, we obtained 42,604 unigenes with an average length of 812 bp. At the protein level, Nova fruit transcriptome showed 77 and 68 % sequence similarities with Rubus coreanus and Fragaria versa, respectively, indicating the evolutionary relationship between them. In addition, 69 % of assembled unigenes were annotated using public databases including NCBI non-redundant, Cluster of Orthologous Groups and Gene ontology database, suggesting that our transcriptome dataset provides a valuable resource for investigating metabolic processes in red raspberry. To analyze the relationship between several novel transcripts and the amounts of metabolites such as ?-aminobutyric acid and anthocyanins, real-time PCR and target metabolite analysis were performed on two different ripening stages of Nova. This is the first attempt using Illumina sequencing platform for RNA sequencing and de novo assembly of Nova fruit without reference genome. Our data provide the most comprehensive transcriptome resource available for Rubus fruits, and will be useful for understanding the ripening process and for breeding R. idaeus cultivars with improved fruit quality.
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Prevalence and phenotypic characterization of Enterococcus spp. isolated from food in Brazil.
Braz. J. Microbiol.
PUBLISHED: 01-01-2014
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We evaluated the frequency of enterococci from food and found 95.2% of positivity, being E. faecium and E. faecalis the most frequent species. High-level streptomycin resistance was observed, as well as gelatinase and hemolysis activity, showing the potential role of environmental strains as reservoir of virulence and resistance traits.
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De-novo RNA sequencing and metabolite profiling to identify genes involved in anthocyanin biosynthesis in Korean black raspberry (Rubus coreanus Miquel).
PLoS ONE
PUBLISHED: 01-01-2014
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The Korean black raspberry (Rubus coreanus Miquel, KB) on ripening is usually consumed as fresh fruit, whereas the unripe KB has been widely used as a source of traditional herbal medicine. Such a stage specific utilization of KB has been assumed due to the changing metabolite profile during fruit ripening process, but so far molecular and biochemical changes during its fruit maturation are poorly understood. To analyze biochemical changes during fruit ripening process at molecular level, firstly, we have sequenced, assembled, and annotated the transcriptome of KB fruits. Over 4.86 Gb of normalized cDNA prepared from fruits was sequenced using Illumina HiSeq™ 2000, and assembled into 43,723 unigenes. Secondly, we have reported that alterations in anthocyanins and proanthocyanidins are the major factors facilitating variations in these stages of fruits. In addition, up-regulation of F3'H1, DFR4 and LDOX1 resulted in the accumulation of cyanidin derivatives during the ripening process of KB, indicating the positive relationship between the expression of anthocyanin biosynthetic genes and the anthocyanin accumulation. Furthermore, the ability of RcMCHI2 (R. coreanus Miquel chalcone flavanone isomerase 2) gene to complement Arabidopsis transparent testa 5 mutant supported the feasibility of our transcriptome library to provide the gene resources for improving plant nutrition and pigmentation. Taken together, these datasets obtained from transcriptome library and metabolic profiling would be helpful to define the gene-metabolite relationships in this non-model plant.
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Defining Binding Efficiency and Specificity of Auxins for SCF(TIR1/AFB)-Aux/IAA Co-receptor Complex Formation.
ACS Chem. Biol.
PUBLISHED: 12-23-2013
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Structure-activity profiles for the phytohormone auxin have been collected for over 70 years, and a number of synthetic auxins are used in agriculture. Auxin classification schemes and binding models followed from understanding auxin structures. However, all of the data came from whole plant bioassays, meaning the output was the integral of many different processes. The discovery of Transport Inhibitor-Response 1 (TIR1) and the Auxin F-Box (AFB) proteins as sites of auxin perception and the role of auxin as molecular glue in the assembly of co-receptor complexes has allowed the development of a definitive quantitative structure-activity relationship for TIR1 and AFB5. Factorial analysis of binding activities offered two uncorrelated factors associated with binding efficiency and binding selectivity. The six maximum-likelihood estimators of Efficiency are changes in the overlap matrixes, inferring that Efficiency is related to the volume of the electronic system. Using the subset of compounds that bound strongly, chemometric analyses based on quantum chemical calculations and similarity and self-similarity indices yielded three classes of Specificity that relate to differential binding. Specificity may not be defined by any one specific atom or position and is influenced by coulomb matrixes, suggesting that it is driven by electrostatic forces. These analyses give the first receptor-specific classification of auxins and indicate that AFB5 is the preferred site for a number of auxinic herbicides by allowing interactions with analogues having van der Waals surfaces larger than that of indole-3-acetic acid. The quality factors are also examined in terms of long-standing models for the mechanism of auxin binding.
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The head module of Mediator directs activation of preloaded RNAPII in vivo.
Nucleic Acids Res.
PUBLISHED: 09-04-2013
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The successful synthesis of a transcript by RNA polymerase II (RNAPII) is a multistage process with distinct rate-limiting steps that can vary depending on the particular gene. A growing number of genes in a variety of organisms are regulated at steps after the recruitment of RNAPII. The best-characterized Saccharomyces cerevisiae gene regulated in this manner is CYC1. This gene has high occupancy of RNAPII under non-inducing conditions, defining it as a poised gene. Here, we find that subunits of the head module of Mediator, Med18 and Med20, and Med19 are required for activation of transcription at the CYC1 promoter in response to environmental cues. These subunits of Mediator are required at the preloaded promoter for normal levels of recruitment and activity of the general transcription factor TFIIH. Strikingly, these Mediator components are dispensable for activation by the same activator at a different gene, which lacks a preloaded polymerase in the promoter region. Based on these results and other studies, we speculate that Mediator plays an essential role in triggering an inactive polymerase at CYC1 into a productively elongating form.
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Ganglioside GM3 Depletion Reverses Impaired Wound Healing in Diabetic Mice by Activating IGF-1 and Insulin Receptors.
J. Invest. Dermatol.
PUBLISHED: 06-21-2013
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Ganglioside GM3 mediates adipocyte insulin resistance, but the role of GM3 in diabetic wound healing, a major cause of morbidity, is unclear. The purpose of this study was to determine whether GM3 depletion promotes diabetic wound healing and directly activates keratinocyte (KC) insulin pathway signaling. GM3 synthase (GM3S) expression is increased in human diabetic foot skin, ob/ob and diet-induced obese diabetic mouse skin, and in mouse KCs exposed to increased glucose. GM3S knockout in diet-induced obese mice prevents the diabetic wound-healing defect. KC proliferation, migration, and activation of insulin receptor (IR) and insulin growth factor-1 receptor (IGF-1R) are suppressed by excess glucose in wild-type cells, but increased in GM3S (-/-) KCs with supplemental glucose. Co-immunoprecipitation of IR, IR substrate 1 (IRS-1), and IGF-1R, and increased IRS-1 and Akt phosphorylation accompany receptor activation. GM3 supplementation or inhibition of IGF-1R or PI3K reverses the increased migration of GM3S(-/-) KCs, whereas IR knockdown only partially suppresses migration.Journal of Investigative Dermatology advance online publication, 2 January 2014; doi:10.1038/jid.2013.532.
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A short educational intervention measurably benefits keloid-prone individuals knowledge of prevention and treatment.
J Drugs Dermatol
PUBLISHED: 05-09-2013
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The Internet is a commonly utilized health information resource that provides access to information of varying quality.
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Severe anion gap acidosis associated with intravenous sodium thiosulfate administration.
J Med Toxicol
PUBLISHED: 05-03-2013
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Severe anion gap (AG) acidosis associated with intravenous sodium thiosulfate (STS) administration has not been previously described in nondialysis chronic kidney disease (CKD) patients.
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Paclitaxel nanosuspensions for targeted chemotherapy - nanosuspension preparation, characterization, and use.
Pharm Dev Technol
PUBLISHED: 04-25-2013
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Abstract Objective: The purpose of this work was to prepare a stable paclitaxel nanosuspension and test it for potential use as a targeted chemotherapeutic. Different particle coatings were employed to assess their impact on cellular uptake in vitro. In vivo work was then performed to demonstrate efficacy in tumor-bearing mouse models. Materials and method: Paclitaxel nanosuspensions were prepared using a homogenization process and coated with excipients. Surface charge was measured by zeta potential, potency by high-performance liquid chromatography, and solubility using an in-line UV probe. Cellular uptake studies were performed via flow cytometry. In vivo experiments were performed to determine residence time, maximum tolerated dose, and the efficacy of paclitaxel nanosuspensions (Paclitaxel-NS). Results: A stable paclitaxel nanosuspension was prepared and coated with various excipients. Studies in mice showed that the nanosuspension was well-tolerated and at least as effective as the IV Taxol control in prolonging mouse survival in a head and neck cancer model as well as an ovarian cancer model with a lower overall drug dose than the traditional IV administration route. Conclusions: The paclitaxel nanosuspension is suitable for cellular uptake. The nanosuspension was effective in prolonging life in two separate xenograft orthotopic murine cancer models through two separate routes of administration.
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Time-dependent correlation of the microbial community and the metabolomics of traditional barley nuruk starter fermentation.
Biosci. Biotechnol. Biochem.
PUBLISHED: 04-07-2013
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The microbial community and the metabolites of barley nuruk were studied to determine the time-dependent correlation between the fermentation of microbes and metabolites. Samples were analyzed by a polyphasic approach based on culture-dependent, culture-independent (PCR-DGGE and qPCR analysis), and metabolite analysis using GC-MS. Barley nuruk consists of varying amounts of bacteria, yeasts, and molds. The PCR-DGGE results showed that only one phylotype, Aspergillus oryzae, was predominant throughout fermentation, reaching a maximum on day 9. The bacterial load was higher on day 6 of fermentation, and then gradually decreased because of increased fungal activity. The shift in fungal and bacterial diversity observed by DGGE was further confirmed by qPCR analysis. In addition, microbes closely related to Pantoea agglomerans and Saccharomycopsis fibuligera appeared to play key roles in the fermentation of barley nuruk. GC-MS analysis combined with multivariate analysis, including PCA, PLS-DA, and OPLS-DA, showed fermentation time-dependent metabolite patterns. A total of 21 metabolites, including organic acids, amino acids, sugars, and sugar alcohols, were identified. In particular, glycerol, malic acid, fructose, glucose, sucrose, and maltose were produced at the early fermentation stages (0-6 d), whereas glutamine, aspartic acid, glutamic acid, mannitol, and xylitol were produced during the latter stages of fermentation (9-18 d). Mixed culture fermentation was found throughout the natural fermentation of barley nuruk starter. Most likely, A. oryzae had a major role in saccharification, along with other mixed cultures.
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The influence of T cell Ig mucin-3 signaling on central nervous system autoimmune disease is determined by the effector function of the pathogenic T cells.
J. Immunol.
PUBLISHED: 04-05-2013
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Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the CNS mediated by self-reactive, myelin-specific T cells. Both CD4(+) and CD8(+) T cells play important roles in the pathogenesis of MS. MS is studied using experimental autoimmune encephalomyelitis (EAE), an animal model mediated by myelin-specific T cells. T cell Ig mucin-3 (Tim-3) is a cell surface receptor expressed on CD4(+) IFN-?-secreting Th1 cells, and triggering Tim-3 signaling ameliorated EAE by inducing death in pathogenic Th1 cells in vivo. This suggested that enhancing Tim-3 signaling might be beneficial in patients with MS. However, Tim-3 is also expressed on activated CD8(+) T cells, microglia, and dendritic cells, and the combined effect of manipulating Tim-3 signaling on these cell types during CNS autoimmunity is unknown. Furthermore, CD4(+) IL-17-secreting Th17 cells also play a role in MS, but do not express high levels of Tim-3. We investigated Tim-3 signaling in EAE models that include myelin-specific Th17, Th1, and CD8(+) T cells. We found that preventing Tim-3 signaling in CD4(+) T cells altered the inflammatory pattern in the CNS due to differential effects on Th1 versus Th17 cells. In contrast, preventing Tim-3 signaling during CD8(+) T cell-mediated EAE exacerbated disease. We also analyzed the importance of Tim-3 signaling in EAE in innate immune cells. Tim-3 signaling in dendritic cells and microglia did not affect the manifestation of EAE in these models. These results indicate that the therapeutic efficacy of targeting Tim-3 in EAE is dependent on the nature of the effector T cells contributing to the disease.
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Differential sensitivities of the growth of Escherichia coli to acrylate under aerobic and anaerobic conditions and its effect on product formation.
Biotechnol. Lett.
PUBLISHED: 04-04-2013
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The effect of acrylate on the growth of Escherichia coli was determined under aerobic and anaerobic conditions in glucose-defined medium. Growth occurred with up to 35 mM acrylate under aerobic conditions but ceased at 5 mM acrylate under anaerobic conditions. This differential sensitivity can be attributed to inhibition of pyruvate formate lyase and/or pflB gene repression, as this enzyme is necessary for anaerobic growth of E. coli. The effect of acrylate on end-product distribution was also determined by growing E. coli first aerobically, then switching to anaerobic conditions. In the absence of acrylate, E. coli generated the typical distribution of mixed-acid products, with about 12 % of pyruvate being metabolically converted to lactate. In contrast, in the presence of 5 mM acrylate, E. coli converted 83 % of pyruvate to lactate, consistent with a reduction in pyruvate formate lyase activity.
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Awareness and Knowledge of the Youth 2008 Physical Activity Guidelines for Americans.
J Phys Act Health
PUBLISHED: 03-14-2013
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BACKGROUND: To measure parental awareness of government physical activity guidelines and knowledge of the amount of physical activity recommended for youth (i.e., "60 minutes/day, 7 days/week") as specified in the 2008 Physical Activity Guidelines for Americans. METHODS: A cross-sectional national sample of adults responded to physical activity guideline questions added to the HealthStyles survey in 2009 (n = 1552). The prevalence of parents aware of government physical activity guidelines and knowledgeable of the youth physical activity guideline, specifically, was estimated overall and by parental demographic characteristics (sex, education, income level, race/ethnicity, age group, marital status) and body mass index. RESULTS: In 2009, 34.8% of parents reported being aware of physical activity guidelines, and 9.7% were knowledgeable of the amount of physical activity recommended for youth. CONCLUSIONS: Many parents lack awareness and knowledge of the youth physical activity guidelines. The low prevalence estimates suggest the 2008 Physical Activity Guidelines for Americans have not been effectively disseminated. These results may also indicate a need for effective communication strategies to educate and inform parents, an important influencer of childrens health behaviors.
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Obesity and other correlates of physical activity and sedentary behaviors among US high school students.
J Obes
PUBLISHED: 03-08-2013
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Understanding correlates of physical activity (PA) can help inform and improve programs that promote PA among youth. We analyzed data from the 2010 National Youth Physical Activity and Nutrition Study, a representative sample of US students in grades 9-12. Logistic regression was used to examine associations between PA correlates (obesity, physical education classes, sports team participation, attitude toward PA, adult support for PA, and environmental support for PA) and participation in daily PA (DPA), vigorous PA (VPA), muscle-strengthening activity (MSA), viewing television (TV), and using computers or video games (C/VG). A positive attitude toward PA and adult support for PA were both associated with increased PA and decreased sedentary behavior. However, among students who lived in neighborhoods that were not safe for PA, a positive attitude toward PA was not associated with increased DPA or decreased sedentary behavior and was less strongly associated with VPA and MSA. Efforts to increase PA among youth should promote a positive attitude toward PA among youth and encourage adult family members to support their efforts to be active. Policies that promote safe neighborhoods may work synergistically with a positive attitude toward PA to increase participation in PA and decrease sedentary behaviors.
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Metabolite profiling of the short-term responses of rice leaves (Oryza sativa cv. Ilmi) cultivated under different LED lights and its correlations with antioxidant activities.
Plant Sci.
PUBLISHED: 02-26-2013
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Metabolite profiling of rice leaves (Oryza sativa cv. Ilmi) was performed to investigate the short-term responses to different light-emitting diode (LED) lights, blue (B), green (G), red (R), white (W), shade (S), by using gas chromatography-ion trap-mass spectrometry (GC-IT-MS) and ultra-performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry (UPLC-Q-TOF-MS) with multivariate analysis. Clear grouping patterns of each light-grown sample, except G and W, were shown in partial least squares-discriminant analysis (PLS-DA). Thirty-two primary metabolites and eleven secondary metabolites were selected and visualized using heatmap. Antioxidant activities of rice leaves followed the order B=W=G>R>S and isoorientin-2-O-glucoside, isovitexin-2-O-glucoside, isoorientin-2-O-(6-?-coumaroyl)-glucoside, and isoscoparin-2-O-glucoside showed similar relative differences and had higher Pearsons correlation coefficients than other metabolites in correlation network. According to the orthogonal projection to latent structures-discriminant analysis (OPLS-DA) between B and R, the levels of amino acids, organic acids, fatty acids, and flavonoid glycosides were relatively high in B, whereas the glucose and fructose levels were high in R.
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Modeling the heterogeneity of multiple sclerosis in animals.
Trends Immunol.
PUBLISHED: 02-22-2013
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Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system (CNS) manifested with varying clinical course, pathology, and inflammatory patterns. There are multiple animal models that reflect different aspects of this heterogeneity. Collectively, these models reveal a balance between pathogenic and regulatory CD4(+) T cells, CD8(+) T cells, and B cells that influences the incidence, timing, and severity of CNS autoimmunity. In this review we discuss experimental autoimmune encephalomyelitis (EAE) models that have been used to study the pathogenic and regulatory roles of these immune cells; models that recapitulate different aspects of the disease seen in patients with MS, and questions remaining for future studies.
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Behaviors related to physical activity and nutrition among U.S. high school students.
J Adolesc Health
PUBLISHED: 02-15-2013
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National data related to physical activity (PA) and nutrition among adolescents are needed to help develop effective obesity prevention programs. The 2010 National Youth Physical Activity and Nutrition Study (NYPANS) was conducted to provide nationally representative data on behaviors and behavioral correlates related to healthy eating and PA.
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A Comparative Study of Baby Immature and Adult Shoots of Aloe Vera on UVB-Induced Skin Photoaging in vitro.
Phytother Res
PUBLISHED: 01-16-2013
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Ultraviolet (UV) irradiation induces photo-damage of the skin, which in turn causes depletion of the dermal extracellular matrix and chronic alterations in skin structure. Skin wrinkle formations are associated with collagen synthesis and matrix metalloproteinase (MMP) expression. The production of type I procollagen is regulated by transforming growth factor-?1 (TGF-?1) expression; the activation of MMP is also correlated with an increase of interleukin-6 (IL-6). Aloe barbadensis M. (Aloe vera) is widely used in cosmetic and pharmaceutical products. In this study, we examined whether baby aloe shoot extract (BAE, immature aloe extract), which is from the one-month-old shoots of Aloe vera, and adult aloe shoot extract (AE), which is from the four-month-old shoots of Aloe vera, have a protective effect on UVB-induced skin photoaging in normal human dermal fibroblasts (NHDFs). The effects of BAE and AE on UVB-induced photoaging were tested by measuring the levels of reactive oxygen species, MMP-1, MMP-3, IL-6, type I procollagen, and TGF-?1 after UVB irradiation. We found that NHDF cells treated with BAE after UVB-irradiation suppressed MMP-1, MMP-3, and IL-6 levels compared to the AE-treated cells. Furthermore, BAE treatment elevated type I procollagen and TGF-?1 levels. Our results suggest that BAE may potentially protect the skin from UVB-induced damage more than AE. Copyright © 2013 John Wiley & Sons, Ltd.
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Culture condition-dependent metabolite profiling of Aspergillus fumigatus with antifungal activity.
Fungal Biol
PUBLISHED: 01-15-2013
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Three sections of Aspergillus (five species, 21 strains) were classified according to culture medium-dependent and time-dependent secondary metabolite profile-based chemotaxonomy. Secondary metabolites were analysed by liquid chromatography-electrospray ionisation tandem mass spectrometry (LC-ESI-MS-MS) and multivariate statistical methods. From the Aspergillus sections that were cultured on malt extract agar (MEA) and Czapek yeast extract agar (CYA) for 7, 12, and 16 d, Aspergillus sections Fumigati (A. fumigatus), Nigri (A. niger), and Flavi (A. flavus, A. oryzae, and A. sojae) clustered separately on the basis of the results of the secondary metabolite analyses at 16 d regardless of culture medium. Based on orthogonal projection to latent structures discriminant analysis by partial least squares discriminant analysis (PLS-DA), we identified the secondary metabolites that helped differentiate sections between A. fumigatus and Aspergillus section Flavi to be gliotoxin G, fumigatin oxide, fumigatin, pseurotin A or D, fumiquinazoline D, fumagillin, helvolic acid, 1,2-dihydrohelvolic acid, and 5,8-dihydroxy-9,12-octadecadienoic acid (5,8-diHODE). Among these compounds, fumagillin, helvolic acid, and 1,2-dihydrohelvolic acid of A. fumigatus showed antifungal activities against Malassezia furfur, which is lipophilic yeast that causes epidermal skin disorders.
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Antimicrobial compounds profile during Cheonggukjang fermentation against Xanthomonas oryzae pv. oryzae (Xoo).
J. Microbiol. Biotechnol.
PUBLISHED: 12-01-2011
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Xanthomonas oryzae causes rice bacterial blight, which has been reported as one of the most destructive diseases of rice. Metabolites were identified through cheonggukjang, a traditional Korean fermented soybean product fermented by the Bacillus spp., to control the bacteria. HPLC, MS, and UPLC-Q-TOF-MS analyses were performed to identify metabolites responsible for antimicrobial activity. In this analysis, the m/z values of 253.0498, 283.0600, 269.0455, 992.6287, and 1,006.6436 were identified as daidzein, glycitein, genistein, surfactin B, and surfactin A, respectively. The levels of surfactin B and surfactin A were found to be high at 24 h (4.35 ?g/ml) and 36 h (3.43 ?g/ml) of fermentation, respectively.
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An integrated biochemistry and genetics outreach program designed for elementary school students.
Genetics
PUBLISHED: 11-30-2011
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Exposure to genetic and biochemical experiments typically occurs late in ones academic career. By the time students have the opportunity to select specialized courses in these areas, many have already developed negative attitudes toward the sciences. Given little or no direct experience with the fields of genetics and biochemistry, it is likely that many young people rule these out as potential areas of study or career path. To address this problem, we developed a 7-week (~1 hr/week) hands-on course to introduce fifth grade students to basic concepts in genetics and biochemistry. These young students performed a series of investigations (ranging from examining phenotypic variation, in vitro enzymatic assays, and yeast genetic experiments) to explore scientific reasoning through direct experimentation. Despite the challenging material, the vast majority of students successfully completed each experiment, and most students reported that the experience increased their interest in science. Additionally, the experiments within the 7-week program are easily performed by instructors with basic skills in biological sciences. As such, this program can be implemented by others motivated to achieve a broader impact by increasing the accessibility of their university and communicating to a young audience a positive impression of the sciences and the potential for science as a career.
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Parkinsonism associated with glucocerebrosidase mutation.
J Clin Neurol
PUBLISHED: 06-28-2011
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Gauchers disease is an autosomal recessive, lysosomal storage disease caused by mutations of the ?-glucocerebrosidase gene (GBA). There is increasing evidence that GBA mutations are a genetic risk factor for the development of Parkinsons disease (PD). We report herein a family of Koreans exhibiting parkinsonism-associated GBA mutations.
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A new style of orthognathic clinic.
J Orthod
PUBLISHED: 06-17-2011
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The Orthognathic Team at the Eastman Dental Hospital has developed a new style of multidisciplinary clinic to supplement the traditional orthognathic consultation. The aim of the new clinic is to increase patient satisfaction and involvement in the consent and decision making process, as well as optimizing the information given to prospective patients regarding all aspects of this complex elective treatment. Results of a survey of patients attending the clinic found that 80% thought that the information given was just the right amount and 96% were satisfied with the new structure. They particularly found it useful to meet a patient who had completed treatment. All of those who attended said that they understood the information given to them and would recommend the clinic to those considering orthognathic treatment. They also liked having other patients there with them on the clinic.
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The response to rapid infusion of fentanyl in the human brain measured using pulsed arterial spin labelling.
MAGMA
PUBLISHED: 06-01-2011
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We evaluated the sensitivity of pulsed Arterial Spin Labelling (pASL) for the detection of changes in regional cerebral blood perfusion (CBP) during and after intra-venous (i.v.) infusion of an opioid agonist (fentanyl) and an opioid antagonist (naloxone).
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Immunohistochemical subclassification of thyroid tumors with a prominent hyalinizing trabecular pattern.
APMIS
PUBLISHED: 05-24-2011
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The purpose of this study was to evaluate the immunohistochemical characteristics of thyroid tumors with a prominent hyalinizing trabecular pattern (TTHTP). Immunohistochemical stains for thyroid transcription factor 1 (TTF-1), thyroglobulin, CD56, cytokeratin (CK) 19, galectin-3, and Ki-67 were performed on 16 cases of TTHTP. All TTHTPs were positive for TTF-1 and thyroglobulin, and nine cases expressed CD56 and Ki-67. Of these nine cases, seven satisfied the strict criteria of Carney, and four cases were positive for CK19 or/and galectin-3 and negative for Ki-67 and CD56. The remaining three cases had no Ki-67, CD56, CK19 or galectin-3 expression. All TTHTPs meeting the criteria of Carney were hyalinizing trabecular tumors (HTT), and TTHTPs which did not satisfy the criteria of Carney were subclassified according to the immunohistochemical results as the HTT type [Ki-67 (+) and CD56 (+)], papillary thyroid carcinoma (PTC) type [CK19 or galectin-3 (+)/Ki-67 (-) and CD56 (-)], or null type [Ki-67 (-), CD56 (-), CK19 (-) and galectin-3 (-)]. TTHTPs with typical histologic features and/or with typical immunohistochemical manifestations can be categorized as HTT, and the remaining TTHTPs should be categorized as the PTC or null type.
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Physical activity and screen time: trends in U.S. children aged 9-13 years, 2002-2006.
J Phys Act Health
PUBLISHED: 05-17-2011
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We examined trends of physical activity and screen time among nationally representative samples of children aged 9-13 years to explore whether children overall are becoming less physically active and less likely to be in compliance with screen time recommendations.
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UK rheumatology consultant workforce provision 2007-9: results from the BSR/Arthritis Research UK Consultant Workforce Register.
Clin Med
PUBLISHED: 04-30-2011
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The objective of this study was to describe the provision of consultant rheumatology services and the pattern of inequalities in UK rheumatology service provision, and to summarise the five-year impact of the new NHS consultant contract and the Musculoskeletal Services Framework in England and Wales. All consultants on the British Society for Rheumatology/Arthritis Research UK Consultant Workforce Register in January 2007 and January 2009 were sent questionnaires about timetable and working conditions and the personal and job-related details currently held about them on the register. Response rates were 87% in 2007 and 86% in 2009. The number of whole-time equivalent (WTE) rheumatologists in the UK increased from 470 to 531 (13%). Levels of provision in 2009 were lower in Scotland (1 WTE per 113,286 population) than the rest of the UK. There are now few regional variations in rheumatology consultant provision within the UK, and the number of WTE consultants is approaching recommended levels.
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Trends by age in youth physical activity: Youth Media Campaign Longitudinal Survey.
Med Sci Sports Exerc
PUBLISHED: 04-20-2011
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This study aimed to characterize longitudinal age trajectories across 5 yr in the prevalence of free-time and organized physical activity participation among US youth by sex, race, and parental education.
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RGS14 at the interface of hippocampal signaling and synaptic plasticity.
Trends Pharmacol. Sci.
PUBLISHED: 04-01-2011
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Learning and memory are encoded within the brain as biochemical and physical changes at synapses that alter synaptic transmission, a process known as synaptic plasticity. Although much is known about factors that positively regulate synaptic plasticity, very little is known about factors that negatively regulate this process. Recently, the signaling protein RGS14 (Regulator of G protein Signaling 14) was identified as a natural suppressor of hippocampal-based learning and memory as well as synaptic plasticity within CA2 hippocampal neurons. RGS14 is a multifunctional scaffolding protein that integrates unconventional G protein and mitogen-activated protein (MAP) kinase signaling pathways that are themselves key regulators of synaptic plasticity, learning, and memory. Here, we highlight the known roles for RGS14 in brain physiology and unconventional G protein signaling pathways, and propose molecular models to describe how RGS14 may integrate these diverse signaling pathways to modulate synaptic plasticity in CA2 hippocampal neurons.
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The clinical features and surgical outcomes of patients with intramedullary spinal cord cavernous malformations.
Acta Neurochir (Wien)
PUBLISHED: 04-01-2011
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Cavernous malformations (CMs) are not uncommon, but most of them are found to be located intracranially. Intramedullary CMs are rare, accounting for only 3-5% of identified total central nervous system lesions. The natural history of intramedullary CMs and their clinical features, including the risk of hemorrhage from a large series, still remains unclear and needs to be elucidated. We review our experience with surgically treated patients with intramedullary CMs and discuss the clinical features and surgical outcomes.
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The impact of caveolin protein expression in tumor stroma on prognosis of breast cancer.
Tumour Biol.
PUBLISHED: 03-09-2011
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We aimed to investigate the expression of caveolin-1, -2, -3, and platelet-derived growth factor (PDGF) ? receptor in breast cancer cells and stroma by immunohistochemistry and to analyze their implications. The expression rates of stromal caveolin-2 and PDGF ? receptor increased as the tumor progressed from ductal carcinoma in situ to microinvasive ductal carcinoma, intraductal component of invasive ductal carcinoma (IDC), and IDC (p<0.001). The expression loss of caveolin-1 in tumor stroma of IDC correlated with high tumor stage (p<0.001), high nodal stage (p=0.011), high cancer stage (p=0.005), estrogen receptor negativity (p=0.003), and tumor recurrence (p=0.003). In addition, the expression loss of caveolin-1 in tumor stroma was correlated with a shorter disease-free survival and an overall survival (p<0.001). In conclusion, the loss of stromal caveolin-1 is related to poor prognosis in IDC.
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Evaluation of intratumoral HER-2 heterogeneity by fluorescence in situ hybridization in invasive breast cancer: a single institution study.
J. Korean Med. Sci.
PUBLISHED: 03-03-2011
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This study aimed to determine the incidence and characteristics of HER-2 gene heterogeneity in invasive breast cancer in a single institution. Included were 971 cases of primary invasive breast cancer diagnosed between 2008 and 2010. Fluorescence in situ hybridization (FISH) image files were retrospectively reviewed and HER-2 gene heterogeneity was defined as more than 5% but less than 50% of analyzed invasive tumor cells with a HER-2/Chr17 ratio higher than 2.2, according to the College of American Pathologists guidelines. HER-2 gene heterogeneity was identified in 24 (2.5%) cases. The mean proportion of invasive tumor cells with a HER-2/chromosome 17 ratio higher than 2.2 was 11.6% (range: 5%-25%). Of 24 cases, HER-2 gene status was not amplified in 8, showed borderline amplification in 2, and amplification in 14. All HER-2 amplification cases were low-grade. In conclusion, HER-2 gene heterogeneity of invasive breast cancer is identified in routine FISH examination. This may affect the results of HER-2 gene amplification status in FISH studies.
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Activation of the receptor for advanced glycation end products system in women with severe preeclampsia.
J. Clin. Endocrinol. Metab.
PUBLISHED: 02-16-2011
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Activation of the receptor for advanced glycation end products (RAGE) mediates cellular injury. Soluble forms of RAGE [soluble RAGE (sRAGE), endogenous secretory (esRAGE)] bind RAGE ligands, thereby preventing downstream signaling and damage.
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Diet and sleep in children with attention deficit hyperactivity disorder: preliminary data in Australian children.
J Child Health Care
PUBLISHED: 02-11-2011
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Sleep disturbances are common and consequential in children with attention deficit hyperactivity disorder (ADHD). Diet also influences ADHD symptoms. Interrelationships between diet, sleep and behaviour in children diagnosed with ADHD are little studied. We investigated, via parental report, the relationships between sleep and diet in 88 Australian children aged 6-13 years old (M = 8.94, SD = 1.78). This pilot data shows that 30 per cent of the children had sleep disturbance (? 2 standard deviations above the mean) with significant relationships between ADHD symptoms, sleep disturbance and diet. Parents who reported more sleep disturbance also reported a higher intake of carbohydrate, fats, and, most particularly, sugar which was also a significant predictor of night time sweating. These findings suggest an interrelationship between diet and sleep in children with ADHD. Given that both sleep and dietary intake are potentially modifiable behaviours within treatment regimes of children with ADHD, further investigation is needed.
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The chemoselective one-step alkylation and isolation of thiophosphorylated cdk2 substrates in the presence of native cysteine.
Chembiochem
PUBLISHED: 02-08-2011
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The elucidation of signalling pathways relies heavily upon the identification of protein kinase substrates. Recent investigations have demonstrated the efficacy of chemical genetics using ATP analogues and modified protein kinases for specific substrate labelling. Here we combine N(6) -(cyclohexyl)ATP?S with an analogue-sensitive cdk2 variant to thiophosphorylate its substrates and demonstrate a pH-dependent, chemoselective, one-step alkylation to facilitate the detection or isolation of thiophosphorylated peptides.
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The association between school-based physical activity, including physical education, and academic performance: a systematic review of the literature.
Prev Med
PUBLISHED: 02-01-2011
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The purpose of this review is to synthesize the scientific literature that has examined the association between school-based physical activity (including physical education) and academic performance (including indicators of cognitive skills and attitudes, academic behaviors, and academic achievement).
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IL-6 trans-signaling system in intra-amniotic inflammation, preterm birth, and preterm premature rupture of the membranes.
J. Immunol.
PUBLISHED: 01-31-2011
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Classic IL-6 signaling is conditioned by the transmembrane receptor (IL-6R) and homodimerization of gp130. During trans-signaling, IL-6 binds to soluble IL-6R (sIL-6R), enabling activation of cells expressing solely gp130. Soluble gp130 (sgp130) selectively inhibits IL-6 trans-signaling. To characterize amniotic fluid (AF) IL-6 trans-signaling molecules (IL-6, sIL-6R, sgp130) in normal gestations and pregnancies complicated by intra-amniotic inflammation (IAI), we studied 301 women during second trimester (n = 39), third trimester (n = 40), and preterm labor with intact (n = 131, 85 negative IAI and 46 positive IAI) or preterm premature rupture of membranes (PPROM; n = 91, 61 negative IAI and 30 positive IAI). ELISA, Western blotting, and real-time RT-PCR were used to investigate AF, placenta, and amniochorion for protein and mRNA expression of sIL-6R, sgp130, IL-6R, and gp130. Tissues were immunostained for IL-6R, gp130, CD15(+) (polymorphonuclear), and CD3(+) (T cell) inflammatory cells. The ability of sIL-6R and sgp130 to modulate basal and LPS-stimulated release of amniochorion matrix metalloprotease-9 was tested ex vivo. We showed that in physiologic gestations, AF sgp130 decreases toward term. AF IL-6 and sIL-6R were increased in IAI, whereas sgp130 was decreased in PPROM. Our results suggested that fetal membranes are the probable source of AF sIL-6R and sgp130. Immunohistochemistry and RT-PCR revealed increased IL-6R and decreased gp130 expression in amniochorion of women with IAI. Ex vivo, sIL-6R and LPS augmented amniochorion matrix metalloprotease-9 release, whereas sgp130 opposed this effect. We conclude that IL-6 trans-signaling molecules are physiologic constituents of the AF regulated by gestational age and inflammation. PPROM likely involves functional loss of sgp130.
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Efficacy of imatinib mesylate neoadjuvant treatment for a locally advanced rectal gastrointestinal stromal tumor.
J Korean Soc Coloproctol
PUBLISHED: 01-25-2011
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Surgery is the standard treatment for a primary gastrointestinal stromal tumor (GIST); however, surgical resection is often not curative, particularly for large GISTs. In the past decade, with imatinib mesylate (IM), management strategies for GISTs have evolved significantly, and now IM is the standard care for patients with locally advanced, recurrent or metastatic GISTs. Adjuvant therapy with imatinib was recently approved for use, and preoperative imatinib is an emerging treatment option for patients who require cytoreductive therapy. IM neoadjuvant therapy for primary GISTs has been reported, but there is no consensus on the dose of the drug, the duration of treatment and the optimal time of surgery. These are critical because drug resistance or tumor progression can develop with a prolonged treatment. This report describes two cases of large rectal malignant GISTs, for which a abdominoperineal resection was initially anticipated. The two patients received IM preoperative treatment; we followed-up with CT or magnetic resonance imaging to access the response. After 9 months of treatment, a multi-disciplinary consensus that maximal benefit from imatinib had been achieved was reached. We determined the best time for surgical intervention and successfully performed sphincter-preserving surgery before resistance to imatinib or tumor progression occurred. We believe that a multidisciplinary team approach, considerating the optimal duration of therapy and the timing of surgery, is required to optimize treatment outcome.
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Correlates of children and parents being physically active together.
J Phys Act Health
PUBLISHED: 11-20-2010
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Co-physical activity (between parents and children), as an outcome variable, and its correlates have not been examined previously. The purpose of this study was to investigate correlates of co-physical activity among a nationally representative sample of 9- to 13-year-old children and their parents.
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Cord blood erythropoietin and interleukin-6 for prediction of intraventricular hemorrhage in the preterm neonate.
J. Matern. Fetal. Neonatal. Med.
PUBLISHED: 10-12-2010
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To evaluate cord blood erythropoietin (EPO) and interleukin-6 (IL-6) levels to predict preterm infants at risk of developing intraventricular hemorrhage (IVH).
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RGS14 is a natural suppressor of both synaptic plasticity in CA2 neurons and hippocampal-based learning and memory.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 09-13-2010
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Learning and memory have been closely linked to strengthening of synaptic connections between neurons (i.e., synaptic plasticity) within the dentate gyrus (DG)-CA3-CA1 trisynaptic circuit of the hippocampus. Conspicuously absent from this circuit is area CA2, an intervening hippocampal region that is poorly understood. Schaffer collateral synapses on CA2 neurons are distinct from those on other hippocampal neurons in that they exhibit a perplexing lack of synaptic long-term potentiation (LTP). Here we demonstrate that the signaling protein RGS14 is highly enriched in CA2 pyramidal neurons and plays a role in suppression of both synaptic plasticity at these synapses and hippocampal-based learning and memory. RGS14 is a scaffolding protein that integrates G protein and H-Ras/ERK/MAP kinase signaling pathways, thereby making it well positioned to suppress plasticity in CA2 neurons. Supporting this idea, deletion of exons 2-7 of the RGS14 gene yields mice that lack RGS14 (RGS14-KO) and now express robust LTP at glutamatergic synapses in CA2 neurons with no impact on synaptic plasticity in CA1 neurons. Treatment of RGS14-deficient CA2 neurons with a specific MEK inhibitor blocked this LTP, suggesting a role for ERK/MAP kinase signaling pathways in this process. When tested behaviorally, RGS14-KO mice exhibited marked enhancement in spatial learning and in object recognition memory compared with their wild-type littermates, but showed no differences in their performance on tests of nonhippocampal-dependent behaviors. These results demonstrate that RGS14 is a key regulator of signaling pathways linking synaptic plasticity in CA2 pyramidal neurons to hippocampal-based learning and memory but distinct from the canonical DG-CA3-CA1 circuit.
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Metabolic analysis of guava (Psidium guajava L.) fruits at different ripening stages using different data-processing approaches.
J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.
PUBLISHED: 08-26-2010
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Gas chromatography coupled with time-of-flight mass spectrometry and principal component analysis were used to obtain the metabolite profiles of guava (Psidium guajava) fruits. Results with two types of data-processing software, ChromaTOF and AMDIS, were compared to explain the differences between the samples. There were some differences in score and loading plot patterns of PCA as well as in the composition of the metabolites. However, little difference was observed in the type of metabolites detected and identified using either type of software. Both the flesh and peel of premature and mature white guava fruits were compared for the analysis of the metabolite profiles. Malic acid, aspartic acid, and glucose were the major metabolites distinguishing the different parts of guava fruits in the PCA loading plot. In addition, the metabolic profiles of the fruits revealed significant changes in some metabolites during ripening. The major components contributing to the separation were serine, citric acid, fructose, sucrose, and some unknowns. In particular, sucrose, fructose, serine and citric acid were related to the ripening of guava fruits. Fructose and sucrose were increased whereas citric acid was decreased during guava fruit ripening.
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NMR of heparin API: investigation of unidentified signals in the USP-specified range of 2.12-3.00 ppm.
Anal Bioanal Chem
PUBLISHED: 07-20-2010
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This article addresses the identification and quantification of the chemical species resulting in resonances at 2.17 and 2.25 ppm in the (1)H nuclear magnetic resonance (NMR) spectrum of pharmaceutical-grade heparin sodium. The NMR signals in question were first confirmed to arise from chemical moieties covalently attached to the heparin molecule through NMR diffusion experiments as well as chemical treatment of heparin active pharmaceutical ingredient (API) containing the resonances. The material responsible for the extra NMR signals was then demonstrated by NMR spiking studies to be something other than oversulfated chondroitin sulfate and was finally identified as an O-acetylation product of heparin through (13)C labeling experiments with subsequent NMR analysis. The extent of O-acetylation was quantified using three orthogonal techniques: (1)H NMR, ion chromatography, and headspace gas chromatography/mass spectrometry. The results of this work showed good agreement between the three quantitative methods developed to analyze the signals in the United States Pharmacopeia-specified region of 2.12-3.00 ppm for heparin API.
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Influence of limit-setting and participation in physical activity on youth screen time.
Pediatrics
PUBLISHED: 06-14-2010
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To examine the associations of demographics, rules associated with television-viewing, and physical activity with daily screen time (including television, non-school-related computer use, and video games) in children and adolescents.
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Clinical features and serum biomarkers in HIV immune reconstitution inflammatory syndrome after cryptococcal meningitis: a prospective cohort study.
PLoS Med.
PUBLISHED: 05-25-2010
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Although antiretroviral therapy (ART) improves survival in persons with cryptococcal meningitis (CM) and AIDS, ART frequently elicits HIV immune reconstitution inflammatory syndrome (IRIS), an exaggerated and frequently deadly inflammatory reaction that complicates recovery from immunodeficiency. The pathogenesis of IRIS is poorly understood and prediction of IRIS is not possible.
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National study of changes in community access to school physical activity facilities: the school health policies and programs study.
J Phys Act Health
PUBLISHED: 05-05-2010
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A Healthy People 2010 developmental objective (22-12) was set to increase the proportion of the nations public and private schools that provide access to their physical activity spaces and facilities for all persons outside of normal school hours. The purpose of this study was to describe the prevalence of indoor and outdoor facilities at schools and the availability of those facilities to the public in 2000 and 2006.
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Synthesis and O-phosphorylation of 3,3,4,4-tetrafluoroaryl-C-nucleoside analogues.
Org. Biomol. Chem.
PUBLISHED: 01-25-2010
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Enantioenriched tetrafluorinated aryl-C-nucleosides were synthesised in four steps from 1-benzyloxy-4-bromo-3,3,4,4-tetrafluorobutan-2-ol. The presence of the tetrafluorinated ethylene group is compatible with O-phosphorylation of the primary alcohol, as demonstrated by the successful preparation of the tetrafluorinated naphthyl-C-nucleotide.
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Long-term health and economic impact of preventing and reducing overweight and obesity in adolescence.
J Adolesc Health
PUBLISHED: 01-13-2010
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Using data from the 2000 National Medical Expenditure Panel Survey and estimates from published studies, this study projected the long-term health and economic impacts of preventing and reducing overweight and obesity in todays adolescents.
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Activation of a poised RNAPII-dependent promoter requires both SAGA and mediator.
Genetics
PUBLISHED: 01-04-2010
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A growing number of promoters have key components of the transcription machinery, such as TATA-binding protein (TBP) and RNA polymerase II (RNAPII), present at the promoter prior to activation of transcription. Thus, while transcriptional output undergoes a dramatic increase between uninduced and induced conditions, occupancy of a large portion of the transcription machinery does not. As such, activation of these poised promoters depends on rate-limiting steps after recruitment of TBP and RNAPII for regulated expression. Little is known about the transcription components required in these latter steps of transcription in vivo. To identify components with critical roles in transcription after recruitment of TBP in Saccharomyces cerevisiae, we screened for loss of gene expression activity from promoter-tethered TBP in >100 mutant strains deleted for a transcription-related gene. The assay revealed a dramatic enrichment for strains containing deletions in genes encoding subunits of the Spt-Ada-Gcn5-acetyltransferase (SAGA) complex and Mediator. Analysis of an authentic postrecruitment-regulated gene (CYC1) reveals that SAGA occupies the promoter under both uninduced and induced conditions. In contrast, Mediator is recruited only after transfer to inducing conditions and correlates with activation of the preloaded polymerase at CYC1. These studies indicate the critical functions of SAGA and Mediator in the mechanism of activation of genes with rate-limiting steps after recruitment of TBP.
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Healthy people 2010 objectives for physical activity, physical education, and television viewing among adolescents: national trends from the Youth Risk Behavior Surveillance System, 1999-2007.
J Phys Act Health
PUBLISHED: 12-17-2009
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To help inform policies and programs, a need exists to understand the extent to which Healthy People 2010 objectives for physical activity, physical education (PE), and television (TV) viewing among adolescents are being achieved.
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Childrens autonomous food acquisition in Mexican shantytowns.
Ecol Food Nutr
PUBLISHED: 11-01-2009
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Childrens independent food-acquisition behaviors have been rarely studied outside of hunter-gatherer contexts, yet millions of children worldwide search, work, trade, or beg for food. This study uses observational, anthropometric, dietary, and ethnographic data to understand preliminarily the nutritive and possible social contexts of autonomous middle childhood food-gaining behaviors in Mexican shantytowns. While we find children forage, work for, and share considerable amounts of food outside the household, this is not associated with significant variation in their anthropometric status or dietary quality; some possible social benefits of food-getting are, however, evident.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.