370 research outputs found

    The nuclear envelopathies and human diseases

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    The nuclear envelope (NE) consists of two membrane layers that segregate the nuclear from the cytoplasmic contents. Recent progress in our understanding of nuclear-lamina associated diseases has revealed intriguing connections between the envelope components and nuclear processes. Here, we review the functions of the nuclear envelope in chromosome organization, gene expression, DNA repair and cell cycle progression, and correlate deficiencies in envelope function with human pathologies

    A proteomic study of TAR-RNA binding protein (TRBP)-associated factors

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    <p>Abstract</p> <p>Background</p> <p>The human TAR RNA-binding protein, TRBP, was first identified and cloned based on its high affinity binding to the small hairpin trans-activation responsive (TAR) RNA of HIV-1. TRBP has more recently been found to be a constituent of the RNA-induced silencing complex (RISC) serving as a Dicer co-factor in the processing of the ~70 nucleotide pre-microRNAs(miRNAs) to 21-25 nucleotide mature miRNAs.</p> <p>Findings</p> <p>Using co-immunoprecipitation and protein-identification by mass spectrometry, we characterized intracellular proteins that complex with TRBP. These interacting proteins include those that have been described to act in protein synthesis, RNA modifications and processing, DNA transcription, and cell proliferation.</p> <p>Conclusions</p> <p>Our findings provide a proteome of factors that may cooperate with TRBP in activities such as miRNA processing and in RNA interference by the RISC complex.</p

    Structurally Homologous All β-Barrel Proteins Adopt Different Mechanisms of Folding

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    AbstractAcidic fibroblast growth factors from human (hFGF-1) and newt (nFGF-1) (Notopthalamus viridescens) are 16-kDa, all β-sheet proteins with nearly identical three-dimensional structures. Guanidine hydrochloride (GdnHCl)-induced unfolding of hFGF-1 and nFGF-1 monitored by fluorescence and far-UV circular dichroism (CD) shows that the FGF-1 isoforms differ significantly in their thermodynamic stabilities. GdnHCl-induced unfolding of nFGF-1 follows a two-state (Native state to Denatured state(s)) mechanism without detectable intermediate(s). By contrast, unfolding of hFGF-1 monitored by fluorescence, far-UV circular dichroism, size-exclusion chromatography, and NMR spectroscopy shows that the unfolding process is noncooperative and proceeds with the accumulation of stable intermediate(s) at 0.96M GdnHCl. The intermediate (in hFGF-1) populated maximally at 0.96M GdnHCl has molten globule-like properties and shows strong binding affinity to the hydrophobic dye, 1-Anilino-8-naphthalene sulfonate (ANS). Refolding kinetics of hFGF-1 and nFGF-1 monitored by stopped-flow fluorescence reveal that hFGF-1 and nFGF-1 adopts different folding mechanisms. The observed differences in the folding/unfolding mechanisms of nFGF-1 and hFGF-1 are proposed to be either due to differential stabilizing effects of the charged denaturant (Gdn+ Cl−) on the intermediate state(s) and/or due to differences in the structural interactions stabilizing the native conformation(s) of the FGF-1 isoforms

    Pulmonary IL- 33 orchestrates innate immune cells to mediate respiratory syncytial virus- evoked airway hyperreactivity and eosinophilia

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    BackgroundRespiratory syncytial virus (RSV) infection is epidemiologically linked to asthma. During RSV infection, IL- 33 is elevated and promotes immune cell activation, leading to the development of asthma. However, which immune cells are responsible for triggering airway hyperreactivity (AHR), inflammation and eosinophilia remained to be clarified. We aimed to elucidate the individual roles of IL- 33- activated innate immune cells, including ILC2s and ST2+ myeloid cells, in RSV infection- triggered pathophysiology.MethodsThe role of IL- 33/ILC2 axis in RSV- induced AHR inflammation and eosinophilia were evaluated in the IL- 33- deficient and YetCre- 13 Rosa- DTA mice. Myeloid- specific, IL- 33- deficient or ST2- deficient mice were employed to examine the role of IL- 33 and ST2 signaling in myeloid cells.ResultsWe found that IL- 33- activated ILC2s were crucial for the development of AHR and airway inflammation, during RSV infection. ILC2- derived IL- 13 was sufficient for RSV- driven AHR, since reconstitution of wild- type ILC2 rescued RSV- driven AHR in IL- 13- deficient mice. Meanwhile, myeloid cell- derived IL- 33 was required for airway inflammation, ST2+ myeloid cells contributed to exacerbation of airway inflammation, suggesting the importance of IL- 33 signaling in these cells. Local and peripheral eosinophilia is linked to both ILC2 and myeloid IL- 33 signaling.ConclusionsThis study highlights the importance of IL- 33- activated ILC2s in mediating RSV- triggered AHR and eosinophilia. In addition, IL- 33 signaling in myeloid cells is crucial for airway inflammation.Respiratory syncytial virus induces ILC2 to produce IL- 5 and IL- 13 through IL- 33, which is crucial for the development of airway hyperreactivity and airway inflammation. Myeloid cell- derived IL- 33 and suppression of tumorigenicity 2- positive myeloid cells contribute to cytokine production and cellular inflammation in airway. Both ILC2 and myeloid cell IL- 33 signaling contribute to local and peripheral eosinophilia.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154896/1/all14091.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154896/2/all14091-sup-0001-Supinfo.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154896/3/all14091_am.pd

    Evaluation of Lentiviral-Mediated Expression of Sodium Iodide Symporter in Anaplastic Thyroid Cancer and the Efficacy of In Vivo Imaging and Therapy

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    Anaplastic thyroid carcinoma (ATC) is one of the most deadly cancers. With intensive multimodalities of treatment, the survival remains low. ATC is not sensitive to 131I therapy due to loss of sodium iodide symporter (NIS) gene expression. We have previously generated a stable human NIS-expressing ATC cell line, ARO, and the ability of iodide accumulation was restored. To make NIS-mediated gene therapy more applicable, this study aimed to establish a lentiviral system for transferring hNIS gene to cells and to evaluate the efficacy of in vitro and in vivo radioiodide accumulation for imaging and therapy. Lentivirus containing hNIS cDNA were produced to transduce ARO cells which do not concentrate iodide. Gene expression, cell function, radioiodide imaging and treatment were evaluated in vitro and in vivo. Results showed that the transduced cells were restored to express hNIS and accumulated higher amount of radioiodide than parental cells. Therapeutic dose of 131I effectively inhibited the tumor growth derived from transduced cells as compared to saline-treated mice. Our results suggest that the lentiviral system efficiently transferred and expressed hNIS gene in ATC cells. The transduced cells showed a promising result of tumor imaging and therapy

    THE EFFECTS AFTER THINNING OF JAPANESE CEDAR AT XITOU

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    This study sat two experimental plots each for 400m2 ha of 40 years old Japanese cedar (Cryptomeria japonica) plantation at National Taiwan University Experimental Forest Xitou Tract: Control (non-thinning) plot and 40% thinning plot. The original planting density was 2000 trees for each ha of all the experimental plots. After complete enumeration of all the experimental plots, measurements of photosynthesis were taken and multiplied by the total leaf area for each sample tree; then accounting for the number of trees in the forest, the percentage of the forest stand that could get the annual carbon sequestration of forest stand was. The results showed significant correlation between tree dominance and increment (R2&gt;0.7) for non-thinning Japanese cedar, higher and bigger diameter trees showed more growth increment but stagnant for overtopped trees. After thinning, all the low-diameter trees have increase significantly in increment for 30-50%. The photosynthesis ability measured results shown that Japanese cedar photosynthetic efficiency have no significant differences after thinning, but due to the total leaf area growth, so that it could increase carbon sequestration efficiency by 22-38% after thinning
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