16,850 research outputs found
The molecular machinery for maturation of primary mtDNA transcripts
No full textAbstract Human mitochondria harbour a circular, polyploid genome (mtDNA) encoding 11 messenger RNAs (mRNAs), two ribosomal RNAs (rRNAs) and 22 transfer RNAs (tRNAs). Mitochondrial transcription produces long, polycistronic transcripts that span almost the entire length of the genome, and hence contain all three types of RNAs. The primary transcripts then undergo a number of processing and maturation steps, which constitute key regulatory points of mitochondrial gene expression. The first step of mitochondrial RNA processing consists of the separation of primary transcripts into individual, functional RNA molecules and can occur by two distinct pathways. Both are carried out by dedicated molecular machineries that substantially differ from RNA processing enzymes found elsewhere. As a result, the underlying molecular mechanisms remain poorly understood. Over the last years, genetic, biochemical and structural studies have identified key players involved in both RNA processing pathways and provided the first insights into the underlying mechanisms. Here, we review our current understanding of RNA processing in mammalian mitochondria and provide an outlook on open questions in the field
Mitochondrial dysfunction in ageing and degenerative disease
No full textThe cytoplasm of eukaryotic cells contains a dynamic network of double-membraned organelles, called mitochondria, which perform the process of oxidative phosphorylation (OXPHOS) that provides cellular energy in the form of ATP. The respiratory chain creates an electrochemical gradient across the inner mitochondrial membrane, which drives ATP synthesis by the ATP synthase. Mitochondria are indispensable for normal cell function and survival, and dysfunction of the OXPHOS system can lead to a variety of disease syndromes, collectively termed mitochondrial encephalomyopathies. Mitochondrial dysfunction has also been proposed to be involved in age-associated diseases such as diabetes mellitus, heart disease and neurodegeneration, as well as in the ageing process itself. Tissues with high metabolism seem to be particularly vulnerable to mitochondrial dysfunction and myopathy is one of the common phenotypes in mitochondrial disorders. However, the pathophysiological mechanisms linking respiratory chain deficiency to the various phenotypic manifestations are poorly understood. We therefore generated a mouse model for mitochondrial myopathy by tissue-specific disruption of the nuclear gene encoding mitochondrial transcription factor A (TFAM). These myopathy mice develop a progressive respiratory chain dysfunction in skeletal muscle with typical morphological changes consistent with mitochondrial myopathy. Surprisingly the overall mitochondrial ATP production rate was close to normal in the knockout muscles, likely due to the compensatory increase of mitochondrial mass in the affected muscles. Thus, other factors besides ATP deficiency are likely of importance in mitochondrial myopathy. There is a large number of correlative studies suggesting that mitochondrial dysfunction in skeletal muscle is causing the peripheral insulin resistance observed in patients with diabetes mellitus type 2 (DM2). Unexpectedly, the myopathy mice exhibited normal insulin sensitivity and increased glucose uptake in skeletal muscle, suggesting that reduced respiratory chain function in peripheral tissues may be protective against DM2. The mitochondrial theory of aging proposes that oxidative damage to mitochondrial DNA (mtDNA) leads to mutations and impaired respiratory chain function, which in turn, increases reactive oxygen species (ROS) production. ROS have been suggested to induce oxidative damage to various molecules of the cell and thereby cause the progressive decline seen in ageing. We generated mice expressing a proof-reading-deficient version of the mtDNA polymerase gamma. These mtDNA mutator mice accumulated mtDNA mutations at an increased rate and developed a progressive respiratory chain deficiency. They also developed premature ageing phenotypes and exhibited a reduced lifespan, supporting the suggestion of a causative link between mitochondrial dysfunction and ageing. However, we found no differences in ROS production, no increased expression of ROS scavenging enzymes, and no or minor changes in levels of oxidative damage in cell lines and tissues from the mtDNA mutator mice. We instead propose that the accumulation of mtDNA mutations beyond a critical threshold leads to bioenergetic failure and loss of vital cells. This cell loss caused by respiratory chain dysfunction may lead to reduced organ function and eventually organ failure, giving rise to age-associated disease and important ageing phenotypes.List of scientific papersI. Wredenberg A, Wibom R, Wilhelmsson H, Graff C, Wiener HH, Burden SJ, Oldfors A, Westerblad H, Larsson NG (2002). "Increased mitochondrial mass in mitochondrial myopathy mice." Proc Natl Acad Sci U S A 99(23): 15066-71. Epub 2002 Nov 4 https://pubmed.ncbi.nlm.nih.gov/12417746II. Wredenberg A, Freyer C, Sandström ME, Katz A, Wibom R, Westerblad H, Larsson NG (2006). "Respiratory chain dysfunction in skeletal muscle does not cause insulin resistance." Biochem Biophys Res Commun 350(1): 202-7. Epub 2006 Sep 18 https://pubmed.ncbi.nlm.nih.gov/16996481III. Trifunovic A, Wredenberg A, Falkenberg M, Spelbrink JN, Rovio AT, Bruder CE, Bohlooly-Y M, Gidlöf S, Oldfors A, Wibom R, Törnell J, Jacobs HT, Larsson NG (2004). "Premature ageing in mice expressing defective mitochondrial DNA polymerase." Nature 429(6990): 417-23 https://pubmed.ncbi.nlm.nih.gov/15164064IV. Trifunovic A, Hansson A, Wredenberg A, Rovio AT, Dufour E, Khvorostov I, Spelbrink JN, Wibom R, Jacobs HT, Larsson NG (2005). "Somatic mtDNA mutations cause aging phenotypes without affecting reactive oxygen species production." Proc Natl Acad Sci U S A 102(50): 17993-8. Epub 2005 Dec 6 https://pubmed.ncbi.nlm.nih.gov/16332961</p
An Article About Albertus C. Van Raalte, Author Unknown, Except for Parts Taken from an Article by Anna C. Post
No full textAn article about Albertus C. Van Raalte, author unknown, except for parts taken from an article by Anna C. Post. The author knew first generation persons in the Holland settlement and therefore, the article has some value.https://digitalcommons.hope.edu/vrp_1890s/1012/thumbnail.jp
Richardson, Barbauld, and the construction of an early modern fan club
No full textMPhilMuch has been written about the life and long works of the eighteenth century epistolary novelist, Samuel Richardson, but the prospect of his position as the first celebrity novelist – responsible for courting his own fame as well as initiating his own fan club – has largely been ignored. The body of manuscripts housed at the National Art Library in the Victoria and Albert Museum in London provides the modern scholar with evidence of the skeletal beginnings of an early fan club. This thesis aims to show how these manuscripts were turned into a saleable commodity by the publisher and entrepreneur Richard Phillips, while under the guiding hand of another, slightly later, literary celebrity, Anna Laetitia Barbauld. In order to restore Richardson’s reputation amongst a new nineteenth century audience, Barbauld was required to construct her own idea of him as an eighteenth century celebrity author, and in doing so the insecurities of a self-professed, apparently diffident man, are revealed. Barbauld’s capacious, but heavily edited selection of letters is analyzed in this thesis, providing ample evidence that Richardson’s correspondents were more than just eager letter writers. By using Barbauld’s biography of Richardson this thesis aims to show how she manipulates the genre of life writing in her construction of him.
This thesis offers an alternative reading of how the Richardson manuscripts are viewed, redefining them as not simply a collection of letters, but as a collective entity, deliberately selected and archived as evidence of an early modern fan club, and its celebrity managing director
Selection of work by Anna Gerber
No full textVarious journals and magazines Anna Gerber has contributed to. Anna Gerber is a graphic designer and writer based in London.
She is the author and designer of All Messed Up: Unpredictable Graphics (Laurence King, 2004) and co-editor and co-designer
of Influences: A Lexicon of Contemporary Graphic Design (Die Gestalten Verlag, 2006) with Anja Lutz. She writes regularily for magazines such as Print, Eye, Creative Review, Varoom and Idea Magazine and her work has also been published in shift!, dot dot dot and +rosebud.
She teaches at the London College of Communication on the BA Graphic Design and MA Design Writing Criticism programmes. She has also held workshops and lectures across the U.K. (including Tate Modern and the V&A Museum), as well as in India, the U.S., Australia and Malaysia.
Anna Gerber is currently engaged in research and developing projects relating to sustainability and how it applies to graphic
design as well as exploring contemporary graphic design in India
Author and Lecturer Anna Bird Stewart will Speak at the University of Dayton
No full textNews release announcing the visitation and speech of author and lecturer Anna Bird Stewart to the University of Dayton
Operatori del processo edilizio
No full textLemma che descrive i diversi attori del processo edilizio, con particolare attenzione al processo edilizio pubblico - ISBN:ISSN 2284-00IX - visibile su: Wikitecnica.com/author/giovenale-anna-mari
Processo edilizio
No full textLemma che descrive e reinterpreta, rispetto alla letteratura scientifica, il concetto di processo edilizio, definendone l'evoluzione nel tempo ISBN:ISSN 2284-00IX - Visibile su: wikitecnica.com/author/giovenale-anna-mari
Metaprogettazione
No full textLemma che descrive il concetto di metaprogettazione e pone in risalto l'importanza nell'architettura contemporanea dello strumento "metaprogetto" - ISBN:ISSN 2284-00IX - visibile su: Wikitecnica.com/author/giovenale-anna-mari
- …
