2,317 research outputs found
Morphine activates neuroinflammation in a manner parallel to endotoxin
Opioids create a neuroinflammatory response within the CNS, compromising opioid-induced analgesia and contributing to various unwanted actions. How this occurs is unknown but has been assumed to be via classic opioid receptors. Herein, we provide direct evidence that morphine creates neuroinflammation via the activation of an innate immune receptor and not via classic opioid receptors. We demonstrate that morphine binds to an accessory protein of Toll-like receptor 4 (TLR4), myeloid differentiation protein 2 (MD-2), thereby inducing TLR4 oligomerization and triggering proinflammation. Small-molecule inhibitors, RNA interference, and genetic knockout validate the TLR4/MD-2 complex as a feasible target for beneficially modifying morphine actions. Disrupting TLR4/MD-2 protein–protein association potentiated morphine analgesia in vivo and abolished morphine-induced proinflammation in vitro, the latter demonstrating that morphine-induced proinflammation only depends on TLR4, despite the presence of opioid receptors. These results provide an exciting, nonconventional avenue to improving the clinical efficacy of opioids.Xiaohui Wang, Lisa C. Loram, Khara Ramos, Armando J. de Jesus, Jacob Thomas, Kui Cheng, Anireddy Reddy, Andrew A. Somogyi, Mark R. Hutchinson, Linda R. Watkins and Hang Yi
The use of yeast inoculation in fermentation for port production; effect on total potential ethyl carbamate
A commercial wine yeast Saccharomyces cerevisiae UCD 522 (pre-cultured in the presence of certain mass-labelled amino acids) was inoculated into a port must which was then allowed to ferment under controlled conditions of temperature and agitation. The influence of potential ethyl carbamate (EC) precursor formed due to yeast pre-culture, upon total potential EC levels was studied at various stages of fermentation. Pre-culture accumulation did not give rise to detectable levels of EC precursor during port fermentation
Cosmological Imprints of Pre-Inflationary Particles
We study some of the cosmological imprints of pre-inflationary particles. We
show that each such particle provides a seed for a spherically symmetric cosmic
defect. The profile of this cosmic defect is fixed and its magnitude is linear
in a single parameter that is determined by the mass of the pre-inflationary
particle. We study the CMB and peculiar velocity imprints of this cosmic defect
and suggest that it could explain some of the large scale cosmological
anomalies.Comment: 31 pages, 7 figure
The complement system in neurodegenerative diseases
Complement is an important component of innate immune defence against pathogens and crucial for efficient immune complex disposal. These core protective activities are dependent in large part on properly regulated complement-mediated inflammation. Dysregulated complement activation, often driven by persistence of activating triggers, is a cause of pathological inflammation in numerous diseases, including neurological diseases. Increasingly, this has become apparent not only in well-recognized neuroinflammatory diseases like multiple sclerosis but also in neurodegenerative and neuropsychiatric diseases where inflammation was previously either ignored or dismissed as a secondary event. There is now a large and rapidly growing body of evidence implicating complement in neurological diseases that cannot be comprehensively addressed in a brief review. Here, we will focus on neurodegenerative diseases, including not only the ‘classical’ neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease, but also two other neurological diseases where neurodegeneration is a neglected feature and complement is implicated, namely, schizophrenia, a neurodevelopmental disorder with many mechanistic features of neurodegeneration, and multiple sclerosis, a demyelinating disorder where neurodegeneration is a major cause of progressive decline. We will discuss the evidence implicating complement as a driver of pathology in these diverse diseases and address briefly the potential and pitfalls of anti-complement drug therapy for neurodegenerative diseases
Dynamics in the satellite system of Triangulum: Is AndXXII a dwarf satellite of M33?
We present results from a spectroscopic survey of the dwarf spheroidal And
XXII and the two extended clusters EC1 and EC2. These three objects are
candidate satellites of the Triangulum galaxy, M33, which itself is likely a
satellite of M31. We use the DEep Imaging Multi-Object Spectrograph mounted on
the Keck-II telescope to derive radial velocities for candidate member stars of
these objects and thereby identify the stars that are most likely actual
members. Eleven most probable stellar members (of 13 candidates) are found for
AndXXII. We obtain an upper limit of sigma_v < 6.0 km s-1 for the velocity
dispersion of AndXXII, [Fe/H] ~ -1.6 for its metallicity, and 255pc for the
Plummer radius of its projected density profile. We construct a colour
magnitude diagram for AndXXII and identify both the red giant branch and the
horizontal branch. The position of the latter is used to derive a heliocentric
distance to And XXII of 853 pm 26 kpc. The combination of the radial velocity,
distance, and angular position of AndXXII indicates that it is a strong
candidate for being the first known satellite of M33 and one of the very few
examples of a galactic satellite of a satellite. N-body simulations imply that
this conclusion is unchanged even if M31 and M33 had a strong encounter in the
past few Gyr. We test the hypothesis that the extended clusters highlight
tidally stripped galaxies by searching for an excess cloud of halo-like stars
in their vicinity. We find such a cloud for the case of EC1 but not EC2. The
three objects imply a dynamical mass for M33 that is consistent with previous
estimates.Comment: 14 pages, 14 figures, revised for MNRAS publicatio
‘Working with the media taught us a lot’: Understanding The Guardian’s Katine initiative
One of the more important ventures in the world of media and development over the past decade has been The Guardian newspaper’s ‘Katine’ project in Uganda. The newspaper, with funding from its readers and Barclays Bank, put more than 2.5 million pounds into a Ugandan sub-county over the course of 4 years. The project was profiled on a dedicated Guardian microsite, with regular updates in the printed edition of the newspaper. In this article, I look at the relationship that developed between journalists and the non-governmental organisation and show that the experience was both disorienting and reorienting for the development project that was being implemented. The scrutiny of the project that appeared on the microsite disoriented the non-governmental organisation, making its work the subject of public criticism. The particular issues explored by journalists also reoriented what the non-governmental organisation did on the ground. I also point to the ways the relationship grew more settled as the project moved along, suggesting the amount of work that sometimes goes into what is often characterised as the relatively uncritical relationship between journalists and non-governmental organisations
Methane in the atmosphere of the transiting hot Neptune GJ436b?
We present an analysis of seven primary transit observations of the hot
Neptune GJ436b at 3.6, 4.5 and m obtained with the Infrared Array Camera
(IRAC) on the Spitzer Space Telescope. After correcting for systematic effects,
we fitted the light curves using the Markov Chain Monte Carlo technique.
Combining these new data with the EPOXI, HST and ground-based and
published observations, the range m can be covered. Due to
the low level of activity of GJ436, the effect of starspots on the combination
of transits at different epochs is negligible at the accuracy of the dataset.
Representative climate models were calculated by using a three-dimensional,
pseudo-spectral general circulation model with idealised thermal forcing.
Simulated transit spectra of GJ436b were generated using line-by-line radiative
transfer models including the opacities of the molecular species expected to be
present in such a planetary atmosphere. A new, ab-initio calculated, linelist
for hot ammonia has been used for the first time. The photometric data observed
at multiple wavelengths can be interpreted with methane being the dominant
absorption after molecular hydrogen, possibly with minor contributions from
ammonia, water and other molecules. No clear evidence of carbon monoxide and
dioxide is found from transit photometry. We discuss this result in the light
of a recent paper where photochemical disequilibrium is hypothesised to
interpret secondary transit photometric data. We show that the emission
photometric data are not incompatible with the presence of abundant methane,
but further spectroscopic data are desirable to confirm this scenario.Comment: 19 pages, 10 figures, 1 table, Astrophysical Journal in pres
Coupled dark matter-dark energy in light of near Universe observations
Cosmological analysis based on currently available observations are unable to
rule out a sizeable coupling among the dark energy and dark matter fluids. We
explore a variety of coupled dark matter-dark energy models, which satisfy
cosmic microwave background constraints, in light of low redshift and near
universe observations. We illustrate the phenomenology of different classes of
dark coupling models, paying particular attention in distinguishing between
effects that appear only on the expansion history and those that appear in the
growth of structure. We find that while a broad class of dark coupling models
are effectively models where general relativity (GR) is modified --and thus can
be probed by a combination of tests for the expansion history and the growth of
structure--, there is a class of dark coupling models where gravity is still
GR, but the growth of perturbations is, in principle modified. While this
effect is small in the specific models we have considered, one should bear in
mind that an inconsistency between reconstructed expansion history and growth
may not uniquely indicate deviations from GR. Our low redshift constraints
arise from cosmic velocities, redshift space distortions and dark matter
abundance in galaxy voids. We find that current data constrain the
dimensionless coupling to be |xi|<0.2, but prospects from forthcoming data are
for a significant improvement. Future, precise measurements of the Hubble
constant, combined with high-precision constraints on the growth of structure,
could provide the key to rule out dark coupling models which survive other
tests. We shall exploit as well weak equivalence principle violation arguments,
which have the potential to highly disfavour a broad family of coupled models.Comment: 34 pages, 6 figures; changes to match published versio
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