3,407 research outputs found

    Topological Analysis of Metabolic Networks Integrating Co-Segregating Transcriptomes and Metabolomes in Type 2 Diabetic Rat Congenic Series

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    Background: The genetic regulation of metabolic phenotypes (i.e., metabotypes) in type 2 diabetes mellitus is caused by complex organ-specific cellular mechanisms contributing to impaired insulin secretion and insulin resistance. Methods: We used systematic metabotyping by 1H NMR spectroscopy and genome-wide gene expression in white adipose tissue to map molecular phenotypes to genomic blocks associated with obesity and insulin secretion in a series of rat congenic strains derived from spontaneously diabetic Goto-Kakizaki (GK) and normoglycemic Brown-Norway (BN) rats. We implemented a network biology strategy approach to visualise shortest paths between metabolites and genes significantly associated with each genomic block. Results: Despite strong genomic similarities (95-99%) among congenics, each strain exhibited specific patterns of gene expression and metabotypes, reflecting metabolic consequences of series of linked genetic polymorphisms in the congenic intervals. We subsequently used the congenic panel to map quantitative trait loci underlying specific metabotypes (mQTL) and genome-wide expression traits (eQTL). Variation in key metabolites like glucose, succinate, lactate or 3-hydroxybutyrate, and second messenger precursors like inositol was associated with several independent genomic intervals, indicating functional redundancy in these regions. To navigate through the complexity of these association networks we mapped candidate genes and metabolites onto metabolic pathways and implemented a shortest path strategy to highlight potential mechanistic links between metabolites and transcripts at colocalized mQTLs and eQTLs. Minimizing shortest path length drove prioritization of biological validations by gene silencing. Conclusions: These results underline the importance of network-based integration of multilevel systems genetics datasets to improve understanding of the genetic architecture of metabotype and transcriptomic regulations and to characterize novel functional roles for genes determining tissue-specific metabolism

    Changes in Protein, Nonnutritional Factors, and Antioxidant Capacity during Germination of L. campestris

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    The changes in SDS-PAGE proteins patterns, oligosaccharides and phenolic compounds of L. campestris seeds, were evaluated during nine germination days. SDS-PAGE pattern showed 12 bands in the original protein seeds, while in the samples after 1–9 germination days, the proteins located in the range of 28–49 and 49–80 kDa indicated an important reduction, and there was an increase in bands about 27 kDa. On the other hand, oligosaccharides showed more than 50% of decrease in its total concentration after 4 germination days; nevertheless after the fifth day, the oligosaccharides concentration increases and rises more than 30% of the original concentration. Phenolic compounds increased their concentration since the first germination day reaching until 450% more than the original seed level. The obtained results are related with liberation or increase of phenolic compounds with antioxidant properties, allowing us to suggest that the germination would be used to produce legume foods for human consumption with better nutraceutical properties

    The Student Movement Volume 107, Issue 9: Power (Outage) to the People: Students Frolic in Winter Wonderland

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    HUMANS Interview with the Speech Pathology Club, Interviewed by: Gloria Oh Meet The Chiefs of The Twin Cities, Nicholas C. Gunn Meet the Student Graduate Liaison of AUGSA, Natasha Richards, Interviewed by: Kavya Mohanram What Are AU Students Thankful For?, Interviewed by: Grace No ARTS & ENTERTAINMENT Anthony León Wins Placido Domingo\u27s Operailia 2022, Aiko J. Ayala Rios Currently..., Solana Campbell Thanks for Making Me Laugh: My Top Ten Thanksgiving Sitcom Episodes, Bella Hamann Top Gun Maverick: A SuperSonic Sequel, Leo Martins NEWS Honors Church: Lessons and Carols, Terika Williams Prime Minister after Prime Minister, Abigail Kim The Seatless Delegate: An Unfulfilled Promise to the Cherokee Nation, Julia Randall Innovation & Entrepreneurship: The Sole Full Winner of the Shark Tank Competition, Yoel Kim IDEAS A Reflect ion on Body Image, Elizabeth Getahun The Frenzy of Fast Fashion, Abby Shim The Scoop on Introverts: What Extroverts Need to Know, Isabelle Martinez To Bee or not to Bee: The Importance, Causes, and Impact of Bee Disappearance, Alexander Navarro PULSE All About AU Engage, Lexie Dunham Thoughts on Daylight Savings, Gloria Oh Thanksgiving and Our Heritage, Zothile Sibanda LAST WORD Romanticizing the Past, Alannah Tjhatrahttps://digitalcommons.andrews.edu/sm-107/1008/thumbnail.jp

    The Sensitivity of HAWC to High-Mass Dark Matter Annihilations

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    The High Altitude Water Cherenkov (HAWC) observatory is a wide field-of-view detector sensitive to gamma rays of 100 GeV to a few hundred TeV. Located in central Mexico at 19 degrees North latitude and 4100 m above sea level, HAWC will observe gamma rays and cosmic rays with an array of water Cherenkov detectors. The full HAWC array is scheduled to be operational in Spring 2015. In this paper, we study the HAWC sensitivity to the gamma-ray signatures of high-mass (multi- TeV) dark matter annihilation. The HAWC observatory will be sensitive to diverse searches for dark matter annihilation, including annihilation from extended dark matter sources, the diffuse gamma-ray emission from dark matter annihilation, and gamma-ray emission from non-luminous dark matter subhalos. Here we consider the HAWC sensitivity to a subset of these sources, including dwarf galaxies, the M31 galaxy, the Virgo cluster, and the Galactic center. We simulate the HAWC response to gamma rays from these sources in several well-motivated dark matter annihilation channels. If no gamma-ray excess is observed, we show the limits HAWC can place on the dark matter cross-section from these sources. In particular, in the case of dark matter annihilation into gauge bosons, HAWC will be able to detect a narrow range of dark matter masses to cross-sections below thermal. HAWC should also be sensitive to non-thermal cross-sections for masses up to nearly 1000 TeV. The constraints placed by HAWC on the dark matter cross-section from known sources should be competitive with current limits in the mass range where HAWC has similar sensitivity. HAWC can additionally explore higher dark matter masses than are currently constrained.Comment: 15 pages, 4 figures, version to be published in PR

    Gene products and processes contributing to lanthanide homeostasis and methanol metabolism in \u3cem\u3eMethylorubrum extorquens\u3c/em\u3e AM1

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    Lanthanide elements have been recently recognized as “new life metals” yet much remains unknown regarding lanthanide acquisition and homeostasis. In Methylorubrum extorquens AM1, the periplasmic lanthanide-dependent methanol dehydrogenase XoxF1 produces formaldehyde, which is lethal if allowed to accumulate. This property enabled a transposon mutagenesis study and growth studies to confirm novel gene products required for XoxF1 function. The identified genes encode an MxaD homolog, an ABC-type transporter, an aminopeptidase, a putative homospermidine synthase, and two genes of unknown function annotated as orf6 and orf7. Lanthanide transport and trafficking genes were also identified. Growth and lanthanide uptake were measured using strains lacking individual lanthanide transport cluster genes, and transmission electron microscopy was used to visualize lanthanide localization. We corroborated previous reports that a TonB-ABC transport system is required for lanthanide incorporation to the cytoplasm. However, cells were able to acclimate over time and bypass the requirement for the TonB outer membrane transporter to allow expression of xoxF1 and growth. Transcriptional reporter fusions show that excess lanthanides repress the gene encoding the TonB-receptor. Using growth studies along with energy dispersive X-ray spectroscopy and transmission electron microscopy, we demonstrate that lanthanides are stored as cytoplasmic inclusions that resemble polyphosphate granules

    All-particle cosmic ray energy spectrum measured by the HAWC experiment from 10 to 500 TeV

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    We report on the measurement of the all-particle cosmic ray energy spectrum with the High Altitude Water Cherenkov (HAWC) Observatory in the energy range 10 to 500 TeV. HAWC is a ground based air-shower array deployed on the slopes of Volcan Sierra Negra in the state of Puebla, Mexico, and is sensitive to gamma rays and cosmic rays at TeV energies. The data used in this work were taken from 234 days between June 2016 to February 2017. The primary cosmic-ray energy is determined with a maximum likelihood approach using the particle density as a function of distance to the shower core. Introducing quality cuts to isolate events with shower cores landing on the array, the reconstructed energy distribution is unfolded iteratively. The measured all-particle spectrum is consistent with a broken power law with an index of 2.49±0.01-2.49\pm0.01 prior to a break at (45.7±0.1(45.7\pm0.1) TeV, followed by an index of 2.71±0.01-2.71\pm0.01. The spectrum also respresents a single measurement that spans the energy range between direct detection and ground based experiments. As a verification of the detector response, the energy scale and angular resolution are validated by observation of the cosmic ray Moon shadow's dependence on energy.Comment: 16 pages, 11 figures, 4 tables, submission to Physical Review
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