116 research outputs found

    Some properties of a low-order model of atmospheric circulation

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    Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Meteorology, 1964.Vita.Includes bibliographical references (leaves 120-122).by John D. Stackpole.Ph.D

    Essential role for non-canonical poly(A) polymerase GLD4 in cytoplasmic polyadenylation and carbohydrate metabolism

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    Regulation of gene expression at the level of cytoplasmic polyadenylation is important for many biological phenomena including cell cycle progression, mitochondrial respiration, and learning and memory. GLD4 is one of the non-canonical poly(A) polymerases that regulates cytoplasmic polyadenylation-induced translation, but its target mRNAs and role in cellular physiology is not well known. To assess the full panoply of mRNAs whose polyadenylation is controlled by GLD4, we performed an unbiased whole genome-wide screen using poy(U) chromatography and thermal elution. We identified hundreds of mRNAs regulated by GLD4, several of which are involved in carbohydrate metabolism including GLUT1, a major glucose transporter. Depletion of GLD4 not only reduced GLUT1 poly(A) tail length, but also GLUT1 protein. GLD4-mediated translational control of GLUT1 mRNA is dependent of an RNA binding protein, CPEB1, and its binding elements in the 3 UTR. Through regulating GLUT1 level, GLD4 affects glucose uptake into cells and lactate levels. Moreover, GLD4 depletion impairs glucose deprivation-induced GLUT1 up-regulation. In addition, we found that GLD4 affects glucose-dependent cellular phenotypes such as migration and invasion in glioblastoma cells. Our observations delineate a novel post-transcriptional regulatory network involving carbohydrate metabolism and glucose homeostasis mediated by GLD4

    Optimization of ribosome profiling using low-input brain tissue from fragile X syndrome model mice

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    Dysregulated protein synthesis is a major underlying cause of many neurodevelopmental diseases including fragile X syndrome. In order to capture subtle but biologically significant differences in translation in these disorders, a robust technique is required. One powerful tool to study translational control is ribosome profiling, which is based on deep sequencing of mRNA fragments protected from ribonuclease (RNase) digestion by ribosomes. However, this approach has been mainly applied to rapidly dividing cells where translation is active and large amounts of starting material are readily available. The application of ribosome profiling to low-input brain tissue where translation is modest and gene expression changes between genotypes are expected to be small has not been carefully evaluated. Using hippocampal tissue from wide type and fragile X mental retardation 1 (Fmr1) knockout mice, we show that variable RNase digestion can lead to significant sample batch effects. We also establish GC content and ribosome footprint length as quality control metrics for RNase digestion. We performed RNase titration experiments for low-input samples to identify optimal conditions for this critical step that is often improperly conducted. Our data reveal that optimal RNase digestion is essential to ensure high quality and reproducibility of ribosome profiling for low-input brain tissue

    The O/OREOS Mission - Astrobiology in Low Earth Orbit

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    The O/OREOS (Organism/Organic Exposure to Orbital Stresses) nanosatellite is the first science demonstration spacecraft and flight mission of the NASA Astrobiology Small- Payloads Program (ASP). O/OREOS was launched successfully on November 19, 2010, to a high-inclination (72), 650-km Earth orbit aboard a US Air Force Minotaur IV rocket from Kodiak, Alaska. O/OREOS consists of 3 conjoined cubesat (each 1000 cu.cm) modules: (i) a control bus, (ii) the Space Environment Survivability of Living Organisms (SESLO) experiment, and (iii) the Space Environment Viability of Organics (SEVO) experiment. Among the innovative aspects of the O/OREOS mission are a real-time analysis of the photostability of organics and biomarkers and the collection of data on the survival and metabolic activity for micro-organisms at 3 times during the 6-month mission. We will report on the spacecraft characteristics, payload capabilities and first operational phase of the O/OREOS mission. The science and technology rationale of O/OREOS supports NASAs scientific exploration program by investigating the local space environment as well as space biology relevant to Moon and Mars missions. It also serves as precursor for experiments on small satellites, the International Space Station (ISS), future free-flyers and lunar surface exposure facilities

    Melanoma Spheroids Grown Under Neural Crest Cell Conditions Are Highly Plastic Migratory/Invasive Tumor Cells Endowed with Immunomodulator Function

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    International audienceBACKGROUND: The aggressiveness of melanoma tumors is likely to rely on their well-recognized heterogeneity and plasticity. Melanoma comprises multi-subpopulations of cancer cells some of which may possess stem cell-like properties. Although useful, the sphere-formation assay to identify stem cell-like or tumor initiating cell subpopulations in melanoma has been challenged, and it is unclear if this model can predict a functional phenotype associated with aggressive tumor cells. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed the molecular and functional phenotypes of melanoma spheroids formed in neural crest cell medium. Whether from metastatic or advanced primary tumors, spheroid cells expressed melanoma-associated markers. They displayed higher capacity to differentiate along mesenchymal lineages and enhanced expression of SOX2, NANOG, KLF4, and/or OCT4 transcription factors, but not enhanced self-renewal or tumorigenicity when compared to their adherent counterparts. Gene expression profiling attributed a neural crest cell signature to these spheroids and indicated that a migratory/invasive and immune-function modulating program could be associated with these cells. In vitro assays confirmed that spheroids display enhanced migratory/invasive capacities. In immune activation assays, spheroid cells elicited a poorer allogenic response from immune cells and inhibited mitogen-dependent T cells activation and proliferation more efficiently than their adherent counterparts. Our findings reveal a novel immune-modulator function of melanoma spheroids and suggest specific roles for spheroids in invasion and in evasion of antitumor immunity. CONCLUSION/SIGNIFICANCE: The association of a more plastic, invasive and evasive, thus a more aggressive tumor phenotype with melanoma spheroids reveals a previously unrecognized aspect of tumor cells expanded as spheroid cultures. While of limited efficiency for melanoma initiating cell identification, our melanoma spheroid model predicted aggressive phenotype and suggested that aggressiveness and heterogeneity of melanoma tumors can be supported by subpopulations other than cancer stem cells. Therefore, it could be constructive to investigate melanoma aggressiveness, relevant to patients and clinical transferability

    The O/OREOS Mission - Astrobiology in Low Earth Orbit

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    The O/OREOS (Organism/Organic Exposure to Orbital Stresses) nanosatellite is the first science demonstration spacecraft and flight mission of the NASA Astrobiology Small- Payloads Program (ASP). O/OREOS was launched successfully on November 19, 2010, to a high-inclination (72), 650-km Earth orbit aboard a US Air Force Minotaur IV rocket from Kodiak, Alaska. O/OREOS consists of 3 conjoined cubesat (each 1000 cu.cm) modules: (i) a control bus, (ii) the Space Environment Survivability of Living Organisms (SESLO) experiment, and (iii) the Space Environment Viability of Organics (SEVO) experiment. Among the innovative aspects of the O/OREOS mission are a real-time analysis of the photostability of organics and biomarkers and the collection of data on the survival and metabolic activity for micro-organisms at 3 times during the 6-month mission. We will report on the spacecraft characteristics, payload capabilities and first operational phase of the O/OREOS mission. The science and technology rationale of O/OREOS supports NASAs scientific exploration program by investigating the local space environment as well as space biology relevant to Moon and Mars missions. It also serves as precursor for experiments on small satellites, the International Space Station (ISS), future free-flyers and lunar surface exposure facilities

    International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

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    Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

    Alien Registration- Stackpole, Ellen D. (Sanford, York County)

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    https://digitalmaine.com/alien_docs/6217/thumbnail.jp

    Alien Registration- Stackpole, Ellen D. (Sanford, York County)

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    https://digitalmaine.com/alien_docs/6217/thumbnail.jp
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