GABA(B) receptor agonist only reduces ethanol drinking in light-drinking mice

Baclofen, a GABA(B) agonist, reduces ethanol intake in animals and humans, but the contrary or no effect was also reported. Our previous study demonstrated that mice characterized as "loss of control over ethanol intake" had different Gabbr1 and Gabbr2 transcription levels, which express, respectively, the GABA(B1) and GABA(B2) subunits in brain areas related to addictive behavior. In the present study, we tested baclofen on ethanol intake in mice exposed to the free-choice paradigm. Adult male Swiss mice, individually housed, had free access to three bottles: ethanol (5% and 10%) and water. The protocol had four phases: acquisition (AC, 10 weeks), withdrawal (W, 4 cycles during 2 weeks of 2 day-free-choice and 2 day-only-water), reexposure (RE, 2 weeks), and adulteration of ethanol solutions with quinine (AD, 2 weeks). Mice characterized as "loss of control" (A, n = 11, preference for ethanol in AC and maintenance of ethanol intake levels in AD), heavy (H, n = 11, preference for ethanol in AC and reduction of ethanol intake levels in AD), and light (L n = 16, preference for water in all phases) drinkers were randomly distributed into two subgroups receiving either intraperitoneal injections of all doses of baclofen (1.25, 2.5, and 5.0 mg/kg, given each dose twice in consecutive days) or saline, being exposed to free-choice. Fluid consumption was measured 24 h later. Baclofen reduced ethanol intake in group L In group H a reduction compared to AC was observed. Group A maintained their high ethanol intake even after baclofen treatment. Activation of the GABA(B) receptor depends on the precise balance between the GABA(B1) and GABA(B2) subunits, so the disproportionate transcription levels, we reported in group A, could explain this lack of response to baclofen. These data highlight the importance to test baclofen in individuals with different ethanol drinking profiles, including humans. (C) 2012 Elsevier Inc. All rights reserved.

Search for light top squark pair production in final states with leptons and b��� jets with the ATLAS detector in sqrts=7 TeV proton-proton collisions

The results of a search for pair production of light top squarks are presented, using 4.7 fb(-1) of root s = 7 TeV proton-proton collisions collected with the ATLAS detector at the Large Hadron Collider. This search targets top squarks with masses similar to, or lighter than, the top quark mass. Final states containing exclusively one or two leptons (e, mu), large missing transverse momentum, light-flavour jets and b-jets are used to reconstruct the top squark pair system. Event-based mass scale variables are used to separate the signal from a large t (t) over bar background. No excess over the Standard Model expectations is found. The results are interpreted in the framework of the Minimal Supersymmetric Standard Model, assuming the top squark decays exclusively to a chargino and a b-quark, while requiring different mass relationships between the Supersymmetric particles in the decay chain. Light top squarks with masses between 123-167 GeV are excluded for neutralino masses around 55 GeV.

Towards a data-driven analysis of hadronic light-by-light scattering

The hadronic light-by-light contribution to the anomalous magnetic moment of the muon was recently analyzed in the framework of dispersion theory, providing a systematic formalism where all input quantities are expressed in terms of on-shell form factors and scattering amplitudes that are in principle accessible in experiment. We briefly review the main ideas behind this framework and discuss the various experimental ingredients needed for the evaluation of one- and two-pion intermediate states. In particular, we identify processes that in the absence of data for doubly-virtual pion–photon interactions can help constrain parameters in the dispersive reconstruction of the relevant input quantities, the pion transition form factor and the helicity partial waves for γ⁎γ⁎→ππ.

Temporal evolution of strut light intensity after implantation of bioresorbable polymeric intracoronary scaffolds in the ABSORB cohort B trial-an application of a new quantitative method based on optical coherence tomography.

BACKGROUND Quantitative light intensity analysis of the strut core by optical coherence tomography (OCT) may enable assessment of changes in the light reflectivity of the bioresorbable polymeric scaffold from polymer to provisional matrix and connective tissues, with full disappearance and integration of the scaffold into the vessel wall. The aim of this report was to describe the methodology and to apply it to serial human OCT images post procedure and at 6, 12, 24 and 36 months in the ABSORB cohort B trial. METHODS AND RESULTS In serial frequency-domain OCT pullbacks, corresponding struts at different time points were identified by 3-dimensional foldout view. The peak and median values of light intensity were measured in the strut core by dedicated software. A total of 303 corresponding struts were serially analyzed at 3 time points. In the sequential analysis, peak light intensity increased gradually in the first 24 months after implantation and reached a plateau (relative difference with respect to baseline [%Dif]: 61.4% at 12 months, 115.0% at 24 months, 110.7% at 36 months), while the median intensity kept increasing at 36 months (%Dif: 14.3% at 12 months, 75.0% at 24 months, 93.1% at 36 months). CONCLUSIONS Quantitative light intensity analysis by OCT was capable of detecting subtle changes in the bioresorbable strut appearance over time, and could be used to monitor the bioresorption and integration process of polylactide struts.

Stimulation of monocytes by placental microparticles involves toll-like receptors and nuclear factor kappa-light-chain-enhancer of activated B cells.

Human pregnancy is accompanied by a mild systemic inflammatory response, which includes the activation of monocytes circulating in maternal blood. This response is exaggerated in preeclampsia, a placental-dependent disorder specific to human pregnancies. We and others showed that placental syncytiotrophoblast membrane microparticles (STBM) generated in vitro from normal placentas stimulated peripheral blood monocytes, which suggest a contribution of STBM to the systemic maternal inflammation. Here, we analyzed the inflammatory potential of STBM prepared from preeclamptic placentas on primary monocytes and investigated the mode of action in vitro. STBM generated in vitro by placental villous explants of normal or preeclamptic placentas were co-incubated with human peripheral blood monocytes. In some cases, inhibitors of specific cellular functions or signaling pathways were used. The analysis of the monocytic response was performed by flow cytometry, enzyme-linked immunoassays, real-time PCR, and fluorescence microscopy. STBM derived from preeclamptic placentas up-regulated the cell surface expression of CD54, and stimulated the secretion of the pro-inflammatory interleukin (IL)-6 and IL-8 in a similar, dose-dependent manner as did STBM prepared from normal placentas. STBM bound to the cell surface of monocytes, but phagocytosis was not necessary for activation. STBM-induced cytokine secretion was impaired in the presence of inhibitors of toll-like receptor (TLR) signaling or when nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation was blocked. Our results suggest that the inflammatory reaction in monocytes may be initiated by the interaction of STBM with TLRs, which in turn signal through NF-κB to mediate the transcription of genes coding for pro-inflammatory factors.

The Plasmodium Class XIV Myosin, MyoB, Has a Distinct Subcellular Location in Invasive and Motile Stages of the Malaria Parasite and an Unusual Light Chain

Myosin B (MyoB) is one of the two short class XIV myosins encoded in the Plasmodium genome. Class XIV myosins are characterized by a catalytic "head," a modified "neck," and the absence of a "tail" region. Myosin A (MyoA), the other class XIV myosin in Plasmodium, has been established as a component of the glideosome complex important in motility and cell invasion, but MyoB is not well characterized. We analyzed the properties of MyoB using three parasite species as follows: Plasmodium falciparum, Plasmodium berghei, and Plasmodium knowlesi. MyoB is expressed in all invasive stages (merozoites, ookinetes, and sporozoites) of the life cycle, and the protein is found in a discrete apical location in these polarized cells. In P. falciparum, MyoB is synthesized very late in schizogony/merogony, and its location in merozoites is distinct from, and anterior to, that of a range of known proteins present in the rhoptries, rhoptry neck or micronemes. Unlike MyoA, MyoB is not associated with glideosome complex proteins, including the MyoA light chain, myosin A tail domain-interacting protein (MTIP). A unique MyoB light chain (MLC-B) was identified that contains a calmodulin-like domain at the C terminus and an extended N-terminal region. MLC-B localizes to the same extreme apical pole in the cell as MyoB, and the two proteins form a complex. We propose that MLC-B is a MyoB-specific light chain, and for the short class XIV myosins that lack a tail region, the atypical myosin light chains may fulfill that role.

Geochemistry of dark-light rhythm sediments of the Japan Sea

Ocean Drilling Program Legs 127 and 128 in the Japan Sea have revealed the existence of numerous dark-light rhythms of remarkable consistency in sediments of late Miocene, latest Pliocene, and especially Pleistocene age. Light-colored units within these rhythms are massive or bioturbated, consist of diatomaceous clays, silty clays, or nannofossil-rich clays, and are generally poor in organic matter. Dark-colored units are homogeneous, laminated, or thinly bedded and include substantial amounts of biogenic material such as well-preserved diatoms, planktonic foraminifers, calcareous nannofossils, and organic matter (maximum 7.4 wt%). The dark-light rhythms show a similar geometrical pattern on three different scales: First-order rhythms consist of a cluster dominated by dark-colored units followed by a cluster dominated by light-colored units (3-5 m). Spectral analysis of a gray-value time series suggests that the frequencies of the first-order rhythms in sediments of latest Pliocene and Pleistocene age correlate to the obliquity and the eccentricity cycles. The second-order dark-light rhythms include a light and a dark-colored unit (10-160 cm). They were formed in time spans of several hundred to several ten thousand years, with variance centering around 10,500 yr. This frequency may correspond to half the precessional cycle. Third-order rhythms appear as laminated or thinly bedded dark-light couplets (2-15 mm) within the dark-colored units of the second-order rhythms and may represent annual frequencies. In interpreting the rhythms, we have to take into account that (1) the occurrence of the first- and second-order rhythms is not necessarily restricted to glacial or interglacial periods as is shown by preliminary stable-isotope analysis and comparison with the published d18O record; (2) they appear to be Milankovitch-controlled; and (3) a significant number of the rhythms are sharply bounded. The origin of the dark-light rhythms is probably related to variations in monsoonal activity in the Japan Sea, which show annual frequencies, but also operates in phase with the orbital cycles.