Motor phenotype and magnetic resonance measures of basal ganglia iron levels in Parkinson's disease

BACKGROUND: In Parkinson's disease the degree of motor impairment can be classified with respect to tremor dominant and akinetic rigid features. While tremor dominance and akinetic rigidity might represent two ends of a continuum rather than discrete entities, it would be important to have non-invasive markers of any biological differences between them in vivo, to assess disease trajectories and response to treatment, as well as providing insights into the underlying mechanisms contributing to heterogeneity within the Parkinson's disease population. METHODS: Here, we used magnetic resonance imaging to examine whether Parkinson's disease patients exhibit structural changes within the basal ganglia that might relate to motor phenotype. Specifically, we examined volumes of basal ganglia regions, as well as transverse relaxation rate (a putative marker of iron load) and magnetization transfer saturation (considered to index structural integrity) within these regions in 40 individuals. RESULTS: We found decreased volume and reduced magnetization transfer within the substantia nigra in Parkinson's disease patients compared to healthy controls. Importantly, there was a positive correlation between tremulous motor phenotype and transverse relaxation rate (reflecting iron load) within the putamen, caudate and thalamus. CONCLUSIONS: Our findings suggest that akinetic rigid and tremor dominant symptoms of Parkinson's disease might be differentiated on the basis of the transverse relaxation rate within specific basal ganglia structures. Moreover, they suggest that iron load within the basal ganglia makes an important contribution to motor phenotype, a key prognostic indicator of disease progression in Parkinson's disease

Evaluating the Immunogenicity of Protein Drugs by Applying In Vitro

The immune system has evolved to become highly specialized in recognizing and responding to pathogens and foreign molecules. Specifically, the function of HLA class II is to ensure that a sufficient sample of peptides derived from foreign molecules is presented to T cells. This leads to an important concern in human drug development as the possible immunogenicity of biopharmaceuticals, especially those intended for chronic administration, can lead to reduced efficacy and an undesired safety profile for biological therapeutics. As part of this review, we will highlight the molecular basis of antigen presentation as a key step in the induction of T cell responses, emphasizing the events associated with peptide binding to polymorphic and polygenic HLA class II molecules. We will further review methodologies that predict HLA class II binding peptides and candidate epitopes. We will focus on tools provided by the Immune Epitope Database and Analysis Resource, discussing the basic features of different prediction methods, the objective evaluation of prediction quality, and general guidelines for practical use of these tools. Finally the use, advantages, and limitations of the methodology will be demonstrated in a review of two previous studies investigating the immunogenicity of erythropoietin and timothy grass pollen

Apparent thinning of human visual cortex during childhood is associated with myelination

Human cortex appears to thin during childhood development. However, the underlying microstructural mechanisms are unknown. Using functional magnetic resonance imaging (fMRI), quantitative MRI (qMRI), and diffusion MRI (dMRI) in children and adults, we tested what quantitative changes occur to gray and white matter in ventral temporal cortex (VTC) from childhood to adulthood, and how these changes relate to cortical thinning. T1 relaxation time from qMRI and mean diffusivity (MD) from dMRI provide independent and complementary measurements of microstructural properties of gray and white matter tissue. In face- and character-selective regions in lateral VTC, T1 and MD decreased from age 5 to adulthood in mid and deep cortex, as well as in their adjacent white matter. T1 reduction also occurred longitudinally in children’s brain regions. T1 and MD decreases 1) were consistent with tissue growth related to myelination, which we verified with adult histological myelin stains, and 2) were correlated with apparent cortical thinning. In contrast, in place-selective cortex in medial VTC, we found no development of T1 or MD after age 5, and thickness was related to cortical morphology. These findings suggest that lateral VTC likely becomes more myelinated from childhood to adulthood, affecting the contrast of MR images and, in turn, the apparent gray–white boundary. These findings are important because they suggest that VTC does not thin during childhood but instead gets more myelinated. Our data have broad ramifications for understanding both typical and atypical brain development using advanced in vivo quantitative measurements and clinical conditions implicating myelin

In vivo evidence of remote neural degeneration in the lumbar enlargement after cervical injury

Objective To characterize remote secondary neurodegeneration of spinal tracts and neurons below a cervical spinal cord injury (SCI) and its relation to the severity of injury, the integrity of efferent and afferent pathways, and clinical impairment. Methods A comprehensive high-resolution MRI protocol was acquired in 17 traumatic cervical SCI patients and 14 controls at 3T. At the cervical lesion, a sagittal T2-weighted scan provided information on the width of preserved midsagittal tissue bridges. In the lumbar enlargement, high-resolution T2*-weighted and diffusion-weighted scans were used to calculate tissue-specific cross-sectional areas and diffusion indices, respectively. Regression analyses determined associations between MRI readouts and the electrophysiologic and clinical measures. Results At the cervical injury level, preserved midsagittal tissue bridges were present in the majority of patients. In the lumbar enlargement, neurodegeneration—in terms of macrostructural and microstructural MRI changes—was evident in the white matter and ventral and dorsal horns. Patients with thinner midsagittal tissue bridges had smaller ventral horn area, higher radial diffusivity in the gray matter, smaller motor evoked potential amplitude from the lower extremities, and lower motor score. In addition, smaller width of midsagittal tissue bridges was also associated with smaller tibialis sensory evoked potential amplitude and lower light-touch score. Conclusions This study shows extensive tissue-specific cord pathology in infralesional spinal networks following cervical SCI, its magnitude relating to lesion severity, electrophysiologic integrity, and clinical impairment of the lower extremity. The clinical eloquence of remote neurodegenerative changes speaks to the application of neuroimaging biomarkers in diagnostic workup and planning of clinical trials

Flavor decomposition of the sea quark helicity distributions in the nucleon from semi-inclusive deep-inelastic scattering

Double-spin asymmetries of semi-inclusive cross sections for the production of identified pions and kaons have been measured in deep-inelastic scattering of polarized positrons on a polarized deuterium target. Five helicity distributions including those for three sea quark flavors were extracted from these data together with re-analyzed previous data for identified pions from a hydrogen target. These distributions are consistent with zero for all three sea flavors. A recently predicted flavor asymmetry in the polarization of the light quark sea appears to be disfavored by the data.Comment: 5 pages, 3 figure

Nuclear Polarization of Molecular Hydrogen Recombined on a Non-metallic Surface

The nuclear polarization of $\mathrm{H}_2$ molecules formed by recombination of nuclear polarized H atoms on the surface of a storage cell initially coated with a silicon-based polymer has been measured by using the longitudinal double-spin asymmetry in deep-inelastic positron-proton scattering. The molecules are found to have a substantial nuclear polarization, which is evidence that initially polarized atoms retain their nuclear polarization when absorbed on this type of surfac

First Measurement of the Tensor Structure Function b1b_1 of the Deuteron

The \Hermes experiment has investigated the tensor spin structure of the deuteron using the 27.6 GeV/c positron beam of \Hera. The use of a tensor polarized deuteron gas target with only a negligible residual vector polarization enabled the first measurement of the tensor asymmetry \At and the tensor structure function \bd for average values of the Bj{\o}rken variable $0.01<0.45$ and of the squared four-momentum transfer $0.5 {\rm GeV^2} <5 {\rm GeV^2}$. The quantities \At and \bd are found to be non-zero. The rise of \bd for decreasing values of $x$ can be interpreted to originate from the same mechanism that leads to nuclear shadowing in unpolarized scattering

The Q^2-Dependence of Nuclear Transparency for Exclusive ρ0\rho^0 Production

Exclusive coherent and incoherent electroproduction of the $\rho^0$ meson from $^1$H and $^{14}$N targets has been studied at the HERMES experiment as a function of coherence length ($l_c$), corresponding to the lifetime of hadronic fluctuations of the virtual photon, and squared four-momentum of the virtual photon ($-Q^2$). The ratio of $^{14}$N to $^1$H cross sections per nucleon, known as nuclear transparency, was found to increase (decrease) with increasing coherence length for coherent (incoherent) $\rho^0$ electroproduction. For fixed coherence length, a rise of nuclear transparency with $Q^2$ is observed for both coherent and incoherent $\rho^0$ production, which is in agreement with theoretical calculations of color transparency.Comment: 5 pages, 4 figure

Evidence for Quark-Hadron Duality in the Proton Spin Asymmetry A1A_1

Spin-dependent lepton-nucleon scattering data have been used to investigate the validity of the concept of quark-hadron duality for the spin asymmetry $A_1$. Longitudinally polarised positrons were scattered off a longitudinally polarised hydrogen target for values of $Q^2$ between 1.2 and 12 GeV$^2$ and values of $W^2$ between 1 and 4 GeV$^2$. The average double-spin asymmetry in the nucleon resonance region is found to agree with that measured in deep-inelastic scattering at the same values of the Bjorken scaling variable $x$. This finding implies that the description of $A_1$ in terms of quark degrees of freedom is valid also in the nucleon resonance region for values of $Q^2$ above 1.6 GeV$^2$.Comment: 5 pages, 1 eps figure, table added, new references added, in print in Phys. Rev. Let

The Q2Q^2-dependence of the generalised Gerasimov-Drell-Hearn integral for the deuteron, proton and neutron

The Gerasimov-Drell-Hearn (GDH) sum rule connects the anomalous contribution to the magnetic moment of the target nucleus with an energy-weighted integral of the difference of the helicity-dependent photoabsorption cross sections. The data collected by HERMES with a deuterium target are presented together with a re-analysis of previous measurements on the proton. This provides a measurement of the generalised GDH integral covering simultaneously the nucleon-resonance and the deep inelastic scattering regions. The contribution of the nucleon-resonance region is seen to decrease rapidly with increasing $Q^2$. The DIS contribution is sizeable over the full measured range, even down to the lowest measured $Q^2$. As expected, at higher $Q^2$ the data are found to be in agreement with previous measurements of the first moment of $g_1$. From data on the deuteron and proton, the GDH integral for the neutron has been derived and the proton--neutron difference evaluated. This difference is found to satisfy the fundamental Bjorken sum rule at $Q^2 = 5$ GeV$^2$.Comment: 12 pages, 10 figure