Noninvasive quantification of axon radii using diffusion MRI

Axon caliber plays a crucial role in determining conduction velocity and, consequently, in the timing and synchronization of neural activation. Noninvasive measurement of axon radii could have significant impact on the understanding of healthy and diseased neural processes. Until now, accurate axon radius mapping has eluded in vivo neuroimaging, mainly due to a lack of sensitivity of the MRI signal to micron-sized axons. Here, we show how – when confounding factors such as extra-axonal water and axonal orientation dispersion are eliminated – heavily diffusion-weighted MRI signals become sensitive to axon radii. However, diffusion MRI is only capable of estimating a single metric, the effective radius, representing the entire axon radius distribution within a voxel that emphasizes the larger axons. Our findings, both in rodents and humans, enable noninvasive mapping of critical information on axon radii, as well as resolve the long-standing debate on whether axon radii can be quantified

Polarization sensitive spectroscopy of charged Quantum Dots

We present an experimental and theoretical study of the polarized photoluminescence spectrum of single semiconductor quantum dots in various charge states. We compare our high resolution polarization sensitive spectral measurements with a new many-carrier theoretical model, which was developed for this purpose. The model considers both the isotropic and anisotropic exchange interactions between all participating electron-hole pairs. With this addition, we calculate both the energies and polarizations of all optical transitions between collective, quantum dot confined charge carrier states. We succeed in identifying most of the measured spectral lines. In particular, the lines resulting from singly-, doubly- and triply- negatively charged excitons and biexcitons. We demonstrate that lines emanating from evenly charged states are linearly polarized. Their polarization direction does not necessarily coincide with the traditional crystallographic direction. It depends on the shells of the single carriers, which participate in the recombination process.Comment: 11 pages, 9 figures. Revised versio

Modulation of nitrogen vacancy charge state and fluorescence in nanodiamonds using electrochemical potential

The negatively charged nitrogen vacancy (NV⁻) center in diamond has attracted strong interest for a wide range of sensing and quantum information processing applications. To this end, recent work has focused on controlling the NV charge state, whose stability strongly depends on its electrostatic environment. Here, we demonstrate that the charge state and fluorescence dynamics of single NV centers in nanodiamonds with different surface terminations can be controlled by an externally applied potential difference in an electrochemical cell. The voltage dependence of the NV charge state can be used to stabilize the NV⁻ state for spin-based sensing protocols and provides a method of charge state-dependent fluorescence sensing of electrochemical potentials. We detect clear NV fluorescence modulation for voltage changes down to 100 mV, with a single NV and down to 20 mV with multiple NV centers in a wide-field imaging mode. These results suggest that NV centers in nanodiamonds could enable parallel optical detection of biologically relevant electrochemical potentials.United States. Army Research Office (W911NF-12-1-0594)United States. National Institutes of Health (1R01NS087950)United States. Defense Advanced Research Projects Agency (D14PC00121)United States. Defense Advanced Research Projects Agency (HR0011-14-C-0018)United States. National Institutes of Health (1R43MH102942-01)National Science Foundation (U.S.) (1122374

Longer duration entry mitigates nystagmus and vertigo in 7-Tesla MRI

IntroductionPatients and technologists commonly describe vertigo, dizziness, and imbalance near high-field magnets, e.g., 7-Tesla (T) magnetic resonance imaging (MRI) scanners. We sought a simple way to alleviate vertigo and dizziness in high-field MRI scanners by applying the understanding of the mechanisms behind magnetic vestibular stimulation and the innate characteristics of vestibular adaptation.MethodsWe first created a three-dimensional (3D) control systems model of the direct and indirect vestibulo-ocular reflex (VOR) pathways, including adaptation mechanisms. The goal was to develop a paradigm for human participants undergoing a 7T MRI scan to optimize the speed and acceleration of entry into and exit from the MRI bore to minimize unwanted vertigo. We then applied this paradigm from the model by recording 3D binocular eye movements (horizontal, vertical, and torsion) and the subjective experience of eight normal individuals within a 7T MRI. The independent variables were the duration of entry into and exit from the MRI bore, the time inside the MRI bore, and the magnetic field strength; the dependent variables were nystagmus slow-phase eye velocity (SPV) and the sensation of vertigo.ResultsIn the model, when the participant was exposed to a linearly increasing magnetic field strength, the per-peak (after entry into the MRI bore) and post-peak (after exiting the MRI bore) responses of nystagmus SPV were reduced with increasing duration of entry and exit, respectively. There was a greater effect on the per-peak response. The entry/exit duration and peak response were inversely related, and the nystagmus was decreased the most with the 5-min duration paradigm (the longest duration modeled). The experimental nystagmus pattern of the eight normal participants matched the model, with increasing entry duration having the strongest effect on the per-peak response of nystagmus SPV. Similarly, all participants described less vertigo with the longer duration entries.ConclusionIncreasing the duration of entry into and exit out of a 7T MRI scanner reduced or eliminated vertigo symptoms and reduced nystagmus peak SPV. Model simulations suggest that central processes of vestibular adaptation account for these effects. Therefore, 2-min entry and 20-s exit durations are a practical solution to mitigate vertigo and other discomforting symptoms associated with undergoing 7T MRI scans. In principle, these findings also apply to different magnet strengths

The Molecular Clockwork of the Fire Ant Solenopsis invicta

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication

Second-Hand Tobacco Smoke in Never Smokers Is a Significant Risk Factor for Coronary Artery Calcification

ObjectivesThe aim of this study was to assess the relationship of the extent of subclinical atherosclerosis measured by coronary artery calcification (CAC) to the extent of second-hand tobacco smoke (SHTS) exposure in asymptomatic people who never smoked.BackgroundAn association between SHTS and CAC was recently reported in a single study, but the quantitative aspects of the relationship are not known.MethodsA cohort of 3,098 never smokers 40 to 80 years of age, enrolled in the FAMRI-IELCAP (Flight Attendant Medical Research Institute International Early Lung Cancer Action Program) screening program, completed a SHTS questionnaire, and had a low-dose nongated computed tomography scan. The questionnaire provided a quantitative score for total SHTS exposure, as well as separately as a child and as an adult at home and at work; 4 categories of exposure to SHTS were identified (minimal, low, moderate, and high exposure). CAC was graded using a previously validated ordinal scale score that ranged from 0 to 12. Logistic regression analysis of the prevalence and ordered logistic regression analysis of the extent of CAC were performed to assess the independent contribution of SHTS adjusted for age, sex, diabetes, hypercholesterolemia, hypertension, and renal disease. Linear and quadratic regression analyses of CAC and SHTS were performed.ResultsThe prevalence of CAC was 24.3% (n = 754) and was significantly higher in those with more than minimal SHTS exposure compared with those with minimal SHTS exposure (26.4% vs. 18.5%, p < 0.0001). The adjusted odds ratios for CAC prevalence were 1.54 (95% confidence interval: 1.17 to 2.20) for low SHTS exposure, 1.60 (95% confidence interval: 1.21 to 2.10) for moderate exposure, and 1.93 (95% confidence interval: 1.49 to 2.51) for high exposure. The association of the extent of SHTS with the extent of CAC was confirmed by the adjusted odds ratio (p < 0.0001).ConclusionsThe presence and extent of CAC were associated with extent of SHTS exposure even when adjusted for other risk factors for CAC, suggesting that SHTS exposure causes CAC

Does the lipid-lowering peroxisome proliferator-activated receptors ligand bezafibrate prevent colon cancer in patients with coronary artery disease?

<p>Abstract</p> <p>Background</p> <p>Epidemiologic studies have suggested that hypertriglyceridemia and insulin resistance are related to the development of colon cancer. Nuclear peroxisome proliferator-activated receptors (PPAR), which play a central role in lipid and glucose metabolism, had been hypothesized as being involved in colon cancerogenesis. In animal studies the lipid-lowering PPAR ligand bezafibrate suppressed colonic tumors. However, the effect of bezafibrate on colon cancer development in humans is unknown. Therefore, we proposed to investigate a possible preventive effect of bezafibrate on the development of colon cancer in patients with coronary artery disease during a 6-year follow-up.</p> <p>Methods</p> <p>Our population included 3011 patients without any cancer diagnosis who were enrolled in the randomized, double blind Bezafibrate Infarction Prevention (BIP) Study. The patients received either 400 mg of bezafibrate retard (1506 patients) or placebo (1505 patients) once a day. Cancer incidence data were obtained by matching a subject's identification numbers with the National Cancer Registry. Each matched record was checked for correct identification.</p> <p>Results</p> <p>Development of new cancer (all types) was recorded in 177 patients: in 79 (5.25%) patients from the bezafibrate group vs. 98 (6.51%) from the placebo group. Development of colon cancer was recorded in 25 patients: in 8 (0.53%) patients from the bezafibrate group vs. 17 (1.13%) from the placebo group, (Fisher's exact test: one side p = 0.05; two side p = 0.07).</p> <p>A difference in the incidence of cancer was only detectable after a 4 year lag and progressively increased with continued follow-up. On multivariable analysis the colon cancer risk in patients who received bezafibrate tended to be lower with a hazard ratio of 0.47 and 95% confidence interval 0.2–1.1.</p> <p>Conclusion</p> <p>Our data, derived from patients with coronary artery disease, support the hypothesis regarding a possible preventive effect of bezafibrate on the development of colon cancer.</p

The landscape of molecular chaperones across human tissues reveals a layered architecture of core and variable chaperones

The sensitivity of the protein-folding environment to chaperone disruption can be highly tissue-specific. Yet, the organization of the chaperone system across physiological human tissues has received little attention. Through computational analyses of large-scale tissue transcriptomes, we unveil that the chaperone system is composed of core elements that are uniformly expressed across tissues, and variable elements that are differentially expressed to fit with tissue-specific requirements. We demonstrate via a proteomic analysis that the muscle-specific signature is functional and conserved. Core chaperones are significantly more abundant across tissues and more important for cell survival than variable chaperones. Together with variable chaperones, they form tissue-specific functional networks. Analysis of human organ development and aging brain transcriptomes reveals that these functional networks are established in development and decline with age. In this work, we expand the known functional organization of de novo versus stress-inducible eukaryotic chaperones into a layered core-variable architecture in multi-cellular organisms