47 research outputs found
Probing Chemical Complexity of Amyloid Plaques in Alzheimer's Disease Mice using Hyperspectral Raman Imaging
One of the distinctive pathological features of Alzheimer's disease (AD) is the deposition of amyloid plaques within the brain of affected individuals. These plaques have traditionally been investigated using labeling techniques such as immunohistochemical imaging. However, the use of labeling can disrupt the structural integrity of the molecules being analyzed. Hence, it is imperative to employ label-free imaging methods for noninvasive examination of amyloid deposits in their native form, thereby providing more relevant information pertaining to AD. This study presents compelling evidence that label-free and nondestructive confocal Raman imaging is a highly effective approach for the identification and chemical characterization of amyloid plaques within cortical regions of an arcAβ mouse model of AD. Furthermore, this investigation elucidates how the spatial correlation of Raman signals can be exploited to identify robust Raman marker bands and discern proteins and lipids from amyloid plaques. Finally, this study uncovers the existence of distinct types of amyloid plaques in the arcAβ mouse brain, exhibiting significant disparities in terms of not only shape and size but also molecular composition
Kinematic Effects of Tidal Interaction on Galaxy Rotation Curves
We use self-consistent N-body models, in conjunction with models of test
particles moving in galaxy potentials, to explore the initial effects of
interactions on the rotation curves of spiral galaxies. Using nearly
self-consistent disk/bulge/halo galaxy models (Kuijken & Dubinski 1995), we
simulate the first pass of galaxies on nearly parabolic orbits; we vary orbit
inclinations, galaxy halo masses and impact parameters. For each simulation, we
mimic observed rotation curves of the model galaxies. Transient
interaction-induced features of the curves include distinctly rising or falling
profiles at large radii and pronounced bumps in the central regions. Remarkably
similar features occur in our statistical sample of optical emission-line
rotation curves of spiral galaxies in tight pairs and n-tuples.Comment: 9 pages, 2 figures, accepted for publication in ApJ Letter
High-Latitude HI in the Low Surface Brightness Galaxy UGC7321
From the analysis of sensitive HI 21-cm line observations, we find evidence
for vertically extended HI emission (|z|<~2.4 kpc) in the edge-on, low surface
brightness spiral galaxy UGC7321. Three-dimensional modelling suggests that the
HI disk of UGC7321 is both warped and flared, but that neither effect can fully
reproduce the spatial distribution and kinematics of the highest z-height gas.
We are able to model the high-latitude emission as an additional HI component
in the form of a ``thick disk'' or ``halo'' with a FWHM~3.3 kpc. We find
tentative evidence that the vertically extended gas declines in rotational
velocity as a function of z, although we are unable to completely rule out
models with constant V(z). In spite of the low star formation rate of UGC7321,
energy from supernovae may be sufficient to sustain this high-latitude gas.
However, alternative origins for this material, such as slow, sustained infall,
cannot yet be excluded.Comment: to appear in the August 20 Astrophysical Journal; 17 pages; version
with full resolution figures available at
http://cfa-www.harvard.edu/~lmatthew
Extinctions at 7um and 15um from the ISOGAL survey
The extinction laws at 7um and 15um are derived for more than 120 sightlines
in the inner Galactic plane based on the ISOGAL survey data and the
near-infrared data from DENIS and 2MASS. The tracers are the ISOGAL point
sources with [7]-[15]<0.4 which are RGB tip stars or early AGB stars with
moderate mass loss. They have well-defined intrinsic color indices (J-Ks)_0,
(Ks-[7])_0 and (Ks-[15])_0. By a linear fitting of the observed color indices
Ks-[7] and Ks-[15] to the observed J-Ks, we obtain the ratio between the
E(Ks-[7]) and E(Ks-[15]) color excesses and E(J-Ks). We infer the selective
extinctions at 7 and 15um in terms of the near-infrared extinction in the Ks
band. The distribution of the derived extinctions around 7 micron (A_7) is well
represented by a Gaussian function, with the peak at about 0.47A_Ks and ranging
from 0.33 to 0.55A_Ks (using the near-infrared extinctions of Rieke & Lebovsky
1985). There is some evidence that A_7/A_Ks may vary significantly depending on
the line of sight. The derived selective extinction at 15um suffers uncertainty
mainly from the dispersion in the intrinsic color index (Ks-[15])_0 which is
affected by dust emission from mass-losing AGB stars. The peak value of A_15 is
around 0.40A_Ks.Comment: 21 pages, 6 figures, accepted for publication in Astronomy and
Astrophysic
Visualizing alpha-synuclein and iron deposition in M83 mouse model of Parkinson's disease in vivo
BACKGROUND
Abnormal alpha-synuclein and iron accumulation in the brain play an important role in Parkinson's disease (PD). Herein, we aim at visualizing alpha-synuclein inclusions and iron deposition in the brains of M83 (A53T) mouse models of PD in vivo .
METHODS
Fluorescently labelled pyrimidoindole-derivative THK-565 was characterized by using recombinant fibrils and brains from 10-11 months old M83 mice, which subsequently underwent in vivo concurrent wide-field fluorescence and volumetric multispectral optoacoustic tomography (vMSOT) imaging. The in vivo results were verified against structural and susceptibility weighted imaging (SWI) magnetic resonance imaging (MRI) at 9.4 Tesla and scanning transmission X-ray microscopy (STXM) of perfused brains. Brain slice immunofluorescence and Prussian blue staining were further performed to validate the detection of alpha-synuclein inclusions and iron deposition in the brain, respectively.
RESULTS
THK-565 showed increased fluorescence upon binding to recombinant alpha-synuclein fibrils and alpha-synuclein inclusions in post-mortem brain slices from patients with Parkinson's disease and M83 mice. i.v. administration of THK-565 in M83 mice showed higher cerebral retention at 20 and 40 minutes post-injection by wide-field fluorescence compared to non-transgenic littermate mice, in congruence with the vMSOT findings. SWI/phase images and Prussian blue indicated the accumulation of iron deposits in the brains of M83 mice, presumably in the Fe form, as evinced by the STXM results.
CONCLUSION
We demonstrated in vivo mapping of alpha-synuclein by means of non-invasive epifluorescence and vMSOT imaging assisted with a targeted THK-565 label and SWI/STXM identification of iron deposits in M83 mouse brains ex vivo
The Disk and Dark Halo Mass of the Barred Galaxy NGC 4123. II. Fluid-Dynamical Models
We report a dynamical determination of the separate contributions of disk and
dark halo masses to the rotation curve of a spiral galaxy. We use
fluid-dynamical models of gas flow in the barred galaxy NGC 4123 to constrain
the dynamical properties of the galaxy: disk M/L, bar pattern speed, and the
central density and scale radius of the dark halo. We derive a realistic barred
potential directly from the light distribution. For each model we assume a
value of the stellar M/L and a bar pattern speed Omega_p and add a dark halo to
fit the rotation curve. We then compute the gas flow velocities with a 2-D gas
dynamical code, and compare the model flow patterns to a 2-D velocity field
derived from Fabry-Perot observations. The strong shocks and non-circular
motions in the observed gas flow require a high stellar M/L and a fast-rotating
bar. Models with I-band disk M/L of 2.0 -- 2.5 h_75, or 80 -- 100% of the
maximum disk value, are highly favored. The corotation radius of the bar must
be <= 1.5 times the bar semi-major axis. These results contradict some recent
claimed ``universal'' galaxy disk/halo relations, since NGC 4123 is of modest
size (rotation curve maximum 145 km/sec, and V_flat = 130 km/sec) yet is quite
disk-dominated. The dark halo of NGC 4123 is less concentrated than favored by
current models of dark halos based on cosmological simulations. Since some 30%
of bright disk galaxies are strongly barred and have dust lanes indicating
shock morphology similar to that of NGC 4123, it is likely that they also have
high stellar M/L and low density halos. We suggest that luminous matter
dominates inside the optical radius R_25 of high surface brightness disk
galaxies.Comment: accepted by ApJ, 20 pages, 11 figures (2 color), uses emulateapj.sty,
onecolfloat.st
Efficient characterization of multiple binding sites of small molecule imaging ligands on amyloid-beta, tau and alpha-synuclein
PURPOSE: There is an unmet need for compounds to detect fibrillar forms of alpha-synuclein (αSyn) and 4-repeat tau, which are critical in many neurodegenerative diseases. Here, we aim to develop an efficient surface plasmon resonance (SPR)-based assay to facilitate the characterization of small molecules that can bind these fibrils. METHODS: SPR measurements were conducted to characterize the binding properties of fluorescent ligands/compounds toward recombinant amyloid-beta (Aβ), K18-tau, full-length 2N4R-tau and αSyn fibrils. In silico modeling was performed to examine the binding pockets of ligands on αSyn fibrils. Immunofluorescence staining of postmortem brain tissue slices from Parkinson's disease patients and mouse models was performed with fluorescence ligands and specific antibodies. RESULTS: We optimized the protocol for the immobilization of Aβ, K18-tau, full-length 2N4R-tau and αSyn fibrils in a controlled aggregation state on SPR-sensor chips and for assessing their binding to ligands. The SPR results from the analysis of binding kinetics suggested the presence of at least two binding sites for all fibrils, including luminescent conjugated oligothiophenes, benzothiazole derivatives, nonfluorescent methylene blue and lansoprazole. In silico modeling studies for αSyn (6H6B) revealed four binding sites with a preference for one site on the surface. Immunofluorescence staining validated the detection of pS129-αSyn positivity in the brains of Parkinson's disease patients and αSyn preformed-fibril injected mice, 6E10-positive Aβ in arcAβ mice, and AT-8/AT-100-positivity in pR5 mice. CONCLUSION: SPR measurements of small molecules binding to Aβ, K18/full-length 2N4R-tau and αSyn fibrils suggested the existence of multiple binding sites. This approach may provide efficient characterization of compounds for neurodegenerative disease-relevant proteinopathies
Gas flow models in the Milky Way embedded bars
The gas distribution and dynamics in the inner Galaxy present many unknowns
as the origin of the asymmetry of the longitude-velocity (lv) diagram of the
Central Molecular Zone (CMZ). On the other hand, there are recent evidences in
the stellar component of the presence of a nuclear bar that could be slightly
lopsided. Our goal is to characterize the nuclear bar observed in 2MASS maps
and to study the gas dynamics in the inner Milky Way taking into account this
secondary bar. We have derived a realistic mass distribution by fitting 2MASS
star counts maps with three components (disk, bulge and nuclear bar) and we
have simulated the gas dynamics, in the deduced gravitational potential, using
a sticky-particles code. Our simulations of the gas dynamics reproduce
successfully the main characteristics of the Milky Way for a bulge orientation
of 20-35 deg with respect to the Sun-Galactic Center (GC) line and a pattern
speed of 30-40 km/s/kpc. In our models the Galactic Molecular Ring (GMR) is not
an actual ring but the inner parts of the spiral arms, while the 3-kpc arm and
its far side counterpart are lateral arms that contour the bar. Our simulations
reproduce, for the first time, the parallelogram shape of the lv-diagram of the
CMZ as the gas response to the nuclear bar. This bar should be oriented by an
angle of ~60-75 deg with respect to the Sun-GC line and its mass amounts to
(2-5.5)10e9 Msun. We show that the observed asymmetry of the CMZ cannot be due
to lopsidedness of the nuclear bar as suggested by the 2MASS maps. We do not
find clear evidences of lopsidedness in the stellar potential. We propose that
the observed asymmetry of the central gas layer can be due to the infalling of
gas into the CMZ in the l=1.3-complexComment: 28 pages, 6 tables, 14 figures. To appear in Astronomy and
Astrophysic
The Milky Way Bulge: Observed properties and a comparison to external galaxies
The Milky Way bulge offers a unique opportunity to investigate in detail the
role that different processes such as dynamical instabilities, hierarchical
merging, and dissipational collapse may have played in the history of the
Galaxy formation and evolution based on its resolved stellar population
properties. Large observation programmes and surveys of the bulge are providing
for the first time a look into the global view of the Milky Way bulge that can
be compared with the bulges of other galaxies, and be used as a template for
detailed comparison with models. The Milky Way has been shown to have a
box/peanut (B/P) bulge and recent evidence seems to suggest the presence of an
additional spheroidal component. In this review we summarise the global
chemical abundances, kinematics and structural properties that allow us to
disentangle these multiple components and provide constraints to understand
their origin. The investigation of both detailed and global properties of the
bulge now provide us with the opportunity to characterise the bulge as observed
in models, and to place the mixed component bulge scenario in the general
context of external galaxies. When writing this review, we considered the
perspectives of researchers working with the Milky Way and researchers working
with external galaxies. It is an attempt to approach both communities for a
fruitful exchange of ideas.Comment: Review article to appear in "Galactic Bulges", Editors: Laurikainen
E., Peletier R., Gadotti D., Springer Publishing. 36 pages, 10 figure
Modelling the inner disc of the Milky Way with manifolds. I - A first step
We study the bar-driven dynamics in the inner part of the Milky Way by using
invariant manifolds. This theory has been successfully applied to describe the
morphology and kinematics of rings and spirals in external galaxies, and now,
for the first time, we apply it to the Milky Way. We compute the orbits
confined by the invariant manifolds of the unstable periodic orbits located at
the ends of the bar. We discuss whether the COBE/DIRBE bar and the Long bar
compose a single bar or two independent bars and perform a number of
comparisons which, taken together, argue strongly in favour of the former. More
specifically, we favour the possibility that the so-called COBE/DIRBE bar is
the boxy/peanut bulge of a bar whose outer thin parts are the so-called Long
bar. This possibility is in good agreement both with observations of external
galaxies, with orbital structure theory and with simulations. We then analyse
in detail the morphology and kinematics given by five representative Galactic
potentials. Two have a Ferrers bar, two have a quadrupole bar and the last one
a composite bar. We first consider only the COBE/DIRBE bar and then extend it
to include the effect of the Long bar. We find that the large-scale structure
given by the manifolds describes an inner ring, whose size is similar to the
near and far 3-kpc arm, and an outer ring, whose properties resemble those of
the Galactic Molecular Ring. We also analyse the kinematics of these two
structures, under the different galactic potentials, and find they reproduce
the main over-densities found in the galactic longitude-velocity CO diagram.
Finally, we consider for what model parameters, the global morphology of the
manifolds may reproduce the two outer spiral arms. We conclude that this would
necessitate either more massive and more rapidly rotating bars, or including in
the potential an extra component describing the spiral arms.Comment: 18 pages, 11 figures, accepted in MNRA