פרסומים

BACKGROUND: Neuropathology played a major role in deciphering disease mechanisms in multiple sclerosis. METHODS: Retrospective review of neuropathological studies, published during the last two decades. RESULTS: The importance of neuropathology is generally seen in its contribution to the diagnosis of diseases of the nervous system, in particular in neuro-oncology. However, when it also includes in its analysis the global three-dimensional extension of brain damage and the temporal sequence of lesion evolution and relates this to molecular changes in the lesions, it offers the potential to decipher disease pathogenesis and to contribute to the development of effective and causative treatments. In multiple sclerosis research neuropathology was essential to discriminate the disease from other inflammatory autoimmune or demyelinating diseases, such as neuromyelitis optica spectrum disorders (NMOSD) or myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD). It defined the hallmark of chronic progressive disease in MS patients as slowly expanding tissue damage around lesions and in the normal appearing white and grey matter. It showed that these changes occur in the course of a tissue resident immune response within the central nervous system, involving tissue resident effector memory cells and plasma cells. Molecular studies in neuropathologically defined micro-dissected MS lesions identified a cascade of oxidative injury, mitochondrial damage and subsequent virtual hypoxia as a major pathway of tissue injury in MS. CONCLUSIONS: The results of these studies were highly relevant for the identification of potential therapeutic targets in MS patients and the design of pivotal clinical trials.

Abstract Control phenomena in biology usually refer to changes in gene expression and protein translation and modification. In this paper, another mode of regulation is highlighted; we propose that photosynthetic organisms can harness the interplay between localization and delocalization of energy transfer by utilizing small conformational changes in the structure of light-harvesting complexes. We examine the mechanism of energy transfer in photosynthetic pigment-protein complexes, first through the scope of theoretical work and then by in vitro studies of these complexes. Next, the biological relevance to evolutionary fitness of this localization-delocalization switch is explored by in vivo experiments on desert crust and marine cyanobacteria, which are both exposed to rapidly changing environmental conditions. These examples demonstrate the flexibility and low energy cost of this mechanism, making it a competitive survival strategy.