423 research outputs found

    Transmembrane segment proteases

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    Summary: Transmembrane segment proteases comprise a novel class of proteases that cleave substrates within hydrophobic membrane-spanning segments. They cleave in parts of proteins that upon first glance should be protected by the hydrophobic environment of the lipid bilayer. At present, no such protease has been isolated and biochemically characterized. They are defined according to the appearance of the respective cleavage products. All trans-membrane segment proteases seem to participate in a regulated two-step proteolytic process that plays a central role in cellular regulation or is part of a protein degradation pathwa

    Protein insertion into the membrane of the endoplasmic reticulum: The architecture of the translocation site

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    In mammalian cells, most membrane proteins are inserted cotranslationally into the membrane of the endoplasmic reticulum (ER), and secretory proteins are translocated across this membrane (for review, see Rapoport 1992). These processes are initiated in the cytoplasm by binding of the signal sequence of the na-scent polypeptide chain to the signal recognition parti-cle (SRP) (Walter and Blobel 1981). The resulting ribosome nascent chain SRP complex is then targeted to the ER membrane by an interaction with the mem-brane-bound SRP receptor (docking protein) (Gilmore et al. 1982; Meyer et al. 1982). At the membrane, the signal sequence is released from SRP in a GTP-requiring step, and the nascent polypeptide is trans-ferred into the ER translocation site (Connolly an

    Eltern von Kindern mit Zerebralparese : ein Einblick in Erfahrungen und Lebensqualität

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    Darstellung des Themas: Die Diagnose Zerebralparese ist die häufigste körperliche Behinderung im frühen Kindesalter. Diese Behinderung hat einen Einfluss auf die Eltern und deren Lebensqualität. Ziel: Das Ziel der Bachelorarbeit ist es, die Erfahrungen von Eltern mit einem Kind mit Zerebralparese aufzuzeigen und welche Bereiche der Lebensqualität davon beeinflusst werden. Die Fragestellung lautet wie folgt: Welche Erfahrungen machen Eltern mit einem Kind mit Zerebralparese und was hat dies für einen Einfluss auf ihre Lebensqualität? Methode: Anhand einer systematischen Literaturrecherche in verschiedenen Datenbanken werden vier Hauptstudien zur Beantwortung der Fragestellung ausgewählt. Diese Hauptstudien werden analysiert und kritisch gewürdigt. Die Ergebnisse werden im Modell der Lebensqualität von Felce & Perry (1995) zugeordnet. Relevante Ergebnisse: Es werden verschiedene Erfahrungen der Eltern aufgezeigt. Die Lebensqualität kann dadurch in allen Bereichen beeinflusst sein. Mangelnde Informationen und Unterstützung, wenig Zeit und viel Stress, sowie Arbeit werden am häufigsten benannt. Schlussfolgerung: Diese Bachelorarbeit zeigt auf, dass die Diagnose Zerebralparese auch einen Einfluss auf die Eltern hat. Deshalb ist es wichtig, dass Eltern den Zugang zu Ergotherapie bekommen, um ihre Lebensqualität zu erhalten oder zu steigern

    High Performance Liquid Chromatography (HPLC) for Ampicillin and Cefuroxime

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    Appropriate levels of an active pharmaceutical ingredient (API) in medicines must be present in a medical product for the patient to receive therapeutic value. High performance liquid chromatography (HPLC) was used to develop a methodology to test for the API in Ampicillin and Cefuroxime drugs. Following the regulations of the Distributed Pharmaceutical Analysis Lab (DPAL) out of Notre Dame system sustainability requirements linearity, precision, accuracy/range, spike/degraded spike, limit of detection /quantitation, tailing factor, and number of theoretical plates were experimentally determined to meet the excepted standards

    Intramembrane-cleaving aspartic proteases and disease: presenilins, signal peptide peptidase and their homologs

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    Recent studies demonstrate that presenilins (PSs) and signal peptide peptidase (SPP) are members of a novel protease family of integral membrane proteins that may utilize a catalytic mechanism similar to classic aspartic proteases such as pepsin, renin and cathepsin D. The defining features of the PSs and SPP are their ability to cleave substrate polypeptides within a transmembrane region, the presence of two active site aspartate residues in adjacent membrane-spanning regions and a conserved PAL motif near their COOH-terminus. PSs appear to be the catalytic subunit of multiprotein complexes that possess γ-secretase activity. Because this activity generates the amyloid β peptide (Aβ) deposited in the brain of patients with Alzheimer's disease (AD), PSs are considered therapeutic targets in AD. In contrast to PSs that are not active unless part of a larger complex, SPP does not appear to require protein co-factors. Because of its requirement for hepatitis C virus maturation and a possible immune modulatory role, SPP is also considered a potential therapeutic target. Four additional PS/SPP homologs have been identified in humans; yet, their functions have not been elucidated. Herein, we will review the recent advances in our understanding of the PS/SPP family of proteases as well as discuss aspects of intramembrane cleavage that are not well understoo

    Percy Julian and the Rise in Inclusive Pedagogy in the Department of Chemistry and Biochemistry

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    As a research fellow at DePauw, Dr. Percy L. Julian included undergratuate students in his research to synthesize physostigmine. Building on that legacy, the Department of Chemistry and Biochemistry continues a longstanding history of supporting undergraduate research. Recongnizing tht there is inequity in who participates in research, our department recently initiated an application process open to all students in our courses to equalize the way in which stuents learn about and get started in research. Students in our structure and propterties of organiz molecules course view and reflect on the Forgotten Genius documentary and the recently awarded HHMU Inclusive Excellence Initiative grant has provided many faculty members development opportunities in inclusive pedagogy. In May, Dr. Julian was appointed posthumously to the DePauw University faculty. The Department of Chemistry and Biochemistry celebrates this appointment and continues to work toward creating a positive and inviting atmosphere for all students at DePauw

    Method Development for the Analysis of Pharmaceuticals Using High Performance Liquid Chromatography

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    Since 2013, there have been 1500 reports of counterfeit drugs to WHO, especially from African, American, and European regions 1. Tackling the problem of poor drug quality, the Distributed Pharmaceutical Analysis Lab (DPAL) provides a quality analysis to quantify active pharmaceutical ingredient contents with a goal to trigger a report to the MRA or WHO2. With the support of DPAL, we would like to perform a series of chromatography experiments using the HPLC in order to identify and quantify the active pharmaceutical ingredients (API) of Amoxicillin and Ciprofloxacin

    The Protein-Conducting Channel in the Membrane of the Endoplasmic Reticulum Is Open Laterally toward the Lipid Bilayer

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    Lipids and proteins were found to contact a nascent type II membrane protein, as well as a nascent secretory protein, during their insertion into the membrane of the endoplasmic reticulum. This suggests that the protein-conducting channel is open laterally toward the lipid bilayer during an early stage of protein insertion. Contact to lipids was confined to the hydrophobic core region of the respective signal or signal anchor sequence. Thus, the nascent polypeptide is positioned in the translocation complex such that the signal or signal anchor sequence faces the lipid bilayer, whereas the hydrophilic, translocating portion is in proteinaceous environment

    Signal Sequence Processing in Rough Microsomes

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    Secretory proteins are synthesized with a signal sequence that is usually cleaved from the nascent protein during the translocation of the polypeptide chain into the lumen of the endoplasmic reticulum. To determine the fate of a cleaved signal sequence, we used a synchronized in vitro translocation system. We found that the cleaved signal peptide of preprolactin is further processed close to its COOH terminus. The resulting fragment accumulated in the microsomal fraction and with time was released into the cytosol. Signal sequence cleavage and processing could be reproduced with reconstituted vesicles containing Sec61, signal recognition particle receptor, and signal peptidase complex
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