Improvement of Morphine-Mediated Analgesia by Inhibition of β-Arrestin 2 Expression in Mice Periaqueductal Gray Matter

Morphine is a well-known μ-opioid receptor (MOR) agonist and an efficient analgesic, but its long-term use inevitably leads to drug addiction and tolerance. Here, we show that specific inhibition of β-arrestin2 with its siRNA lentivirus microinjected in mice periaqueductal gray matter (PAG) significantly improved both acute and chronic morphine analgesia and delayed the tolerance in the hotplate test. The specific effect of β-arrestin2 was proven by overexpression or knockdown of its homology β-arrestin1 in PAG, which showed no significant effects on morphine analgesia. These findings suggest that specific siRNA targeting β-arrestin2 may constitute a new approach to morphine therapy and other MOR agonist-mediated analgesia and tolerance

Intravenous postoperative fluid prescriptions for children: A survey of practice

<p>Abstract</p> <p>Background</p> <p>Postoperative deaths and neurological injury have resulted from hyponatraemia associated with the use of hypotonic saline solutions following surgery. We aimed to determine the rates and types of intravenous fluids being prescribed postoperatively for children in the UK.</p> <p>Methods</p> <p>A questionnaire was sent to members of the British Association of Paediatric Surgeons (BAPS) and Association of Paediatric Anaesthetists of Great Britain and Ireland (APAGBI) based at UK paediatric centres. Respondents were asked to prescribe postoperative fluids for scenarios involving children of different ages. The study period was between May 2006 and November 2006.</p> <p>Results</p> <p>The most frequently used solution was sodium chloride 0.45% with glucose 5% although one quarter of respondents still used sodium chloride 0.18% with glucose 4%. Isotonic fluids were used by 41% of anaesthetists and 9.8% of surgeons for the older child, but fewer for infants. Standard maintenance rates or greater were prescribed by over 80% of respondents.</p> <p>Conclusion</p> <p>Most doctors said they would prescribe hypotonic fluids at volumes equal to or greater than traditional maintenance rates at the time of the survey. A survey to describe practice since publication of National Patient Safety Agency (NPSA) recommendations is required.</p

Two Directly Imaged, Wide-orbit Giant Planets around the Young, Solar Analog TYC 8998-760-1

Even though tens of directly imaged companions have been discovered in the past decades, the number of directly confirmed multiplanet systems is still small. Dynamical analysis of these systems imposes important constraints on formation mechanisms of these wide-orbit companions. As part of the Young Suns Exoplanet Survey we report the detection of a second planetary-mass companion around the 17 Myr-old, solar-type star TYC 8998-760-1 that is located in the Lower Centaurus Crux subgroup of the Scorpius–Centaurus association. The companion has a projected physical separation of 320 au and several individual photometric measurements from 1.1 to 3.8 microns constrain a companion mass of 6 ± 1 M Jup, which is equivalent to a mass ratio of q = 0.57 ± 0.10% with respect to the primary. With the previously detected 14 ± 3 M Jup companion that is orbiting the primary at 160 au, TYC 8998-760-1 is the first directly imaged multiplanet system that is detected around a young, solar analog. We show that circular orbits are stable, but that mildly eccentric orbits for either/both components (e > 0.1) are chaotic on gigayear timescales, implying in situ formation or a very specific ejection by an unseen third companion. Due to the wide separations of the companions TYC 8998-760-1 is an excellent system for spectroscopic and photometric follow-up with space-based observatories such as the James Webb Space Telescope

Evalutating the potential of desis to infer plant taxonomical and functional diversities in europwean forests

Abstract. Tackling the accelerated human-induced biodiversity loss requires tools able to map biodiversity and its changes globally. Remote sensing (RS) offers unique capabilities of characterizing Earth surfaces; therefore, it could map plant biodiversity continuously and globally. This approach is supported by the Spectral Variation Hypothesis (SVH), which states that spectra and species (taxonomic and trait) diversities are linked through environmental heterogeneity. In this work, we evaluate the capability of the DESIS hyperspectral imager to capture plant diversity patterns as measured in dedicated plots of the network FunDivEUROPE. We computed functional and taxonomical diversity metrics from field taxonomic, structural, and foliar measurements in vegetation plots sampled in Spain and Romania. In addition, we also computed functional diversity metrics both from the DESIS reflectance factors and from vegetation parameters estimated via inversion of a radiative transfer model. Results showed that only metrics computed from spectral reflectance were able to capture taxonomic variability in the area. However, the lack of sensitivity was related to the insufficient plot size and the lack of spatial match between remote sensing and field data, but also the differences between the information contained in the field traits and remote sensing data, and the potential uncertainties in the remote estimates of vegetation parameters. Thus, while DESIS showed some sensitivity to plant diversity, further efforts are needed to deploy suitable biodiversity evaluation and validation plots and networks that support the development of biodiversity remote sensing products

Study of intragastric structuring ability of sodium alginate based o/w emulsions under in vitro physiological pre-absorptive digestion conditions

In the present work, the intragastric structuring ability of o/w emulsions either stabilised (1–4%, w/w of sodium alginate (SA)) or structured with sheared ionic gel (1–3%, w/w of SA crosslinked with Ca2+) in the absence (saliva and gastric phases constituted of deionised water) or presence of in vitro pre-absorptive conditions (physiological simulated saliva and gastric fluids) was investigated. Visualisation of the morphological aspects of the gastric chymes, in the absence of multivalent counterions, demonstrated that SA stabilised systems underwent a remarkable swelling in the pH range of 2–3, whilst at the same pH range, ionic SA gel structured systems maintained their major structure configuration. When the aforementioned systems were exposed to physiological intragastric fluids, a reduction of the length and the hydrodynamic volume of the alginate fibres was detected regardless the structuring approach. On their exposure to physiological intragastric conditions (pH = 2), SA stabilised emulsions underwent sol–gel transition achieving a ca. 3- to 4-order increase of storage modulus (at 1 Hz). In the case of ionic sheared gel structured emulsions, exposure to physiological intragastric fluids resulted in a 10-fold reduction ability of their acid structuring ability, most likely due to the dialysis of egg-box dimer conformations by monovalent cations and protons and the sterical hindering of hydrogen bonding of MM and GG sequences under acidic conditions. Using of non-physiological simulated intragastric fluids was associated with overestimated structuring performance of SA regardless its physical state

New insights into globoids of protein storage vacuoles in wheat aleurone using synchrotron soft X-ray microscopy

Mature developed seeds are physiologically and biochemically committed to store nutrients, principally as starch, protein, oils, and minerals. The composition and distribution of elements inside the aleurone cell layer reflect their biogenesis, structural characteristics, and physiological functions. It is therefore of primary importance to understand the mechanisms underlying metal ion accumulation, distribution, storage, and bioavailability in aleurone subcellular organelles for seed fortification purposes. Synchrotron radiation soft X-ray full-field imaging mode (FFIM) and low-energy X-ray fluorescence (LEXRF) spectromicroscopy were applied to characterize major structural features and the subcellular distribution of physiologically important elements (Zn, Fe, Na, Mg, Al, Si, and P). These direct imaging methods reveal the accumulation patterns between the apoplast and symplast, and highlight the importance of globoids with phytic acid mineral salts and walls as preferential storage structures. C, N, and O chemical topographies are directly linked to the structural backbone of plant substructures. Zn, Fe, Na, Mg, Al, and P were linked to globoid structures within protein storage vacuoles with variable levels of co-localization. Si distribution was atypical, being contained in the aleurone apoplast and symplast, supporting a physiological role for Si in addition to its structural function. These results reveal that the immobilization of metals within the observed endomembrane structures presents a structural and functional barrier and affects bioavailability. The combination of high spatial and chemical X-ray microscopy techniques highlights how in situ analysis can yield new insights into the complexity of the wheat aleurone layer, whose precise biochemical composition, morphology, and structural characteristics are still not unequivocally resolved

Cooperative Catalytic Effect of ZrO2 and a-Fe2O3 Nanoparticles on BiVO4 Photoanodes for Enhanced Photoelectrochemical Water Splitting

Photoelectrochemical water splitting with metal oxide semiconductors offers a cost-competitive alternative for the generation of solar fuels. Most of the materials studied so far suffer from poor charge-transfer kinetics at the semiconductor/liquid interface, making compulsory the use of catalytic layers to overcome the large overpotentials required for the water oxidation reaction. Herein, we report a very soft electrolytic synthesis deposition method, which allows remarkably enhanced water oxidation kinetics of BiVO4 photoanodes by the sequential addition of Zr and Fe precursors. Upon a heat treatment cycle, these precursors are converted into monoclinic ZrO2 and α-Fe2O3 nanoparticles, which mainly act as catalysts, leading to a five-fold increase of the water oxidation photocurrent of BiVO4. This method provides a versatile platform that is easy to apply to different semiconductor materials, fully reproducible, and facile to scale-up on large area conductive substrates with attractive implications for technological deploymentWe thank financial support from the University Jaume I through the project P1⋅1B2011-50. Serveis Centrals at UJI (SCIC) are also acknowledged

A model for removing the increased recall of recent events from the temporal distribution of autobiographical memory

The reminiscence bump is the tendency to recall relatively many personal events from the period in which the individual was between 10 and 30 years old. This effect has only been found in autobiographical memory studies that used participants who were older than 40 years of age. The increased recall of recent events possibly obscures the reminiscence bump in the results of younger participants. In this study, a model was proposed that removes the increase for recent events from the temporal distribution. The model basically estimates a retention function based on the 10 most recent years from the observed distributions and divides the observed distributions by predictions derived from the estimated retention function. The model was examined with three simulated data sets and one experimental data set. The results of the experiment offered two practical examples of how the model could be used to investigate the temporal distribution of autobiographical memories

Immune Evasion by Yersinia enterocolitica: Differential Targeting of Dendritic Cell Subpopulations In Vivo

CD4+ T cells are essential for the control of Yersinia enterocolitica (Ye) infection in mice. Ye can inhibit dendritic cell (DC) antigen uptake and degradation, maturation and subsequently T-cell activation in vitro. Here we investigated the effects of Ye infection on splenic DCs and T-cell proliferation in an experimental mouse infection model. We found that OVA-specific CD4+ T cells had a reduced potential to proliferate when stimulated with OVA after infection with Ye compared to control mice. Additionally, proliferation of OVA-specific CD4+ T cells was markedly reduced when cultured with splenic CD8α+ DCs from Ye infected mice in the presence of OVA. In contrast, T-cell proliferation was not impaired in cultures with CD4+ or CD4−CD8α− DCs isolated from Ye infected mice. However, OVA uptake and degradation as well as cytokine production were impaired in CD8α+ DCs, but not in CD4+ and CD4−CD8α− DCs after Ye infection. Pathogenicity factors (Yops) from Ye were most frequently injected into CD8α+ DCs, resulting in less MHC class II and CD86 expression than on non-injected CD8α+ DCs. Three days post infection with Ye the number of splenic CD8α+ and CD4+ DCs was reduced by 50% and 90%, respectively. The decreased number of DC subsets, which was dependent on TLR4 and TRIF signaling, was the result of a faster proliferation and suppressed de novo DC generation. Together, we show that Ye infection negatively regulates the stimulatory capacity of some but not all splenic DC subpopulations in vivo. This leads to differential antigen uptake and degradation, cytokine production, cell loss, and cell death rates in various DC subpopulations. The data suggest that these effects might be caused directly by injection of Yops into DCs and indirectly by affecting the homeostasis of CD4+ and CD8α+ DCs. These events may contribute to reduced T-cell proliferation and immune evasion of Ye

Morphine activation of mu opioid receptors causes disinhibition of neurons in the ventral tegmental area mediated by β-arrestin2 and c-Src

Abstract The tyrosine kinase, c-Src, participates in mu opioid receptor (MOP) mediated inhibition in sensory neurons in which β-arrestin2 (β-arr2) is implicated in its recruitment. Mice lacking β-arr2 exhibit increased sensitivity to morphine reinforcement; however, whether β-arr2 and/or c-Src participate in the actions of opioids in neurons within the reward pathway is unknown. It is also unclear whether morphine acts exclusively through MOPs, or involves delta opioid receptors (DOPs). We examined the involvement of MOPs, DOPs, β-arr2 and c-Src in the inhibition by morphine of GABAergic inhibitory postsynaptic currents (IPSCs) recorded from neurons in the mouse ventral tegmental area. Morphine inhibited spontaneous IPSC frequency, mainly through MOPs, with only a negligible effect remaining in MOP−/− neurons. However, a reduction in the inhibition by morphine for DOP−/− c.f. WT neurons and a DPDPE-induced decrease of IPSC frequency revealed a role for DOPs. The application of the c-Src inhibitor, PP2, to WT neurons also reduced inhibition by morphine, while the inactive PP3, and the MEK inhibitor, SL327, had no effect. Inhibition of IPSC frequency by morphine was also reduced in β-arr2−/− neurons in which PP2 caused no further reduction. These data suggest that inhibition of IPSCs by morphine involves a β-arr2/c-Src mediated mechanism