Quantum Zeno Effect Explains Magnetic-Sensitive Radical-Ion-Pair Reactions

Chemical reactions involving radical-ion pairs are ubiquitous in biology, since not only are they at the basis of the photosynthetic reaction chain, but are also assumed to underlie the biochemical magnetic compass used by avian species for navigation. Recent experiments with magnetic-sensitive radical-ion pair reactions provided strong evidence for the radical-ion-pair magnetoreception mechanism, verifying the expected magnetic sensitivities and chemical product yield changes. It is here shown that the theoretical description of radical-ion-pair reactions used since the 70's cannot explain the observed data, because it is based on phenomenological equations masking quantum coherence effects. The fundamental density matrix equation derived here from basic quantum measurement theory considerations naturally incorporates the quantum Zeno effect and readily explains recent experimental observations on low- and high-magnetic-field radical-ion-pair reactions.Comment: 10 pages, 5 figure

Distinct Lysosomal Network Protein Profiles in Parkinsonian Syndrome Cerebrospinal Fluid.

BackgroundClinical diagnosis of parkinsonian syndromes like Parkinson's disease (PD), corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) is hampered by overlapping symptomatology and lack of diagnostic biomarkers, and definitive diagnosis is only possible post-mortem.ObjectiveSince impaired protein degradation plays an important role in many neurodegenerative disorders, we hypothesized that profiles of select lysosomal network proteins in cerebrospinal fluid could be differentially expressed in these parkinsonian syndromes.MethodsCerebrospinal fluid samples were collected from PD patients (n = 18), clinically diagnosed 4-repeat tauopathy patients; corticobasal syndrome (CBS) (n = 3) and PSP (n = 8); and pathologically diagnosed PSP (n = 8) and CBD patients (n = 7). Each patient set was compared to its appropriate control group consisting of age and gender matched individuals. Select lysosomal network protein levels were detected via Western blotting. Factor analysis was used to test the diagnostic sensitivity, specificity and accuracy of the select lysosomal network protein expression profiles.ResultsPD, CBD and PSP were markedly different in their cerebrospinal fluid lysosomal network protein profiles. Lysosomal-associated membrane proteins 1 and 2 were significantly decreased in PD; early endosomal antigen 1 was decreased and lysozyme increased in PSP; and lysosomal-associated membrane proteins 1 and 2, microtubule-associated protein 1 light chain 3 and lysozyme were increased in CBD. A panel of lysosomal-associated membrane protein 2, lysozyme and microtubule-associated protein 1 light chain discriminated between controls, PD and 4-repeat tauopathies.ConclusionsThis study offers proof of concept that select lysosomal network proteins are differentially expressed in cerebrospinal fluid of Parkinson's disease, corticobasal syndrome and progressive supranuclear palsy. Lysosomal network protein analysis could be further developed as a diagnostic fluid biomarker in parkinsonian syndromes

Density profiles of plasmas confined by the field of a Levitating Dipole Magnet

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Physics, February 2009."September 2008." Cataloged from PDF version of thesis.Includes bibliographical references (p. 211-218).A 4-channel microwave interferometer (center frequency: 60 GHz) has been constructed to measure the density profiles of plasmas confined within the Levitated Dipole Experiment (LDX). LDX is the first and only experiment built to study plasmas confined by the field of a levitating, dipole magnet in a geometry that exploits plasma compressibility to achieve stability. Theoretical predictions--based partly on observations of planetary magnetospheres-suggest that dipole-confined plasmas will be driven by fluctuations into pressure and density profiles that are "stationary" to MHD interchange modes. The stationary pressure profile is characterized by an equal amount of entropy per flux-tube while the stationary density profile is characterized by an equal number of particles per flux-tube. These predictions are of interest to nuclear fusion research since they imply that the pressure and density profiles of dipole-confined plasmas can be simultaneously peaked and stable. Measurements with the interferometer show that the total density of LDX plasmas is strongly affected by the following parameters: levitated vs. mechanical support of the central dipole coil; input ECRH frequency and power; background pressure of neutral particles; plasma species. The gradients of the density profiles are, however, largely independent of the experimental conditions and approximate the value predicted for the stationary profile. Non-linear analyses suggest that dipole-confined plasmas are maintained in their stationary pressure and density profiles by a process of self-organized convection. We present measurements indicating that this self-organization process is observed in LDX.by Alexander C. Boxer.Ph.D

Digitally Continuous Multivalued Functions, Morphological Operations and Thinning Algorithms

In a recent paper (Escribano et al. in Discrete Geometry for Computer Imagery 2008. Lecture Notes in Computer Science, vol. 4992, pp. 81–92, 2008) we have introduced a notion of continuity in digital spaces which extends the usual notion of digital continuity. Our approach, which uses multivalued functions, provides a better framework to define topological notions, like retractions, in a far more realistic way than by using just single-valued digitally continuous functions. In this work we develop properties of this family of continuous functions, now concentrating on morphological operations and thinning algorithms. We show that our notion of continuity provides a suitable framework for the basic operations in mathematical morphology: erosion, dilation, closing, and opening. On the other hand, concerning thinning algorithms, we give conditions under which the existence of a retraction F:X⟶X∖D guarantees that D is deletable. The converse is not true, in general, although it is in certain particular important cases which are at the basis of many thinning algorithms

Temporal Structure of Human Gaze Dynamics is Invariant During Free Viewing

We investigate the dynamic structure of human gaze and present an experimental study of the frequency components of the change in gaze position over time during free viewing of computer-generated fractal images. We show that changes in gaze position are scale-invariant in time with statistical properties that are characteristic of a random walk process. We quantify and track changes in the temporal structure using a well-defined scaling parameter called the Hurst exponent, H. We find H is robust regardless of the spatial complexity generated by the fractal images. In addition, we find the Hurst exponent is invariant across all participants, including those with distinct changes to higher order visual processes due to neural degeneration. The value we find for H of 0.57 shows that the gaze dynamics during free viewing of fractal images are consistent with a random walk process with persistent movements. Our research suggests the human visual system may have a common strategy that drives the dynamics of human gaze during exploration

Promoting tau secretion and propagation by hyperactive p300/CBP via autophagy-lysosomal pathway in tauopathy.

BackgroundThe trans-neuronal propagation of tau has been implicated in the progression of tau-mediated neurodegeneration. There is critical knowledge gap in understanding how tau is released and transmitted, and how that is dysregulated in diseases. Previously, we reported that lysine acetyltransferase p300/CBP acetylates tau and regulates its degradation and toxicity. However, whether p300/CBP is involved in regulation of tau secretion and propagation is unknown.MethodWe investigated the relationship between p300/CBP activity, the autophagy-lysosomal pathway (ALP) and tau secretion in mouse models of tauopathy and in cultured rodent and human neurons. Through a high-through-put compound screen, we identified a new p300 inhibitor that promotes autophagic flux and reduces tau secretion. Using fibril-induced tau spreading models in vitro and in vivo, we examined how p300/CBP regulates tau propagation.ResultsIncreased p300/CBP activity was associated with aberrant accumulation of ALP markers in a tau transgenic mouse model. p300/CBP hyperactivation blocked autophagic flux and increased tau secretion in neurons. Conversely, inhibiting p300/CBP promoted autophagic flux, reduced tau secretion, and reduced tau propagation in fibril-induced tau spreading models in vitro and in vivo.ConclusionsWe report that p300/CBP, a lysine acetyltransferase aberrantly activated in tauopathies, causes impairment in ALP, leading to excess tau secretion. This effect, together with increased intracellular tau accumulation, contributes to enhanced spreading of tau. Our findings suggest that inhibition of p300/CBP as a novel approach to correct ALP dysfunction and block disease progression in tauopathy

Peripheral Innate Immune Activation Correlates With Disease Severity in GRN Haploinsufficiency.

Objective: To investigate associations between peripheral innate immune activation and frontotemporal lobar degeneration (FTLD) in progranulin gene (GRN) haploinsufficiency. Methods: In this cross-sectional study, ELISA was used to measure six markers of innate immunity (sCD163, CCL18, LBP, sCD14, IL-18, and CRP) in plasma from 30 GRN mutation carriers (17 asymptomatic, 13 symptomatic) and 29 controls. Voxel based morphometry was used to model associations between marker levels and brain atrophy in mutation carriers relative to controls. Linear regression was used to model relationships between plasma marker levels with mean frontal white matter integrity [fractional anisotropy (FA)] and the FTLD modified Clinical Dementia Rating Scale sum of boxes score (FTLD-CDR SB). Results: Plasma sCD163 was higher in symptomatic GRN carriers [mean 321 ng/ml (SD 125)] compared to controls [mean 248 ng/ml (SD 58); p < 0.05]. Plasma CCL18 was higher in symptomatic GRN carriers [mean 56.9 pg/ml (SD 19)] compared to controls [mean 40.5 pg/ml (SD 14); p < 0.05]. Elevation of plasma LBP was associated with white matter atrophy in the right frontal pole and left inferior frontal gyrus (p FWE corrected <0.05) in all mutation carriers relative to controls. Plasma LBP levels inversely correlated with bilateral frontal white matter FA (R2 = 0.59, p = 0.009) in mutation carriers. Elevation in plasma was positively correlated with CDR-FTLD SB (b = 2.27 CDR units/μg LBP/ml plasma, R2 = 0.76, p = 0.003) in symptomatic carriers. Conclusion: FTLD-GRN is associated with elevations in peripheral biomarkers of macrophage-mediated innate immunity, including sCD163 and CCL18. Clinical disease severity and white matter integrity are correlated with blood LBP, suggesting a role for peripheral immune activation in FTLD-GRN

Altered Lysosomal Proteins in Neural-Derived Plasma Exosomes in Preclinical Alzheimer Disease

OBJECTIVE: Diverse autolysosomal proteins were quantified in neurally derived blood exosomes from patients with Alzheimer disease (AD) and controls to investigate disordered neuronal autophagy. METHODS: Blood exosomes obtained once from patients with AD (n = 26) or frontotemporal dementia (n = 16), other patients with AD (n = 20) both when cognitively normal and 1 to 10 years later when diagnosed, and case controls were enriched for neural sources by anti-human L1CAM antibody immunoabsorption. Extracted exosomal proteins were quantified by ELISAs and normalized with the CD81 exosomal marker. RESULTS: Mean exosomal levels of cathepsin D, lysosome-associated membrane protein 1 (LAMP-1), and ubiquitinylated proteins were significantly higher and of heat-shock protein 70 significantly lower for AD than controls in cross-sectional studies (p ≤ 0.0005). Levels of cathepsin D, LAMP-1, and ubiquitinylated protein also were significantly higher for patients with AD than for patients with frontotemporal dementia (p ≤ 0.006). Step-wise discriminant modeling of the protein levels correctly classified 100% of patients with AD. Exosomal levels of all proteins were similarly significantly different from those of matched controls in 20 patients 1 to 10 years before and at diagnosis of AD (p ≤ 0.0003). CONCLUSIONS: Levels of autolysosomal proteins in neurally derived blood exosomes distinguish patients with AD from case controls and appear to reflect the pathology of AD up to 10 years before clinical onset. These preliminary results confirm in living patients with AD the early appearance of neuronal lysosomal dysfunction and suggest that these proteins may be useful biomarkers in large prospective studies