Ionized Gas Motions and the Structure of Feedback Near a Forming Globular Cluster in NGC 5253

We observed Brackett $\alpha$ 4.05$\mu$m emission towards the supernebula in NGC 5253 with NIRSPEC on Keck II in adaptive optics mode, NIRSPAO, to probe feedback from its exciting embedded super star cluster (SSC). NIRSPEC's Slit-Viewing Camera was simultaneously used to image the K-band continuum at $\sim$$0.1''$ resolution. We register the IR continuum with HST imaging, and find that the visible clusters are offset from the K-band peak, which coincides with the Br $\alpha$ peak of the supernebula and its associated molecular cloud. The spectra of the supernebula exhibit Br $\alpha$ emission with a strong, narrow core. The linewidths are 65-76 km s$^{-1}$, FWHM, comparable to those around individual ultra-compact HII regions within our Galaxy. A weak, broad (FWHM$\simeq$150-175 km s$^{-1}$) component is detected on the base of the line, which could trace a population of sources with high-velocity winds. The core velocity of Br $\alpha$ emission shifts by +13 km s$^{-1}$ from NE to SW across the supernebula, possibly indicating a bipolar outflow from an embedded object, or linked to a foreground redshifted gas filament. The results can be explained if the supernebula comprises thousands of ionized wind regions around individual massive stars, stalled in their expansion due to critical radiative cooling and unable to merge to drive a coherent cluster wind. Based on the absence of an outflow with large mass loss, we conclude that feedback is currently ineffective at dispersing gas, and the SSC retains enriched material out of which it may continue to form stars.Comment: 24 pages, 9 figure

ALMA CO(3-2) Observations of Star-Forming Filaments in a Gas-Poor Dwarf Spheroidal Galaxy

We report ALMA observations of $^{12}$CO(3-2) and $^{13}$CO(3-2) in the gas-poor dwarf galaxy NGC 5253. These 0.3"(5.5 pc) resolution images reveal small, dense molecular gas clouds that are located in kinematically distinct, extended filaments. Some of the filaments appear to be falling into the galaxy and may be fueling its current star formation. The most intense CO(3-2) emission comes from the central $\sim$100 pc region centered on the luminous radio-infrared HII region known as the supernebula. The CO(3-2) clumps within the starburst region are anti-correlated with H$\alpha$ on $\sim$5 pc scales, but are well-correlated with radio free-free emission. Cloud D1, which enshrouds the supernebula, has a high $^{12}$CO/$^{13}$CO ratio, as does another cloud within the central 100 pc starburst region, possibly because the clouds are hot. CO(3-2) emission alone does not allow determination of cloud masses as molecular gas temperature and column density are degenerate at the observed brightness, unless combined with other lines such as $^{13}$CO.Comment: 7 pages, 5 figures, Accepted to Ap

ELISA analysis of β-secretase cleavage of the Swedish amyloid precursor protein in the secretory and endocytic pathways

Limiting beta amyloid (Aβ) production could become an important therapeutic target in Alzheimer's disease (AD). Aβ is derived by the sequential cleavage of amyloid precursor protein (APP) by β- and γ-secretases. A double missense mutation in APP found in a Swedish pedigree (APPsw) elevates Aβ40 and Aβ42 production. Aβ production and, therefore, β-secretase cleavage of APPsw reportedly occur in the endoplasmic reticulum (ER), Golgi and endocytic compartments. However, the relative contribution of β-secretase cleavage occurring in each compartment has not been determined. Experiments described here use a novel ELISA to measure the β-cleaved product, APPswβ. Using this ELISA, we provide new information regarding the relative amount of β-secretase cleavage of APPsw that occurs in secretory and endocytic pathways. Using a dilysine retrieval motif to retain APPsw in the ER, we discovered that less than 15% of the β-secretase cleavage was still detected. Experiments utilizing endocytosis-impaired mutants of APPsw revealed that little or no β-secretase cleavage of APPsw appears to take place through endocytosis. Surprisingly, deletion of the entire cytoplasmic tail increased both APPswβ and Aβ secretion, suggesting that protein interactions with this region normally impede β-secretase cleavage. These results suggest that APPsw is cleaved by β-secretase late in the secretory pathway.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66393/1/j.0022-3042.2002.00764.x.pd

The Effect of Electronic Cigarette User Modifications and E-liquid Adulteration on the Particle Size Profile of an Aerosolized Product

Electronic cigarettes (e-cigarettes) are an alternate nicotine delivery system that generate a condensation aerosol to be inhaled by the user. The size of the droplets formed in the aerosol can vary and contributes to drug deposition and ultimate bioavailability in the lung. The growing popularity of e-cigarette products has caused an increase in internet sources promoting the use of drugs other than nicotine (DOTNs) in e-cigarettes. The purpose of this study was to determine the effect of various e-cigarette and e-liquid modifications, such as coil resistance, battery voltage, and glycol and drug formulation, on the aerosol particle size. E-liquids containing 12 mg/mL nicotine prepared in glycol compositions of 100% propylene glycol (PG), 100% vegetable glycerin (VG), or 50:50 PG:VG were aerosolized at three voltages and three coil resistances. Methamphetamine and methadone e-liquids were prepared at 60 mg/mL in 50:50 PG:VG and all e-liquids were aerosolized onto a 10 stage Micro-Orifice Uniform Deposit Impactor. Glycol deposition correlated with drug deposition, and the majority of particles centered between 0.172–0.5 μm in diameter, representing pulmonary deposition. The 100% PG e-liquid produced the largest aerosol particles and the 100% VG and 50:50 PG:VG e-liquids produced ultra-fine particles \u3c0.3 μm. The presence of ultrafine particles indicates that drugs can be aerosolized and reach the pulmonary alveolar regions, highlighting a potential for abuse and risk of overdose with DOTNs aerosolized in an e-cigarette system

Nutrient-specific solubility patterns of leaf litter across 41 lowland tropical woody species

Abstract. Leaching is a mechanism for the release of nutrients from litter or senesced leaves that can drive interactions among plants, microbes, and soil. Although leaching is well established in conceptual models of litter decomposition, potential nutrient solubility of mineral elements from recently senesced litter has seldom been quantified. Using a standardized extraction (1:50 litter-to-water ratio and four-hour extraction) and recently senesced leaf litter of 41 tropical tree and liana species, we investigated how solubility varies among elements, and whether the solubility of elements could be predicted by litter traits (e.g., lignin, total element concentrations). In addition, we investigated nutrient forms (i.e., inorganic and organic) and ratios in leachate. Water-soluble elements per unit litter mass were strongly predicted by total initial litter element concentrations for potassium (K; r 2 ¼ 0.79), sodium (Na; r 2 ¼ 0.51) and phosphorus (P; r 2 ¼ 0.66), while a significant but weaker positive relationship was found for nitrogen (N; r 2 ¼ 0.36). There was no significant relationship for carbon (C) or calcium (Ca). Element-specific solubility varied markedly. On average 100% of total K, 35% of total P, 28% of total Na, 5% of total N, 4% of total Ca, and 3% of total C were soluble. For soluble P, 90% was inorganic orthophosphate. The high solubility of K, Na, and P as inorganic orthophosphate suggests that these nutrients can become rapidly available to litter microbes with no metabolic cost. Few common predictors of decomposition rates were correlated with element solubility, although soluble C (milligrams per gram of litter) was negatively related to lignin content (r 2 ¼ 0.19; P , 0.004). Solubility of elements was linked within a species: when a species ranked high in the soluble fraction of one element, it also ranked high in the solubility of other elements. Overall nutrient-specific patterns of solubility from recently senesced litter emphasize that litter elements cannot be treated equally in our conceptual and empirical models of decomposition. The relatively high potential solubility of P as orthophosphate from fresh litter advances our understanding of ecological stoichiometric ratios and nutrient bioavailability in tropical forests

Identifying nonalcoholic fatty liver disease patients with active fibrosis by measuring extracellular matrix remodeling rates in tissue and blood.

Excess collagen synthesis (fibrogenesis) in the liver plays a causal role in the progression of nonalcoholic fatty liver disease (NAFLD). Methods are needed to identify patients with more rapidly progressing disease and to demonstrate early response to treatment. We describe here a novel method to quantify hepatic fibrogenesis flux rates both directly in liver tissue and noninvasively in blood. Twenty-one patients with suspected NAFLD ingested heavy water (2 H2 O, 50-mL aliquots) two to three times daily for 3-5 weeks prior to a clinically indicated liver biopsy. Liver collagen fractional synthesis rate (FSR) and plasma lumican FSR were measured based on 2 H labeling using tandem mass spectrometry. Patients were classified by histology for fibrosis stage (F0-F4) and as having nonalcoholic fatty liver or nonalcoholic steatohepatitis (NASH). Magnetic resonance elastography measurements of liver stiffness were also performed. Hepatic collagen FSR in NAFLD increased with advancing disease stage (e.g., higher in NASH than nonalcoholic fatty liver, positive correlation with fibrosis score and liver stiffness) and correlated with hemoglobin A1C. In addition, plasma lumican FSR demonstrated a significant correlation with hepatic collagen FSR.ConclusionUsing a well-characterized cohort of patients with biopsy-proven NAFLD, this study demonstrates that hepatic scar in NASH is actively remodeled even in advanced fibrosis, a disease that is generally regarded as static and slowly progressive. Moreover, hepatic collagen FSR correlates with established risks for fibrotic disease progression in NASH, and plasma lumican FSR correlates with hepatic collagen FSR, suggesting applications as direct or surrogate markers, respectively, of hepatic fibrogenesis in humans. (Hepatology 2017;65:78-88)

Improved timed-mating, non-invasive method using fewer unproven female rats with pregnancy validation via early body mass increases

For studies requiring accurate conception-timing, reliable, efficient methods of detecting oestrus reduce time and costs, whilst improving welfare. Standard methods use vaginal cytology to stage cycle, and breeders are paired–up using approximately five proven females with proven males to achieve at least one conception on a specific day. We describe an alternative, fast, consistent, non-invasive method of timed-mating using detection of lordosis behaviour in Wistar and Lister-Hooded rats that used unproven females with high success rates. Rats under reverse-lighting had body masses recorded pre-mating, day (d) 3-4, d8, d10 and d18 of pregnancy. Using only the presence of the oestrus dance to time-mate females for 24-hrs, 89% Wistar and 88% Lister-Hooded rats successfully conceived. We did not observe behavioural oestrus in Sprague-Dawleys without males present. Significant body mass increases following mating distinguished pregnant from non-pregnant rats, as early as d4 of pregnancy (10% ± 1.0 increase cf 3% ± 1.2). The pattern of increases throughout gestation was similar for all pregnant rats until late pregnancy, when there were smaller increases for primi- and multiparous rats (32% ± 2.5; 25% ± 2.4), whereas nulliparous rats had highest gains (38% ± 1.5). This method demonstrated a distinct refinement of the previous timed-mating common practice used, as disturbance of females was minimised. Only the number required of nulli-, primi- or multiparous rats were mated, and body mass increases validated pregnancy status. This new breeding-management method is now established practice for two strains of rat and resulted in a reduction in animal use

Language and social/emotional problems identified at a universal developmental assessment at 30 months

Non peer reviewedPublisher PD