Neurology

Contains research objectives and reports on five research projects.U.S. Public Health Service (MH-06175-02)U.S. Navy (Office of Naval Research (Nonr-1841(70))U. S. Air Force (AF 49(638)-1313)U.S. Public Health Service (B-3055-4)U.S. Public Health Service (B-3090-4

Neurology

Contains reports on four research projects.U. S. Public Health Service (B-3055-4)U. S. Public Health Service (B-3090-4)U. S. Public Health Service (MH-06175-02)U.S. Navy (Office of Naval Research (Nonr-1841 (70))U. S. Air Force (AF49(638)-1313

Neurology

Contains reports on six research projects.U. S. Public Health Service (B-3055-4, B-3090-4, MH-06175-02)U. S. Air Force (AF49(638)-1313)U.S. Navy. Office of Naval Research (Nonr-1841(70)

Neurology

Contains reports on seven research projects.U. S. Public Health Service (B-3055-3,U. S. Public Health Service (B-3090-3)U. S. Public Health Service (38101-22)Office of Naval Research (Nonr-1841 (70))Air Force (AF33(616)-7588)Air Force (AFAOSR 155-63)Army Chemical Corps (DA-18-108-405-Cml-942)National Institutes of Health (Grant MH-04734-03

Neurology

Contains research objectives and reports on six research projects.National Science Foundation (Grant G-16526)National Institutes of Health (Grant MH-04737-03)U.S. Public Health Service (B-3055-3)U.S. Public Health Service (B-3090-3)U.S. Public Health Service (MH-06175-01A1)Office of Naval Research (Nonr-1841(70))Air Force (AFOSR 155-63)Army Chemical Corps (DA- 18-108-405-CML-942

Numerical Simulation of Asymmetrically Altered Growth as Initiation Mechanism of Scoliosis

The causes of idiopathic scoliosis are still uncertain; buckling is mentioned often, but never proven. The authors hypothesize another option: unilateral postponement of growth of MM Rotatores or of ligamentum flavum and intertransverse ligament. In this paper, both buckling and the two new theories of scoliotic initiation are studied using a new finite element model that simulates the mechanical behavior of the human spine. This model was validated by the stiffness data of Panjabi et al. (J. Biomech. 9:185–192, 1976). After a small correction of the prestrain of some ligaments and the MM Rotatores the model appeared to be valid. The postponement in growth was translated in the numerical model in an asymmetrical stiffness. The spine was loaded axially and the resulting deformation was analyzed for the presence of the coupling of lateral deviation and axial rotation that is characteristic for scoliosis. Only unilateral postponement of growth of ligamentum flavum and intertransverse ligament appeared to initiate scoliosis. Buckling did not initiate scoliosis

Altered microRNA expression in frontotemporal lobar degeneration with TDP-43 pathology caused by progranulin mutations

<p>Abstract</p> <p>Background</p> <p>Frontotemporal lobar degeneration (FTLD) is a progressive neurodegenerative disorder that can be triggered through genetic or sporadic mechanisms. MicroRNAs (miRNAs) have become a major therapeutic focus as their pervasive expression and powerful regulatory roles in disease pathogenesis become increasingly apparent. Here we examine the role of miRNAs in FTLD patients with TAR DNA-binding protein 43 pathology (FTLD-TDP) caused by genetic mutations in the progranulin (<it>PGRN</it>) gene.</p> <p>Results</p> <p>Using miRNA array profiling, we identified the 20 miRNAs that showed greatest evidence (unadjusted P < 0.05) of dysregulation in frontal cortex of eight FTLD-TDP patients carrying <it>PGRN </it>mutations when compared to 32 FTLD-TDP patients with no apparent genetic abnormalities. Quantitative real-time PCR (qRT-PCR) analyses provided technical validation of the differential expression for 9 of the 20 miRNAs in frontal cortex. Additional qRT-PCR analyses showed that 5 out of 9 miRNAs (miR-922, miR-516a-3p, miR-571, miR-548b-5p, and miR-548c-5p) were also significantly dysregulated (unadjusted P < 0.05) in cerebellar tissue samples of <it>PGRN </it>mutation carriers, consistent with a systemic reduction in PGRN levels. We developed a list of gene targets for the 5 candidate miRNAs and found 18 genes dysregulated in a reported FTLD mRNA study to exhibit anti-correlated miRNA-mRNA patterns in affected cortex and cerebellar tissue. Among the targets is brain-specific angiogenesis inhibitor 3, which was recently identified as an important player in synapse biology.</p> <p>Conclusions</p> <p>Our study suggests that miRNAs may contribute to the pathogenesis of FTLD-TDP caused by <it>PGRN </it>mutations and provides new insight into potential future therapeutic options.</p

Limits on WWZWWZ and WWγWW\gamma couplings from WWWW and WZWZ production in pp‾p\overline{p} collisions at s=1.8\sqrt{s} = 1.8 TeV

Direct limits are set on $WWZ$ and $WW\gamma$ three-boson couplings in a search for $WW$ and $WZ$ production with high transverse momentum in $p\overline{p}$ collisions at $\sqrt{s} = 1.8$ TeV, using the Collider Detector at Fermilab. The results are in agreement with the SU(2) $\times$ U(1) model of electroweak interactions. Assuming Standard Model $WW\gamma$ coupling, the the limits are interpreted as direct evidence for a non-zero $WWZ$ coupling at subprocess energies near 500 GeV. Alternatively, assumiong identical $WWZ$ and $WW\gamma$ couplings, bounds $-0.11 < \kappa < 2.27$ and $-0.81 < \lambda < 0.84$ are obtained at $95\%$ CL for a form factor scale 1000 GeV.Comment: 16 pages, submitted to PRL, URL: http://www-cdf.fnal.gov/physics/pub95/cdf2951_vvprl.p

LATE-NC staging in routine neuropathologic diagnosis : an update

An international consensus report in 2019 recommended a classification system for limbic-predominant age-related TDP-43 encephalopathy neuropathologic changes (LATE-NC). The suggested neuropathologic staging system and nomenclature have proven useful for autopsy practice and dementia research. However, some issues remain unresolved, such as cases with unusual features that do not fit with current diagnostic categories. The goal of this report is to update the neuropathologic criteria for the diagnosis and staging of LATE-NC, based primarily on published data. We provide practical suggestions about how to integrate available genetic information and comorbid pathologies [e.g., Alzheimer's disease neuropathologic changes (ADNC) and Lewy body disease]. We also describe recent research findings that have enabled more precise guidance on how to differentiate LATE-NC from other subtypes of TDP-43 pathology [e.g., frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS)], and how to render diagnoses in unusual situations in which TDP-43 pathology does not follow the staging scheme proposed in 2019. Specific recommendations are also made on when not to apply this diagnostic term based on current knowledge. Neuroanatomical regions of interest in LATE-NC are described in detail and the implications for TDP-43 immunohistochemical results are specified more precisely. We also highlight questions that remain unresolved and areas needing additional study. In summary, the current work lays out a number of recommendations to improve the precision of LATE-NC staging based on published reports and diagnostic experience.Peer reviewe