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Fulfilling a bevy of biological roles, copper is an essential metal for healthy brain function. Cu dyshomeostasis has been demonstrated to be involved in some neurological conditions including Menkes and Alzheimer's diseases. We have previously reported localized Cu-rich aggregates in astrocytes of the subventricular zone (SVZ) in rodent brains with Cu concentrations in the hundreds of millimolar. Metallothionein, a cysteine-rich protein critical to metal homeostasis and known to participate in a variety of neuroprotective and neuroregenerative processes, was proposed as a binding protein. Here, we present an analysis of metallothionein(1,2) knockout (MTKO) mice and age-matched controls using X-ray fluorescence microscopy. In large structures such as the corpus callosum, cortex, and striatum, there is no significant difference in Cu, Fe, or Zn concentrations in MTKO mice compared to age-matched controls. In the astrocyte-rich subventricular zone where Cu-rich aggregates reside, approximately 1/3 as many Cu-rich aggregates persist in MTKO mice resulting in a decrease in periventricular Cu concentration. Aggregates in both wild-type and MTKO mice show XANES spectra characteristic of CuxSy multimetallic clusters and have similar [S]/[Cu] ratios. Consistent with assignment as a CuxSy multimetallic cluster, the astrocyte-rich SVZ of both MTKO and wild-type mice exhibit autofluorescent bodies, though MTKO mice exhibit fewer. Furthermore, XRF imaging of Au-labeled lysosomes and ubiquitin demonstrates a lack of co-localization with Cu-rich aggregates suggesting they are not involved in a degradation pathway. Overall, these data suggest that Cu in aggregates is bound by either metallothionein-3 or a yet unknown protein similar to metallothionein. Keywords: X-ray fluorescence microscopy, Subventricular zone, Cu, Metallothionein

Photosynthetic water oxidation is a fundamental process that sustains the biosphere. A Mn_{4}Ca cluster embedded in the photosystem II protein environment is responsible for the production of atmospheric oxygen. Here, time-resolved x-ray emission spectroscopy (XES) is used to observe the process of oxygen formation in real time. These experiments reveal that the oxygen evolution step, initiated by three sequential laser flashes, is accompanied by rapid (within 50 μs) changes to the Mn Kβ XES spectrum. However, no oxidation of the Mn_{4}Ca core above the all-Mn^{IV} state is detected to precede O─O bond formation, and the observed changes are therefore assigned to O─O bond-formation dynamics. We propose that O─O bond formation occurs prior to the transfer of the final (fourth) electron from the Mn_{4}Ca cluster to the oxidized tyrosine Tyr_{Z} residue. This model resolves the kinetic limitations associated with O─O bond formation and suggests an evolutionary adaptation to avoid releasing harmful peroxide species.

The neurotoxic effect of manganese (Mn) establishes itself in a condition known as manganism or Mn induced parkinsonism. While this condition was first diagnosed about 170 years ago, the mechanism of the neurotoxic action of Mn remains unknown. Moreover, the possibility that Mn exposure combined with other genetic and environmental factors can contribute to the development of Parkinson's disease has been discussed in the literature and several epidemiological studies have demonstrated a correlation between Mn exposure and an elevated risk of Parkinson's disease. Here, we introduce X-ray fluorescence imaging as a new quantitative tool for analysis of the Mn distribution in the brain with high spatial resolution. The animal model employed mimics deficits observed in affected human subjects. The obtained maps of Mn distribution in the brain demonstrate the highest Mn content in the globus pallidus, the thalamus, and the substantia nigra pars compacta. To test the hypothesis that Mn transport into/distribution within brain cells mimics that of other biologically relevant metal ions, such as iron, copper, or zinc, their distributions were compared. It was demonstrated that the Mn distribution does not follow the distributions of any of these metals in the brain. The majority of Mn in the brain was shown to occur in the mobile state, confirming the relevance of the chelation therapy currently used to treat Mn intoxication. In cells with accumulated Mn, it can cause neurotoxic action by affecting the mitochondrial respiratory chain. This can result in increased susceptibility of the neurons of the globus pallidus, thalamus, and substantia nigra pars compacta to various environmental or genetic insults. The obtained data is the first demonstration of Mn accumulation in the substantia nigra pars compacta, and thus, can represent a link between Mn exposure and its potential effects for development of Parkinson's disease.

Professor Declan Kiberd is Chair of Anglo-Irish Literature and Drama at University College Dublin, where he has taught for many years after having taught at the University of Kent at Canterbury and Trinity College Dublin. He is a director of the Abbey Theatre. He has been Parnell Fellow at Magdalene College Cambridge, and a visiting professor at Duke University and the Sorbonne. He has also been Director of the Yeats International Summer School (1985-7), Patron of the Dublin Shaw Society (1995-2000), a columnist with The Irish Times (1985-7) and The Irish Press (1987-93), the presenter of the RTÉ Arts programme, Exhibit A(1984-6), and a regular essayist and reviewer in The Irish Times, TLS,London Review of Books and The New York Times. Professor Kiberd is the author of many books including his seminal Inventing Ireland: The Literature of the Modern Nation (1995), Irish Classics (2000), and The Irish Writer and the World (2005), as well as Ulysses and Us, published just this year, and he was also the editor of the Penguin edition of theAnnotated Students’ Ulysses (1992). He is one of the most important voices in Irish Studies. Beyond that, he is also a prominent public intellectual, and he continues to be an inspirational figure for generations of students. In this interview, we discussed the relevance of the comparative approach to Irish Studies and the future of Comparative Literature in Ireland and worldwide.