Reheating Effects in the Matter Power Spectrum and Implications for Substructure

The thermal and expansion history of the Universe before big bang nucleosynthesis is unknown. We investigate the evolution of cosmological perturbations through the transition from an early matter era to radiation domination. We treat reheating as the perturbative decay of an oscillating scalar field into relativistic plasma and cold dark matter. After reheating, we find that subhorizon perturbations in the decay-produced dark matter density are significantly enhanced, while subhorizon radiation perturbations are instead suppressed. If dark matter originates in the radiation bath after reheating, this suppression may be the primary cutoff in the matter power spectrum. Conversely, for dark matter produced nonthermally from scalar decay, enhanced perturbations can drive structure formation during the cosmic dark ages and dramatically increase the abundance of compact substructures. For low reheat temperatures, we find that as much as 50% of all dark matter is in microhalos with M > 0.1 Earth masses at z=100, compared to a fraction of 1e-10 in the standard case. In this scenario, ultradense substructures may constitute a large fraction of dark matter in galaxies today.Comment: 20 pages, 13 figures; references added and minor changes made; to appear in PR

Cosmological Signatures of Interacting Neutrinos

We investigate signatures of neutrino scattering in the Cosmic Microwave Background (CMB) and matter power spectra, and the extent to which present cosmological data can distinguish between a free streaming or tightly coupled fluid of neutrinos. If neutrinos have strong non-standard interactions, for example, through the coupling of neutrinos to a light boson, they may be kept in equilibrium until late times. We show how the power spectra for these models differ from more conventional neutrino scenarios, and use CMB and large scale structure data to constrain these models. CMB polarization data improves the constraints on the number of massless neutrinos, while the Lyman--$\alpha$ power spectrum improves the limits on the neutrino mass. Neutrino mass limits depend strongly on whether some or all of the neutrino species interact and annihilate. The present data can accommodate a number of tightly-coupled relativistic degrees of freedom, and none of the interacting-neutrino scenarios considered are ruled out by current data -- although considerations regarding the age of the Universe disfavor a model with three annihilating neutrinos with very large neutrino masses.Comment: 17 pages, 14 figures, minor changes and references added, published in Phys. Rev.

Complex folding and misfolding effects of deer-specific amino acid substitutions in the β2-α2 loop of murine prion protein

The β2–α2 loop of PrPC is a key modulator of disease-associated prion protein misfolding. Amino acids that differentiate mouse (Ser169, Asn173) and deer (Asn169, Thr173) PrPC appear to confer dramatically different structural properties in this region and it has been suggested that amino acid sequences associated with structural rigidity of the loop also confer susceptibility to prion disease. Using mouse recombinant PrP, we show that mutating residue 173 from Asn to Thr alters protein stability and misfolding only subtly, whilst changing Ser to Asn at codon 169 causes instability in the protein, promotes oligomer formation and dramatically potentiates fibril formation. The doubly mutated protein exhibits more complex folding and misfolding behaviour than either single mutant, suggestive of differential effects of the β2–α2 loop sequence on both protein stability and on specific misfolding pathways. Molecular dynamics simulation of protein structure suggests a key role for the solvent accessibility of Tyr168 in promoting molecular interactions that may lead to prion protein misfolding. Thus, we conclude that ‘rigidity’ in the β2–α2 loop region of the normal conformer of PrP has less effect on misfolding than other sequence-related effects in this region

Diurnal patterns of soluble amyloid precursor protein metabolites in the human central nervous system

The amyloid-β (Aβ) protein is diurnally regulated in both the cerebrospinal fluid and blood in healthy adults; circadian amplitudes decrease with aging and the presence of cerebral Aβ deposits. The cause of the Aβ diurnal pattern is poorly understood. One hypothesis is that the Amyloid Precursor Protein (APP) is diurnally regulated, leading to APP product diurnal patterns. APP in the central nervous system is processed either via the β-pathway (amyloidogenic), generating soluble APP-β (sAPPβ) and Aβ, or the α-pathway (non-amyloidogenic), releasing soluble APP-α (sAPPα). To elucidate the potential contributions of APP to the Aβ diurnal pattern and the balance of the α- and β- pathways in APP processing, we measured APP proteolytic products over 36 hours in human cerebrospinal fluid from cognitively normal and Alzheimer's disease participants. We found diurnal patterns in sAPPα, sAPPβ, Aβ40, and Aβ42, which diminish with increased age, that support the hypothesis that APP is diurnally regulated in the human central nervous system and thus results in Aβ diurnal patterns. We also found that the four APP metabolites were positively correlated in all participants without cerebral Aβ deposits. This positive correlation suggests that the α- and β- APP pathways are non-competitive under normal physiologic conditions where APP availability may be the limiting factor that determines sAPPα and sAPPβ production. However, in participants with cerebral Aβ deposits, there was no correlation of Aβ to sAPP metabolites, suggesting that normal physiologic regulation of cerebrospinal fluid Aβ is impaired in the presence of amyloidosis. Lastly, we found that the ratio of sAPPβ to sAPPα was significantly higher in participants with cerebral Aβ deposits versus those without deposits. Therefore, the sAPPβ to sAPPα ratio may be a useful biomarker for cerebral amyloidosis

Polarizing Bubble Collisions

We predict the polarization of cosmic microwave background (CMB) photons that results from a cosmic bubble collision. The polarization is purely E-mode, symmetric around the axis pointing towards the collision bubble, and has several salient features in its radial dependence that can help distinguish it from a more conventional explanation for unusually cold or hot features in the CMB sky. The anomalous "cold spot" detected by the Wilkinson Microwave Anisotropy Probe (WMAP) satellite is a candidate for a feature produced by such a collision, and the Planck satellite and other proposed surveys will measure the polarization on it in the near future. The detection of such a collision would provide compelling evidence for the string theory landscape.Comment: Published version. 15 pages, 8 figure

Charged-particle decay and suppression of small-scale power

We study the suppression of the small-scale power spectrum due to the decay of charged matter to dark matter prior to recombination. Prior to decay, the charged particles couple to the photon-baryon fluid and participate in its acoustic oscillations. However, after decaying to neutral dark matter the photon-baryon fluid is coupled only gravitationally to the newly-created dark matter. This generically leads to suppression of power on length scales that enter the horizon prior to decay. For decay times of approximately 3.5 years this leads to suppression of power on subgalactic scales, bringing the observed number of Galactic substructures in line with observation. Decay times of a few years are possible if the dark matter is purely gravitationally interacting, such as the gravitino in supersymmetric models or a massive Kaluza-Klein graviton in models with universal extra dimensions.Comment: 4 pages, 3 figures, submitted to Phys. Rev. Let

Solvation-guided design of fluorescent probes for discrimination of amyloids

The deposition of insoluble protein aggregates in the brain is a hallmark of many neurodegenerative diseases. While their exact role in neurodegeneration remains unclear, the presence of these amyloid deposits often precedes clinical symptoms. As a result, recent progress in imaging methods that utilize amyloid-specific small molecule probes have become a promising avenue for antemortem disease diagnosis. Here, we present a series of amino-aryl cyanoacrylate (AACA) fluorophores that show a turn-on fluorescence signal upon binding to amyloids in solution and in tissue. Using a theoretical model for environmental sensitivity of fluorescence together with ab initio computational modeling of the effects of polar environment on electron density distribution and conformational dynamics, we designed, synthesized, and evaluated a set of fluorophores that (1) bind to aggregated forms of Alzheimer's-related beta-amyloid peptides with low micromolar to high nanomolar affinities and (2) have the capability to fluorescently discriminate different amyloids based on differences in amino acid composition within the binding pocket through exploitation of their solvatochromic properties. These studies showcase the rational design of a family of amyloid-binding imaging agents that could be integrated with new optical approaches for the clinical diagnosis of amyloidoses, where accurate identification of the specific neurodegenerative disease could aid in the selection of a proper course for treatment

Experimental Oral Transmission of Chronic Wasting Disease to Reindeer (Rangifer tarandus tarandus)

Chronic wasting disease (CWD), a transmissible spongiform encephalopathy of cervids, remains prevalent in North American elk, white-tailed deer and mule deer. A natural case of CWD in reindeer (Rangifer tarandus tarandus) has not been reported despite potential habitat overlap with CWD-infected deer or elk herds. This study investigates the experimental transmission of CWD from elk or white-tailed deer to reindeer by the oral route of inoculation. Ante-mortem testing of the three reindeer exposed to CWD from white-tailed deer identified the accumulation of pathological PrP (PrPCWD) in the recto-anal mucosa associated lymphoid tissue (RAMALT) of two reindeer at 13.4 months post-inoculation. Terminal CWD occurred in the two RAMALT-positive reindeer at 18.5 and 20 months post-inoculation while one other reindeer in the white-tailed deer CWD inoculum group and none of the 3 reindeer exposed to elk CWD developed disease. Tissue distribution analysis of PrPCWD in CWD-affected reindeer revealed widespread deposition in central and peripheral nervous systems, lymphoreticular tissues, the gastrointestinal tract, neuroendocrine tissues and cardiac muscle. Analysis of prion protein gene (PRNP) sequences in the 6 reindeer identified polymorphisms at residues 2 (V/M), 129 (G/S), 138 (S/N) and 169 (V/M). These findings demonstrate that (i) a sub-population of reindeer are susceptible to CWD by oral inoculation implicating the potential for transmission to other Rangifer species, and (ii) certain reindeer PRNP polymorphisms may be protective against CWD infection

The diverse roles of mononuclear phagocytes in prion disease pathogenesis

Transmissible spongiform encephalopathies (TSEs), or prion diseases, are neurological diseases that can be transmitted through a number of different routes. A wide range of mammalian species are affected by the disease. After peripheral exposure, some TSE agents accumulate in lymphoid tissues at an early stage of disease prior to spreading to the nerves and the brain. Much research has focused on identifying the cells and molecules involved in the transmission of TSE agents from the site of exposure to the brain and several crucial cell types have been associated with this process. The identification of the key cells that influence the different stages of disease transmission might identify targets for therapeutic intervention. This review highlights the involvement of mononuclear phagocytes in TSE disease. Current data suggest these cells may exhibit a diverse range of roles in TSE disease from the transport or destruction of TSE agents in lymphoid tissues, to mediators or protectors of neuropathology in the brain