80 research outputs found

    Lipid Metabolites Enhance Secretion Acting on SNARE Microdomains and Altering the Extent and Kinetics of Single Release Events in Bovine Adrenal Chromaffin Cells

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    Lipid molecules such as arachidonic acid (AA) and sphingolipid metabolites have been implicated in modulation of neuronal and endocrine secretion. Here we compare the effects of these lipids on secretion from cultured bovine chromaffin cells. First, we demonstrate that exogenous sphingosine and AA interact with the secretory apparatus as confirmed by FRET experiments. Examination of plasma membrane SNARE microdomains and chromaffin granule dynamics using total internal reflection fluorescent microscopy (TIRFM) suggests that sphingosine production promotes granule tethering while arachidonic acid promotes full docking. Our analysis of single granule release kinetics by amperometry demonstrated that both sphingomyelinase and AA treatments enhanced drastically the amount of catecholamines released per individual event by either altering the onset phase of or by prolonging the off phase of single granule catecholamine release kinetics. Together these results demonstrate that the kinetics and extent of the exocytotic fusion pore formation can be modulated by specific signalling lipids through related functional mechanisms

    A sub-Neptune transiting the young field star HD 18599  at 40 pc

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    Transiting exoplanets orbiting young nearby stars are ideal laboratories for testing theories of planet formation and evolution. However, to date only a handful of stars with age <1 Gyr have been found to host transiting exoplanets. Here we present the discovery and validation of a sub-Neptune around HD 18599 , a young (300 Myr), nearby (d = 40 pc) K star. We validate the transiting planet candidate as a bona fide planet using data from the TESS , Spitzer , and Gaia  missions, ground-based photometry from IRSF , LCO , PEST , and NGTS , speckle imaging from Gemini, and spectroscopy from CHIRON , NRES , FEROS , and Minerva-Australis . The planet has an orbital period of 4.13 d , and a radius of 2.7 R⊕ . The RV data yields a 3-σ mass upper limit of 30.5 M⊕  which is explained by either a massive companion or the large observed jitter typical for a young star. The brightness of the host star (V∌9 mag) makes it conducive to detailed characterization via Doppler mass measurement which will provide a rare view into the interior structure of young planets

    Estimating Grizzly and Black Bear Population Abundance and Trend in Banff National Park Using Noninvasive Genetic Sampling

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    We evaluated the potential of two noninvasive genetic sampling methods, hair traps and bear rub surveys, to estimate population abundance and trend of grizzly (Ursus arctos) and black bear (U. americanus) populations in Banff National Park, Alberta, Canada. Using Huggins closed population mark-recapture models, we obtained the first precise abundance estimates for grizzly bears ( = 73.5, 95% CI = 64–94 in 2006;  = 50.4, 95% CI = 49–59 in 2008) and black bears ( = 62.6, 95% CI = 51–89 in 2006;  = 81.8, 95% CI = 72–102 in 2008) in the Bow Valley. Hair traps had high detection rates for female grizzlies, and male and female black bears, but extremely low detection rates for male grizzlies. Conversely, bear rubs had high detection rates for male and female grizzlies, but low rates for black bears. We estimated realized population growth rates, lambda, for grizzly bear males ( = 0.93, 95% CI = 0.74–1.17) and females ( = 0.90, 95% CI = 0.67–1.20) using Pradel open population models with three years of bear rub data. Lambda estimates are supported by abundance estimates from combined hair trap/bear rub closed population models and are consistent with a system that is likely driven by high levels of human-caused mortality. Our results suggest that bear rub surveys would provide an efficient and powerful means to inventory and monitor grizzly bear populations in the Central Canadian Rocky Mountains

    Clamp loader ATPases and the evolution of DNA replication machinery

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    Clamp loaders are pentameric ATPases of the AAA+ family that operate to ensure processive DNA replication. They do so by loading onto DNA the ring-shaped sliding clamps that tether the polymerase to the DNA. Structural and biochemical analysis of clamp loaders has shown how, despite differences in composition across different branches of life, all clamp loaders undergo the same concerted conformational transformations, which generate a binding surface for the open clamp and an internal spiral chamber into which the DNA at the replication fork can slide, triggering ATP hydrolysis, release of the clamp loader, and closure of the clamp round the DNA. We review here the current understanding of the clamp loader mechanism and discuss the implications of the differences between clamp loaders from the different branches of life

    HD 183579b: a warm sub-Neptune transiting a solar twin detected by TESS

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    We report the discovery and characterization of a transiting warm sub-Neptune planet around the nearby bright (V = 8.75 mag, K = 7.15 mag) solar twin HD 183579, delivered by the Transiting Exoplanet Survey Satellite (TESS). The host star is located 56.8 ± 0.1 pc away with a radius of R* = 0.97 ± 0.02 R⊙ and a mass of M* = 1.03 ± 0.05 M⊙. We confirm the planetary nature by combining space and ground-based photometry, spectroscopy, and imaging. We find that HD 183579b (TOI-1055b) has a radius of Rp = 3.53 ± 0.13 R⊕ on a 17.47 d orbit with a mass of Mp = 11.2 ± 5.4 M⊕ (3σ mass upper limit of 27.4 M⊕). HD 183579b is the fifth brightest known sub-Neptune planet system in the sky, making it an excellent target for future studies of the interior structure and atmospheric properties. By performing a line-by-line differential analysis using the high-resolution and signal-to-noise ratio HARPS spectra, we find that HD 183579 joins the typical solar twin sample, without a statistically significant refractory element depletion

    B0 meson decays to rho0 K*0, f0 K*0, and rho-K*+, including higher K* resonances

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    We present branching fraction measurements for the decays B0 -> rho0 K*0, B0 -> f0 K*0, and B0 -> rho- K*+, where K* is an S-wave (K pi)_0* or a K*(892) meson; we also measure B0 -> f0 K_2*(1430)^0. For the K*(892) channels, we report measurements of longitudinal polarization fractions (for rho final states) and direct CP-violation asymmetries. These results are obtained from a sample of (471.0 +/- 2.8) x 10^6 BBbar pairs collected with the BaBar detector at the PEP-II asymmetric-energy e+ e- collider at the SLAC National Accelerator Laboratory. We observe rho0 K*(892)^0, rho0 (K pi)_0^{*0}, f0 K*(892)^0, and rho- K*(892)+ with greater than 5 sigma significance, including systematics. We report first evidence for f0 (K pi)_0^{*0} and f0 K_2*(1430)^0, and place an upper limit on rho- (K pi)_0^{*+}. Our results in the K*(892) channels are consistent with no direct CP-violation.Comment: 17 pages, 6 postscript figures, submitted to Phys. Rev.

    Twenty years on, the Methadone Treatment Protocol in Ireland: Reflections on General Practice

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    Background: Opioid dependence, characterised by socio economic disadvantage and significant morbidity and mortality, remains a major public health problem in Ireland. Through the methadone treatment protocol (MTP), Irish general practice has been a leader in the introduction and expansion of Irish harm reduction services, including opioid substitution treatment (OST), needle and syringe programs (NSP) and naloxone provision. These services have been effective in engaging opiate users in treatment, reducing human deficiency virus (HIV) and hepatitis C virus (HCV) transmission and reducing drug related morbidities. Challenges remain in relation to choice of substitution treatments, timely access to OST services, adequate coverage of NSP, naloxone provision and increasing drug related deaths.Methods: A narrative review was conducted and designed to present a broad perspective on the Irish MTP, and to describe its history and development in terms of clinical care, stakeholder views and changing trends.Results: Three themes emerged from the analysis; The History of the Methadone Treatment Protocol, Service User and Provider Views, and Challenges and Developments. Despite initial concern about methadone maintenance treatment (MMT) in Ireland, increased participation by Irish GPs in the treatment of opioid dependence is observed over the last two decades. There are now over 10,000 people on methadone treatment in Ireland, with 40% treated in general practice. The MTP provides structure, remuneration and guidance to GPs and is underpinned by; training, ongoing education and a system of quality assurance provided by the Irish College of General Practice (ICGP). Challenges include the negative views of patients around how methadone services are delivered, the stigma associated with methadone treatment, the lack of choice around substitution medication, waiting lists for treatment in certain areas and rates of fatal overdose.Conclusion: Twenty years of the MTP has been the mainstay of harm reduction services in Ireland. It has provided a network of specially trained GPs who provide methadone to over 10,000 patients across Ireland within a structured framework of training, quality assurance and remuneration. With the ongoing commitment of Irish specialists in the field of addiction medicine, further improvements to support and treat patients can be made
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