Iron deficiency in parkinsonism : region-specific iron dysregulation in Parkinson's disease and multiple system atrophy

Alpha synuclein pathology is widespread and found in diverse cell types in multiple system atrophy (MSA) as compared to Parkinson's disease (PD). The reason for this differential distribution is unknown. Regional differences in the distribution of iron are associated with neurodegenerative diseases, and here we characterize the relationship between iron homeostasis proteins and regional concentration, distribution and form of iron in MSA and PD. In PD substantia nigra, tissue iron and expression of the iron export protein ferroportin increased, while the iron storage protein ferritin expression was unchanged. In the basis pontis of MSA cases, increased total iron concentration coupled with a disproportionate increase in ferritin in dysmorphic microglia and a reduction in ferroportin expression. This is supported by isothermal remanent magnetisation evidence consistent with elevated concentrations of ferritin-bound iron in MSA basis pontis. Conventional opinion holds that excess iron is involved in neurodegeneration. Our data support that this may be the case in PD. While region-specific changes in iron are evident in both PD and MSA, the mechanisms of iron dysregulation appear quite distinct, with a failure to export iron from the MSA basis pontis coupling with significant intracellular accumulation of ferritin iron. This pattern also occurs, to a lesser extent, in the MSA putamen. Despite the excess tissue iron, the manner of iron dysregulation in MSA is reminiscent of changes in anemia of chronic disease, and our preliminary data, coupled with the widespread pathology and involvement of multiple cell types, may evidence a deficit in bioavailabile iron

Analysing the impact of iron dysmetabolism on regional metal ion distribution in the brain

An Iron Overload and an H-Ferritin Deficient Mouse Model were used to examine the impact of disrupted iron metabolism on the brain. Brain sections were imaged and compared using Synchrotron μXRF spectroscopy. Quantitative measurement of the relative metal ion concentrations for iron, copper and zinc were made across selected regions of interest in the brain. It was generally found that metal ion concentrations of iron and zinc decreased in specific regions in the Iron Overload condition compared with the control, with copper increasing in only one region. Few regions differed in metal ion concentration between the H-Ferritin Deficient Model and the control. The three conditions exhibited similar / identical results for metal ion concentrations in many brain regions, indicating the validity of the method used for comparison between samples. It is clear that there exists a complex relationship between these trace metal

Tsuji functions with segments of Julia

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46297/1/209_2005_Article_BF01112579.pd

Brain iron accumulation affects myelin-related molecular systems implicated in a rare neurogenetic disease family with neuropsychiatric features

The ‘neurodegeneration with brain iron accumulation’ (NBIA) disease family entails movement or cognitive impairment, often with psychiatric features. To understand how iron loading affects the brain, we studied mice with disruption of two iron regulatory genes, hemochromatosis (Hfe) and transferrin receptor 2 (Tfr2). Inductively coupled plasma atomic emission spectroscopy demonstrated increased iron in the Hfe-/- × Tfr2mut brain (P=0.002, n =5/group), primarily localized by Perls’ staining to myelinated structures. Western immunoblotting showed increases of the iron storage protein ferritin light polypeptide and microarray and real-time reverse transcription-PCR revealed decreased transcript levels (P<0.04, n =5/group) for five other NBIA genes, phospholipase A2 group VI, fatty acid 2-hydroxylase, ceruloplasmin, chromosome 19 open reading frame 12 and ATPase type 13A2. Apart from the ferroxidase ceruloplasmin, all are involved in myelin homeostasis; 16 other myelin-related genes also showed reduced expression (P<0.05), although gross myelin structure and integrity appear unaffected (P>0.05). Overlap (P<0.0001) of differentially expressed genes in Hfe-/- × Tfr2mut brain with human gene co-expression networks suggests iron loading influences expression of NBIA-related and myelin-related genes co-expressed in normal human basal ganglia. There was overlap (P<0.0001) of genes differentially expressed in Hfe-/- × Tfr2mut brain and post-mortem NBIA basal ganglia. Hfe-/- × Tfr2mut mice were hyperactive (P<0.0112) without apparent cognitive impairment by IntelliCage testing (P>0.05). These results implicate myelin-related systems involved in NBIA neuropathogenesis in early responses to iron loading. This may contribute to behavioral symptoms in NBIA and hemochromatosis and is relevant to patients with abnormal iron status and psychiatric disorders involving myelin abnormalities or resistant to conventional treatments

The teaching of recent and violent conflicts as challenges for history education

This paper has been written with the support of Projects EDU2015-65088P from the DGICYT (Ministry of Education, Spain) and also the Project PICT2012-1594 from the ANPCYT (Argentina) coordinated by the autho

The effect of Ku on telomere replication time is mediated by telomere length but is independent of histone tail acetylation

Peer reviewedPublisher PD

Extremal Multicenter Black Holes: Nilpotent Orbits and Tits Satake Universality Classes

Four dimensional supergravity theories whose scalar manifold is a symmetric coset manifold U[D=4]/Hc are arranged into a finite list of Tits Satake universality classes. Stationary solutions of these theories, spherically symmetric or not, are identified with those of an euclidian three-dimensional sigma-model, whose target manifold is a Lorentzian coset U[D=3]/H* and the extremal ones are associated with H* nilpotent orbits in the K* representation emerging from the orthogonal decomposition of the algebra U[D=3] with respect to H*. It is shown that the classification of such orbits can always be reduced to the Tits-Satake projection and it is a class property of the Tits Satake universality classes. The construction procedure of Bossard et al of extremal multicenter solutions by means of a triangular hierarchy of integrable equations is completed and converted into a closed algorithm by means of a general formula that provides the transition from the symmetric to the solvable gauge. The question of the relation between H* orbits and charge orbits W of the corresponding black holes is addressed and also reduced to the corresponding question within the Tits Satake projection. It is conjectured that on the vanishing locus of the Taub-NUT current the relation between H*-orbit and W-orbit is rigid and one-to-one. All black holes emerging from multicenter solutions associated with a given H* orbit have the same W-type. For the S^3 model we provide a complete survey of its multicenter solutions associated with all of the previously classified nilpotent orbits of sl(2) x sl(2) within g[2,2]. We find a new intrinsic classification of the W-orbits of this model that might provide a paradigm for the analogous classification in all the other Tits Satake universality classes.Comment: 83 pages, LaTeX; v2: few misprints corrected and references adde

Different battlegrounds, similar concerns? The “history wars” and the teaching of history in Australia and England

Debates about the purpose and content of history education in schools have been prevalent in most Westernised democratic nations over the last thirty years. At expense are essential questions concerning national identity/ies, competing narratives and the aims of history education. The impact of “history wars” have been felt within both Australia and England, as conservative commentators – including politicians and historians – have raised concerns about the depth and effectiveness of history education and have sought to make significant changes to the history curriculum for schools. This analysis examines the history wars in Australia and England, exploring the view that history education has been in danger and/or crisis and examining the curricular implications of a move toward greater recognition of national narratives. It raises some essential tensions that remain regarding two aspects of history teaching in both nations – (i) historiography and (ii) chronological understanding

Changes in the Policy Environment For Infant and Young Child feeding in Vietnam, Bangladesh, and Ethiopia, and the Role of Targeted Advocacy

There is limited literature examining shifts in policy environments for nutrition and infant and young child feeding (IYCF) over time, and on the potential contribution of targeted advocacy to improved policy environments in low- and middle-income countries. This study tracked changes in the policy environment over a four-year period in three countries, and examined the role of targeted nutrition and IYCF advocacy strategies by a global initiative