Gut-seeded α-synuclein fibrils promote gut dysfunction and brain pathology specifically in aged mice

Parkinson’s disease is a synucleinopathy that is characterized by motor dysfunction, death of midbrain dopaminergic neurons and accumulation of α-synuclein (α-Syn) aggregates. Evidence suggests that α-Syn aggregation can originate in peripheral tissues and progress to the brain via autonomic fibers. We tested this by inoculating the duodenal wall of mice with α-Syn preformed fibrils. Following inoculation, we observed gastrointestinal deficits and physiological changes to the enteric nervous system. Using the AAV-PHP.S capsid to target the lysosomal enzyme glucocerebrosidase for peripheral gene transfer, we found that α-Syn pathology is reduced due to the increased expression of this protein. Lastly, inoculation of α-Syn fibrils in aged mice, but not younger mice, resulted in progression of α-Syn histopathology to the midbrain and subsequent motor defects. Our results characterize peripheral synucleinopathy in prodromal Parkinson’s disease and explore cellular mechanisms for the gut-to-brain progression of α-Syn pathology

Bragg scattering of Cooper pairs in an ultra-cold Fermi gas

We present a theoretical treatment of Bragg scattering of a degenerate Fermi gas in the weakly interacting BCS regime. Our numerical calculations predict correlated scattering of Cooper pairs into a spherical shell in momentum space. The scattered shell of correlated atoms is centered at half the usual Bragg momentum transfer, and can be clearly distinguished from atoms scattered by the usual single-particle Bragg mechanism. We develop an analytic model that explains key features of the correlated-pair Bragg scattering, and determine the dependence of this scattering on the initial pair correlations in the gas.Comment: Manuscript substantially revised. Version 2 contains a more detailed discussion of the collisional interaction used in our theory, and is based on three-dimensional solution

Nonlinear atom-optical delta-kicked harmonic oscillator using a Bose-Einstein condensate

We experimentally investigate the atom-optical delta-kicked harmonic oscillator for the case of nonlinearity due to collisional interactions present in a Bose-Einstein condensate. A Bose condensate of rubidium atoms tightly confined in a static harmonic magnetic trap is exposed to a one-dimensional optical standing-wave potential that is pulsed on periodically. We focus on the quantum anti-resonance case for which the classical periodic behavior is simple and well understood. We show that after a small number of kicks the dynamics is dominated by dephasing of matter wave interference due to the finite width of the condensate's initial momentum distribution. In addition, we demonstrate that the nonlinear mean-field interaction in a typical harmonically confined Bose condensate is not sufficient to give rise to chaotic behavior.Comment: 4 pages, 3 figure

Time Dilation from Spectral Feature Age Measurements of Type Ia Supernovae

We have developed a quantitative, empirical method for estimating the age of Type Ia supernovae (SNe Ia) from a single spectral epoch. The technique examines the goodness of fit of spectral features as a function of the temporal evolution of a large database of SNe Ia spectral features. When a SN Ia spectrum with good signal-to-noise ratio over the rest frame range 3800 to 6800 A is available, the precision of a spectral feature age (SFA) is (1-sigma) ~ 1.4 days. SFA estimates are made for two spectral epochs of SN 1996bj (z=0.574) to measure the rate of aging at high redshift. In the 10.05 days which elapsed between spectral observations, SN 1996bj aged 3.35 $\pm$ 3.2 days, consistent with the 6.38 days of aging expected in an expanding Universe and inconsistent with no time dilation at the 96.4 % confidence level. The precision to which individual features constrain the supernova age has implications for the source of inhomogeneities among SNe Ia.Comment: 14 pages (LaTex), 7 postscript figures to Appear in the Astronomical Journa

A study protocol for a randomised crossover study evaluating the effect of diets differing in carbohydrate quality on ileal content and appetite regulation in healthy humans

A major component of the digesta reaching the colon from the distal ileum is carbohydrate. This carbohydrate is subject to microbial fermentation and can radically change bacterial populations in the colon and the metabolites they produce, particularly short-chain fatty acids (SCFA). However, very little is currently known about the forms and levels of carbohydrate in the ileum and the composition of the ileal microbiota in humans. Most of our current understanding of carbohydrate that is not absorbed by the small intestine comes from ileostomy models, which may not reflect the physiology of an intact gastrointestinal tract. We will investigate how ileal content changes depending on diet using a randomised crossover study in healthy humans. Participants will be inpatients at the research facility for three separate 4-day visits. During each visit, participants will consume one of three diets, which differ in carbohydrate quality: 1) low-fibre refined diet; 2) high-fibre diet with intact cellular structures; 3) high-fibre diet where the cellular structures have been disrupted (e.g. milling, blending). On day 1, a nasoenteric tube will be placed into the distal ileum and its position confirmed under fluoroscopy. Ileal samples will be collected via the nasoenteric tube and metabolically profiled, which will determine the amount and type of carbohydrate present, and the composition of the ileal microbiota will be measured. Blood samples will be collected to assess circulating hormones and metabolites. Stool samples will be collected to assess faecal microbiota composition. Subjective appetite measures will be collected using visual analogue scales. Breath hydrogen will be measured in real-time as a marker of intestinal fermentation. Finally, an continuous fermentation model will be inoculated with ileal fluid in order to understand the shift in microbial composition and SCFA produced in the colon following the different diets. ISRCTN11327221. [Abstract copyright: Copyright: © 2019 Byrne CS et al.

Spectroscopy of High-Redshift Supernovae from the ESSENCE Project: The First Two Years

We present the results of spectroscopic observations of targets discovered during the first two years of the ESSENCE project. The goal of ESSENCE is to use a sample of ~200 Type Ia supernovae (SNe Ia) at moderate redshifts (0.2 < z < 0.8) to place constraints on the equation of state of the Universe. Spectroscopy not only provides the redshifts of the objects, but also confirms that some of the discoveries are indeed SNe Ia. This confirmation is critical to the project, as techniques developed to determine luminosity distances to SNe Ia depend upon the knowledge that the objects at high redshift are the same as the ones at low redshift. We describe the methods of target selection and prioritization, the telescopes and detectors, and the software used to identify objects. The redshifts deduced from spectral matching of high-redshift SNe Ia with low-redshift SNe Ia are consistent with those determined from host-galaxy spectra. We show that the high-redshift SNe Ia match well with low-redshift templates. We include all spectra obtained by the ESSENCE project, including 52 SNe Ia, 5 core-collapse SNe, 12 active galactic nuclei, 19 galaxies, 4 possibly variable stars, and 16 objects with uncertain identifications.Comment: 38 pages, 9 figures (many with multiple parts), submitted to A

Constraints on Cosmological Models from Hubble Space Telescope Observations of High-z Supernovae

We have coordinated Hubble Space Telescope photometry with ground-based discovery for three supernovae: two SN Ia near z~0.5 (SN 1997ce, SN 1997cj) and a third event at z=0.97 (SN 1997ck). The superb spatial resolution of HST separates each supernova from its host galaxy and leads to good precision in the light curves. The HST data combined with ground-based photometry provide good temporal coverage. We use these light curves and relations between luminosity, light curve shape, and color calibrated from low-z samples to derive relative luminosity distances which are accurate to 10% at z~0.5 and 20% at z=1. The redshift-distance relation is used to place constraints on the global mean matter density, Omega_matter, and the normalized cosmological constant, Omega_Lambda. When the HST sample is combined with the distance to SN 1995K (z=0.48), analyzed by the same precepts, it suggests that matter alone is insufficient to produce a flat Universe. Specifically, for Omega_matter+Omega_Lambda=1, Omega_matter is less than 1 with >95% confidence, and our best estimate of Omega_matter is -0.1 +/- 0.5 if Omega_Lambda=0. Although the present result is based on a very small sample whose systematics remain to be explored, it demonstrates the power of HST measurements for high redshift supernovae.Comment: Submitted to ApJ Letters, 3 figures, 1 plate, additional tabl