Patterns of Activity Expressed by Juvenile Horseshoe Crabs

Adult American horseshoe crabs, Limulus polyphemus, possess endogenous circadian and circatidal clocks controlling visual sensitivity and locomotion, respectively. The goal of this study was to determine the types of activity rhythms expressed by juvenile horseshoe crabs (n = 24) when exposed to a 14:10 light/dark cycle (LD) for 10 days, followed by 10 days of constant darkness (DD). Horseshoe crab activity was recorded with a digital time-lapse video system that used an infrared-sensitive camera so animals could be monitored at night. In LD, 15 animals expressed daily patterns of activity, 6 displayed a circatidal pattern, and the remaining 3 were arrhythmic. Of the 15 animals with daily patterns of locomotion, 7 had a significant preference (P \u3c 0.05) for diurnal activity and 3 for nocturnal activity; the remainder did not express a significant preference for day or night activity. In DD, 13 horseshoe crabs expressed circatidal rhythms and 8 maintained a pattern of about 24 h. Although these results suggest the presence of a circadian clock influencing circatidal patterns of locomotion, these apparent circadian rhythms may actually represent the expression of just one of the two bouts of activity driven by the putative circalunidian clocks that control their tidal rhythms. Overall, these results indicate that, like adults, juvenile horseshoe crabs express both daily and tidal patterns of activity and that at least one, and maybe both, of these patterns is driven by endogenous clocks

Action Boundary Proximity Effects on Perceptual-Motor Judgments

INTRODUCTION: Designed as a more ecological measure of reaction times, the Perception-Action Coupling Task (PACT) has shown good reliability and within-subject stability. However, a lengthy testing period was required. Perceptual-motor judgments are known to be affected by proximity of the stimulus to the action boundary. The current study sought to determine the effects of action boundary proximity on PACT performance, and whether redundant levels of stimuli, eliciting similar responses, can be eliminated to shorten the PACT.METHODS: There were 9 men and 7 women who completed 4 testing sessions, consisting of 3 familiarization cycles and 6 testing cycles of the PACT. For the PACT, subjects made judgments on whether a series of balls presented on a tablet afford "posting" (can fit) through a series of apertures. There were 8 ratios of ball to aperture size (B-AR) presented, ranging from 0.2 to 1.8, with each ratio appearing 12 times (12 trials) per cycle. Reaction times and judgment accuracy were calculated, and averaged across all B-ARs. Ratios and individual trials within each B-AR were systematically eliminated. Variables were re-averaged, and intraclass correlation coefficients (ICC) and coefficients of variation (CVTE) were calculated in an iterative manner.RESULTS: With elimination of the 0.2 and 1.8 B-ARs, the PACT showed good reliability (ICC = 0.81-0.99) and consistent within-subject stability (CVTE = 2.2-14.7%). Reliability (ICC = 0.81-0.97) and stability (CVTE = 2.6-15.6%) were unaffected with elimination of up to 8 trials from each B-AR.DISCUSSION: The shortened PACT resulted in an almost 50% reduction in total familiarization/testing time required, significantly increasing usability.Johnson CD, LaGoy AD, Pepping G-J, Eagle SR, Beethe AZ, Bower JL, Alfano CA, Simpson RJ, Connaboy C. Action boundary proximity effects on perceptual-motor judgments. Aerosp Med Hum Perform. 2019; 90(12):1000-1008

Intersession Reliability and Within-Session Stability of a Novel Perception-Action Coupling Task

BACKGROUND: The perception-action coupling task (PACT) was designed as a more ecologically valid measure of alertness/reaction times compared to currently used measures by aerospace researchers. The purpose of this study was to assess the reliability, within-subject variability, and systematic bias associated with the PACT. METHODS: There were 16 subjects (men/women = 9/7; age = 27.8 +/- 3.6 yr) who completed 4 identical testing sessions. The PACT requires subjects to make judgements on whether a virtual ball could fit into an aperture. For each session, subjects completed nine cycles of the PACT, with each cycle lasting 5 min. Judgement accuracy and reaction time parameters were calculated for each cycle. Systematic bias was assessed with repeated-measures ANOVA, reliability with intraclass correlation coefficients (ICC), and within-subject variability with coefficients of variation (CVTE). RESULTS: Initiation time (Mean = 0.1065 s) showed the largest systematic bias, requiring the elimination of three cycles to reduce bias, with all other variables requiring, at the most, one. All variables showed acceptable reliability (ICC > 0.70) and within-subject variability (CVTE <20%) with only one cycle after elimination of the first three cycles. CONCLUSIONS: With a three-cycle familiarization period, the PACT was found to be reliable and stable

Chemical Chaperones Improve Protein Secretion and Rescue Mutant Factor VIII in Mice with Hemophilia A.

nefficient intracellular protein trafficking is a critical issue in the pathogenesis of a variety of diseases and in recombinant protein production. Here we investigated the trafficking of factor VIII (FVIII), which is affected in the coagulation disorder hemophilia A. We hypothesized that chemical chaperones may be useful to enhance folding and processing of FVIII in recombinant protein production, and as a therapeutic approach in patients with impaired FVIII secretion. A tagged B-domain-deleted version of human FVIII was expressed in cultured Chinese Hamster Ovary cells to mimic the industrial production of this important protein. Of several chemical chaperones tested, the addition of betaine resulted in increased secretion of FVIII, by increasing solubility of intracellular FVIII aggregates and improving transport from endoplasmic reticulum to Golgi. Similar results were obtained in experiments monitoring recombinant full-length FVIII. Oral betaine administration also increased FVIII and factor IX (FIX) plasma levels in FVIII or FIX knockout mice following gene transfer. Moreover, in vitro and in vivo applications of betaine were also able to rescue a trafficking-defective FVIII mutant (FVIIIQ305P). We conclude that chemical chaperones such as betaine might represent a useful treatment concept for hemophilia and other diseases caused by deficient intracellular protein trafficking

Cost-Effectiveness of Disease-Modifying Therapies in the Management of Multiple Sclerosis for the Medicare Population

AbstractObjectiveTo evaluate the cost-effectiveness of disease-modifying therapies (DMTs) for the management of multiple sclerosis (MS) compared to best supportive care in the United States.MethodsCost-effectiveness analysis was undertaken using a state transition model of disease natural history and the impact of DMTs for the representative Medicare beneficiary with MS. Costs and outcomes were evaluated from the health-care payer perspective using a 50-year time horizon. Natural history data were drawn from a longitudinal cohort study. The effectiveness of the DMTs was evaluated through a systematic review. Utility data were taken from a study of patients with clinically definite MS in Nova Scotia. Resource use and cost data were derived from the Sonya Slifka database and associated literature.ResultsWhen based on placebo-controlled evidence, the marginal cost-effectiveness of interferon beta (IFNβ) and glatiramer acetate compared to best supportive care is expected to be in excess of $100,000 per quality-adjusted life-year gained. When evidence from head-to-head trials is incorporated into the model, the cost-effectiveness of 6 MIU IFNβ-1a is expected to be considerably less favorable. Treatment discontinuation upon progression to Expanded Disability Status Scale 7.0 is expected to improve the cost-effectiveness of all DMTs.ConclusionsFurther research is required to examine the long-term clinical effectiveness and cost-effectiveness of these therapies. There is no definitive guidance in the United States concerning discontinuation of DMTs; this study suggests that the prudent use of a treatment discontinuation rule may considerably improve the cost-effectiveness of DMTs

Magnetic Field, Force, and Inductance Computations for an Axially Symmetric Solenoid

The pumping of liquid oxygen (LOX) by magnetic fields (B field), using an array of electromagnets, is a current topic of research and development at Kennedy Space Center, FL. Oxygen is paramagnetic so that LOX, like a ferrofluid, can be forced in the direction of a B field gradient. It is well known that liquid oxygen has a sufficient magnetic susceptibility that a strong magnetic gradient can lift it in the earth's gravitational field. It has been proposed that this phenomenon can be utilized in transporting (i.e., pumping) LOX not only on earth, but on Mars and in the weightlessness of space. In order to design and evaluate such a magnetic pumping system, it is essential to compute the magnetic and force fields, as well as inductance, of various types of electromagnets (solenoids). In this application, it is assumed that the solenoids are air wrapped, and that the current is essentially time independent

Cellular Models of Aggregation-Dependent Template-Directed Proteolysis to Characterize Tau Aggregation Inhibitors for Treatment of Alzheimer's Disease

Copyright © 2015, The American Society for Biochemistry and Molecular Biology. Acknowledgements-We thank Drs Timo Rager and Rolf Hilfiker (Solvias, Switzerland) for polymorph analyses.Peer reviewedPublisher PD

The role of discharge variability in determining alluvial stratigraphy

We illustrate the potential for using physics-based modeling to link alluvial stratigraphy to large river morphology and dynamics. Model simulations, validated using ground penetrating radar data from the Río Paraná, Argentina, demonstrate a strong relationship between bar-scale set thickness and channel depth, which applies across a wide range of river patterns and bar types. We show that hydrologic regime, indexed by discharge variability and flood duration, exerts a first-order influence on morphodynamics and hence bar set thickness, and that planform morphology alone may be a misleading variable for interpreting deposits. Indeed, our results illustrate that rivers evolving under contrasting hydrologic regimes may have very similar morphology, yet be characterized by marked differences in stratigraphy. This realization represents an important limitation on the application of established theory that links river topography to alluvial deposits, and highlights the need to obtain field evidence of discharge variability when developing paleoenvironmental reconstructions. Model simulations demonstrate the potential for deriving such evidence using metrics of paleocurrent variance

Evolution of cosmic star formation in the SCUBA-2 Cosmology Legacy Survey

We present a new exploration of the cosmic star formation history and dust obscuration in massive galaxies at redshifts 0.5 1010M⊙ galaxies at 0.5 10. One third of this is accounted for by 450-μm-detected sources, while one-fifth is attributed to UV-luminous sources (brighter than L∗UV), although even these are largely obscured. By extrapolating our results to include all stellar masses, we estimate a total SFRD that is in good agreement with previous results from IR and UV data at z ≲ 3, and from UV-only data at z ∼ 5. The cosmic star formation history undergoes a transition at z ∼ 3–4, as predominantly unobscured growth in the early Universe is overtaken by obscured star formation, driven by the build-up of the most massive galaxies during the peak of cosmic assembly

Squirrelpox virus: assessing prevalence, transmission and environmental degradation

Red squirrels (Sciurus vulgaris) declined in Great Britain and Ireland during the last century, due to habitat loss and the introduction of grey squirrels (Sciurus carolinensis), which competitively exclude the red squirrel and act as a reservoir for squirrelpox virus (SQPV). The disease is generally fatal to red squirrels and their ecological replacement by grey squirrels is up to 25 times faster where the virus is present. We aimed to determine: (1) the seropositivity and prevalence of SQPV DNA in the invasive and native species at a regional scale; (2) possible SQPV transmission routes; and, (3) virus degradation rates under differing environmental conditions. Grey (n = 208) and red (n = 40) squirrel blood and tissues were sampled. Enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qPCR) techniques established seropositivity and viral DNA presence, respectively. Overall 8% of squirrels sampled (both species combined) had evidence of SQPV DNA in their tissues and 22% were in possession of antibodies. SQPV prevalence in sampled red squirrels was 2.5%. Viral loads were typically low in grey squirrels by comparison to red squirrels. There was a trend for a greater number of positive samples in spring and summer than in winter. Possible transmission routes were identified through the presence of viral DNA in faeces (red squirrels only), urine and ectoparasites (both species). Virus degradation analyses suggested that, after 30 days of exposure to six combinations of environments, there were more intact virus particles in scabs kept in warm (25°C) and dry conditions than in cooler (5 and 15°C) or wet conditions. We conclude that SQPV is present at low prevalence in invasive grey squirrel populations with a lower prevalence in native red squirrels. Virus transmission could occur through urine especially during warm dry summer conditions but, more notably, via ectoparasites, which are shared by both species