Neuromotor Control of Eccentric Cycling

The purpose of this thesis was to investigate and quantify how eccentric (ECC) cycling influences the modulation of the underlying neuromotor mechanisms. Study one investigated post-exercise changes in global corticospinal excitability (CSE) by eliciting a motor-evoked potential in a non-exercised upper limb muscle following concentric (CON) and ECC cycling. No significant differences in global CSE were shown between CON and ECC cycling. However, individual responses of global CSE varied between cycling modes and time points. The variability likely related unfamiliarity with non-specific workload prescription of, and limited controllability of muscle actions during, ECC cycling. Study two addressed the controllability of ECC cycling through modification of a semi-recumbent ECC cycle ergometer to isolate ECC contractions during ECC cycling. The regenerative braking capacity of the built-in electric servo motors were programmed to function as a ‘trip’ mechanism, isolating ECC muscle actions to the opposing (OPP) phase of ECC cycling. Laboratory testing demonstrated the effectiveness of the ‘trip’ mechanism in isolating ECC muscle actions during ECC cycling. These results support using this modified ECC cycle ergometer among unfamiliarised participants performing novel ECC cycling. Study three developed a reliable peak ECC resistance test specific to semi-recumbent ECC cycling. Participants performed six peak ECC torque protocol (PETP) tests on an isokinetic dynamometer in a replicable semi-recumbent ECC cycling position. The PETP test was reliable in determining peak torque (ICC \u3e 0.90) and peak power output (ICC \u3e 0.90) during a single session. The PETP test is the first known maximal test specifically developed for ECC cycling and could be used to more effectively prescribe ECC cycling workloads, due to specificity of measurement compared within commonly used CON cycling tests. Study four aimed to develop a single-session familiarisation protocol for submaximal ECC cycling, based on naïve participants producing reliable muscle activation patterns at a PETP test-prescribed power output. Participants produced reliable (ICC \u3e 0.50) and lowly variable muscle activation patterns of the primary active muscles, within a single 15 min ECC cycling session. Overall, naïve participants were capable of becoming familiarised with ECC cycling during a single 15 min session. Study five implemented the newly developed methods, described in studies two, three and four, to investigate modulation of neuromotor excitability in an exercised (i.e., local) and non-exercised (i.e., global) muscle following ECC cycling. The main result showed that neuromotor excitability is differentially modulated by ECC cycling. Specifically, global neuromotor excitability increases following ECC cycling. Alternatively, local neuromotor excitability decreases, likely due to spinal inhibition. The outcomes of this study provide evidence of active neural coupling between the upper and lower limbs during ECC cycling that could be beneficial for neurorehabilitation. To conclude, this thesis presents new knowledge about the modulation of neuromotor mechanisms following ECC cycling and provides researchers and clinicians new methods with which to control ECC cycling and therefore, improve the application of future findings

Ethics and Metaphysics

In this chapter, Dorothy Walsh argues that any ethical theory requires an underlying speculative metaphysics

The Biogeochemistry of Hydrogen Sulfide: Phytoplankton Production in the Surface Ocean

Hydrogen sulfide can exist in oxic waters in the form of a dissolved gas, dissociated ions, dissolved metal sulfide complexes, and particulate metal sulfides. The sum of the dissolved species is termed total dissolved sulfide (TDS). In addition to the hydrolysis of carbonyl sulfide, it has been speculated that phytoplankton may produce TDS. We present results from preliminary culture studies which demonstrate that phytoplankton produce TDS and particulate acid-volatile sulfide (pAVS). The phylogenetic order of TDS + pAVS production (per unit cell volume) for the oceanic species examined is Synechococcus sp. \u3e Emiliania huxleyi ≈ Pyramimonas obovata \u3e Thalassiosira oceanica. Moreover, TDS and pAVS production increases when the concentrations of uncomplexed trace metals in culture media are also increased, suggesting metal detoxification via the formation of metal sulfide complexes

Polarization and kinematics in Cygnus A

From optical spectropolarimetry of Cygnus A we conclude that the scattering medium in the ionization cones in Cygnus A is moving outward at a speed of 170+-34 km/s, and that the required momentum can be supplied by the radiation pressure of an average quasar. Such a process could produce a structure resembling the observed ionization cones, which are thought to result from shadowing by a circumnuclear dust torus. We detect a polarized red wing in the [O III] emission lines arising from the central kiloparsec of Cygnus A. This wing is consistent with line emission created close to the boundary of the broad-line region.Comment: 5 pages, accepted for publication in MNRAS letter

Interleukin-6, age, and corpus callosum integrity.

The contribution of inflammation to deleterious aging outcomes is increasingly recognized; however, little is known about the complex relationship between interleukin-6 (IL-6) and brain structure, or how this association might change with increasing age. We examined the association between IL-6, white matter integrity, and cognition in 151 community dwelling older adults, and tested whether age moderated these associations. Blood levels of IL-6 and vascular risk (e.g., homocysteine), as well as health history information, were collected. Processing speed assessments were administered to assess cognitive functioning, and we employed tract-based spatial statistics to examine whole brain white matter and regions of interest. Given the association between inflammation, vascular risk, and corpus callosum (CC) integrity, fractional anisotropy (FA) of the genu, body, and splenium represented our primary dependent variables. Whole brain analysis revealed an inverse association between IL-6 and CC fractional anisotropy. Subsequent ROI linear regression and ridge regression analyses indicated that the magnitude of this effect increased with age; thus, older individuals with higher IL-6 levels displayed lower white matter integrity. Finally, higher IL-6 levels were related to worse processing speed; this association was moderated by age, and was not fully accounted for by CC volume. This study highlights that at older ages, the association between higher IL-6 levels and lower white matter integrity is more pronounced; furthermore, it underscores the important, albeit burgeoning role of inflammatory processes in cognitive aging trajectories

The Mass Distribution and Assembly of the Milky Way from the Properties of the Magellanic Clouds

We present a new measurement of the mass of the Milky Way (MW) based on observed properties of its largest satellite galaxies, the Magellanic Clouds (MCs), and an assumed prior of a {\Lambda}CDM universe. The large, high-resolution Bolshoi cosmological simulation of this universe provides a means to statistically sample the dynamical properties of bright satellite galaxies in a large population of dark matter halos. The observed properties of the MCs, including their circular velocity, distance from the center of the MW, and velocity within the MW halo, are used to evaluate the likelihood that a given halo would have each or all of these properties; the posterior PDF for any property of the MW system can thus be constructed. This method provides a constraint on the MW virial mass, 1.2 +0.7 -0.3(stat.) +0.3 -0.4 (sys.) x 10^12 M\odot (68% confidence), which is consistent with recent determinations that involve very different assumptions. In addition, we calculate the posterior PDF for the density profile of the MW and its satellite accretion history. Although typical satellites of 10^12 M\odot halos are accreted over a wide range of epochs over the last 10 Gyr, we find a \sim72% probability that the Magellanic Clouds were accreted within the last Gyr, and a 50% probability that they were accreted together.Comment: 9 pages, replaced with version published in ApJ. Animations available at http://risa.stanford.edu/milkyway

Identification of a Homology-Independent Linchpin Domain Controlling Mouse and Bank Vole Prion Protein Conversion

Prions are unorthodox pathogens that cause fatal neurodegenerative diseases in humans and other mammals. Prion propagation occurs through the self-templating of the pathogenic conformer PrPSc, onto the cell-expressed conformer, PrPC. Here we study the conversion of PrPC to PrPSc using a recombinant mouse PrPSc conformer (mouse protein-only recPrPSc) as a unique tool that can convert bank vole but not mouse PrPC substrates in vitro. Thus, its templating ability is not dependent on sequence homology with the substrate. In the present study, we used chimeric bank vole/mouse PrPC substrates to systematically determine the domain that allows for conversion by Mo protein-only recPrPSc. Our results show that that either the presence of the bank vole amino acid residues E227 and S230 or the absence of the second N-linked glycan are sufficient to allow PrPC substrates to be converted by Mo protein-only recPrPSc and several native infectious prion strains. We propose that residues 227 and 230 and the second glycan are part of a C-terminal domain that acts as a linchpin for bank vole and mouse prion conversion

APP Homodimers Transduce an Amyloid-β-Mediated Increase in Release Probability at Excitatory Synapses

SummaryAccumulation of amyloid-β peptides (Aβ), the proteolytic products of the amyloid precursor protein (APP), induces a variety of synaptic dysfunctions ranging from hyperactivity to depression that are thought to cause cognitive decline in Alzheimer’s disease. While depression of synaptic transmission has been extensively studied, the mechanisms underlying synaptic hyperactivity remain unknown. Here, we show that Aβ40 monomers and dimers augment release probability through local fine-tuning of APP-APP interactions at excitatory hippocampal boutons. Aβ40 binds to the APP, increases the APP homodimer fraction at the plasma membrane, and promotes APP-APP interactions. The APP activation induces structural rearrangements in the APP/Gi/o-protein complex, boosting presynaptic calcium flux and vesicle release. The APP growth-factor-like domain (GFLD) mediates APP-APP conformational changes and presynaptic enhancement. Thus, the APP homodimer constitutes a presynaptic receptor that transduces signal from Aβ40 to glutamate release. Excessive APP activation may initiate a positive feedback loop, contributing to hippocampal hyperactivity in Alzheimer’s disease

Which circulating antioxidant vitamins are confounded by socioeconomic deprivation? The MIDSPAN family study

<p><b>Background:</b> Antioxidant vitamins are often described as having “independent” associations with risk of cancer, cardiovascular disease (CVD) and mortality. We aimed to compare to what extent a range of antioxidant vitamins and carotenoids are associated with adulthood and childhood markers of socioeconomic deprivation and to adverse lifestyle factors.</p> <p><b>Methods and Findings:</b> Socioeconomic and lifestyle measures were available in 1040 men and 1298 women from the MIDSPAN Family Study (30–59 years at baseline) together with circulating levels of vitamins A, C, E, and carotenoids (α-carotene, β-carotene, lutein and lycopene). Markers of socioeconomic deprivation in adulthood were consistently as strongly associated with lower vitamin C and carotenoid levels as markers of adverse lifestyle; the inverse association with overcrowding was particularly consistent (vitamin C and carotenoids range from 19.1% [95% CI 30.3–6.0] to 38.8% [49.9–25.3] lower among those in overcrowded residencies). These associations were consistent after adjusting for month, classical CVD risk factors, body mass index, physical activity, vitamin supplements, dietary fat and fibre intake. Similar, but weaker, associations were seen for childhood markers of deprivation. The association of vitamin A or E were strikingly different; several adult adverse lifestyle factors associated with higher levels of vitamin A and E, including high alcohol intake for vitamin A (9.5% [5.7–13.5]) and waist hip ratio for vitamin E (9.5% [4.8–14.4]), with the latter associations partially explained by classical risk factors, particularly cholesterol levels.</p> <p><b>Conclusions:</b> Plasma vitamin C and carotenoids have strong inverse associations with adulthood markers of social deprivation, whereas vitamin A and E appear positively related to specific adverse lifestyle factors. These findings should help researchers better contextualize blood antioxidant vitamin levels by illustrating the potential limitations associated with making causal inferences without consideration of social deprivation.</p&gt