University of Graz

Abstract: The International Panel on MS Diagnosis presents revised diagnostic criteria for multiple sclerosis (MS). The focus remains on the objective demonstration of dissemination of lesions in both time and space. Magnetic resonance imaging is integrated with dinical and other paraclinical diagnostic methods. The revised criteria facilitate the diagnosis of MS in patients with a variety of presentations, including "monosymptomatic" disease suggestive of MS, disease with a typical relapsing-remitting course, and disease with insidious progression, without clear attacks and remissions. Previously used terms such as "clinically definite" and "probable MS" are no longer recommended. The outcome of a diagnostic evaluation is either MS, "possible MS" (for those at risk for MS, but for whom diagnostic evaluation is equivocal), or "not MS."

Abstract: For many years people have speculated that electroencephalographic activity or other electrophysiological measures of brain function might provide a new non-muscular channel for sending messages and commands to the external world - a brain-computer interface (BCI). Over the past 15 years, productive BCI research programs have arisen. Encouraged by new understanding of brain function, by the advent of powerful low-cost computer equipment, and by growing recognition of the needs and potentials of people with disabilities, these programs concentrate on developing new augmentative communication and control technology for those with severe neuromuscular disorders, such as amyotrophic lateral sclerosis, brainstem stroke, and spinal cord injury. The immediate goal is to provide these users, who may be completely paralyzed, or 'locked in', with basic communication capabilities so that they can express their wishes to caregivers or even operate word processing programs or neuroprostheses. Present-day BCIs determine the intent of the user from a variety of different electrophysiological signals. These signals include slow cortical potentials, P300 potentials, and mu or beta rhythms recorded from the scalp, and cortical neuronal activity recorded by implanted electrodes. They are translated in real-time into commands that operate a computer display or other device. Successful operation requires that the user encode commands in these signals and that the BCI derive the commands from the signals. Thus, the user and the BCI system need to adapt to each other both initially and continually so as to ensure stable performance. Current BCIs have maximum information transfer rates up to 10-25bits/min. This limited capacity can be valuable for people whose severe disabilities prevent them from using conventional augmentative communication methods. At the same time, many possible applications of BCI technology, such as neuroprosthesis control, may require higher information transfer rates. Future progress will depend on: recognition that BCI research and development is an interdisciplinary problem, involving neurobiology, psychology, engineering, mathematics, and computer science; identification of those signals, whether evoked potentials, spontaneous rhythms, or neuronal firing rates, that users are best able to control independent of activity in conventional motor output pathways; development of training methods for helping users to gain and maintain that control; delineation of the best algorithms for translating these signals into device commands; attention to the identification and elimination of artifacts such as electromyographic and electro-oculographic activity; adoption of precise and objective procedures for evaluating BCI performance; recognition of the need for long-term as well as short-term assessment of BCI performance; identification of appropriate BCI applications and appropriate matching of applications and users; and attention to factors that affect user acceptance of augmentative technology, including ease of use, cosmesis, and provision of those communication and control capacities that are most important to the user. Development of BCI technology will also benefit from greater emphasis on peer-reviewed research publications and avoidance of the hyperbolic and often misleading media attention that tends to generate unrealistic expectations in the public and skepticism in other researchers. With adequate recognition and effective engagement of all these issues, BCI systems could eventually provide an important new communication and control option for those with motor disabilities and might also give those without disabilities a supplementary control channel or a control channel useful in special circumstances.

Abstract: Lipid peroxidation often occurs in response to oxidative stress, and a great diversity of aldehydes are formed when lipid hydroperoxides break down in biological systems. Some of these aldehydes are highly reactive and may be considered as second toxic messengers which disseminate and augment initial free radical events. The aldehydes most intensively studied so far are 4-hydroxynonenal, 4-hydroxyhexenal, and malonaldehyde. The purpose of this review is to provide a comprehensive summary on the chemical properties of these aldehydes, the mechanisms of their formation and their occurrence in biological systems and methods for their determination. We will also review the reactions of 4-hydroxyalkenals and malonaldehyde with biomolecules (amino acids, proteins, nucleic acid bases), their metabolism in isolated cells and excretion in whole animals, as well as the many types of biological activities described so far, including cytotoxicity, genotoxicity, chemotactic activity, and effects on cell proliferation and gene expression. Structurally related compounds, such as acrolein, crotonaldehyde, and other 2-alkenals are also briefly discussed, since they have some properties in common with 4-hydroxyalkenals.

Abstract: An internally or externally paced event results not only in the generation of an event-related potential (ERP) but also in a change in the ongoing EEG/MEG in form of an event-related desynchronization (ERD) or event-related synchronization (ERS). The ERP on the one side and the ERD/ERS on the other side are different responses of neuronal structures in the brain. While the former is phase-locked, the latter is not phase-locked to the event. The most important difference between both phenomena is that the ERD/ERS is highly frequency band-specific, whereby either the same or different locations on the scalp can display ERD and ERS simultaneously. Quantification of ERD/ERS in time and space is demonstrated on data from a number of movement experiments.

Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.