66 research outputs found
Migraine aura: retracting particle-like waves in weakly susceptible cortex
Cortical spreading depression (SD) has been suggested to underlie migraine aura. Despite a precise match in speed, the spatio-temporal patterns of SD and aura symptoms on the cortical surface ordinarily differ in aspects of size and shape. We show that this mismatch is reconciled by utilizing that both pattern types bifurcate from an instability point of generic reaction-diffusion models. To classify these spatio-temporal pattern we suggest a susceptibility scale having the value [sigma]=1 at the instability point. We predict that human cortex is only weakly susceptible to SD ([sigma]<1), and support this prediction by directly matching visual aura symptoms with anatomical landmarks using fMRI retinotopic mapping. We discuss the increased dynamical repertoire of cortical tissue close to [sigma]=1, in particular, the resulting implications on migraine pharmacology that is hitherto tested in the regime ([sigma]>>1), and potentially silent aura occurring below a second bifurcation point at [sigma]=0 on the susceptible scale
Leftward Lateralization of Auditory Cortex Underlies Holistic Sound Perception in Williams Syndrome
BACKGROUND: Individuals with the rare genetic disorder Williams-Beuren syndrome (WS) are known for their characteristic auditory phenotype including strong affinity to music and sounds. In this work we attempted to pinpoint a neural substrate for the characteristic musicality in WS individuals by studying the structure-function relationship of their auditory cortex. Since WS subjects had only minor musical training due to psychomotor constraints we hypothesized that any changes compared to the control group would reflect the contribution of genetic factors to auditory processing and musicality. METHODOLOGY/PRINCIPAL FINDINGS: Using psychoacoustics, magnetoencephalography and magnetic resonance imaging, we show that WS individuals exhibit extreme and almost exclusive holistic sound perception, which stands in marked contrast to the even distribution of this trait in the general population. Functionally, this was reflected by increased amplitudes of left auditory evoked fields. On the structural level, volume of the left auditory cortex was 2.2-fold increased in WS subjects as compared to control subjects. Equivalent volumes of the auditory cortex have been previously reported for professional musicians. CONCLUSIONS/SIGNIFICANCE: There has been an ongoing debate in the neuroscience community as to whether increased gray matter of the auditory cortex in musicians is attributable to the amount of training or innate disposition. In this study musical education of WS subjects was negligible and control subjects were carefully matched for this parameter. Therefore our results not only unravel the neural substrate for this particular auditory phenotype, but in addition propose WS as a unique genetic model for training-independent auditory system properties
N-Glycans and Glycosylphosphatidylinositol-Anchor Act on Polarized Sorting of Mouse PrPC in Madin-Darby Canine Kidney Cells
The cellular prion protein (PrPC) plays a fundamental role in prion disease. PrPC is a glycosylphosphatidylinositol (GPI)-anchored protein with two variably occupied N-glycosylation sites. In general, GPI-anchor and N-glycosylation direct proteins to apical membranes in polarized cells whereas the majority of mouse PrPC is found in basolateral membranes in polarized Madin-Darby canine kidney (MDCK) cells. In this study we have mutated the first, the second, and both N-glycosylation sites of PrPC and also replaced the GPI-anchor of PrPC by the Thy-1 GPI-anchor in order to investigate the role of these signals in sorting of PrPC in MDCK cells. Cell surface biotinylation experiments and confocal microscopy showed that lack of one N-linked oligosaccharide leads to loss of polarized sorting of PrPC. Exchange of the PrPC GPI-anchor for the one of Thy-1 redirects PrPC to the apical membrane. In conclusion, both N-glycosylation and GPI-anchor act on polarized sorting of PrPC, with the GPI-anchor being dominant over N-glycans
Space Division Multiplexing in Optical Fibres
Optical communications technology has made enormous and steady progress for
several decades, providing the key resource in our increasingly
information-driven society and economy. Much of this progress has been in
finding innovative ways to increase the data carrying capacity of a single
optical fibre. In this search, researchers have explored (and close to
maximally exploited) every available degree of freedom, and even commercial
systems now utilize multiplexing in time, wavelength, polarization, and phase
to speed more information through the fibre infrastructure. Conspicuously, one
potentially enormous source of improvement has however been left untapped in
these systems: fibres can easily support hundreds of spatial modes, but today's
commercial systems (single-mode or multi-mode) make no attempt to use these as
parallel channels for independent signals.Comment: to appear in Nature Photonic
Mysid crustaceans as standard models for the screening and testing of endocrine-disrupting chemicals
Author Posting. © Springer, 2007. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Ecotoxicology 16 (2007): 205-219, doi:10.1007/s10646-006-0122-0.Investigative efforts into the potential endocrine-disrupting effects of chemicals have mainly
concentrated on vertebrates, with significantly less attention paid to understanding potential
endocrine disruption in the invertebrates. Given that invertebrates account for at least 95% of all
known animal species and are critical to ecosystem structure and function, it remains essential to
close this gap in knowledge and research. The lack of progress regarding endocrine disruption in
invertebrates is still largely due to: (1) our ignorance of mode-of-action, physiological control, and
hormone structure and function in invertebrates; (2) lack of a standardized invertebrate assay; (3)
the irrelevance to most invertebrates of the proposed activity-based biological indicators for
endocrine disruptor exposure (androgen, estrogen and thyroid); (4) limited field studies. Past and
ongoing research efforts using the standard invertebrate toxicity test model, the mysid shrimp, have
aimed at addressing some of these issues. The present review serves as an update to a previous
publication on the use of mysid shrimp for the evaluation of endocrine disruptors (Verslycke et al.,
2004a). It summarizes recent investigative efforts that have significantly advanced our
understanding of invertebrate-specific endocrine toxicity, population modeling, field studies, and
transgeneration standard test development using the mysid model.Supported by a Fellowship of the Belgian American Educational Foundation
Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases
The production of peroxide and superoxide is an inevitable consequence of
aerobic metabolism, and while these particular "reactive oxygen species" (ROSs)
can exhibit a number of biological effects, they are not of themselves
excessively reactive and thus they are not especially damaging at physiological
concentrations. However, their reactions with poorly liganded iron species can
lead to the catalytic production of the very reactive and dangerous hydroxyl
radical, which is exceptionally damaging, and a major cause of chronic
inflammation. We review the considerable and wide-ranging evidence for the
involvement of this combination of (su)peroxide and poorly liganded iron in a
large number of physiological and indeed pathological processes and
inflammatory disorders, especially those involving the progressive degradation
of cellular and organismal performance. These diseases share a great many
similarities and thus might be considered to have a common cause (i.e.
iron-catalysed free radical and especially hydroxyl radical generation). The
studies reviewed include those focused on a series of cardiovascular, metabolic
and neurological diseases, where iron can be found at the sites of plaques and
lesions, as well as studies showing the significance of iron to aging and
longevity. The effective chelation of iron by natural or synthetic ligands is
thus of major physiological (and potentially therapeutic) importance. As
systems properties, we need to recognise that physiological observables have
multiple molecular causes, and studying them in isolation leads to inconsistent
patterns of apparent causality when it is the simultaneous combination of
multiple factors that is responsible. This explains, for instance, the
decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference
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