Phosphorylated α-synuclein-immunoreactive retinal neuronal elements in Parkinson's disease subjects

Visual symptoms are relatively common in Parkinson's disease (PD) and optical coherence tomography has indicated possible retinal thinning. Accumulation of aggregated α-synuclein is thought to be a central pathogenic event in the PD brain but there have not as yet been reports of retinal synucleinopathy. Retinal wholemounts were prepared from subjects with a primary clinicopathological diagnosis of PD (N = 9), dementia with Lewy bodies (DLB; N = 3), Alzheimer's disease (N = 3), progressive supranuclear palsy (N = 2) as well as elderly normal control subjects (N = 4). These were immunohistochemically stained with an antibody against α-synuclein phosphorylated at serine 129, which is a specific molecular marker of synucleinopathy. Phosphorylated α-synuclein-immunoreactive (p-syn IR) nerve fibers were present in 7/9 PD subjects and in 1/3 DLB subjects; these were sparsely distributed and superficially located near or at the inner retinal surface. The fibers were either long and straight or branching, often with multiple en-passant varicosities along their length. The straight fibers most often had an orientation that was radial with respect to the optic disk. Together, these features are suggestive of either retinopetal/centrifugal fibers or of ganglion cell axons. In one PD subject there were sparse p-syn IR neuronal cell bodies with dendritic morphology suggestive of G19 retinal ganglion cells or intrinsically photosensitive ganglion cells. There were no stained nerve fibers or other specific staining in any of the non-PD or non-DLB subjects. It is possible that at least some of the observed visual function impairments in PD subjects might be due to α-synucleinopathy.

The European Council’s Guidelines for the Area of Freedom, Security and Justice 2020: Subverting the ‘Lisbonisation’ of Justice and Home Affairs? CEPS Essay No. 13, 14 July 2014

In its Conclusions of 26-27 June 2014, the European Council has adopted the new “Strategic Guidelines for Legislative and Operational Planning for the coming years within the EU’s Area of Freedom, Security and Justice (AFSJ)”. These Guidelines reveal a pre-Lisbon Treaty mindset among the EU member states and the Justice and Home Affairs Council. This essay argues that the Guidelines are mainly driven by the interests and agendas of national Ministries of Interior and Justice and are only “strategic” to the extent that they aim at first, re-injecting ‘intergovernmentalism’ or bringing back the old EU Third Pillar ways of working to the new EU institutional setting of the AFSJ and second, at sidelining the EU Charter of Fundamental Rights and rule of law in the AFSJ. The paper argues that the European Council Guidelines seek to prevent the advances in Justice and Home Affairs cooperation as envisaged in the Treaty of Lisbon, particularly its emphasis on supranational democratic, legal and judicial accountability. As a consequence of this move to ‘de-Lisbonise’ JHA cooperation, fundamental rights and rule of law-related initiatives will be neglected and the interest of the individual will be displaced from the centre of gravity in the coming AFSJ 2020 policy agenda.

Genetic association of CD247 (CD3ζ) with SLE in a large-scale multiethnic study

A classic T-cell phenotype in systemic lupus erythematosus (SLE) is the downregulation and replacement of the CD3ζ chain that alters T-cell receptor signaling. However, genetic associations with SLE in the human CD247 locus that encodes CD3ζ are not well established and require replication in independent cohorts. Our aim was therefore to examine, localize and validate CD247-SLE association in a large multiethnic population. We typed 44 contiguous CD247 single-nucleotide polymorphisms (SNPs) in 8922 SLE patients and 8077 controls from four ethnically distinct populations. The strongest associations were found in the Asian population (11 SNPs in intron 1, 4.99 × 10(-4) < P < 4.15 × 10(-2)), where we further identified a five-marker haplotype (rs12141731-rs2949655-rs16859085-rs12144621-rs858554; G-G-A-G-A; P(hap) = 2.12 × 10(-5)) that exceeded the most associated single SNP rs858554 (minor allele frequency in controls = 13%; P = 4.99 × 10(-4), odds ratio = 1.32) in significance. Imputation and subsequent association analysis showed evidence of association (P < 0.05) at 27 additional SNPs within intron 1. Cross-ethnic meta-analysis, assuming an additive genetic model adjusted for population proportions, showed five SNPs with significant P-values (1.40 × 10(-3) < P< 3.97 × 10(-2)), with one (rs704848) remaining significant after Bonferroni correction (P(meta) = 2.66 × 10(-2)). Our study independently confirms and extends the association of SLE with CD247, which is shared by various autoimmune disorders and supports a common T-cell-mediated mechanism.

Administrative and review guidelines for the program project grant application.

Mode of access: Internet.

Sources of hydrographic and meteorological data on the Great Lakes /

Cover title.

Forensic laboratories : handbook for facility planning, design, construction, and moving /

"NCJ 168106."

Recommended practice, symbols, terms, units, and uncertainty analysis for radiometric sensor calibration /

"September 1998."

National Institutes of Health bulletin.

First two issues lack numbering.

The effects of alcohol on performance in a driving simulator of alcoholics and social drinkers. Final report.

Federal Highway Administration, Washington, D.C.

Service life prediction based on sorptivity for highway concrete exposed to sulfate attack and freeze-thaw conditions /

"March 2002."

Arts, humanities, and culture on the NII : draft for public comment /

Reprint (pp. 117-142). Originally published: Information Infrastructure: Reaching Society's Goals. Gaithersburg, MD : National Institute of Standards and Technology, 1994.