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Striatal dopamine D1-type receptor availability: no difference from control but association with cortical thickness in methamphetamine users.
Chronic methamphetamine use poses potentially devastating consequences for directly affected individuals and for society. Lower dopamine D2-type receptor availability has been observed in striata of methamphetamine users as compared with controls, but an analogous comparison of D1-type receptors has been conducted only on post-mortem material, with no differences in methamphetamine users from controls in the caudate nucleus and putamen and higher D1-receptor density in the nucleus accumbens. Released from neurons when methamphetamine is self-administered, dopamine binds to both D1- and D2-type receptors in the striatum, with downstream effects on cortical activity. Thus, both receptor subtypes may contribute to methamphetamine-induced alterations in cortical morphology and behavior. In this study, 21 methamphetamine-dependent subjects and 23 healthy controls participated in positron emission tomography and structural magnetic resonance imaging for assessment of striatal D1- and D2-type receptor availability and cortical gray-matter thickness, respectively. Although D2-type receptor availability (BPnd) was lower in the methamphetamine group, as shown previously, the groups did not differ in D1-type BPnd. In the methamphetamine group, mean cortical gray-matter thickness was negatively associated with cumulative methamphetamine use and craving for the drug. Striatal D1-type but not D2-type BPnd was negatively associated with global mean cortical gray-matter thickness in the methamphetamine group, but no association was found between gray-matter thickness and BPnd for either dopamine receptor subtype in the control group. These results suggest a role of striatal D1-type receptors in cortical adaptation to chronic methamphetamine use
Macrophage TNF-α mediates parathion-induced airway hyperreactivity in guinea pigs.
Organophosphorus pesticides (OPs) are implicated in human asthma. We previously demonstrated that, at concentrations that do not inhibit acetylcholinesterase activity, the OP parathion causes airway hyperreactivity in guinea pigs as a result of functional loss of inhibitory M2 muscarinic receptors on parasympathetic nerves. Because macrophages are associated with asthma, we investigated whether macrophages mediate parathion-induced M2 receptor dysfunction and airway hyperreactivity. Airway physiology was measured in guinea pigs 24 h after a subcutaneous injection of parathion. Pretreatment with liposome-encapsulated clodronate induced alveolar macrophage apoptosis and prevented parathion-induced airway hyperreactivity in response to electrical stimulation of the vagus nerves. As determined by qPCR, TNF-α and IL-1β mRNA levels were increased in alveolar macrophages isolated from parathion-treated guinea pigs. Parathion treatment of alveolar macrophages ex vivo did not significantly increase IL-1β and TNF-α mRNA but did significantly increase TNF-α protein release. Consistent with these data, pretreatment with the TNF-α inhibitor etanercept but not the IL-1β receptor inhibitor anakinra prevented parathion-induced airway hyperreactivity and protected M2 receptor function. These data suggest a novel mechanism of OP-induced airway hyperreactivity in which low-level parathion activates macrophages to release TNF-α-causing M2 receptor dysfunction and airway hyperreactivity. These observations have important implications regarding therapeutic approaches for treating respiratory disease associated with OP exposures
T-Bet and Eomes Regulate the Balance between the Effector/Central Memory T Cells versus Memory Stem Like T Cells
Memory T cells are composed of effector, central, and memory stem cells. Previous studies have implicated that both T-bet and Eomes are involved in the generation of effector and central memory CD8 T cells. The exact role of these transcription factors in shaping the memory T cell pool is not well understood, particularly with memory stem T cells. Here, we demonstrate that both T-bet or Eomes are required for elimination of established tumors by adoptively transferred CD8 T cells. We also examined the role of T-bet and Eomes in the generation of tumor-specific memory T cell subsets upon adoptive transfer. We showed that combined T-bet and Eomes deficiency resulted in a severe reduction in the number of effector/central memory T cells but an increase in the percentage of CD62LhighCD44low Sca-1+ T cells which were similar to the phenotype of memory stem T cells. Despite preserving large numbers of phenotypic memory stem T cells, the lack of both of T-bet and Eomes resulted in a profound defect in antitumor memory responses, suggesting T-bet and Eomes are crucial for the antitumor function of these memory T cells. Our study establishes that T-bet and Eomes cooperate to promote the phenotype of effector/central memory CD8 T cell versus that of memory stem like T cells. © 2013 Li et al
Small RNA Profile in Moso Bamboo Root and Leaf Obtained by High Definition Adapters
Moso bamboo (Phyllostachy heterocycla cv. pubescens L.) is an economically important fast-growing tree. In order to gain better understanding of gene expression regulation in this important species we used next generation sequencing to profile small RNAs in leaf and roots of young seedlings. Since standard kits to produce cDNA of small RNAs are biased for certain small RNAs, we used High Definition adapters that reduce ligation bias. We identified and experimentally validated five new microRNAs and a few other small non-coding RNAs that were not microRNAs. The biological implication of microRNA expression levels and targets of microRNAs are discussed
Interface Coupling in Twisted Multilayer Graphene by Resonant Raman Spectroscopy of Layer Breathing Modes.
Raman spectroscopy is the prime nondestructive characterization tool for graphene and related layered materials. The shear (C) and layer breathing modes (LBMs) are due to relative motions of the planes, either perpendicular or parallel to their normal. This allows one to directly probe the interlayer interactions in multilayer samples. Graphene and other two-dimensional (2d) crystals can be combined to form various hybrids and heterostructures, creating materials on demand with properties determined by the interlayer interaction. This is the case even for a single material, where multilayer stacks with different relative orientations have different optical and electronic properties. In twisted multilayer graphene there is a significant enhancement of the C modes due to resonance with new optically allowed electronic transitions, determined by the relative orientation of the layers. Here we show that this applies also to the LBMs, which can be now directly measured at room temperature. We find that twisting has a small effect on LBMs, quite different from the case of the C modes. This implies that the periodicity mismatch between two twisted layers mostly affects shear interactions. Our work shows that ultralow-frequency Raman spectroscopy is an ideal tool to uncover the interface coupling of 2d hybrids and heterostructures
Ultra-strong Adhesion of Graphene Membranes
As mechanical structures enter the nanoscale regime, the influence of van der
Waals forces increases. Graphene is attractive for nanomechanical systems
because its Young's modulus and strength are both intrinsically high, but the
mechanical behavior of graphene is also strongly influenced by the van der
Waals force. For example, this force clamps graphene samples to substrates, and
also holds together the individual graphene sheets in multilayer samples. Here
we use a pressurized blister test to directly measure the adhesion energy of
graphene sheets with a silicon oxide substrate. We find an adhesion energy of
0.45 \pm 0.02 J/m2 for monolayer graphene and 0.31 \pm 0.03 J/m2 for samples
containing 2-5 graphene sheets. These values are larger than the adhesion
energies measured in typical micromechanical structures and are comparable to
solid/liquid adhesion energies. We attribute this to the extreme flexibility of
graphene, which allows it to conform to the topography of even the smoothest
substrates, thus making its interaction with the substrate more liquid-like
than solid-like.Comment: to appear in Nature Nanotechnolog
A Computation in a Cellular Automaton Collider Rule 110
A cellular automaton collider is a finite state machine build of rings of
one-dimensional cellular automata. We show how a computation can be performed
on the collider by exploiting interactions between gliders (particles,
localisations). The constructions proposed are based on universality of
elementary cellular automaton rule 110, cyclic tag systems, supercolliders, and
computing on rings.Comment: 39 pages, 32 figures, 3 table
The J-triplet Cooper pairing with magnetic dipolar interactions
Recently, cold atomic Fermi gases with the large magnetic dipolar interaction
have been laser cooled down to quantum degeneracy. Different from
electric-dipoles which are classic vectors, atomic magnetic dipoles are
quantum-mechanical matrix operators proportional to the hyperfine-spin of
atoms, thus provide rich opportunities to investigate exotic many-body physics.
Furthermore, unlike anisotropic electric dipolar gases, unpolarized magnetic
dipolar systems are isotropic under simultaneous spin-orbit rotation. These
features give rise to a robust mechanism for a novel pairing symmetry: orbital
p-wave (L=1) spin triplet (S=1) pairing with total angular momentum of the
Cooper pair J=1. This pairing is markedly different from both the He-B
phase in which J=0 and the He- phase in which is not conserved. It
is also different from the p-wave pairing in the single-component electric
dipolar systems in which the spin degree of freedom is frozen
Presymptomatic risk assessment for chronic non-communicable diseases
The prevalence of common chronic non-communicable diseases (CNCDs) far
overshadows the prevalence of both monogenic and infectious diseases combined.
All CNCDs, also called complex genetic diseases, have a heritable genetic
component that can be used for pre-symptomatic risk assessment. Common single
nucleotide polymorphisms (SNPs) that tag risk haplotypes across the genome
currently account for a non-trivial portion of the germ-line genetic risk and
we will likely continue to identify the remaining missing heritability in the
form of rare variants, copy number variants and epigenetic modifications. Here,
we describe a novel measure for calculating the lifetime risk of a disease,
called the genetic composite index (GCI), and demonstrate its predictive value
as a clinical classifier. The GCI only considers summary statistics of the
effects of genetic variation and hence does not require the results of
large-scale studies simultaneously assessing multiple risk factors. Combining
GCI scores with environmental risk information provides an additional tool for
clinical decision-making. The GCI can be populated with heritable risk
information of any type, and thus represents a framework for CNCD
pre-symptomatic risk assessment that can be populated as additional risk
information is identified through next-generation technologies.Comment: Plos ONE paper. Previous version was withdrawn to be updated by the
journal's pdf versio
Driven coherent oscillations of a single electron spin in a quantum dot
The ability to control the quantum state of a single electron spin in a
quantum dot is at the heart of recent developments towards a scalable
spin-based quantum computer. In combination with the recently demonstrated
exchange gate between two neighbouring spins, driven coherent single spin
rotations would permit universal quantum operations. Here, we report the
experimental realization of single electron spin rotations in a double quantum
dot. First, we apply a continuous-wave oscillating magnetic field, generated
on-chip, and observe electron spin resonance in spin-dependent transport
measurements through the two dots. Next, we coherently control the quantum
state of the electron spin by applying short bursts of the oscillating magnetic
field and observe about eight oscillations of the spin state (so-called Rabi
oscillations) during a microsecond burst. These results demonstrate the
feasibility of operating single-electron spins in a quantum dot as quantum
bits.Comment: Total 25 pages. 11 pages main text, 5 figures, 9 pages supplementary
materia
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