The Effects of Apolipoprotein F Deficiency on High Density Lipoprotein Cholesterol Metabolism in Mice

Apolipoprotein F (apoF) is 29 kilodalton secreted sialoglycoprotein that resides on the HDL and LDL fractions of human plasma. Human ApoF is also known as Lipid Transfer Inhibitor protein (LTIP) based on its ability to inhibit cholesteryl ester transfer protein (CETP)-mediated transfer events between lipoproteins. In contrast to other apolipoproteins, ApoF is predicted to lack strong amphipathic alpha helices and its true physiological function remains unknown. We previously showed that overexpression of Apolipoprotein F in mice reduced HDL cholesterol levels by 20–25% by accelerating clearance from the circulation. In order to investigate the effect of physiological levels of ApoF expression on HDL cholesterol metabolism, we generated ApoF deficient mice. Unexpectedly, deletion of ApoF had no substantial impact on plasma lipid concentrations, HDL size, lipid or protein composition. Sex-specific differences were observed in hepatic cholesterol content as well as serum cholesterol efflux capacity. Female ApoF KO mice had increased liver cholesteryl ester content relative to wild type controls on a chow diet (KO: 3.4+/−0.9 mg/dl vs. WT: 1.2+/−0.3 mg/dl, p<0.05). No differences were observed in ABCG1-mediated cholesterol efflux capacity in either sex. Interestingly, ApoB-depleted serum from male KO mice was less effective at promoting ABCA1-mediated cholesterol efflux from J774 macrophages relative to WT controls

International Veterinary Epilepsy Task Force consensus proposal: Medical treatment of canine epilepsy in Europe

In Europe, the number of antiepileptic drugs (AEDs) licensed for dogs has grown considerably over the last years. Nevertheless, the same questions remain, which include, 1) when to start treatment, 2) which drug is best used initially, 3) which adjunctive AED can be advised if treatment with the initial drug is unsatisfactory, and 4) when treatment changes should be considered. In this consensus proposal, an overview is given on the aim of AED treatment, when to start long-term treatment in canine epilepsy and which veterinary AEDs are currently in use for dogs. The consensus proposal for drug treatment protocols, 1) is based on current published evidence-based literature, 2) considers the current legal framework of the cascade regulation for the prescription of veterinary drugs in Europe, and 3) reflects the authors’ experience. With this paper it is aimed to provide a consensus for the management of canine idiopathic epilepsy. Furthermore, for the management of structural epilepsy AEDs are inevitable in addition to treating the underlying cause, if possible

Planet Populations as a Function of Stellar Properties

Exoplanets around different types of stars provide a window into the diverse environments in which planets form. This chapter describes the observed relations between exoplanet populations and stellar properties and how they connect to planet formation in protoplanetary disks. Giant planets occur more frequently around more metal-rich and more massive stars. These findings support the core accretion theory of planet formation, in which the cores of giant planets form more rapidly in more metal-rich and more massive protoplanetary disks. Smaller planets, those with sizes roughly between Earth and Neptune, exhibit different scaling relations with stellar properties. These planets are found around stars with a wide range of metallicities and occur more frequently around lower mass stars. This indicates that planet formation takes place in a wide range of environments, yet it is not clear why planets form more efficiently around low mass stars. Going forward, exoplanet surveys targeting M dwarfs will characterize the exoplanet population around the lowest mass stars. In combination with ongoing stellar characterization, this will help us understand the formation of planets in a large range of environments.Comment: Accepted for Publication in the Handbook of Exoplanet

Striking a Balance: Socioeconomic Development and Conservation in Grassland through Community-Based Zoning

The goal of preserving nature is often in conflict with economic development and the aspirations of the rural poor. Nowhere is this more striking than in native grasslands, which have been extensively converted until a mere fraction of their original extent remains. This is not surprising; grasslands flourish in places coveted by humans, primed for agriculture, plantations, and settlements that nearly always trump conservation efforts. The Umgano grassland conservation and poverty reduction project in KwaZulu-Natal Province, South Africa uses community-based spatial planning to balance the conversion of its lower-conservation value grasslands to a timber plantation, while conserving higher-value grasslands for heritage purposes and managed livestock grazing. Ten years after project launch, we measured the ecological and socioeconomic impacts of the project using Normalized Differential Vegetation Index remote sensing data and over 500 household interviews, as compared with similar non-conserved areas. Zoned management of the Umgano area had resulted in between 9% and 17% greater average peak production in the grassland areas compared to control sites. There was also a 21% gain in incomes for the roughly one hundred people employed by the forestry efforts, when compared to others in their village. Community-based spatial zoning is an overlooked tool for balancing conservation and development but may require, as we found in Umgano, certain critical factors including strong local leadership, an accountable financial management mechanism to distribute income, outside technical expertise for the zoning design, and community support

Dissection of Hypothalamic-Pituitary-Adrenal Axis Pathology in 1-Month-Abstinent Alcohol-Dependent Men, Part 2: Response to Ovine Corticotropin-Releasing Factor and Naloxone

Pituitary and adrenal responsiveness is suppressed in abstinent alcohol-dependent individuals. To clarify the specific organizational disruption in hypothalamic-pituitary-adrenal functioning during early abstinence, the authors separately assessed each level of the stress-response axis. In this second of a two-part study, ovine corticotropin-releasing factor (oCRH) was used to stimulate the pituitary corticotrophs, and naloxone was used to activate the axis at the hypothalamic level. In addition, pulsatile characteristics of corticotropin and cortisol were assessed over a 12-hr period (0800 to 2000 hr). Methods : Eleven abstinent alcohol-dependent men and 10 healthy comparison participants were assessed. All participants were between the ages of 30 and 50 years, and alcohol-dependent patients were abstinent from 4 to 6 weeks. Basal concentrations of corticotropin and cortisol were obtained every 10 min from 0800 to 2000 hr and subjected to pulsatile analysis. Plasma corticotropin and cortisol concentrations were then obtained every 5 to 10 min after low-dose, intravenously administered doses of oCRH (0.4 μg/kg) or naloxone (0.125 mg/kg). Medications were administered at 2000 hr and the two challenge studies were separated by 48 hr. Results : Pulsatile analysis revealed that the mean corticotropin amplitude was increased in alcohol-dependent patients relative to controls ( p < 0.05). Other pulsatile characteristics of corticotropin and all cortisol pulsatile measures were not significantly different between the two groups. The integrated cortisol response to oCRH was significantly lower in alcohol-dependent patients compared with controls ( p < 0.01), but the integrated corticotropin response was not significantly different. In contrast, neither the corticotropin nor the cortisol response to naloxone was significantly different between groups. Conclusions : Adrenocorticoid hyposensitivity persists after oCRH infusion for at least 1 month after cessation of drinking, whereas hyporesponsiveness of the pituitary corticotrophs to CRH seems to resolve with continued abstinence. The authors suggest that adrenocortical hyporesponsiveness during prolonged abstinence may impact relapse risk.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65174/1/01.ALC.0000158939.25531.EE.pd

Measurement of the branching fraction and CP content for the decay B(0) -> D(*+)D(*-)

This is the pre-print version of the Article. The official published version can be accessed from the links below. Copyright @ 2002 APS.We report a measurement of the branching fraction of the decay B0→D*+D*- and of the CP-odd component of its final state using the BABAR detector. With data corresponding to an integrated luminosity of 20.4  fb-1 collected at the Υ(4S) resonance during 1999–2000, we have reconstructed 38 candidate signal events in the mode B0→D*+D*- with an estimated background of 6.2±0.5 events. From these events, we determine the branching fraction to be B(B0→D*+D*-)=[8.3±1.6(stat)±1.2(syst)]×10-4. The measured CP-odd fraction of the final state is 0.22±0.18(stat)±0.03(syst).This work is supported by DOE and NSF (USA), NSERC (Canada), IHEP (China), CEA and CNRS-IN2P3 (France), BMBF (Germany), INFN (Italy), NFR (Norway), MIST (Russia), and PPARC (United Kingdom). Individuals have received support from the A.P. Sloan Foundation, Research Corporation, and Alexander von Humboldt Foundation

Geomorphic and stratigraphic evidence for an unusual tsunami or storm a few centuries ago at Anegada, British Virgin Islands

© The Author(s), 2010. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Natural Hazards 63 (2012): 51-84, doi:10.1007/s11069-010-9622-6.Waters from the Atlantic Ocean washed southward across parts of Anegada, east-northeast of Puerto Rico, during a singular event a few centuries ago. The overwash, after crossing a fringing coral reef and 1.5 km of shallow subtidal flats, cut dozens of breaches through sandy beach ridges, deposited a sheet of sand and shell capped with lime mud, and created inland fields of cobbles and boulders. Most of the breaches extend tens to hundreds of meters perpendicular to a 2-km stretch of Anegada’s windward shore. Remnants of the breached ridges stand 3 m above modern sea level, and ridges seaward of the breaches rise 2.2–3.0 m high. The overwash probably exceeded those heights when cutting the breaches by overtopping and incision of the beach ridges. Much of the sand-and-shell sheet contains pink bioclastic sand that resembles, in grain size and composition, the sand of the breached ridges. This sand extends as much as 1.5 km to the south of the breached ridges. It tapers southward from a maximum thickness of 40 cm, decreases in estimated mean grain size from medium sand to very fine sand, and contains mud laminae in the south. The sand-and-shell sheet also contains mollusks—cerithid gastropods and the bivalve Anomalocardia—and angular limestone granules and pebbles. The mollusk shells and the lime-mud cap were probably derived from a marine pond that occupied much of Anegada’s interior at the time of overwash. The boulders and cobbles, nearly all composed of limestone, form fields that extend many tens of meters generally southward from limestone outcrops as much as 0.8 km from the nearest shore. Soon after the inferred overwash, the marine pond was replaced by hypersaline ponds that produce microbial mats and evaporite crusts. This environmental change, which has yet to be reversed, required restriction of a former inlet or inlets, the location of which was probably on the island’s south (lee) side. The inferred overwash may have caused restriction directly by washing sand into former inlets, or indirectly by reducing the tidal prism or supplying sand to post-overwash currents and waves. The overwash happened after A.D. 1650 if coeval with radiocarbon-dated leaves in the mud cap, and it probably happened before human settlement in the last decades of the 1700s. A prior overwash event is implied by an inland set of breaches. Hypothetically, the overwash in 1650–1800 resulted from the Antilles tsunami of 1690, the transatlantic Lisbon tsunami of 1755, a local tsunami not previously documented, or a storm whose effects exceeded those of Hurricane Donna, which was probably at category 3 as its eye passed 15 km to Anegada’s south in 1960.The work was supported in part by the Nuclear Regulatory Commission under its project N6480, a tsunami-hazard assessment for the eastern United States

Paternal and maternal influences on differences in birth weight between Europeans and Indians born in the UK.

BACKGROUND: Ethnic groups differ significantly in adult physique and birth weight. We aimed to improve understanding of maternal versus paternal contributions to ethnic differences in birth weight, by comparing the offspring of same-ethnic versus mixed-ethnic unions amongst Europeans and South Asian Indians in the UK. METHODOLOGY AND PRINCIPAL FINDINGS: We used data from the UK Office for National Statistics Longitudinal Study (LS) and the Chelsea and Westminster Hospital (CWH), London. In the combined sample at all gestational ages, average birth weight of offspring with two European parents was significantly greater than that of offspring with two Indian parents [Δ = 344 (95% CI 329, 360) g]. Compared to offspring of European mothers, the offspring of Indian mothers had lower birth weight, whether the father was European [Δ = -152 (95% CI -92, -212) g] or Indian [Δ = -254 (95% -315, -192) g]. After adjustment for various confounding factors, average birth weight of offspring with European father and Indian mother was greater than that of offspring with two Indian parents [LS: Δ = 249 (95% CI 143, 354) g; CWH: Δ = 236 (95% CI 62, 411) g]. Average birth weight of offspring with Indian father and European mother was significantly less than that of offspring with two European parents [LS: Δ = -117 (95% CI -207, -26) g; CWH: Δ = -83 (-206, 40) g]. CONCLUSIONS/SIGNIFICANCE: Birth weight of offspring with mixed-ethnic parentage was intermediate between that of offspring with two European or two Indian parents, demonstrating a paternal as well as a maternal contribution to ethnic differences in fetal growth. This can be interpreted as demonstrating paternal modulation of maternal investment in offspring. We suggest long-term nutritional experience over generations may drive such ethnic differences through parental co-adaptation

Appropriateness of acute admissions and last in-patient day for patients with long term neurological conditions

<p>Abstract</p> <p>Background</p> <p>To examine the appropriateness of admissions and in-patient stay for patients with long term neurological conditions (LTNCs). To identify variables predictive of appropriateness and explore management alternatives.</p> <p>Methods</p> <p>Adults admitted as acute patients to Derby Hospitals NHS Foundation Trust (England). Data were collected prospectively and examined by a multi-disciplinary expert panel to determine the appropriateness of admission and length of stay (LoS). Management alternatives were discussed.</p> <p>Results</p> <p>A total of 119 participants were recruited. 32 admissions were inappropriate and 83 were for an inappropriate duration. Whether a participant lived in their own home was predictive of an inappropriate admission. The number of LTNCs, number of presenting complaints and whether the participant lived alone in their own home were predictive of an inappropriate LoS. For admissions judged to be inappropriate, the panel suggested management alternatives.</p> <p>Conclusion</p> <p>Patients with LTNCs are being admitted to hospital when other services, e.g. ambulatory care, are available which could meet their needs. Inefficiencies in hospital procedures, such as discharge planning and patient transfers, continue to exist. Recognition of the need to plan for discharge at admission and to ensure in-patient services are provided in a timely manner may contribute towards improved efficiency.</p