185,179 research outputs found

    MoR-21L plays a functional role in VSMC.

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    (a) Location of moRs and miRs sequences on the predicted secondary structure surrounding the pre-miR-21 hairpin. The RNA structure prediction software mFold was used to predict pre-miR-21 secondary structure. (b) Increased expression of moR-21 and miR-21 in injured mouse carotid artery. Data are shown as mean ± SEM and are from 3 independent experiments. (c) Abundance of moR-21 and miR-21 in VSMC cultured under different conditions. VSMC were cultured in serum free medium (SFM) and medium containing 10% fetal bovine serum (FBS) or PDGF. BSA is the control for PDGF. Data are shown as mean ± SEM and are from 4 independent experiments. (d) Effects of over-expression of moR-21, miR-21, and scrambled mimetics on VSMC proliferation. VSMC were transfected with 20nM scrambled control, moR-21, and or miR-21 mimetics. Cell proliferation was measured at 0, 1, 2, and 3 days using Cell TiterGlo. Data are presented as relative proliferation, compared with scrambled mimetic-transfected cells on day 0. Data are shown as mean ± SEM and are from 5 independent experiments. P values were determined by one way repeated measure ANOVA. NS: nonsignificant, *: PP<0.001.</p

    moR-21 plays a role in gene regulation and has a different target gene set from miR-21.

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    (a) Differentially expressed transcripts in moR-21 over-expressed VSMC compared with scrambled control-treated cells. In moR-21-treated cells, 460 and 378 transcripts were down- or up-regulated, respectively. Fold change cutoff is 1.3 and adjusted PP-value cutoff t-test. NS: non-significant, **: PP<0.001.</p

    Interactions between atypical opioid agonists and MOR

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    Endomorphins (EMs) are endogenous peptides with high selectivity for MOR; they induce strong antinociception by binding to both central and peripheral MOR but, unlike morphine, they are effective in reducing neuropathic pain and their analgesic effect seems to be dissociated by immunomodulatory, cardiovascular and respiratory effects. As native EMs show poor bioavailability and rapid degradation in vivo, we designed and assayed novel EM-1 (YPWF-NH2) derivatives bearing chemical modification aimed to improve their application as analgesics. The ionic bond between a protonated amine and a conserved Asp in the third TMH of the opioid receptor is considered the driving force for ligand-receptor interaction of all opioid agonists, being the amine of Tyr the key pharmacophore for opioid peptides. The removal or derivatization of this pharmacophore usually transforms agonists into inactive compounds or antagonists, with only few compounds maintaining an agonist behaviour when deprived of such amino group. Recently, we discovered the novel EM-1 derivative c[YpwFG]; it displayed good affinity to MOR (Ki 34 nM), is an effective and potent analgesic for visceral pain when administered peripherally (i.p ED50 1,25 mg/kg; s.c. ED50 2,7 mg/kg), and retains central analgesic effects (tail-flick test) only at high doses (20 mg/kg). Interestingly, it triggers MOR internalization similarly to DAMGO but displayed an opposite effect on MOR transcription. This cyclopeptide is a structurally atypical opioid agonist, being deprived of the key pharmacophore, therefore we performed investigations by 2D-NMR, conformational analysis, and molecular docking to provide insights into its interaction with and activation of MOR. The resulting receptor-bound structure served as a general model to design new MOR-active compounds containing the sequence wF, to optimize ligand-receptor interactions. This search lead to c[YGwFG], which showed a 10- fold higher affinity for the MOR (Ki 3,6 nM) as well as good analgesic properties in vivo. Finally, we verified the predictive power of the general model by designing a non-EM-like opioid compound, the cyclic tetrapeptide c[d(1-NH2)beta-AwF]. In summary, these results suggest that alternative interactions might duly replace the electrostatic interaction of the protonated nitrogen with the Asp residue, which has not to be considered a conditio sine qua non for opioid receptor activatio

    Overlap and segregation of MOR (red) and CB<sub>1</sub>-R (green) at different levels through the striatum.

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    Four sections are presented between 1.25 and -0.2 mm relative to bregma (left). Examples of MOR-dominant staining in the rostral dorsomedial striatum (A), overlap between MOR and CB1-R in the dorsolateral striosomes (B), MOR-dominant ventral striosomes (C) and CB1-R-dominant striosomes (D) are presented at high power. Low power images were taken with the Axiozoom. Projection images on the right were taken with the LSM510. Scale bars are 1 mm in the left column and 20 μm in A-D.</p

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    An investigation into the recent vegetation history of Great Wood, near Eggleston Co. Durham using fine resolution pollen analysis of Mor humus and relevant historical evidence.

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    This study investigated the recent vegetation history of an ancient woodland, Great Wood, near Eggleston Co. Durham which has been part of the lands of Eggleston Hall since at least 1614. Mor humus was extracted from two sites within the woodland canopy and consecutive 1cm samples were analysed from each sediment. The reasons for this fine resolution sampling was firstly, because the soil profiles were only between 14-20cms and only represented a time scale of a few hundred years, and secondly to provide fine temporal resolution to correspond with the fine spatial resolution obtainable under a closed canopy. Sediment analysis was undertaken to investigate the stratification of the soil in order to identify signs of disturbance. Mor # 1 proved to be highly stratified, whereas as mor # 2 was less stratified, possibly disturbed and had signs of charcoal at the lowest levels. It was therefore concluded that mor # 2 only represented part of the time scale that mor # 1 illustrated, as it was a more recently formed humus, the earlier part having been burnt away. An absolute time scale was not used but a relative time scale was assigned using documentary and anecdotal historical evidence. This took into account the development of the nearby village and the social and economic changes of the region, and also the association of the woodland with Eggleston Hall and the consequent utilisation of the woodland for timber and recreational purposes. The pollen record of mor # 1 was thought to represent the vegetation history from approximately 1750 to the present time, whereas the pollen record of mor # 2 shows the vegetation history from the late nineteenth century onwards. This time scale was deduced from the following:1. There were signs of a more open canopy, due to a greater proportion of herb pollen to tree pollen, and evidence of pollen representing a more regional source area such as Triticum and possibly Calluna. This was thought to represent 1750- 1820 when tillage increased in importance and there were reports of arable activity in the adjoining townfield probably causing a reduction in grazing pressure in the wood and allowing regeneration. This was promoted by the Enclosure Act in 1785, an attempt to establish mineral rights and to make the dales more commercially viable for agriculture and was a result of marginal land being used for tillage during the Napoleonic wars. However, signs of succession and canopy closure began to develop and there were also some signs of management deduced from Fagus pollen appearing and documentary evidence of the path construction through the woods.2. The herb pollen to tree pollen ratio began to fall and canopy closure continued but was not thought to be complete, due to selective management and extraction of timber. The disappearance of Triticum was believed to be due to a change in agricultural trends. Fagus pollen which was quite significant, disappeared abruptly due to the trees in the vicinity of the site being removed.3. Complete canopy closure shown by a consistently high tree pollen to herb pollen ratio with Quercus dominating, arose when management of the wood was abandoned in the 1920's.The fine resolution obtained, both temporally and spatially, demonstrated that mor humus was a useful medium for pollen analysis and with consideration of the underlying principles and mechanisms, meaningful interpretation of the pollen record was possible. Problems encountered with extraction of samples and during processing were discussed

    "Closing the R&D Gap, Evaluating the Sources of R&D Spending"

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    Both spending and tax policies have been implemented in the United States with the goal of stimulating private sector research and development (R&D). Karier questions whether current R&D policy, especially the research and experimentation tax credit, can contribute to closing the gap between nondefense expenditures on R&D in the United States and such expenditures in other countries, such as Japan and Germany. He also explores possible changes to our current R&D policy to make it more effective.

    Caractères économiques du pays de Morlaix : Ar Mor et Ar C'hoat

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    Guezennec R. Caractères économiques du pays de Morlaix : Ar Mor et Ar C'hoat. In: Norois, n°2, Avril-Juin 1964. pp. 183-185
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