scholarly journals Cell and animal models of mtDNA biology: progress and prospects

2007 ◽  
Vol 292 (2) ◽  
pp. C658-C669 ◽  
Author(s):  
Shaharyar M. Khan ◽  
Rafal M. Smigrodzki ◽  
Russell H. Swerdlow
Keyword(s):  
Gene Therapy ◽  
Animal Models ◽  
Human Disease ◽  
Mitochondrial Genetics ◽  
Mtdna Mutation ◽  
Mtdna Mutations ◽  
The Past ◽  
The Future ◽  
Basic Biology ◽  
Over Time

The past two decades have witnessed an evolving understanding of the mitochondrial genome’s (mtDNA) role in basic biology and disease. From the recognition that mutations in mtDNA can be responsible for human disease to recent efforts showing that mtDNA mutations accumulate over time and may be responsible for some phenotypes of aging, the field of mitochondrial genetics has greatly benefited from the creation of cell and animal models of mtDNA mutation. In this review, we critically discuss the past two decades of efforts and insights gained from cell and animal models of mtDNA mutation. We attempt to reconcile the varied and at times contradictory findings by highlighting the various methodologies employed and using human mtDNA disease as a guide to better understanding of cell and animal mtDNA models. We end with a discussion of scientific and therapeutic challenges and prospects for the future of mtDNA transfection and gene therapy.

The Historyless Heathen and the Stagnating Pagan: History as Non-Native Category?

2018 ◽  
Vol 28 (1) ◽  
pp. 52-91 ◽  
Author(s):  
Kathryn Gin Lum
Keyword(s):  
Nineteenth Century ◽  
Core Component ◽  
Change Over Time ◽  
The Past ◽  
The Future ◽  
Religious Perspectives ◽  
Over Time

AbstractThis article asks whether and how J. Z. Smith's contention that religion is a “non-native category” might be applied to the discipline of history. It looks at how nineteenth-century Americans constructed their own understandings of “proper history”—authenticatable, didactic, and progressive—against the supposed historylessness of “heathen” Hawaiians and stagnation of “pagan” Chinese. “True” history, for these nineteenth-century historians, changed in the past and pointed to change in the future. The article asks historians to think about how they might be replicating some of the same assumptions about forward-moving history by focusing on change over time as a core component of historical narration. It urges historians to instead also incorporate the native historical imaginations of our subjects into our own methods, paying attention to when those imaginations are cyclical and reiterative as well as directional, and letting our subjects' assumptions about time and history, often shaped by religious perspectives, orient our own decisions about how to structure the stories we tell.

scholarly journals Anti-Memorials and the Art of Forgetting: Critical Reflections on a Memorial Design Practice

2008 ◽  
Vol 15 ◽  
Author(s):  
SueAnne Ware
Keyword(s):  
Human Activity ◽  
The Other ◽  
Complex Spectrum ◽  
Design Practice ◽  
Design Work ◽  
The Past ◽  
Heroin Overdose ◽  
The Future ◽  
Changes Over Time ◽  
Over Time

Andreas Huyssen writes, ‘Remembrance as a vital human activity shapes our links to the past, and the ways we remember define us in the present. As individuals and societies, we need the past to construct and to anchor our identities and to nurture a vision of the future.’ Memory is continually affected by a complex spectrum of states such as forgetting, denial, repression, trauma, recounting and reconsidering, stimulated by equally complex changes in context and changes over time. The apprehension and reflective comprehension of landscape is similarly beset by such complexities. Just as the nature and qualities of memory comprise inherently fading, shifting and fleeting impressions of things which are themselves ever-changing, an understanding of a landscape, as well as the landscape itself, is a constantly evolving, emerging response to both immense and intimate influences. There is an incongruity between the inherent changeability of both landscapes and memories, and the conventional, formal strategies of commemoration that typify the constructed landscape memorial. The design work presented in this paper brings together such explorations of memory and landscape by examining the ‘memorial’. This article examines two projects. One concerns the fate of illegal refugees travelling to Australia: The SIEVX Memorial Project. The other, An Anti-Memorial to Heroin Overdose Victims, was designed by the author as part of the 2001 Melbourne Festival.

Legitimacy

2020 ◽  
pp. 87-105
Author(s):  
George E. Mitchell ◽  
Hans Peter Schmitz ◽  
Tosca Bruno-van Vijfeijken
Keyword(s):  
Stakeholder Expectations ◽  
The Past ◽  
New Approaches ◽  
Wide Range ◽  
The Future ◽  
Governance Transparency ◽  
Over Time

Chapter 5 explores how the foundations for TNGO legitimacy have changed over time, creating imperatives for TNGOs to invest in new capabilities and adopt new practices. In the past, TNGOs derived legitimacy from their espoused principles, representational claims, elite expertise, demonstrated financial stewardship, commitment to charity, and patterns of conformity. More recently, TNGOs themselves have helped to bring about a shift toward new bases for legitimacy that focus on effectiveness, strategy, leadership, governance, transparency, and responsiveness. However, transitioning to the legitimacy practices of the future is complicated by the persistence of an antiquated architecture that still demands that TNGO conform to legacy expectations. Nevertheless, new approaches to enhancing legitimacy provide a wide range of opportunities that invite organizations to proactively align their aspirations with emerging stakeholder expectations.

scholarly journals How predictable is extinction? Forecasting species survival at million-year timescales

2019 ◽  
Vol 374 (1788) ◽  
pp. 20190392 ◽  
Author(s):  
Peter Smits ◽  
Seth Finnegan
Keyword(s):  
Fossil Record ◽  
Human Impacts ◽  
Rank Order ◽  
Extinction Risk ◽  
Geographical Range ◽  
The Past ◽  
The Future ◽  
Out Of Sample ◽  
Extinction Events ◽  
Over Time

A tenet of conservation palaeobiology is that knowledge of past extinction patterns can help us to better predict future extinctions. Although the future is unobservable, we can test the strength of this proposition by asking how well models conditioned on past observations would have predicted subsequent extinction events at different points in the geological past. To answer this question, we analyse the well-sampled fossil record of Cenozoic planktonic microfossil taxa (Foramanifera, Radiolaria, diatoms and calcareous nanoplankton). We examine how extinction probability varies over time as a function of species age, time of observation, current geographical range, change in geographical range, climate state and change in climate state. Our models have a 70–80% probability of correctly forecasting the rank order of extinction risk for a random out-of-sample species pair, implying that determinants of extinction risk have varied only modestly through time. We find that models which include either historical covariates or account for variation in covariate effects over time yield equivalent forecasts, but a model including both is overfit and yields biased forecasts. An important caveat is that human impacts may substantially disrupt range-risk dynamics so that the future will be less predictable than it has been in the past. This article is part of a discussion meeting issue ‘The past is a foreign country: how much can the fossil record actually inform conservation?’

scholarly journals Creation of Cybrid Cultures Containing mtDNA Mutations m.12315G>A and m.1555G>A, Associated with Atherosclerosis

Biomolecules ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 499 ◽  
Author(s):  
Margarita A. Sazonova ◽  
Vasily V. Sinyov ◽  
Anastasia I. Ryzhkova ◽  
Marina D. Sazonova ◽  
Zukhra B. Khasanova ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Drug Therapy ◽  
Mitochondrial Genome ◽  
Cell Lines ◽  
Threshold Value ◽  
Mtdna Mutation ◽  
Single Nucleotide ◽  
Mtdna Mutations ◽  
Cybrid Cell ◽  
In Cells

In the present work, a pilot creation of four cybrid cultures with high heteroplasmy level was performed using mitochondrial genome mutations m.12315G>A and m.1555G>A. According to data of our preliminary studies, the threshold heteroplasmy level of mutation m.12315G>A is associated with atherosclerosis. At the same time, for a mutation m.1555G>A, such a heteroplasmy level is associated with the absence of atherosclerosis. Cybrid cultures were created by fusion of rho0-cells and mitochondria from platelets with a high heteroplasmy level of the investigated mutations. To create rho0-cells, THP-1 culture of monocytic origin was taken. According to the results of the study, two cybrid cell lines containing mutation m.12315G>A with the heteroplasmy level above the threshold value (25% and 44%, respectively) were obtained. In addition, two cybrid cell lines containing mutation m.1555G>A with a high heteroplasmy level (24%) were obtained. Cybrid cultures with mtDNA mutation m.12315G>A can be used to model both the occurrence and development of atherosclerosis in cells and the titration of drug therapy for patients with atherosclerosis. With the help of cybrid cultures containing single nucleotide replacement of mitochondrial genome m.1555G>A, it is possible to develop approaches to the gene therapy of atherosclerosis.

Therapeutic immunomodulators from nematode parasites

2008 ◽  
Vol 10 ◽  
Author(s):  
William Harnett ◽  
Margaret M. Harnett
Keyword(s):  
Animal Models ◽  
Inflammatory Disease ◽  
Human Disease ◽  
Mode Of Action ◽  
Therapeutic Efficacy ◽  
Allergic Diseases ◽  
The Past ◽  
Nematode Parasites ◽  
Helminth Infections ◽  
Immunomodulatory Properties

There has been an alarming increase in the incidence of autoimmune and allergic diseases in Western countries in the past few decades. However, in countries endemic for parasitic helminth infections, such diseases remain relatively rare. Hence, it has been hypothesised that helminths may protect against the development of autoimmunity and allergy. This article reviews the evidence supporting this idea with respect to helminths of the phylum Nematoda (nematodes), considering data from human studies and animal models of inflammatory disease. The nature and mode of action of nematode-derived molecules with immunomodulatory properties are considered, and their therapeutic efficacy in models of autoimmunity and allergy described. The recent and future use of nematodes and their products in treating human disease are also discussed.

scholarly journals Animal Models for imaging

2002 ◽  
Vol 18 (5-6) ◽  
pp. 365-374 ◽  
Author(s):  
Barbara Y. Croft
Keyword(s):  
Animal Models ◽  
Human Disease ◽  
Imaging Techniques ◽  
Primary Model ◽  
The Future ◽  
Research Choices

Animal models can be used in the study of disease. This chapter discusses imaging animal models to elucidate the process of human disease. The mouse is used as the primary model. Though this choice simplifies many research choices, it necessitates compromises forin vivoimaging. In the future, we can expect improvements in both animal models and imaging techniques.

scholarly journals The Past, Present and Future of Nordic Courts

2021 ◽  
pp. 291-308
Author(s):  
Anna Nylund
Keyword(s):  
Dispute Resolution ◽  
The State ◽  
Legal Language ◽  
The Past ◽  
Current Trends ◽  
The Future ◽  
Resolution Processes ◽  
Over Time

AbstractBased on the insights from the previous chapters in this volume, this concluding chapter discusses key traits of Nordic courts: colloquial legal language, generalist judges, ‘unrefined’ and fragmentary laws, high trust in the state and judges, and corporatism. The development of these traits over time is explored as well as the emergence of new traits that could be labelled ‘Nordic’. It also discusses how two current trends—Europeanisation and privatisation of dispute resolution processes—influence Nordic courts. The question whether a unified Nordic procedural culture still exists is raised. Finally, the future of Nordic courts is discussed.

Animal Models of Neurodegenerative Diseases

2016 ◽  
Author(s):  
David Baglietto-Vargas ◽  
Rahasson R. Ager ◽  
Rodrigo Medeiros ◽  
Frank M. LaFerla
Keyword(s):  
Animal Models ◽  
Life Expectancy ◽  
Neurodegenerative Diseases ◽  
Neurodegenerative Disorders ◽  
Human Disease ◽  
Molecular Mechanisms ◽  
Preclinical Studies ◽  
Pathological Features ◽  
The Past ◽  
The Brain

The incidence and prevalence of neurodegenerative disorders (e.g., Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD), etc.) are growing rapidly due to increasing life expectancy. Researchers over the past two decades have focused their efforts on the development of animal models to dissect the molecular mechanisms underlying neurodegenerative disorders. Existing models, however, do not fully replicate the symptomatic and pathological features of human diseases. This chapter focuses on animal models of AD, as this disorder is the most prevalent of the brain degenerative conditions afflicting society. In particular, it briefly discusses the current leading animal models, the translational relevance of the preclinical studies using such models, and the limitations and shortcomings of using animals to model human disease. It concludes with a discussion of potential means to improve future models to better recapitulate human conditions.

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