1,149 research outputs found
Reply: Mitochondrial DNA copy number differentiates the Leber's hereditary optic neuropathy affected individuals from the unaffected mutation carriers
No full textAssociation of the mtDNA m.4171C>A/MT-ND1 mutation with both optic neuropathy and bilateral brainstem lesions
No full textBackground: An increasing number of mitochondrial DNA (mtDNA) mutations, mainly in complex I genes, have
been associated with variably overlapping phenotypes of Leber’s hereditary optic neuropathy (LHON),
mitochondrial encephalomyopathy with stroke-like episodes (MELAS) and Leigh syndrome (LS). We here describe
the first case in which the m.4171C>A/MT-ND1 mutation, previously reported only in association with LHON, leads
also to a Leigh-like phenotype.
Case presentation: A 16-year-old male suffered subacute visual loss and recurrent vomiting and vertigo associated
with bilateral brainstem lesions affecting the vestibular nuclei. His mother and one sister also presented subacute
visual loss compatible with LHON. Sequencing of the entire mtDNA revealed the homoplasmic m.4171C>A/MT-ND1
mutation, previously associated with pure LHON, on a haplogroup H background. Three additional non-synonymous
homoplasmic transitions affecting ND2 (m.4705T>C/MT-ND2 and m.5263C>T/MT-ND2) and ND6 (m.14180T>C/MT-ND6)
subunits, well recognized as polymorphisms in other mtDNA haplogroups but never found on the haplogroup H
background, were also present.
Conclusion: This case widens the phenotypic expression of the rare m.4171C>A/MT-ND1 LHON mutation, which
may also lead to Leigh-like brainstem lesions, and indicates that the co-occurrence of other ND non-synonymous
variants, found outside of their usual mtDNA backgrounds, may have increased the pathogenic potential of the
primary LHON mutation
Corrigendum to âResponse to: Mitochondrial neuropathy affects peripheral and cranial nerves and is primary or secondary or bothâ [Neuromuscular Disorders 26/8 (2016) 549](S0960896616302899)(10.1016/j.nmd.2016.06.007)
No full textThe authors regret that the order of the first and last names was listed incorrectly in the above letter. The correct order for the authors' names is: Michelangelo Mancuso, Daniele Orsucci, Corrado Angelini, Enrico Bertini, Claudio Bruno, Valerio Carelli, Giacomo P. Comi, Massimiliano Filosto, Costanza Lamperti, Maurizio Moggio, Tiziana Mongini, Isabella Moroni, Paola Tonin, Antonio Toscano, Gabriele Siciliano, on behalf of the Nation-wide Italian Collaborative Network of Mitochondrial Diseases. Moreover, as this was a letter, only the affiliation of the corresponding author (M. Mancuso) was given. The corresponding author's address is not the affiliation for all other authors except for Daniele Orsucci and Gabriele Siciliano who share the same affiliation: Department of Clinical and Experimental Medicine, Neurological Institute, University of Pisa, Pisa, Italy. The authors would like to apologise for any inconvenience caused
Mitochondrial DNA: Impacting Central and Peripheral Nervous Systems
No full textBecause of their high-energy metabolism, neurons are strictly dependent on mitochondria, which generate cellular ATP through oxidative phosphorylation. The mitochondrial genome encodes for critical components of the oxidative phosphorylation pathway machinery, and therefore, mutations in mitochondrial DNA (mtDNA) cause energy production defects that frequently have severe neurological manifestations. Here, we review the principles of mitochondrial genetics and focus on prototypical mitochondrial diseases to illustrate how primary defects in mtDNA or secondary defects in mtDNA due to nuclear genome mutations can cause prominent neurological and multisystem features. In addition, we discuss the pathophysiological mechanisms underlying mitochondrial diseases, the cellular mechanisms that protect mitochondrial integrity, and the prospects for therapy
Clinical syndromes associated with mtDNA mutations: Where we stand after 30 years
No full textThe landmark year 1988 can be considered as the birthdate of mitochondrial medicine, when the first pathogenic mutations affecting mtDNA were associated with human diseases. Three decades later, the field still expands and we are not ‘scraping the bottom of the barrel’ yet. Despite the tremendous progress in terms of molecular characterization and genotype/phenotype correlations, for the vast majority of cases we still lack a deep understanding of the pathogenesis, good models to study, and effective therapeutic options. However, recent technological advances including somatic cell reprogramming to induced pluripotent stem cells (iPSCs), organoid technology, and tailored endonucleases provide unprecedented opportunities to fill these gaps, casting hope to soon cure the major primary mitochondrial phenotypes reviewed here. This group of rare diseases represents a key model for tackling the pathogenic mechanisms involving mitochondrial biology relevant to much more common disorders that affect our currently ageing population, such as diabetes and metabolic syndrome, neurodegenerative and inflammatory disorders, and cancer
Introduction. Dystopian Worlds: A Multidisciplinary Approach to Analyse Transformations in Literature, Media and Politics
No full textThis collected book contains the proceedings of a conference held
at Universita Cattolica del Sacro Cuore of Milan in September 2022.
The conference was an occasion of dialogue and discussion among
several disciplines involved in the study of dystopias and their relevance
in the contemporary scenario. The “Dystopian Worlds beyond
Storytelling” project—involving political theorists, sociologists,
historians, linguists, literature scholars, media, communications
and performing arts researchers, and many others—was born
around the convergence of multiple fields of analysis, signalling the
heterogeneity and richness of the phenomena underlying the fears
of contemporary societies and their representations and discourses
in public debate and popular culture. The book is structured in five
parts, each one expressing a particular point of view on the role of
dystopias in the twenty-first century. These parts are not sectorial,
since our aim is to provide a transdisciplinary focus on the issue of
dystopia in reading through the lens of a wide range of perspectives
and extracting a pluralistic vision of such a complex theme
Dominant Optic Atrophy (DOA): Modeling the Kaleidoscopic Roles of OPA1 in Mitochondrial Homeostasis
No full textIn the year 2000, the discovery of OPA1 mutations as causative for dominant optic atrophy (DOA) was pivotal to rapidly expand the field of mitochondrial dynamics and describe the complex machinery governing this pathway, with a multitude of other genes and encoded proteins involved in neurodegenerative disorders of the optic nerve. OPA1 turned out to be a much more complex protein than initially envisaged, connecting multiple pathways beyond its strict role in mitochondrial fusion, such as sensing of OXPHOS needs and mitochondrial DNA maintenance. As a consequence, an increasing need to investigate OPA1 functions at multiple levels has imposed the development of multiple tools and models that are here reviewed. Translational mitochondrial medicine, with the ultimate objective of translating basic science necessary to understand pathogenic mechanisms into therapeutic strategies, requires disease modeling at multiple levels: from the simplest, like in yeast, to cell models, including the increasing use of reprogrammed stem cells (iPSCs) from patients, to animal models. In the present review, we thoroughly examine and provide the state of the art of all these approaches
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Fantastic Architecture and the Building of Europe in Valerio Evangelisti's Eymerich Fiction
No full textConcomitant with the horizontal expansion of EU territory through physical and political enlargement is a genealogy narrative, which emphasizes the ostensible roots of Europeanness in classical antiquity and Christianity. In the face of this sanitized genealogy, which lies at the heart of the European constitutional project, a range of alternative and more inclusive narratives circulate in contemporary European popular fiction. This paper focuses on a series of fantasy novels by the Italian author Valerio Evangelisti, featuring Inquisitor Eymerich as hero-investigator. In his highly popular novels, Evangelisti seeks to uncover layers of shared historical memory untainted with post-Enlightenment rhetoric.
The central architectural tropes of Evangelisti’s imaginary world are those of a castle and a convent, epitomizing the temporal and sacral power in European history. Each isolated from its outside environment and built on layer upon layer of subterranean chambers and corridors, the castle and the convent conceal a past quite different from the one championed in the official European genealogy. Memories of pagan worship and Islamic or Judaic learning – banished from the official rhetoric – continue to thrive, dark and threatening, in the subterranean strata of Evangelisti’s European edifice. Evangelisti thus provides an incisive critique of the official European story of origin, which threatens to suppress any alternative visions of European history or unorthodox avenues for European identity formation
Melanopsin Retinal Ganglion Cells and Pupil: Clinical Implications for Neuro-Ophthalmology
No full textMelanopsin retinal ganglion cells (mRGCs) are intrinsically photosensitive RGCs that mediate many relevant non-image forming functions of the eye, including the pupillary light reflex, through the projections to the olivary pretectal nucleus. In particular, the post-illumination pupil response (PIPR), as evaluated by chromatic pupillometry, can be used as a reliable marker of mRGC function in vivo. In the last years, pupillometry has become a promising tool to assess mRGC dysfunction in various neurological and neuro-ophthalmological conditions. In this review we will present the most relevant findings of pupillometric studies in glaucoma, hereditary optic neuropathies, ischemic optic neuropathies, idiopathic intracranial hypertension, multiple sclerosis, Parkinson's disease, and mood disorders. The use of PIPR as a marker for mRGC function is also proposed for other neurodegenerative disorders in which circadian dysfunction is documented
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