661 research outputs found
P2Yâ Nucleotide Receptors Expressed Heterologously in Sympathetic Neurons Inhibit Both N-Type Ca²⺠and M-Type Kâş Currents
The P2Yâ receptor is a uridine/adenosine triphosphate (UTP/ATP)-sensitive G-protein-linked nucleotide receptor that previously has been reported to stimulate the phosphoinositide signaling pathway. Messenger RNA for this receptor has been detected in brain tissue. We have investigated the coupling of the molecularly defined rat P2Yâ receptor to neuronal N-type Ca²⺠channels and to M-type Kâş channels by heterologous expression in rat superior cervical sympathetic (SCG) neurons. After the injection of P2YâcRNA, UTP inhibited the currents carried by both types of ion channel. As previously reported [Filippov AK, Webb TE, Barnard EA, Brown DA (1997) Inhibition by heterologously expressed P2Yânucleotide receptors of N-type calcium currents in rat sympathetic neurones. Br J Pharmacol 121:849â851], UTP inhibited the Ca²⺠current (I_{Ca(N)} by up to 64%, with an ICâ
â of âź0.5 Îźm. We now find that UTP also inhibited the Kâş_{M} current (I_{K(M)} by up to 61%, with an ICâ
â of âź1.5 Îźm. UTP had no effect on either current in neurons not injected with P2Yâ cRNA. Structureâactivity relations for the inhibition of I_{Ca(N)} and I_{K(M)} in P2Yâ cRNA-injected neurons were similar, with UTP ⼠ATP > ITP ⍠GTP,UDP. However, coupling to these two channels involved different G-proteins: pretreatment withPertussis toxin (PTX) did not affect UTP-induced inhibition of I_{K(M)} but reduced inhibition of I_{Ca(N)} by âź60% and abolished the voltage-dependent component of this inhibition. In unclamped neurons, UTP greatly facilitated depolarization-induced action potential discharges. Thus, the single P2Yâ receptor can couple to at least two G-proteins to inhibit both Ca²âş_{N} and Kâş_{M} channels with near-equal facility. This implies that the P2Yâ receptor may induce a broad range of effector responses in the nervous system
The molecular cloning and characterisation of cDNA coding for the alpha subunit of the acetylcholine receptor
The published version of this article is available at Oxford Journals in Nucleic Acids Research at
http://nar.oxfordjournals.org/content/10/19/5809.full.pdf+htmlA rare cDNA coding for most of the Îą subunit of the Torpedo nicotinic acetylcholine receptor has been cloned into bacteria. The use of a mismatched oligonucleotide primer of reverse transcriptase facilitated the design of an efficient, specific probe for recombinant bacteria. DNA sequence analysis has enabled the elucidation of a large part of the polypeptide primary sequence which is discussed in relation to its acetylcholine binding activity and the location of receptor within the plasma membrane.
When used as a radioactive probe, the cloned cDNA binds specifically to a single Torpedo mRNA species of about 2350 nucleotides in length but fails to show significant cross-hybridisation with a subunit mRNA extracted from cat muscle
Aspects of Non-minimal Gauge Mediation
A large class of non-minimal gauge mediation models, such as (semi-)direct
gauge mediation, predict a hierarchy between the masses of the supersymmetric
standard model gauginos and those of scalar particles. We perform a
comprehensive study of these non-minimal gauge mediation models, including mass
calculations in semi-direct gauge mediation, to illustrate these features, and
discuss the phenomenology of the models. We point out that the cosmological
gravitino problem places stringent constraints on mass splittings, when the
Bino is the NLSP. However, the GUT relation of the gaugino masses is broken
unlike the case of minimal gauge mediation, and an NLSP other than the Bino
(especially the gluino NLSP) becomes possible, relaxing the cosmological
constraints. We also discuss the collider signals of the models.Comment: 56 pages, 8 figures; v2:minor corrections, references added; v3:minor
correction
A meta-analytic review of stand-alone interventions to improve body image
Objective
Numerous stand-alone interventions to improve body image have been developed. The
present review used meta-analysis to estimate the effectiveness of such interventions, and
to identify the specific change techniques that lead to improvement in body image.
Methods
The inclusion criteria were that (a) the intervention was stand-alone (i.e., solely focused on
improving body image), (b) a control group was used, (c) participants were randomly
assigned to conditions, and (d) at least one pretest and one posttest measure of body
image was taken. Effect sizes were meta-analysed and moderator analyses were conducted.
A taxonomy of 48 change techniques used in interventions targeted at body image
was developed; all interventions were coded using this taxonomy.
Results
The literature search identified 62 tests of interventions (N = 3,846). Interventions produced
a small-to-medium improvement in body image (d+ = 0.38), a small-to-medium reduction in
beauty ideal internalisation (d+ = -0.37), and a large reduction in social comparison tendencies
(d+ = -0.72). However, the effect size for body image was inflated by bias both within
and across studies, and was reliable but of small magnitude once corrections for bias were
applied. Effect sizes for the other outcomes were no longer reliable once corrections for
bias were applied. Several features of the sample, intervention, and methodology moderated
intervention effects. Twelve change techniques were associated with improvements in
body image, and three techniques were contra-indicated.
Conclusions
The findings show that interventions engender only small improvements in body image, and
underline the need for large-scale, high-quality trials in this area. The review identifies effective
techniques that could be deployed in future interventions
Strong coupling, discrete symmetry and flavour
We show how two principles - strong coupling and discrete symmetry - can work
together to generate the flavour structure of the Standard Model. We propose
that in the UV the full theory has a discrete flavour symmetry, typically only
associated with tribimaximal mixing in the neutrino sector. Hierarchies in the
particle masses and mixing matrices then emerge from multiple strongly coupled
sectors that break this symmetry. This allows for a realistic flavour
structure, even in models built around an underlying grand unified theory. We
use two different techniques to understand the strongly coupled physics:
confinement in N=1 supersymmetry and the AdS/CFT correspondence. Both
approaches yield equivalent results and can be represented in a clear,
graphical way where the flavour symmetry is realised geometrically.Comment: 31 pages, 5 figures, updated references and figure
Selection Against Glycosylation in Ruminant Pancreatic Ribonucleases by Replacements in the Ancestral Carbohydrate Attachment Site
Supporting self-management after attending a structured education programme: a qualitative longitudinal investigation of type 1 diabetes patientsâ experiences and views
Background: Structured education programmes for patients with diabetes and other chronic conditions are being widely adopted. However, follow-up studies suggest that course graduates may struggle to sustain the self-care practices taught on their courses over time. This study explored the support needs of patients with type 1 diabetes after attending a structured education programme promoting an empowerment approach and training in use of flexible intensive insulin therapy, a regimen now widely advocated and used to manage this condition. The objective was to inform future support offered to course graduates.
Methods: Repeat, in-depth interviews with 30 type 1 diabetes patients after attending Dose Adjustment for Normal Eating (DAFNE) courses in the UK, and six and 12âmonths later. Data were analysed using an inductive, thematic approach.
Results: While the flexible intensive insulin treatment approach taught on DAFNE courses was seen as a logical and effective way of managing oneâs diabetes, it was also considered more technically complex than other insulin regimens. To sustain effective disease self-management using flexible intensive insulin treatment over time, patients often expected, and needed, on-going input and support from health care professionals trained in the approach. This included: help determining insulin dose adjustments; reassurance; and, opportunities to trouble-shoot issues of concern. While some benefits were identified to receiving follow-up support in a group setting, most patients stated a preference or need for tailored and individualised support from appropriately-trained clinicians, accessible on an âas and when neededâ basis.
Conclusions: Our findings highlight potential limitations to group-based forms of follow-up support for sustaining diabetes self-management. To maintain the clinical benefits of structured education for patients with type 1 diabetes over time, course graduates may benefit from and prefer ongoing, one-to-one support from health care professionals trained in the programmeâs practices and principles. This support should be tailored and personalised to reflect patientsâ specific and unique experiences of applying their education and training in the context of their everyday lives, and could be the subject of future research
Mapping the contribution of β3-containing GABA(A )receptors to volatile and intravenous general anesthetic actions
BACKGROUND: Agents belonging to diverse chemical classes are used clinically as general anesthetics. The molecular targets mediating their actions are however still only poorly defined. Both chemical diversity and substantial differences in the clinical actions of general anesthetics suggest that general anesthetic agents may have distinct pharmacological targets. It was demonstrated previously that the immobilizing action of etomidate and propofol is completely, and the immobilizing action of isoflurane partly mediated, by β3-containing GABA(A )receptors. This was determined by using the β3(N265M) mice, which carry a point mutation known to decrease the actions of general anesthetics at recombinant GABA(A )receptors. In this communication, we analyzed the contribution of β3-containing GABA(A )receptors to the pharmacological actions of isoflurane, etomidate and propofol by means of β3(N265M) mice. RESULTS: Isoflurane decreased core body temperature and heart rate to a smaller degree in β3(N265M) mice than in wild type mice, indicating a minor but significant role of β3-containing GABA(A )receptors in these actions. Prolonged time intervals in the ECG and increased heart rate variability were indistinguishable between genotypes, suggesting no involvement of β3-containing GABA(A )receptors. The anterograde amnesic action of propofol was indistinguishable in β3(N265M) and wild type mice, suggesting that it is independent of β3-containing GABA(A )receptors. The increase of heart rate variability and prolongation of ECG intervals by etomidate and propofol were also less pronounced in β3(N265M) mice than in wild type mice, pointing to a limited involvement of β3-containing GABA(A )receptors in these actions. The lack of etomidate- and propofol-induced immobilization in β3(N265M) mice was also observed in congenic 129X1/SvJ and C57BL/6J backgrounds, indicating that this phenotype is stable across different backgrounds. CONCLUSION: Our results provide evidence for a defined role of β3-containing GABA(A )receptors in mediating some, but not all, of the actions of general anesthetics, and confirm the multisite model of general anesthetic action. This pharmacological separation of anesthetic endpoints also suggests that subtype-selective substances with an improved side-effect profile may be developed
Nanodiamonds for device applications: An investigation of the properties of boron-doped detonation nanodiamonds
Š 2018 The Author(s). The inclusion of boron within nanodiamonds to create semiconducting properties would create a new class of applications in the field of nanodiamond electronics. Theoretical studies have differed in their conclusions as to whether nm-scale NDs would support a stable substitutional boron state, or whether such a state would be unstable, with boron instead aggregating or attaching to edge structures. In the present study detonation-derived NDs with purposefully added boron during the detonation process have been studied with a wide range of experimental techniques. The DNDs are of ~4 nm in size, and have been studied with CL, PL, Raman and IR spectroscopies, AFM and HR-TEM and electrically measured with impedance spectroscopy; it is apparent that the B-DNDs studied here do indeed support substitutional boron species and hence will be acting as semiconducting diamond nanoparticles. Evidence for moderate doping levels in some particles (âź10 17 B cm -3 ), is found alongside the observation that some particles are heavily doped (âź10 20 B cm -3 ) and likely to be quasi-metallic in character. The current study has therefore shown that substitutional boron doping in nm NDs is in fact possible, opening-up the path to a whole host of new applications for this interesting class of nano-particles
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