Det räcker inte att laga bron över livsfloden, man måste även lära barnen att simma! : En kvalitativ studie för att få en djupare förståelse om socialarbetare upplever att barn som deltar i Trappan-insatsen får en känsla av sammanhang?

The aim of this qualitative study was to get a deeper understanding of social workers experience that children who participate in the Trappan-insatsen get a sense of coherence. To achieve an empirical material social workers who perform Trappan-samtal have been interviewed. The study shows that it is important that children get help and support to talk about the trauma they experienced. The support of the narrative, however, differ depending on the child's age, it is important to have a flexible approach as a Trappan-user. It appears that it is essential that parents give their consent to the children so they can talk about the violence. It also emerges that information to the children is an important part of understanding the process. The study shows that social workers feel that the children participating in the staircase mission get a sense of coherence.

Innebörden av att kunna 'house hop' rörelsekunnande som kroppslig förståelse

I den här artikeln presenterar jag en del av mitt avhandlingsprojekt (Nyberg, 2014) där syftet var att undersöka vad rörelseförmåga kan innebära i termer av vad ’man kan’ när man kan röra sig på olika sätt. Syftet med artikeln är att visa hur en fenomenografisk analys av elevers olika sätt att röra sig kan bidra till hur kunskapen om rörelsekunnande kan utvecklas. Den fenomenografiska analysen innebär att, i det här fallet, systematiskt undersöka hur elevers ’kroppsliga förståelse’ av en rörelse uttrycks genom olika sätt att röra sig. Resultatet av analysen visar även vilka aspekter av rörelsen som är möjliga att urskilja och erfara, vilket bidrar till en förståelse av vad det innebär att kunna en rörelse. I artikeln diskuterar jag hur en fenomenografisk ansats kan underlätta för lärare i idrott och hälsa att bortse från sina egna underförstådda antaganden om vad det innebär att behärska en rörelse och hur undervisningen i idrott och hälsa kan bidra till utveckling av rörelseförmåga.

Den grafiska identitetens betydelse i småföretagarens värld : En undersökning för ökad förståelse om den grafiska identitetens betydelse för småföretagare

För att skapa ett bra varumärke krävs en tydlig grafisk identitet. Syftet med föreliggande rapport var att undersöka med semi-strukturerade djupintervjuer hur småföretagare (1-10 personer) ser på och arbetar med sin grafiska identitet. Studien avsåg även med en enkätundersökning förstå konsumenters attityder mot företag som har eller saknar en tydlig grafisk identitet. Resultatet av intervjuerna visade att företagarna anser att deras grafiska identitet inte är den viktigaste resursen. Det viktigaste är företagets rykte och kunders omdömen. Företagarna nöjer sig med en signatur och en hemsida, utvecklandet av den grafiska identiteten har inte hög prioritet. Av enkätundersökningen framgick det att företag som har en konsekvent grafisk identitet har större sannolikhet att bli anlitade än de som inte arbetar konsekvent med detta. Resultatet visar även att de som arbetar konsekvent med sin grafiska identitet uppfattas som mer seriösa än de som inte är konsekventa i detsamma.

Att öppna ögonen : En kvalitativ studie om hur fyra personer som lever i en internationell parrelation har utvecklat sin kulturella förståelse

Dagens globala värld har öppnat upp möjligheter som gjort det lättare för människor från olika delar av världen att träffas. En av anledningarna till att människor invandrar till Sverige är kärlek. Dagens allt mer globaliserade värld gör att demografin i Sverige ändras med en ökning av den etniska och kulturella mångfalden. Detta ställer krav på våra myndigheter om att socialarbetare ska ha kulturell förståelse. Men hur utvecklar man denna kulturella förståelse? Denna studie riktar fokus till svenskfödda som lever i en internationell parrelation för att undersöka hur de genom mötet med sin partner och sin omvärld har utvecklat sin kulturella förståelse. Kvalitativa halvstrukturerade intervjuer har genomförts med fyra svenskfödda män och kvinnor som lever i en internationell parrelation med partners från Asien. Resultatet visar hur de tankeprocesser som intervjupersonerna gått igenom för att utveckla sin kulturella förståelse har sett ut. Intervjupersonerna har olika erfarenheter av möten, av diskriminering och av fördomar, vilket har gjort att de i olika grad har utvecklat sin kulturella förståelse. En grundläggande faktor till hur de hade utvecklat sin kulturella förståelse var intresset för andra kulturer och att resa. Sammantaget skapar resultatet en bild av hur intervjupersonerna har utvecklat sin kulturella förståelse genom hur deras tankeprocesser sett ut före och efter de nya erfarenheterna.

Räkna med bråk : En litteraturstudie om viktiga aspekter för att elever i årskurs 4-6 skall utveckla förståelse för bråk

Syftet med denna systematiska litteraturstudie är att få kunskap om viktiga aspekter för att elever i årskurs 4-6 skall utveckla förståelse för bråk. Utifrån syftet formulerades följande frågeställning: Vilka undervisningsmetoder kan underlätta elevers förståelse av bråk. Databaserna LIBRIS, Teacher´s reference center och ERIC användes för söka efter relevanta vetenskapligt granskade artiklar. Resultatet visar att många elever tycker att det är svårt med bråk och att de inte förstår syftet med att lära sig bråk i skolan. Vidare visar resultatet att om lärarna åskådliggör bråk för eleverna på många olika sätt i undervisningen ökar elevernas förståelse för bråk. Studien visar även att användning av konkreta material såsom modeller och bilder gör det enklare för elever att bland annat förstå beräkningar med bråk. Att lärarna samtalar med eleverna om bråk är också en viktig aspekt för att öka elevers förståelse för bråk.

Räkna med bråk : En litteraturstudie om viktiga aspekter för att elever i årskurs 4-6 skall utveckla förståelse för bråk

Syftet med denna systematiska litteraturstudie är att få kunskap om viktiga aspekter för att elever i årskurs 4-6 skall utveckla förståelse för bråk. Utifrån syftet formulerades följande frågeställning: Vilka undervisningsmetoder kan underlätta elevers förståelse av bråk. Databaserna LIBRIS, Teacher´s reference center och ERIC användes för söka efter relevanta vetenskapligt granskade artiklar. Resultatet visar att många elever tycker att det är svårt med bråk och att de inte förstår syftet med att lära sig bråk i skolan. Vidare visar resultatet att om lärarna åskådliggör bråk för eleverna på många olika sätt i undervisningen ökar elevernas förståelse för bråk. Studien visar även att användning av konkreta material såsom modeller och bilder gör det enklare för elever att bland annat förstå beräkningar med bråk. Att lärarna samtalar med eleverna om bråk är också en viktig aspekt för att öka elevers förståelse för bråk.

Samverkan Trafikförsörjningsprogram

Med stöd i Förordning (2010:185) med instruktion för Trafikverket 2§ punkt 12 utgår vi ifrån att Trafikverket ska vara ett stöd i arbetet att utveckla ett effektivt och hållbart transportsystem utifrån ett trafikslagsövergripande synsätt i nära dialog med RKM för att skapa en långsiktig infrastrukturplanering, i det att Trafikverket ska stödja arbetet med att ta fram trafikförsörjningsprogrammen (TFP). Föreliggande rapport fokuserar på Trafikverkets roll i samverkan med de Regionala kollektivtrafikmyndigheterna.   För att närmare studera, utveckla och tydliggöra ramarna för trafikverkets stöd och ansvar för kollektivtrafikfrågor, använder vi i denna rapport en förståelseorienterad metod som bygger på att förstå och tolka den kontext som Trafikverket agerar i. Föreliggande text är en inventering av olika utformningar av kollektivtrafikmyndigheter i landet samt Trafikverkets olika Regionkontor. Fokus är i huvudsak riktad mot hur de är organiserade och hur de arbetar för att hantera olika frågor. Syftet är att med denna samlade kunskap se hur samverkansutmaningar har hanterats i olika lösningar och på så sätt öppna upp för ett ömsesidigt lärande och stärka förutsättningarna för samverkan.   Föreliggande studie visar att samverkan mellan kollektivtrafikmyndigheterna och Trafikverket inte är statisk utan en del i en dynamisk process som baseras på kunskap, personliga relationer och förtroende. Genom att få kunskap om den andra organisationen och skapa sig en förståelse om hur man kan samverka för att uppnå bättre effekter av sina satsningar skapas en grund för samarbete. Det är sedan genom personliga relationer som ett förtroende skapas mellan parterna och som fördjupar samarbetet. Ett samarbete likt den mellan Trafikverket och Kollektivtrafikmyndigheterna som varken är bundet till hierarkiska eller beroendemässiga parametrar kräver förtroende och relationella band mellan parterna för att fungera. Den kunskapsintegration som uppstår mellan organisationerna när man klarar av att länka och integrera människors kunskaper och färdigheter genom sina personliga relationer och organisatoriska processer bidrar till ökad organisatorisk kapacitet för respektive organisation. Samspelet mellan organisationerna bidrar till att respektive organisation på ett bättre sätt kan anpassa sig till föränderliga samhällsbehov och skapa interna strukturer som följer de förändrade behov som finns i samhället.

Modernismens förespråkare : Gösta Stenman och hans konstsalong

This dissertation, based on material from Stenman s vast private archive, examines the role played by Swedish-speaking Finnish art dealer Gösta Stenman (1888-1947) and his art gallery, Stenmans Konstsalong, in the Finnish and Swedish art worlds from 1911 to 1947. This archive is examined here for the first time. The analytical framework used for this empirical study derives from Pierre Bourdieu s sociological theories. An art-sociological approach allows for the inclusion of more mechanisms at work in the art world than are typically embraced in such inquiries. This approach provides a fuller understanding of how Stenman attained his standing and central role in the art world in Finland as well as Sweden; enabling us to appreciate how he came to occupy such a prominent position in current art historical writing. All of these issues constitute new areas of research. Taking his cues from the contemporary art world of Paris, Stenman became the year 1914 a modern art dealer like no other in the Nordic countries. This dissertation represents the first academic investigation into his operations, strategies, and objectives, offering insight into not only the art dealer himself but also the functioning of the art market one of the most vital aspects of the art world. A by-product of this work, is that the modern art market in Finland is portrayed, including essential issues related to its growth and development as well as how it altered the conditions under which art could be produced, exhibited and promoted and what this entailed for the art world at large, artists and patrons alike. This first systematic analysis of the operations of Stenman s Konstsalong offers greater understanding of the art worlds of Sweden and Finland in the early twentieth century. The work also looks at how an agent of the art market could move between the fields of art in Sweden and Finland. The manner in which Stenman promoted individual artists, including his relationships with Tyko Sallinen, Helene Schjerfbeck, Juho Mäkelä, Jalmari Ruokokoski, Siri Derkert, Esther Kjerner, Eva Bagge, and many others, also falls within this purview. Stenman s contract with Sallinen from 1913 stands out as a new phenomenon in Finnish art promotion, whereby an artistic career became established via a far-sighted, strategic promotional program. The case study of Stenman s promotion of Schjerfbeck in Sweden provides evidence of the increasingly advanced nature of Stenman s strategies. The title of the dissertation, The Promoter of Modernism, attempts to convey that Stenman was the consummate modernist, modern in his thoughts, his actions, and his approach to art. Keywords: Gösta Stenman, Stenmans konstsalong, Stenmans dotter, art market, modernism, collecting, Novembergruppen, Helene Schjerfbeck, Tyko Sallinen, Juho Mäkelä, Jalmari Ruokokoski, Wäinö Aaltonen, Siri Derkert, Åke Göransson, Esther Kjerner, Eva Bagge.

A Literary Turn : Rethinking the Roles of Generalization and Theory in Anglo-American Moral Philosophy

This work investigates the role of narrative literature in late-20th century and contemporary Anglo-American moral philosophy. It aims to show the trend of reading narrative literature for purposes of moral philosophy from the 1970 s and early 80 s to the present day as a part of a larger movement in Anglo-American moral philosophy, and to present a view of its significance for moral philosophy overall. Chapter 1 provides some preliminaries concerning the view of narrative literature which my discussion builds on. In chapter 2 I give an outline of how narrative literature is considered in contemporary Anglo-American moral philosophy, and connect this use to the broad trend of neo-Aristotelian ethics in this context. In chapter 3 I connect the use of literature to the idea of the non-generalizability of moral perception and judgment, which is central to the neo-Aristotelian trend, as well as to a range of moral particularisms and anti-theoretical positions of late 20th century and contemporary ethics. The joint task of chapters 2 and 3 is to situate the trend of reading narrative literature for the purposes of moral philosophy in the present context of moral philosophy. In the following two chapters, 4 and 5, I move on from the particularizing power of narrative literature, which is emphasized by neo-Aristotelians and particularists alike, to a broader under-standing of the intellectual potential of narrative literature. In chapter 4 I argue that narrative literature has its own forms of generalization which are enriching for our understanding of the workings of ethical generalizations in philosophy. In chapter 5 I discuss Iris Murdoch s and Martha Nussbaum s respective ways of combining ethical generality and particularity in a philosophical framework where both systematic moral theory and narrative literature are taken seriously. In chapter 6 I analyse the controversy between contemporary anti-theoretical conceptions of ethics and Nussbaum s refutation of these. I present my suggestion for how the significance of the ethics/literature discussion for moral philosophy can be understood if one wants to overcome the limitations of both Nussbaum s theory-centred, equilibrium-seeking perspective, and the anti-theorists repudiation of theory. I call my position the inclusive approach .

Poetics of Subjectivity : Existence and Expressivity in Simone de Beauvoir's Philosophy

In the last thirty years, primarily feminist scholars have drawn attention to and re-evaluated the philosophy of Simone de Beauvoir (1908 1986). Her philosophical practice has been described as non-systematic, and her literary writing has been viewed as part of her non-systematic mode of philosophising. This dissertation radically deepens the question concerning Beauvoir s philosophical motivations for turning to literature as a mode to express subjectivity. It explicates the central concepts of Beauvoir s philosophy of existence, which are subjectivity, ambiguity, paradox and temporality, and their background in the modern traditions of existential philosophy and phenomenology. It also clarifies Beauvoir s main reason to turn to literature in order to express subjectivity as both singular and universal: as a specific mode of communication, literature is able to make the universality of existence manifest in the concrete, singular and temporal texture of life. In addition, the thesis gives examples of how Beauvoir s literary works contribute to an understanding of the complexity of subjectivity. I use the expression poetics of subjectivity to refer to the systematic relation between Beauvoir s existential and phenomenological notion of subjectivity and her literary works, and to her articulations of a creative mode of using language, especially in the novel. The thesis is divided into five chapters, of which the first three investigate Beauvoir s philosophy of existence at the intersection of the modern traditions of thought that began with René Descartes and Søren Kierkegaard s intuitions about subjectivity. Chapter 1 interprets Beauvoir s notion of ambiguity, as compared to paradox, and argues that both determine her notion of existence. Chapters 2 and 3 investigate the phenomenological side of Beauvoir s philosophy through a study of her response to early French interpretations of transcendental subjectivity, especially in the works of Jean-Paul Sartre and Maurice Merleau-Ponty. My analysis shows that Edmund Husserl s distinction between different levels of subjective experience is central to Beauvoir s understanding of subjectivity and to the different ego concepts she uses. Chapter 4 is a study of Beauvoir s reflections on the expression of subjective thought, and, more specifically, her philosophical conceptions of the metaphysical novel and the autobiography as two modes of indirect communication. Chapter 5, finally, compares two modes of investigating concrete subjectivity; Beauvoir s conceptual study of femininity in Le deuxième sexe and her literary expression of subjectivity in the novel L Invitée. My analysis reveals and explicates Beauvoir s original contribution to a comprehensive understanding of the becoming and paradox of human existence: the fundamental insight that these phenomena are sexed, historically as well as imaginatively.

Om naturens förvandlingar : Vetenskap, kunskap och frihet i Rudolf Steiners tidiga tänkande. Idéhistoriska perspektiv på Waldorfpedagogiken

TRANSFORMATIONS OF NATURE Science, Knowledge and Freedom in the Early Thinking of Rudolf Steiner. Perspectives on Waldorf Education in the light of the History of Ideas Waldorf Education is based on the worldview that Rudolf Steiner (1861-1925) developed to a wide-ranging anthroposophical movement in the first decades of the 20th century. This thesis takes as its departure the early thinking of Rudolf Steiner that precedes anthroposophy, and its main purpose is to uncover the tradition of ideas represented in Steiner´s early life and which, in different ways, have emerged in the practice of Waldorf Education. Through systematic analysis I attempt to bring to light different aspects of Steiner’s early thinking: his concept of science, his epistemological startingpoints and his philosophy of freedom. By departing from J. W. Goethe’s qualitative concept of science, Steiner strove in his early works to formulate a monistic worldview which appears to be closely related to the Romantic Movement and its philosophy of nature. Characteristic traits of his thinking are, on the one hand, a critique of a one-sided enlightenment and, on the other hand, an aspiration to see the world as a living organic unity. Human beings can, by developing our intuitive faculties, get a deeper understanding of the indissoluble relationship between man and nature. Against this background Steiner´s early thinking can be read as a special kind of romantic development narrative. Steiner’s early thinking also opens the way for romantic perspectives on Waldorf Education. It appears that many central aims and conceptions in Waldorf Education can be illuminated by the epistemological perspective upon which Steiner elaborated early in his life. An organic curriculum, phenomenological didactics and high ideal of freedom can be considered seen as educational applications of conceptions that played an important role in Goethe and his age. Thus, Waldorf Education provides in our contemporary society an exceptional set of educational values: a holistic education with romantic undertones.

A quantum chemical investigation of the metal centres in cytochrome c oxidase

Quantum effects are often of key importance for the function of biological systems at molecular level. Cellular respiration, where energy is extracted from the reduction of molecular oxygen to water, is no exception. In this work, the end station of the electron transport chain in mitochondria, cytochrome c oxidase, is investigated using quantum chemical methodology. Cytochrome c oxidase contains two haems, haem a and haem a3. Haem a3, with its copper companion, CuB, is involved in the final reduction of oxygen into water. This binuclear centre receives the necessary electrons from haem a. Haem a, in turn, receives its electrons from a copper ion pair in the vicinity, called CuA. Density functional theory (DFT) has been used to clarify the charge and spin distributions of haem a, as well as changes in these during redox activity. Upon reduction, the added electron is shown to be evenly distributed over the entire haem structure, important for the accommodation of the prosthetic group within the protein. At the same time, the spin distribution of the open-shell oxidised state is more localised to the central iron. The exact spin density distribution has been disputed in the literature, however, different experiments indicating different distributions of the unpaired electron. The apparent contradiction is shown to be due to the false assumption of a unit amount of unpaired electron density; in fact, the oxidised state has about 1.3 unpaired electrons. The validity of the DFT results have been corroborated by wave function based coupled cluster calculations. Point charges, for use in classical force field based simulations, have been parameterised for the four metal centres, using a newly developed methodology. In the procedure, the subsystem for which point charges are to be obtained, is surrounded by an outer region, with the purpose of stabilising the inner region, both electronically and structurally. Finally, the possibility of vibrational promotion of the electron transfer step between haem a and a3 has been investigated. Calculating the full vibrational spectra, at DFT level, of a combined model of the two haems, revealed several normal modes that do shift electron density between the haems. The magnitude of the shift was found to be moderate, at most. The proposed mechanism could have an assisting role in the electron transfer, which still seems to be dominated by electron tunnelling.

Understanding the chemistry of atmospheric aerosol particle formation via observations of physical properties

It is widely accepted that the global climate is heating up due to human activities, such as burning of fossil fuels. Therefore we find ourselves forced to make decisions on what measures, if any, need to be taken to decrease our warming effect on the planet before any irrevocable damage occurs. Research is being conducted in a variety of fields to better understand all relevant processes governing Earth s climate, and to assess the relative roles of anthropogenic and biogenic emissions into the atmosphere. One of the least well quantified problems is the impact of small aerosol particles (both of anthropogenic and biogenic origin) on climate, through reflecting solar radiation and their ability to act as condensation nuclei for cloud droplets. In this thesis, the compounds driving the biogenic formation of new particles in the atmosphere have been examined through detailed measurements. As directly measuring the composition of these newly formed particles is extremely difficult, the approach was to indirectly study their different characteristics by measuring the hygroscopicity (water uptake) and volatility (evaporation) of particles between 10 and 50 nm. To study the first steps of the formation process in the sub-3 nm range, the nucleation of gaseous precursors to small clusters, the chemical composition of ambient naturally charged ions were measured. The ion measurements were performed with a newly developed mass spectrometer, which was first characterized in the laboratory before being deployed at a boreal forest measurement site. It was also successfully compared to similar, low-resolution instruments. The ambient measurements showed that sulfuric acid clusters dominate the negative ion spectrum during new particle formation events. Sulfuric acid/ammonia clusters were detected in ambient air for the first time in this work. Even though sulfuric acid is believed to be the most important gas phase precursor driving the initial cluster formation, measurements of the hygroscopicity and volatility of growing 10-50 nm particles in Hyytiälä showed an increasing role of organic vapors of a variety of oxidation levels. This work has provided additional insights into the compounds participating both in the initial formation and subsequent growth of atmospheric new aerosol particles. It will hopefully prove an important step in understanding atmospheric gas-to-particle conversion, which, by influencing cloud properties, can have important climate impacts. All available knowledge needs to be constantly updated, summarized, and brought to the attention of our decision-makers. Only by increasing our understanding of all the relevant processes can we build reliable models to predict the long-term effects of decisions made today.

MECHANISMS AND EFFECTS OF MITOCHONDRIAL DNA INSTABILITY AND COPY NUMBER MANIPULATION

Defects in mitochondrial DNA (mtDNA) maintenance cause a range of human diseases, including autosomal dominant progressive external ophthalmoplegia (adPEO). This study aimed to clarify the molecular background of adPEO. We discovered that deoxynucleoside triphosphate (dNTP) metabolism plays a crucial in mtDNA maintenance and were thus prompted to search for therapeutic strategies based on the modulation of cellular dNTP pools or mtDNA copy number. Human mtDNA is a 16.6 kb circular molecule present in hundreds to thousands of copies per cell. mtDNA is compacted into nucleoprotein clusters called nucleoids. mtDNA maintenance diseases result from defects in nuclear encoded proteins that maintain the mtDNA. These syndromes typically afflict highly differentiated, post-mitotic tissues such as muscle and nerve, but virtually any organ can be affected. adPEO is a disease where mtDNA molecules with large-scale deletions accumulate in patients tissues, particularly in skeletal muscle. Mutations in five nuclear genes, encoding the proteins ANT1, Twinkle, POLG, POLG2 and OPA1, have previously been shown to cause adPEO. Here, we studied a large North American pedigree with adPEO, and identified a novel heterozygous mutation in the gene RRM2B, which encodes the p53R2 subunit of the enzyme ribonucleotide reductase (RNR). RNR is the rate-limiting enzyme in dNTP biosynthesis, and is required both for nuclear and mitochondrial DNA replication. The mutation results in the expression of a truncated form of p53R2, which is likely to compete with the wild-type allele. A change in enzyme function leads to defective mtDNA replication due to altered dNTP pools. Therefore, RRM2B is a novel adPEO disease gene. The importance of adequate dNTP pools and RNR function for mtDNA maintenance has been established in many organisms. In yeast, induction of RNR has previously been shown to increase mtDNA copy number, and to rescue the phenotype caused by mutations in the yeast mtDNA polymerase. To further study the role of RNR in mammalian mtDNA maintenance, we used mice that broadly overexpress the RNR subunits Rrm1, Rrm2 or p53R2. Active RNR is a heterotetramer consisting of two large subunits (Rrm1) and two small subunits (either Rrm2 or p53R2). We also created bitransgenic mice that overexpress Rrm1 together with either Rrm2 or p53R2. In contrast to the previous findings in yeast, bitransgenic RNR overexpression led to mtDNA depletion in mouse skeletal muscle, without mtDNA deletions or point mutations. The mtDNA depletion was associated with imbalanced dNTP pools. Furthermore, the mRNA expression levels of Rrm1 and p53R2 were found to correlate with mtDNA copy number in two independent mouse models, suggesting nuclear-mitochondrial cross talk with regard to mtDNA copy number. We conclude that tight regulation of RNR is needed to prevent harmful alterations in the dNTP pool balance, which can lead to disordered mtDNA maintenance. Increasing the copy number of wild-type mtDNA has been suggested as a strategy for treating PEO and other mitochondrial diseases. Only two proteins are known to cause a robust increase in mtDNA copy number when overexpressed in mice; the mitochondrial transcription factor A (TFAM), and the mitochondrial replicative helicase Twinkle. We studied the mechanisms by which Twinkle and TFAM elevate mtDNA levels, and showed that Twinkle specifically implements mtDNA synthesis. Furthermore, both Twinkle and TFAM were found to increase mtDNA content per nucleoid. Increased mtDNA content in mouse tissues correlated with an age-related accumulation of mtDNA deletions, depletion of mitochondrial transcripts, and progressive respiratory dysfunction. Simultaneous overexpression of Twinkle and TFAM led to a further increase in the mtDNA content of nucleoids, and aggravated the respiratory deficiency. These results suggested that high mtDNA levels have detrimental long-term effects in mice. These data have to be considered when developing and evaluating treatment strategies for elevating mtDNA copy number.