48 research outputs found

    Identification of an RNA Polymerase III Regulator Linked to Disease-Associated Protein Aggregation.

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    Protein aggregation is associated with age-related neurodegenerative disorders, such as Alzheimer's and polyglutamine diseases. As a causal relationship between protein aggregation and neurodegeneration remains elusive, understanding the cellular mechanisms regulating protein aggregation will help develop future treatments. To identify such mechanisms, we conducted a forward genetic screen in a C. elegans model of polyglutamine aggregation and identified the protein MOAG-2/LIR-3 as a driver of protein aggregation. In the absence of polyglutamine, MOAG-2/LIR-3 regulates the RNA polymerase III-associated transcription of small non-coding RNAs. This regulation is lost in the presence of polyglutamine, which mislocalizes MOAG-2/LIR-3 from the nucleus to the cytosol. We then show biochemically that MOAG-2/LIR-3 can also catalyze the aggregation of polyglutamine-expanded huntingtin. These results suggest that polyglutamine can induce an aggregation-promoting activity of MOAG-2/LIR-3 in the cytosol. The concept that certain aggregation-prone proteins can convert other endogenous proteins into drivers of aggregation and toxicity adds to the understanding of how cellular homeostasis can be deteriorated in protein misfolding diseases

    Neuroendocrine neoplasms of the small intestine and the appendix - management guidelines (recommended by the Polish Network of Neuroendocrine Tumours).

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    This study presents the revised Polish guidelines regarding the management of patients suffering from neuroendocrine neoplasms (NENs) of the small intestine and appendix. The small intestine, especially the ileum, is the most common location for these neoplasms. Most are well differentiated and slow growing. Their symptoms may be atypical, which can result in delayed or accidental diagnosis. Appendicitis is usually the first manifestation of NEN in this location. Typical symptoms of carcinoid syndrome occur in approximately 20-30% of patients suffering from small intestinal NENs with distant metastases. The main cause of death in patients with carcinoid syndrome is carcinoid heart disease. The most useful laboratory test is the determination of chromogranin A, while concentration of 5-hydroxyindoleacetic acid is helpful in the diagnostics of carcinoid syndrome. For visualisation, ultrasound, computed tomography, magnetic resonance imaging, colonoscopy, video capsule endoscopy, double-balloon enteroscopy, and somatostatin receptor scintigraphy may be used. A detailed his-tological report is crucial for the proper diagnostics and therapy of NENs of the small intestine and appendix. The treatment of choice is surgical management, either radical or palliative. The pharmacological treatment of the hormonally active and non-active small intestinal NENs as well as NENs of the appendix is based on long-acting somatostatin analogues. In patients with generalised NENs of the small intestine in progress during the SSA treatment, with good expression of somatostatin receptors, the first-line treatment should be radio-isotope therapy, while targeted therapies, such as everolimus, should be considered afterwards. When the above therapies are exhausted, in certain cases chemotherapy may be considered

    Analysis of the background of the Jena <sup>14</sup>C-AMS facility

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    The background of the Jena 14C-AMS facility (accelerator mass spectrometry) was analyzed with respect to nuclide, charge state, and energy on the high-energy side. This was performed by ion optical considerations, measurements of the total energy with a PIN diode, measurements of two-dimensional energy loss-residual energy spectra (DE, ERes) with an ionization chamber, and energy loss calculations

    Data analysis at the Jena <sup>14</sup>C laboratory

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    The Jena Analysis Code (JAC) was developed at the Jena radiocarbon laboratory for the analysis of all 14C accelerator mass spectrometry (AMS) data measured there. The fundamental principles and algorithms of JAC are presented here, along with the equally important checking procedures. JAC places emphasis on the uncertainty due to background subtraction and other contributions to the statistical uncertainty of 14C event

    Accelerator mass spectroscopy of radiocarbon

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    Use of pilot beams in accelerator mass spectrometry

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    Improvements of the Jena AMS system

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    A new slit stabilization circuit and a modified generator drive were installed on an AMS system based on a 3 MV Tandetron (TM), produced by High Voltage Engineering Europa (HVEE). Furthermore our test procedure used at the Jena AMS system for the rectifiers of the Cockroft-Walton generator is presented. (C) 2009 Published by Elsevier B.V
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