The Neurotoxicity of DOPAL: Behavioral and Stereological Evidence for Its Role in Parkinson Disease Pathogenesis

BACKGROUND: The etiology of Parkinson disease (PD) has yet to be fully elucidated. We examined the consequences of injections of 3,4-dihydroxyphenylacetaldehyde (DOPAL), a toxic metabolite of dopamine, into the substantia nigra of rats on motor behavior and neuronal survival. METHODS/PRINCIPAL FINDINGS: A total of 800 nl/rat of DOPAL (1 µg/200 nl) was injected stereotaxically into the substantia nigra over three sites while control animals received similar injections of phosphate buffered saline. Rotational behavior of these rats was analyzed, optical density of striatal tyrosine hydroxylase was calculated, and unbiased stereological counts of the substantia nigra were made. The rats showed significant rotational asymmetry ipsilateral to the lesion, supporting disruption of dopaminergic nigrostriatal projections. Such disruption was verified since the density of striatal tyrosine hydroxylase decreased significantly (p<0.001) on the side ipsilateral to the DOPAL injections when compared to the non-injected side. Stereological counts of neurons stained for Nissl in pars compacta of the substantia nigra significantly decreased (p<0.001) from control values, while counts of those in pars reticulata were unchanged after DOPAL injections. Counts of neurons immunostained for tyrosine hydroxylase also showed a significant (p=0.032) loss of dopaminergic neurons. In spite of significant loss of dopaminergic neurons, DOPAL injections did not induce significant glial reaction in the substantia nigra. CONCLUSIONS: The present study provides the first in vivo quantification of substantia nigra pars compacta neuronal loss after injection of the endogenous toxin DOPAL. The results demonstrate that injections of DOPAL selectively kills SN DA neurons, suggests loss of striatal DA terminals, spares non-dopaminergic neurons of the pars reticulata, and triggers a behavioral phenotype (rotational asymmetry) consistent with other PD animal models. This study supports the "catecholaldehyde hypothesis" as an important link for the etiology of sporadic PD

Obesity and osteoarthritis in knee, hip and/or hand: An epidemiological study in the general population with 10 years follow-up

<p>Abstract</p> <p>Background</p> <p>Obesity is one of the most important risk factors for osteoarthritis (OA) in knee(s). However, the relationship between obesity and OA in hand(s) and hip(s) remains controversial and needs further investigation. The purpose of this study was to investigate the impact of obesity on incident osteoarthritis (OA) in hip, knee, and hand in a general population followed in 10 years.</p> <p>Methods</p> <p>A total of 1854 people aged 24–76 years in 1994 participated in a Norwegian study on musculoskeletal pain in both 1994 and 2004. Participants with OA or rheumatoid arthritis in 1994 and those above 74 years in 1994 were excluded, leaving n = 1675 for the analyses. The main outcome measure was OA diagnosis at follow-up based on self-report. Obesity was defined by a body mass index (BMI) of 30 and above.</p> <p>Results</p> <p>At 10-years follow-up the incidence rates were 5.8% (CI 4.3–7.3) for hip OA, 7.3% (CI 5.7–9.0) for knee OA, and 5.6% (CI 4.2–7.1) for hand OA. When adjusting for age, gender, work status and leisure time activities, a high BMI (> 30) was significantly associated with knee OA (OR 2.81; 95%CI 1.32–5.96), and a dose-response relationship was found for this association. Obesity was also significantly associated with hand OA (OR 2.59; 1.08–6.19), but not with hip OA (OR 1.11; 0.41–2.97). There was no statistically significant interaction effect between BMI and gender, age or any of the other confounding variables.</p> <p>Conclusion</p> <p>A high BMI was significantly associated with knee OA and hand OA, but not with hip OA.</p

Disturbance and Recovery of Salt Marsh Arthropod Communities following BP Deepwater Horizon Oil Spill

Oil spills represent a major environmental threat to coastal wetlands, which provide a variety of critical ecosystem services to humanity. The U.S. Gulf of Mexico is a hub of oil and gas exploration activities that historically have impacted intertidal habitats such as salt marsh. Following the BP Deepwater Horizon oil spill, we sampled the terrestrial arthropod community and marine invertebrates found in stands of Spartina alterniflora, the most abundant plant in coastal salt marshes. Sampling occurred in 2010 as oil was washing ashore and a year later in 2011. In 2010, intertidal crabs and terrestrial arthropods (insects and spiders) were suppressed by oil exposure even in seemingly unaffected stands of plants; however, Littoraria snails were unaffected. One year later, crab and arthropods had largely recovered. Our work is the first attempt that we know of assessing vulnerability of the salt marsh arthropod community to oil exposure, and it suggests that arthropods are both quite vulnerable to oil exposure and quite resilient, able to recover from exposure within a year if host plants remain healthy

π+\pi^+ photoproduction on the proton for photon energies from 0.725 to 2.875 GeV

Differential cross sections for the reaction $\gamma p \to n \pi^+$ have been measured with the CEBAF Large Acceptance Spectrometer (CLAS) and a tagged photon beam with energies from 0.725 to 2.875 GeV. Where available, the results obtained here compare well with previously published results for the reaction. Agreement with the SAID and MAID analyses is found below 1 GeV. The present set of cross sections has been incorporated into the SAID database, and exploratory fits have been made up to 2.7 GeV. Resonance couplings have been extracted and compared to previous determinations. With the addition of these cross sections to the world data set, significant changes have occurred in the high-energy behavior of the SAID cross-section predictions and amplitudes.Comment: 18 pages, 10 figure

Differential cross sections and spin density matrix elements for the reaction gamma p -> p omega

High-statistics differential cross sections and spin density matrix elements for the reaction gamma p -> p omega have been measured using the CLAS at Jefferson Lab for center-of-mass (CM) energies from threshold up to 2.84 GeV. Results are reported in 112 10-MeV wide CM energy bins, each subdivided into cos(theta_CM) bins of width 0.1. These are the most precise and extensive omega photoproduction measurements to date. A number of prominent structures are clearly present in the data. Many of these have not previously been observed due to limited statistics in earlier measurements

Observation of an Exotic S=+1S=+1 Baryon in Exclusive Photoproduction from the Deuteron

In an exclusive measurement of the reaction $\gamma d \to K^+ K^- p n$, a narrow peak that can be attributed to an exotic baryon with strangeness $S=+1$ is seen in the $K^+n$ invariant mass spectrum. The peak is at $1.542\pm 0.005$ GeV/c$^2$ with a measured width of 0.021 GeV/c$^2$ FWHM, which is largely determined by experimental mass resolution. The statistical significance of the peak is $5.2 \pm 0.6 \sigma$. The mass and width of the observed peak are consistent with recent reports of a narrow $S=+1$ baryon by other experimental groups.Comment: 5 pages, 5 figure

Measurement of the Polarized Structure Function σLT′\sigma_{LT^\prime} for p(e⃗,e′p)πop(\vec{e},e'p)\pi^o in the Δ(1232)\Delta(1232) Resonance Region

The polarized longitudinal-transverse structure function $\sigma_{LT^\prime}$ has been measured in the $\Delta(1232)$ resonance region at $Q^2=0.40$ and 0.65 GeV$^2$. Data for the $p(\vec e,e'p)\pi^o$ reaction were taken at Jefferson Lab with the CEBAF Large Acceptance Spectrometer (CLAS) using longitudinally polarized electrons at an energy of 1.515 GeV. For the first time a complete angular distribution was measured, permitting the separation of different non-resonant amplitudes using a partial wave analysis. Comparison with previous beam asymmetry measurements at MAMI indicate a deviation from the predicted $Q^2$ dependence of $\sigma_{LT^{\prime}}$ using recent phenomenological models.Comment: 5 pages, LaTex, 4 eps figures: to be published in PRC/Rapid Communications. Version 2 has revised Q^2 analysi

Search for the Θ+\Theta^+ pentaquark in the reaction γd→pK−K+n\gamma d \to p K^- K^+ n

A search for the \thp in the reaction $\gamma d \to pK^-K^+n$ was completed using the CLAS detector at Jefferson Lab. A study of the same reaction, published earlier, reported the observation of a narrow \thp resonance. The present experiment, with more than 30 times the integrated luminosity of our earlier measurement, does not show any evidence for a narrow pentaquark resonance. The angle-integrated upper limit on \thp production in the mass range of 1.52 to 1.56 GeV/c$^2$ for the $\gamma d \to pK^-\Theta^+$ reaction is 0.3 nb (95% CL). This upper limit depends on assumptions made for the mass and angular distribution of \thp production. Using \lamstar production as an empirical measure of rescattering in the deuteron, the cross section upper limit for the elementary $\gamma n \to K^-\Theta^+$ reaction is estimated to be a factor of 10 higher, {\it i.e.}, $\sim 3$ nb (95% CL).Comment: 5 figures, submitted to PRL, revised for referee comment

Survey of A_LT' asymmetries in semi-exclusive electron scattering on He4 and C12

Single spin azimuthal asymmetries A_LT' were measured at Jefferson Lab using 2.2 and 4.4 GeV longitudinally polarized electrons incident on He4 and C12 targets in the CLAS detector. A_LT' is related to the imaginary part of the longitudinal-transverse interference and in quasifree nucleon knockout it provides an unambiguous signature for final state interactions (FSI). Experimental values of A_LT' were found to be below 5%, typically |A_LT'| < 3% for data with good statistical precision. Optical Model in Eikonal Approximation (OMEA) and Relativistic Multiple-Scattering Glauber Approximation (RMSGA) calculations are shown to be consistent with the measured asymmetries.Comment: 9 pages, 5 figure

Onset of asymptotic scaling in deuteron photodisintegration

We investigate the transition from the nucleon-meson to quark-gluon description of the strong interaction using the photon energy dependence of the $d(\gamma,p)n$ differential cross section for photon energies above 0.5 GeV and center-of-mass proton angles between $30^{\circ}$ and $150^{\circ}$. A possible signature for this transition is the onset of cross section $s^{-11}$ scaling with the total energy squared, $s$, at some proton transverse momentum, $P_T$. The results show that the scaling has been reached for proton transverse momentum above about 1.1 GeV/c. This may indicate that the quark-gluon regime is reached above this momentum.Comment: Accepted by PRL; 5 pages, 2 figure