WldS but not Nmnat1 protects dopaminergic neurites from MPP+ neurotoxicity

<p>Abstract</p> <p>Background</p> <p>The <it>Wld^S</it>mouse mutant ("Wallerian degeneration-slow") delays axonal degeneration in a variety of disorders including <it>in vivo </it>models of Parkinson's disease. The mechanisms underlying <it>Wld^S</it>-mediated axonal protection are unclear, although many studies have attributed <it>Wld^S</it>neuroprotection to the NAD⁺-synthesizing Nmnat1 portion of the fusion protein. Here, we used dissociated dopaminergic cultures to test the hypothesis that catalytically active Nmnat1 protects dopaminergic neurons from toxin-mediated axonal injury.</p> <p>Results</p> <p>Using mutant mice and lentiviral transduction of dopaminergic neurons, the present findings demonstrate that <it>Wld^S</it>but not Nmnat1, Nmnat3, or cytoplasmically-targeted Nmnat1 protects dopamine axons from the parkinsonian mimetic N-methyl-4-phenylpyridinium (MPP⁺). Moreover, NAD⁺synthesis is not required since enzymatically-inactive <it>Wld^S</it>still protects. In addition, NAD⁺by itself is axonally protective and together with <it>Wld^S</it>is additive in the MPP⁺model.</p> <p>Conclusions</p> <p>Our data suggest that NAD⁺and <it>Wld^S</it>act through separate and possibly parallel mechanisms to protect dopamine axons. As MPP⁺is thought to impair mitochondrial function, these results suggest that <it>Wld^S</it>might be involved in preserving mitochondrial health or maintaining cellular metabolism.</p

Luttinger Liquid in the Core of Screw Dislocation in Helium-4

On the basis of first-principle Monte Carlo simulations we find that the screw dislocation along the hexagonal axis of an hcp He4 crystal features a superfluid core. This is the first example of a regular quasi-one-dimensional supersolid, and one of the cleanest cases of a regular Luttinger-liquid system. In contrast, the same type of screw dislocation in solid Hydrogen is insulating.Comment: replaced with revised versio

Identification of Erosional Terraces on Seamounts: Implications for Interisland Connectivity and Subsidence in the Galápagos Archipelago

Shallow seamounts at ocean island hotspots and in other settings may record emergence histories in the form of submarine erosional terraces. Exposure histories are valuable for constraining paleo-elevations and sea levels in the absence of more traditional markers, such as drowned coral reefs. However, similar features can also be produced through primary volcanic processes, which complicate the use of terraced seamounts as an indicator of paleo-shorelines. In the western Galápagos Archipelago, we utilize newly collected bathymetry along with seafloor observations from human-occupied submersibles to document the location and depth of erosional terraces on seamounts near the islands of Santiago, Santa Cruz, Floreana, Isabela, and Fernandina. We directly observed erosional features on 22 seamounts with terraces. We use these observations and bathymetric analysis to develop a framework to identify terrace-like morphologic features and classify them as either erosional or volcanic in origin. From this framework we identify 79 erosional terraces on 30 seamounts that are presently found at depths of 30 to 300 m. Although intermittent subaerial connectivity between the islands has been hypothesized, the depths of these erosional terraces in the Santiago region are the first direct evidence of paleo-connectivity in the modern archipelago. Collectively, the terraces have non-randomly distributed depths. We suggest that peaks in the distribution of terrace depths likely represent long durations of exposure (i.e., sea-level still or lowstands). By comparing these peaks to those of subsidence adjusted sea-level curves, we identify the average subsidence rate that best reproduces the observed terrace distributions. These rates are 0.2–0.4 m/ka for this portion of the central Galápagos, since the formation of the seamounts, consistent with previous independent estimates. Using these subsidence rates and evidence for erosional terraces at depths up to 300 m, we conclude that all islands in the central archipelago have been intermittently connected starting between 435 and 900 ka. Individual island pairs have likely been repeatedly subaerially connected for short intervals since that time

Bound states of edge dislocations: The quantum dipole problem in two dimensions

We investigate bound state solutions of the 2D Schr\"odinger equation with a dipole potential originating from the elastic effects of a single edge dislocation. The knowledge of these states could be useful for understanding a wide variety of physical systems, including superfluid behavior along dislocations in solid $^4$He. We present a review of the results obtained by previous workers together with an improved variational estimate of the ground state energy. We then numerically solve the eigenvalue problem and calculate the energy spectrum. In our dimensionless units, we find a ground state energy of -0.139, which is lower than any previous estimate. We also make successful contact with the behavior of the energy spectrum as derived from semiclassical considerations.Comment: 6 pages, 3 figures, submitted to PR

Framework for Defining and Assessing Benefits of a Modular Assembly Design Approach for Exploration Systems

A comprehensive modular assembly system model has been proposed that extends the art from modular hardware, to include in-space assembly, servicing and repair and it s critical components of infrastructure, agents and assembly operations. Benefits of modular assembly have been identified and a set of metrics defined that extends the art beyond the traditional measures of performance, with emphasis on criteria that allow life-cycle mission costs to be used as a figure of merit (and include all substantive terms that have an impact on the evaluation). The modular assembly approach was used as a basis for developing a Solar Electric Transfer Vehicle (SETV) concept and three modular assembly scenarios were developed. The modular assembly approach also allows the SETV to be entered into service much earlier than competing conventional configurations and results in a great deal of versatility in accommodating different launch vehicle payload capabilities, allowing for modules to be pre-assembled before launch or assembled on orbit, without changing the space vehicle design

Detecting and monitoring the symptoms of Parkinson's disease using smartphones:a pilot study

Background: Remote, non-invasive and objective tests that can be used to support expert diagnosis for Parkinson's disease (PD) are lacking. Methods: Participants underwent baseline in-clinic assessments, including the Unified Parkinson's Disease Rating Scale (UPDRS), and were provided smartphones with an Android operating system that contained a smartphone application that assessed voice, posture, gait, finger tapping, and response time. Participants then took the smart phones home to perform the five tasks four times a day for a month. Once a week participants had a remote (telemedicine) visit with a Parkinson disease specialist in which a modified (excluding assessments of rigidity and balance) UPDRS performed. Using statistical analyses of the five tasks recorded using the smartphone from 10 individuals with PD and 10 controls, we sought to: (1) discriminate whether the participant had PD and (2) predict the modified motor portion of the UPDRS. Results: Twenty participants performed an average of 2.7 tests per day (68.9% adherence) for the study duration (average of 34.4 days) in a home and community setting. The analyses of the five tasks differed between those with Parkinson disease and those without. In discriminating participants with PD from controls, the mean sensitivity was 96.2% (SD 2%) and mean specificity was 96.9% (SD 1.9%). The mean error in predicting the modified motor component of the UPDRS (range 11-34) was 1.26 UPDRS points (SD 0.16). Conclusion: Measuring PD symptoms via a smartphone is feasible and has potential value as a diagnostic support tool

Superheating fields of superconductors: Asymptotic analysis and numerical results

The superheated Meissner state in type-I superconductors is studied both analytically and numerically within the framework of Ginzburg-Landau theory. Using the method of matched asymptotic expansions we have developed a systematic expansion for the solutions of the Ginzburg-Landau equations in the limit of small $\kappa$, and have determined the maximum superheating field $H_{\rm sh}$ for the existence of the metastable, superheated Meissner state as an expansion in powers of $\kappa^{1/2}$. Our numerical solutions of these equations agree quite well with the asymptotic solutions for $\kappa<0.5$. The same asymptotic methods are also used to study the stability of the solutions, as well as a modified version of the Ginzburg-Landau equations which incorporates nonlocal electrodynamics. Finally, we compare our numerical results for the superheating field for large-$\kappa$ against recent asymptotic results for large-$\kappa$, and again find a close agreement. Our results demonstrate the efficacy of the method of matched asymptotic expansions for dealing with problems in inhomogeneous superconductivity involving boundary layers.Comment: 14 pages, 8 uuencoded figures, Revtex 3.

Monogenetic near-island seamounts in the Galapagos Archipelago

Author Posting. © American Geophysical Union, 2020. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry, Geophysics, Geosystems 21(12), (2020): e2020GC008914, https://doi.org/10.1029/2020GC008914.Rarely have small seamounts on the flanks of hotspot derived ocean‐island volcanoes been the targets of sampling, due to sparse high‐resolution mapping near ocean islands. In the Galápagos Archipelago, for instance, sampling has primarily targeted the subaerial volcanic edifices, with only a few studies focusing on large‐volume submarine features. Sampling restricted to these large volcanic features may present a selection bias, potentially resulting in a skewed view of magmatic and source processes because mature magmatic systems support mixing and volcanic accretion that overprints early magmatic stages. We demonstrate how finer‐scale sampling of satellite seamounts surrounding the volcanic islands in the Galápagos can be used to lessen this bias and thus, better constrain the evolution of these volcanoes. Seamounts were targeted in the vicinity of Floreana and Fernandina Islands, and between Santiago and Santa Cruz. In all regions, individual seamounts are typically monogenetic, but each seamount field requires multigenerational magmatic episodes to account for their geochemical variability. This study demonstrates that in the southern and eastern regions the seamounts are characterized by greater geochemical variability than the islands they surround but all three regions have (Sr‐Nd‐He) isotopic signatures that resemble neighboring islands. Variations in seamount chemistry from alkalic to tholeiitic near Fernandina support the concept that islands along the center of the hotspot track undergo greater mean depths of melting, as predicted by plume theory. Patterns of geochemical and isotopic enrichment of seamounts within each region support fine‐scale mantle heterogeneities in the mantle plume sourcing the Galápagos hotspot.This work was carried out with funding from National Science Foundation Division of Ocean Sciences (OCE‐1634952 to V. D. Wanless, OCE‐1634685 to S. A. Soule). The authors have no competing interests to declare. We thank Sally Gibson and three anonymous reviewers for providing detailed and critical feedback on this manuscript.2021-05-0

Storm Effects on Regional Beach Water Quality Along the Southern California Shoreline

Two regional studies conducted during dry weather demonstrated that the Southern California Bight (SCB) shoreline has good water quality, except near areas that drain land-based runoff. Here, we repeat those regional studies 36 h after a rainstorm to assess the influence of runoff under high flow conditions. Two hundred and fifty-four shoreline sites between Santa Barbara, California and Ensenada, Mexico were sampled using a stratified-random sampling design with four strata: sandy beaches, rocky shoreline, shoreline adjacent to urban runoff outlets that flow intermittently, and shoreline adjacent to outlets that flow year-round. Each site was sampled for total coliforms, fecal coliforms (or E. coli), and enterococci. Sixty percent of the shoreline failed water quality standards after the storm compared to only 6% during dry weather. Failure of water quality standards increased to more than 90% for shoreline areas adjacent to urban runoff outlets. During dry weather, most water quality failures occurred for only one of the three bacterial indicators and concentrations were barely above State of California standards; following the storm, most failures were for multiple indicators and exceeded State of California standards by a large margin. The condition of the shoreline in Mexico and the United States was similar following rainfall, which was not the case during dry weather

Motor asymmetry and substantia nigra volume are related to spatial delayed response performance in Parkinson disease

Studies suggest motor deficit asymmetry may help predict the pattern of cognitive impairment in individuals with Parkinson disease (PD). We tested this hypothesis using a highly validated and sensitive spatial memory task, spatial delayed response (SDR), and clinical and neuroimaging measures of PD asymmetry. We predicted SDR performance would be more impaired by PD-related changes in the right side of the brain than in the left. PD (n = 35) and control (n = 28) participants performed the SDR task. PD participants either had worse motor deficits on the right (RPD) or left (LPD) side of the body. Some participants also had magnetic resonance imaging for measurement of their substantia nigra (SN) volumes. The LPD group performed worse on the SDR task than the RPD and control groups. Right SN volume accounted for a unique and significant portion of the variance in SDR error, with smaller volume predicting poorer performance. In conclusion, left motor dysfunction and smaller right SN volume are associated with poorer spatial memory