Persistent activation of transducin by bleached rhodopsin in salamander rods.

The hydrolysis-resistant GTP analogue GTP-gamma-S was introduced into rods isolated from the retina of the salamander Ambystoma tigrinum to study the origin of the persistent excitation induced by intense bleaching illumination. Dialysis of a dark-adapted rod with a whole-cell patch pipette containing 2 mM GTP-gamma-S resulted in a gradual decrease in circulating current. If the rod was first bleached and its sensitivity allowed to stabilize for at least 30 min, then dialysis with GTP-gamma-S produced a much faster current decay. The circulating current could be restored by superfusion with the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine, suggesting that the decay in current originated from persistent excitation of the phosphodiesterase by transducin bound to GTP-gamma-S. We conclude that the persistent excitation which follows bleaching is likely to involve the GTP-binding protein transducin, which mediates the normal photoresponse. This observation suggests that a form of rhodopsin which persists long after bleaching can activate transducin much as does photoisomerized rhodopsin, although with considerably lower gain

Bleached pigment activates transduction in salamander cones.

We have used suction electrode recording together with rapid steps into 0.5 mM IBMX solution to investigate changes in guanylyl cyclase velocity produced by pigment bleaching in isolated cones of the salamander Ambystoma tigrinum. Both backgrounds and bleaches accelerate the time course of current increase during steps into IBMX. We interpret this as evidence that the velocity of the guanylyl cyclase is increased in background light or after bleaching. Our results indicate that cyclase velocity increases nearly linearly with increasing percent pigment bleached but nonlinearly (and may saturate) with increasing back-ground intensity. In cones (as previously demonstrated for rods), light-activated pigment and bleached pigment appear to have somewhat different effects on the transduction cascade. The effect of bleaching on cyclase rate is maintained for at least 15-20 min after the light is removed, much longer than is required after a bleach for circulating current and sensitivity to stabilize in an isolated cone. The effect on the cyclase rate can be completely reversed by treatment with liposomes containing 11-cis retinal. The effects of bleaching can also be partially reversed by beta-ionone, an analogue of the chromophore 11-cis-retinal which does not form a covalent attachment to opsin. Perfusion of a bleached cone with beta-ionone produces a rapid increase in circulating current and sensitivity, which rapidly reverses when the beta-ionone is removed. Perfusion with beta-ionone also causes a partial reversal of the bleach-induced acceleration of cyclase velocity. We conclude that bleaching produces an "equivalent background" excitation of the transduction cascade in cones, perhaps by a mechanism similar to that in rods

Analysis of the Herschel DEBRIS Sun-like star sample

This paper presents a study of circumstellar debris around Sun-like stars using data from the Herschel DEBRIS Key Programme. DEBRIS is an unbiased survey comprising the nearest ∼90 stars of each spectral type A-M. Analysis of the 275 F-K stars shows that excess emission from a debris disc was detected around 47 stars, giving a detection rate of 17.1 +2.6−2.3  per cent, with lower rates for later spectral types. For each target a blackbody spectrum was fitted to the dust emission to determine its fractional luminosity and temperature. The derived underlying distribution of fractional luminosity versus blackbody radius in the population showed that most detected discs are concentrated at f ∼ 10−5 and at temperatures corresponding to blackbody radii 7–40 au, which scales to ∼40 au for realistic dust properties (similar to the current Kuiper belt). Two outlying populations are also evident; five stars have exceptionally bright emission ( f > 5 × 10−5), and one has unusually hot dust <4 au. The excess emission distributions at all wavelengths were fitted with a steady-state evolution model, showing that these are compatible with all stars being born with a narrow belt that then undergoes collisional grinding. However, the model cannot explain the hot dust systems – likely originating in transient events – and bright emission systems – arising potentially from atypically massive discs or recent stirring. The emission from the present-day Kuiper belt is predicted to be close to the median of the population, suggesting that half of stars have either depleted their Kuiper belts (similar to the Solar system) or had a lower planetesimal formation efficiency.This work was supported by the European Union through European Research Council grant number 279973 (MCW, GMK). GMK was also supported by the Royal Society as a Royal Society University Research Fellow

Kuiper belt analogues in nearby M-type planet-host systems

We present the results of a Herschel survey of 21 late-type stars that host planets discovered by the radial velocity technique. The aims were to discover new discs in these systems and to search for any correlation between planet presence and disc properties. In addition to the known disc around GJ 581, we report the discovery of two new discs, in the GJ 433 and GJ 649 systems. Our sample therefore yields a disc detection rate of 14 per cent, higher than the detection rate of 1.2 per cent among our control sample of DEBRIS M-type stars with 98 per cent confidence. Further analysis however shows that the disc sensitivity in the control sample is about a factor of two lower in fractional luminosity than for our survey, lowering the significance of any correlation between planet presence and disc brightness below 98 per cent. In terms of their specific architectures, the disc around GJ 433 lies at a radius somewhere between 1 and 30 au. The disc around GJ 649 lies somewhere between 6 and 30 au, but is marginally resolved and appears more consistent with an edge-on inclination. In both cases the discs probably lie well beyond where the known planets reside (0.06–1.1 au), but the lack of radial velocity sensitivity at larger separations allows for unseen Saturn–mass planets to orbit out to ~5 au, and more massive planets beyond 5 au. The layout of these M-type systems appears similar to Sun-like star + disc systems with low-mass planets.This work was supported by the European Union through ERC grant number 279973 (GMK & MCW)

Kuiper belt structure around nearby super-Earth host stars

We present new observations of the Kuiper belt analogues around HD 38858 and HD 20794, hosts of super-Earth mass planets within 1 au. As two of the four nearby G-type stars (with HD 69830 and 61 Vir) that form the basis of a possible correlation between low-mass planets and debris disc brightness, these systems are of particular interest. The disc around HD 38858 is well resolved with Herschel and we constrain the disc geometry and radial structure. We also present a probable James Clerk Maxwell Telescope sub-mm continuum detection of the disc and a CO J = 2–1 upper limit. The disc around HD 20794 is much fainter and appears marginally resolved with Herschel, and is constrained to be less extended than the discs around 61 Vir and HD 38858. We also set limits on the radial location of hot dust recently detected around HD 20794 with near-IR interferometry. We present High Accuracy Radial velocity Planet Searcher upper limits on unseen planets in these four systems, ruling out additional super-Earths within a fewau, and Saturn-mass planets within 10 au. We consider the disc structure in the three systems with Kuiper belt analogues (HD 69830 has only a warm dust detection), concluding that 61 Vir and HD 38858 have greater radial disc extent than HD 20794. We speculate that the greater width is related to the greater minimum planet masses (10–20 M⊕ versus 3–5 M⊕), arising from an eccentric planetesimal population analogous to the Solar system’s scattered disc. We discuss alternative scenarios and possible means to distinguish among them.We thank the referee for a thoughtful review. This work was supported by the European Union through ERC grant number 279973 (GMK, LM, and MCW). LM also acknowledges support by both STFC and ESO through graduate studentships. MM, CL, FP, and SU acknowledge the Swiss National Science Foundation (SNSF) for the continuous support of the RV research programmes.This is the final published version. It first appeared at http://mnras.oxfordjournals.org/content/449/3/3121.abstract

A qualitative study of physical activity and dietary practices of people accessing opioid agonist treatment in Ireland

Background: Active heroin use presents a time of chaotic behaviours, while opioid agonist treatment (OAT) offers an opportunity for people with opiate substance use disorder to improve health and functioning. Lifestyle behaviours of physical activity and healthy dietary practices are increasingly studied for their role in maintaining physical and mental health among people with mental disorders. Aim: This research aimed to explore service user experiences of change with respect to physical activity and dietary practices since entering OAT. This research also explored barriers and facilitators to positive lifestyle behaviours among those accessing OAT. Methods: Qualitative descriptive interviews were conducted with (n=10) service users using pre-determined themes to explore the aforementioned topic. Results: Participants largely viewed lifestyle behaviours as having improved since entering OAT. A number of barriers, such as methadone related symptomology, physical ill-health, and social circumstances were impeding lifestyle behaviours. Physical activity was also impacted by a number of psychological barriers, such as perceived stigma. Facilitators to lifestyle behaviours discussed by participants demonstrated new routines and support structures associated with the OAT service. Conclusions: Lifestyle behaviours appear to be positively modified during OAT allied to additional health care supports in place for service users and a potential for improved health and social function. A number of barriers, particularly psychological, remain with respect to behaviour change for this population. This research explores these, with learnings for services to support behaviour change

Keratoconus associated with choroidal neovascularization: a case report

<p>Abstract</p> <p>Introduction</p> <p>Keratoconus and choroidal neovascularization can occur as a result of dysfunction of the epithelium and its basement membrane.</p> <p>Case presentation</p> <p>A 17-year-old Asian man, who was diagnosed with myopic choroidal neovascularization in both eyes and who subsequently underwent intravitreal injection of ranibizumab (Lucentis^®) five times over six months, presented with further vision decrease and pain in his right eye. Examination showed corneal steepening and stromal edema in the inferocentral cornea of his right eye, both of which were indicative of advanced keratoconus with acute hydrops. Corneal topography also showed features consistent with keratoconus in his left eye. Fluorescein angiography and optical coherence tomography revealed choroidal neovascularization-associated subretinal hemorrhages and lacquer cracks in both eyes.</p> <p>Conclusion</p> <p>Keratoconus and choroidal neovascularization, possibly resulting from dysfunction of the epithelium and its basement membrane, can occur together in the same individual. This would suggest a possible connection in pathogenesis between these two conditions.</p

Premenopausal endogenous oestrogen levels and breast cancer risk: a meta-analysis.

BACKGROUND: Many of the established risk factors for breast cancer implicate circulating hormone levels in the aetiology of the disease. Increased levels of postmenopausal endogenous oestradiol (E2) have been found to increase the risk of breast cancer, but no such association has been confirmed in premenopausal women. We carried out a meta-analysis to summarise the available evidence in women before the menopause. METHODS: We identified seven prospective studies of premenopausal endogenous E2 and breast cancer risk, including 693 breast cancer cases. From each study we extracted odds ratios of breast cancer between quantiles of endogenous E2, or for unit or s.d. increases in (log transformed) E2, or (where odds ratios were unavailable) summary statistics for the distributions of E2 in breast cancer cases and unaffected controls. Estimates for a doubling of endogenous E2 were obtained from these extracted estimates, and random-effect meta-analysis was used to obtain a pooled estimate across the studies. RESULTS: Overall, we found weak evidence of a positive association between circulating E2 levels and the risk of breast cancer, with a doubling of E2 associated with an odds ratio of 1.10 (95% CI: 0.96, 1.27). CONCLUSION: Our findings are consistent with the hypothesis of a positive association between premenopausal endogenous E2 and breast cancer risk

The frequency and validity of self-reported diagnosis of Parkinson's Disease in the UK elderly: MRC CFAS cohort

BACKGROUND: Estimates of the incidence and prevalence of chronic diseases can be made using established cohort studies but these estimates may have lower reliability if based purely on self-reported diagnosis. METHODS: The MRC Cognitive Function & Ageing Study (MRC CFAS) has collected longitudinal data from a population-based random sample of 13004 individuals over the age of 65 years from 5 centres within the UK. Participants were asked at baseline and after a two-year follow-up whether they had received a diagnosis of Parkinson's disease. Our aim was to make estimates of the incidence and prevalence of PD using self-reporting, and then investigate the validity of self-reported diagnosis using other data sources where available, namely death certification and neuropathological examination. RESULTS: The self-reported prevalence of Parkinson's disease (PD) amongst these individuals increases with age from 0.7% (95%CI 0.5–0.9) for 65–75, 1.4% (95%CI 1.0–1.7) for 75–85, and 1.6% (95%CI 1.0–2.3) for 85+ age groups respectively. The overall incidence of self reported PD in this cohort was 200/100,000 per year (95%CI 144–278). Only 40% of the deceased individuals reporting prevalent PD and 35% of those reporting incident PD had diagnoses of PD recorded on their death certificates. Neuropathological examination of individuals reporting PD also showed typical PD changes in only 40%, with the remainder showing basal ganglia pathologies causing parkinsonism rather than true PD pathology. CONCLUSION: Self-reporting of PD status may be used as a screening tool to identify patients for epidemiological study, but inevitably identifies a heterogeneous group of movement disorders patients. Within this group, age, male sex, a family history of PD and reduced cigarette smoking appear to act as independent risk factors for self-reported PD

Early initiation of antiretroviral therapy following in utero HIV infection is associated with low viral reservoirs but other factors determine subsequent plasma viral rebound

BACKGROUND: Early HIV diagnosis allows combination antiretroviral therapy (cART) initiation in the first days of life following in utero (IU) infection. The impact of early cART initiation on infant viral reservoir size in the setting of high-frequency cART non-adherence is unknown. METHODS: Peripheral blood total HIV DNA from 164 early treated (day 0-21 of life) IU HIV-infected South African infants was measured using droplet digital PCR at birth and following suppressive cART. We evaluated the impact of cART initiation timing on HIV reservoir size and decay, and on the risk of subsequent plasma viraemia in cART-suppressed infants. FINDINGS: Baseline HIV DNA (median 2.8 log10 copies/million PBMC, range 0.7 - 4.8) did not correlate with age at cART initiation (0-21 days) but instead with maternal antenatal cART use. In 98 infants with plasma viral suppression on cART, HIV DNA half-life was 28 days. However, the probability of maintenance of plasma aviraemia was low (0.46 at 12 months) and not influenced by HIV DNA load. Unexpectedly, longer time to viral suppression was associated with protection against subsequent viral rebound. CONCLUSIONS: With effective prophylaxis against mother-to-child transmission, cART initiation timing in the first 3 weeks of life is not critical to reservoir size