1,131 research outputs found
Diastereofacial selectivity in reactions of substituted cyclohexyl radicals. An experimental and theoretical study
Depopulation of dense α-synuclein aggregates is associated with rescue of dopamine neuron dysfunction and death in a new Parkinson's disease model.
Parkinson's disease (PD) is characterized by the presence of α-synuclein aggregates known as Lewy bodies and Lewy neurites, whose formation is linked to disease development. The causal relation between α-synuclein aggregates and PD is not well understood. We generated a new transgenic mouse line (MI2) expressing human, aggregation-prone truncated 1-120 α-synuclein under the control of the tyrosine hydroxylase promoter. MI2 mice exhibit progressive aggregation of α-synuclein in dopaminergic neurons of the substantia nigra pars compacta and their striatal terminals. This is associated with a progressive reduction of striatal dopamine release, reduced striatal innervation and significant nigral dopaminergic nerve cell death starting from 6 and 12 months of age, respectively. In the MI2 mice, alterations in gait impairment can be detected by the DigiGait test from 9 months of age, while gross motor deficit was detected by rotarod test at 20 months of age when 50% of dopaminergic neurons in the substantia nigra pars compacta are lost. These changes were associated with an increase in the number and density of 20-500 nm α-synuclein species as shown by dSTORM. Treatment with the oligomer modulator anle138b, from 9 to 12 months of age, restored striatal dopamine release, prevented dopaminergic cell death and gait impairment. These effects were associated with a reduction of the inner density of large α-synuclein aggregates and an increase in dispersed small α-synuclein species as revealed by dSTORM. The MI2 mouse model recapitulates the progressive dopaminergic deficit observed in PD, showing that early synaptic dysfunction is associated to fine behavioral motor alterations, precedes dopaminergic axonal loss and neuronal death that become associated with a more consistent motor deficit upon reaching a certain threshold. Our data also provide new mechanistic insight for the effect of anle138b's function in vivo supporting that targeting α-synuclein aggregation is a promising therapeutic approach for PD
Influence of Retardation on the Vibrational Wave Function and Binding Energy of the Helium Dimer
Because of the extremely small binding energy of the helium dimer, the nuclear wave function is delocalized over an extremely large range of separations. One might therefore expect the properties of this extraordinary species to be sensitive to the potential at very large internuclear distances, r, where relativistic corrections to the usual van der Waals interaction may be important. We have estimated the effect of retardation, which changes the r-6 dependence of the potential to r-7 in the limit of large r, and have found that the binding energy and expectation value (r) are indeed significantly affected by its inclusion
Coefficient of restitution for elastic disks
We calculate the coefficient of restitution, , starting from a
microscopic model of elastic disks. The theory is shown to agree with the
approach of Hertz in the quasistatic limit, but predicts inelastic collisions
for finite relative velocities of two approaching disks. The velocity
dependence of is calculated numerically for a wide range of
velocities. The coefficient of restitution furthermore depends on the elastic
constants of the material via Poisson's number. The elastic vibrations absorb
kinetic energy more effectively for materials with low values of the shear
modulus.Comment: 25 pages, 12 Postscript figures, LaTex2
Interferometry with Bose-Einstein Condensates in Microgravity
Atom interferometers covering macroscopic domains of space-time are a
spectacular manifestation of the wave nature of matter. Due to their unique
coherence properties, Bose-Einstein condensates are ideal sources for an atom
interferometer in extended free fall. In this paper we report on the
realization of an asymmetric Mach-Zehnder interferometer operated with a
Bose-Einstein condensate in microgravity. The resulting interference pattern is
similar to the one in the far-field of a double-slit and shows a linear scaling
with the time the wave packets expand. We employ delta-kick cooling in order to
enhance the signal and extend our atom interferometer. Our experiments
demonstrate the high potential of interferometers operated with quantum gases
for probing the fundamental concepts of quantum mechanics and general
relativity.Comment: 8 pages, 3 figures; 8 pages of supporting materia
Towards a Proof Theory of G\"odel Modal Logics
Analytic proof calculi are introduced for box and diamond fragments of basic
modal fuzzy logics that combine the Kripke semantics of modal logic K with the
many-valued semantics of G\"odel logic. The calculi are used to establish
completeness and complexity results for these fragments
Simulation for the oblique impact of a lattice system
The oblique collision between an elastic disk and an elastic wall is
numerically studied.
We investigate the dependency of the tangential coefficient of restitution on
the incident angle of impact.
From the results of simulation, our model reproduces experimental results and
can be explained by a phenomenological theory of the oblique impact.Comment: 30 pages, 9 figures, submitted to J. Phys. Soc. Japa
Glucosylsphingosine Is a Highly Sensitive and Specific Biomarker for Primary Diagnostic and Follow-Up Monitoring in Gaucher Disease in a Non-Jewish, Caucasian Cohort of Gaucher Disease Patients
Gaucher disease (GD) is the most common lysosomal storage disorder (LSD). Based on a deficient β-glucocerebrosidase it leads to an accumulation of glucosylceramide. Standard diagnostic procedures include measurement of enzyme activity, genetic testing as well as analysis of chitotriosidase and CCL18/PARC as biomarkers. Even though chitotriosidase is the most well-established biomarker in GD, it is not specific for GD. Furthermore, it may be false negative in a significant percentage of GD patients due to mutation. Additionally, chitotriosidase reflects the changes in the course of the disease belatedly. This further enhances the need for a reliable biomarker, especially for the monitoring of the disease and the impact of potential treatments.Here, we evaluated the sensitivity and specificity of the previously reported biomarker Glucosylsphingosine with regard to different control groups (healthy control vs. GD carriers vs. other LSDs).Only GD patients displayed elevated levels of Glucosylsphingosine higher than 12 ng/ml whereas the comparison controls groups revealed concentrations below the pathological cut-off, verifying the specificity of Glucosylsphingosine as a biomarker for GD. In addition, we evaluated the biomarker before and during enzyme replacement therapy (ERT) in 19 patients, demonstrating a decrease in Glucosylsphingosine over time with the most pronounced reduction within the first 6 months of ERT. Furthermore, our data reveals a correlation between the medical consequence of specific mutations and Glucosylsphingosine.In summary, Glucosylsphingosine is a very promising, reliable and specific biomarker for GD
Some Like It Fat: Comparative Ultrastructure of the Embryo in Two Demosponges of the Genus Mycale (Order Poecilosclerida) from Antarctica and the Caribbean
0000-0002-7993-1523© 2015 Riesgo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License [4.0], which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The attached file is the published version of the article
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