454 research outputs found

    Deconstructing Voice-over-IP

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    Unified distributed configurations have led to many technical advances, including robots and flip-flop gates. In this work, authors show the synthesis of consistent hashing. We present new “fuzzy” archetypes, which we call ARGAS

    Classroom Teachers Learning to Navigate the Internet for Increasing Student Critical Reading and Writing Skills: A Mixed Methods Study

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    The focus of this mixed methods case study was a three-month professional development workshop designed to guide junior high school classroom teachers as they learned to integrate new literacies skills into their curriculum. The participants were all educators in one district that was in the process of transitioning to the Common Core State Standards and the SMARTER Balanced Assessments. Significant gains were obtained in teachers’ self-reported personal technology knowledge and technology experiences during the study. Along with the gains, factors were seen that might impede teachers from learning about or using the Internet for academic purposes

    Biologic Cycling of Silica across a Grassland Bioclimosequence

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    The dynamics of biologic Si cycling in grassland ecosystems are largely unknown and likely to impact mineral weathering rates regionally and diatom productivity globally; key regulatory processes in the global Si cycle are closely tied to the global carbon cycle. Across a bioclimatic sequence spanning major grassland ecosystems in the Great Plains, soil biogenic silica depth distributions are similar to that of soil organic carbon; however, unlike soil organic carbon, quantities of soil biogenic silica decrease with increasing precipitation, despite an increase in annual biogenic inputs through litterfall across the same gradient. Though comprising only 1–3% of the total Si pool, faster turnover of biogenic Si and annual cycling by grasses should positively impact mineral dissolution. Our results suggest that the largest reservoir of biogenic Si in terrestrial ecosystems resides in soils, and emphasize the potential significance of grasslands in the global biogeochemical cycle of Si

    MEF2C regulates outflow tract alignment and transcriptional control of Tdgf1

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    Congenital heart defects are the most common birth defects in humans, and those that affect the proper alignment of the outflow tracts and septation of the ventricles are a highly significant cause of morbidity and mortality in infants. A late differentiating population of cardiac progenitors, referred to as the anterior second heart field (AHF), gives rise to the outflow tract and the majority of the right ventricle and provides an embryological context for understanding cardiac outflow tract alignment and membranous ventricular septal defects. However, the transcriptional pathways controlling AHF development and their roles in congenital heart defects remain incompletely elucidated. Here, we inactivated the gene encoding the transcription factor MEF2C in the AHF in mice. Loss of Mef2c function in the AHF results in a spectrum of outflow tract alignment defects ranging from overriding aorta to double-outlet right ventricle and dextro-transposition of the great arteries. We identify Tdgf1, which encodes a Nodal co-receptor (also known as Cripto), as a direct transcriptional target of MEF2C in the outflow tract via an AHFrestricted Tdgf1 enhancer. Importantly, both the MEF2C and TDGF1 genes are associated with congenital heart defects in humans. Thus, these studies establish a direct transcriptional pathway between the core cardiac transcription factor MEF2C and the human congenital heart disease gene TDGF1. Moreover, we found a range of outflow tract alignment defects resulting from a single genetic lesion, supporting the idea that AHF-derived outflow tract alignment defects may constitute an embryological spectrum rather than distinct anomalies

    Getting to the heart of the matter: long non-coding RNAs in cardiac development and disease

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    Cardiogenesis in mammals requires exquisite control of gene expression and faulty regulation of transcriptional programs underpins congenital heart disease (CHD), the most common defect among live births. Similarly, many adult cardiac diseases involve transcriptional changes and sometimes have a developmental basis. Long non‐coding RNAs (lncRNAs) are a novel class of transcripts that regulate cellular processes by controlling gene expression; however, detailed insights into their biological and mechanistic functions are only beginning to emerge. Here, we discuss recent findings suggesting that lncRNAs are important factors in regulation of mammalian cardiogenesis and in the pathogenesis of CHD as well as adult cardiac disease. We also outline potential methodological and conceptual considerations for future studies of lncRNAs in the heart and other contexts.National Heart, Lung, and Blood Institute (Bench to Bassinet Program U01HL098179)National Heart, Lung, and Blood Institute (Bench to Bassinet Program U01HL098188

    Grazing and No-Till Cropping Impacts on Nitrogen Retention in Dryland Agroecosystems

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    As the world\u27s population increases, marginal lands such as drylands are likely to become more important for food production. One proven strategy for improving crop production in drylands involves shifting from conventional tillage to no-till to increase water use efficiency, especially when this shift is coupled with more intensive crop rotations. Practices such as no-till that reduce soil disturbance and increase crop residues may promote C and N storage in soil organic matter, thus promoting N retention and reducing N losses. By sampling soils 15 yr after a N tracer addition, this study compared long-term soil N retention across several agricultural management strategies in current and converted shortgrass steppe ecosystems: grazed and ungrazed native grassland, occasionally mowed planted perennial grassland, and three cropping intensities of no-till dryland cropping. We also examined effects of the environmental variables site location and topography on N retention. Overall, the long-term soil N retention of \u3e18% in these managed semiarid ecosystems was high compared with published values for other cropped or grassland ecosystems. Cropping practices strongly influenced long-term N retention, with planted perennial grass systems retaining \u3e90% of N in soil compared with 30% for croplands. Grazing management, topography, and site location had smaller effects on long-term N retention. Estimated 15-yr N losses were low for intact and cropped systems. This work suggests that semiarid perennial grass ecosystems are highly N retentive and that increased intensity of semiarid land management can increase the amount of protein harvested without increasing N losses

    Using Microbial Community Interactions within Plant Microbiomes to Advance an Evergreen Agricultural Revolution

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    Innovative plant breeding and technology transfer fostered the Green Revolution (GR), which transformed agriculture worldwide by increasing grain yields in developing countries. The GR temporarily alleviated world hunger, but also reduced biodiversity, nutrient cycling, and carbon (C) sequestration that agricultural lands can provide. Meanwhile, economic disparity and food insecurity within and among countries continues. Subsequent agricultural advances, focused on objectives such as increasing crop yields or reducing the risk of a specific pest, have failed to meet food demands at the local scale or to restore lost ecosystem services. An increasing human population, climate change, growing per capita food and energy demands, and reduced ecosystem potential to provide agriculturally relevant services have created an unrelenting need for improved crop production practices. Meeting this need in a sustainable fashion will require interdisciplinary approaches that integrate plant and microbial ecology with efforts to advance crop production while mitigating effects of a changing climate. Metagenomic advances are revealing microbial dynamics that can simultaneously improve crop production and soil restoration while enhancing crop resistance to environmental change. Restoring microbial diversity to contemporary agroecosystems could establish ecosystem services while reducing production costs for agricultural producers. Our framework for examining plant-microbial interactions at multiple scales, modeling outcomes to broadly explore potential impacts, and interacting with extension and training networks to transfer microbial based agricultural technologies across socioeconomic scales, offers an integrated strategy for advancing agroecosystem sustainability while minimizing potential for the kind of negative ecological and socioeconomic feedbacks that have resulted from many widely adopted agricultural technologies

    CYP450 phenotyping and metabolite identification of quinine by accurate mass UPLC-MS analysis: a possible metabolic link to blackwater fever

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    BACKGROUND: The naturally occurring alkaloid drug, quinine is commonly used for the treatment of severe malaria. Despite centuries of use, its metabolism is still not fully understood, and may play a role in the haemolytic disorders associated with the drug. METHODS: Incubations of quinine with CYPs 1A2, 2C9, 2C19, 2D6, and 3A4 were conducted, and the metabolites were characterized by accurate mass UPLC-MS(E) analysis. Reactive oxygen species generation was also measured in human erythrocytes incubated in the presence of quinine with and without microsomes. RESULTS: The metabolites 3-hydroxyquinine, 2’-oxoquininone, and O-desmethylquinine were observed after incubation with CYPs 3A4 (3-hydroxyquinine and 2’-oxoquininone) and 2D6 (O-desmethylquinine). In addition, multiple hydroxylations were observed both on the quinoline core and the quinuclidine ring system. Of the five primary abundance CYPs tested, 3A4, 2D6, 2C9, and 2C19 all demonstrated activity toward quinine, while 1A2 did not. Further, quinine produced robust dose-dependent oxidative stress in human erythrocytes in the presence of microsomes. CONCLUSIONS: Taken in context, these data suggest a CYP-mediated link between quinine metabolism and the poorly understood haemolytic condition known as blackwater fever, often associated with quinine ingestion
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