148 research outputs found
IL-1 receptor signaling in the basolateral amygdala modulates binge-like ethanol consumption in male C57BL/6J mice
Proinflammatory cytokines have been implicated in alcohol-induced neurodegeneration, but the role of the neuroimmune system in alcohol related behaviors has only recently come to the forefront. Herein, the effects of binge-like drinking on IL-1β mRNA and immunoreactivity within the amygdala were measured following the “drinking in the dark” (DID) paradigm, a model of binge-like ethanol drinking in C57BL/6J mice. Moreover, the role of IL-1 receptor signaling in the amygdala on ethanol consumption was assessed. Results indicated that a history of binge-like ethanol drinking promoted a significant increase of IL-1β mRNA expression within the amygdala, and immunohistochemistry analyses revealed that the basolateral amygdala (BLA), but not central amygdala (CeA), exhibited significantly increased IL-1β immunoreactivity. Fluoro-Jade® C labeling indicated that multiple cycles of the DID paradigm were not sufficient to elicit neuronal death. Bilateral infusions of IL-1 receptor antagonist (IL-1Ra) reduced ethanol consumption when infused into the BLA but not the CeA. These observations were specific to ethanol drinking as the IL-1Ra did not alter either sucrose drinking or open-field locomotor activity. The current findings highlight a specific role for IL-1 receptor signaling in modulating binge-like ethanol consumption and indicate that proinflammatory cytokines can be induced prior to dependence or any evidence of neuronal cell death. These findings provide a framework in which to understand how neuroimmune adaptations may alter ethanol consumption and therein contributing to alcohol abuse
Four small puzzles that Rosetta doesn't solve
A complete macromolecule modeling package must be able to solve the simplest
structure prediction problems. Despite recent successes in high resolution
structure modeling and design, the Rosetta software suite fares poorly on
deceptively small protein and RNA puzzles, some as small as four residues. To
illustrate these problems, this manuscript presents extensive Rosetta results
for four well-defined test cases: the 20-residue mini-protein Trp cage, an even
smaller disulfide-stabilized conotoxin, the reactive loop of a serine protease
inhibitor, and a UUCG RNA tetraloop. In contrast to previous Rosetta studies,
several lines of evidence indicate that conformational sampling is not the
major bottleneck in modeling these small systems. Instead, approximations and
omissions in the Rosetta all-atom energy function currently preclude
discriminating experimentally observed conformations from de novo models at
atomic resolution. These molecular "puzzles" should serve as useful model
systems for developers wishing to make foundational improvements to this
powerful modeling suite.Comment: Published in PLoS One as a manuscript for the RosettaCon 2010 Special
Collectio
The Nab Experiment: A Precision Measurement of Unpolarized Neutron Beta Decay
Neutron beta decay is one of the most fundamental processes in nuclear
physics and provides sensitive means to uncover the details of the weak
interaction. Neutron beta decay can evaluate the ratio of axial-vector to
vector coupling constants in the standard model, , through
multiple decay correlations. The Nab experiment will carry out measurements of
the electron-neutrino correlation parameter with a precision of and the Fierz interference term to
in unpolarized free neutron beta decay. These results, along with a more
precise measurement of the neutron lifetime, aim to deliver an independent
determination of the ratio with a precision of that will allow an evaluation of and sensitively
test CKM unitarity, independent of nuclear models. Nab utilizes a novel, long
asymmetric spectrometer that guides the decay electron and proton to two large
area silicon detectors in order to precisely determine the electron energy and
an estimation of the proton momentum from the proton time of flight. The Nab
spectrometer is being commissioned at the Fundamental Neutron Physics Beamline
at the Spallation Neutron Source at Oak Ridge National Lab. We present an
overview of the Nab experiment and recent updates on the spectrometer,
analysis, and systematic effects.Comment: Presented at PPNS201
Energetic signatures of single base bulges: thermodynamic consequences and biological implications
DNA bulges are biologically consequential defects that can arise from template-primer misalignments during replication and pose challenges to the cellular DNA repair machinery. Calorimetric and spectroscopic characterizations of defect-containing duplexes reveal systematic patterns of sequence-context dependent bulge-induced destabilizations. These distinguishing energetic signatures are manifest in three coupled characteristics, namely: the magnitude of the bulge-induced duplex destabilization (ΔΔGBulge); the thermodynamic origins of ΔΔGBulge (i.e. enthalpic versus entropic); and, the cooperativity of the duplex melting transition (i.e. two-state versus non-two state). We find moderately destabilized duplexes undergo two-state dissociation and exhibit ΔΔGBulge values consistent with localized, nearest neighbor perturbations arising from unfavorable entropic contributions. Conversely, strongly destabilized duplexes melt in a non-two-state manner and exhibit ΔΔGBulge values consistent with perturbations exceeding nearest-neighbor expectations that are enthalpic in origin. Significantly, our data reveal an intriguing correlation in which the energetic impact of a single bulge base centered in one strand portends the impact of the corresponding complementary bulge base embedded in the opposite strand. We discuss potential correlations between these bulge-specific differential energetic profiles and their overall biological implications in terms of DNA recognition, repair and replication
Influence of Helium and Nitrogen Gases on the Properties of Cold Gas Dynamic Sprayed Pure Titanium Coatings
Escalas concorrentes para a mensuraçãoda qualidade percebida: uma comparação entre a Servqual e a RSQ
Double Label Immuno Fluorescence Studies on Nanometer Filaments and Micro Tubules During Mitosis in Endothelial Cells
- …