OBJECTIVES/GOALS: Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by dysregulated collagen accumulation in the lung parenchyma. Our goal is to investigate the role of O-linked N-Acetylglucosamine (O-GlcNAc) transferase (OGT) in pulmonary fibrosis to ultimately discover novel therapies for fibrosis resolution. METHODS/STUDY POPULATION: Lung tissue from IPF and non-IPF donors was subjected to immunohistochemistry (IHC) to assess O-GlcNAc levels. Primary human lung fibroblasts were treated with OGT or O-GlcNAcase (OGA) inhibitors followed by transforming growth factor-beta 1 (TGF-β1) stimulation to assess O-GlcNAc regulation of fibroblast-to-myofibroblast transition (FMT) markers [alpha smooth muscle actin (α-SMA) and type 1 and type 3 collagen (COL1α1, COL3α1)] In Drosophila melanogaster, OGT knockdown (KD)/overexpression (OE) was conditionally induced to assess pericardin, a type IV collagen-like protein, regulation by immunofluorescence. Lastly, a mouse model of bleomycin-induced pulmonary fibrosis was examined following OGT KD and assessed for fibrosis resolution via histology, hydroxyproline assay, and western blotting. RESULTS/ANTICIPATED RESULTS: O-GlcNAc staining was increased in IPF lung tissue compared to non-IPF control lungs. In primary human lung fibroblasts, TGF-α1 administration resulted in increased FMT markers (α-SMA, COL1α1, and COL3α1), which were reduced or increased by OGT or OGA inhibition, respectively. Genetic manipulation in the Drosophila models showed decreased pericardin expression with OGT KD compared to the wild-type, whereas OGT OE increased pericardin compared to control. Additionally, OGT KD in bleomycin treated aged mice resulted in reduced collagen levels at the transcript and protein level and concurrent fibrosis resolution as assessed by Masson’s trichrome staining and total hydroxyproline analysis. Collectively, showing OGT/O-GlcNAc regulating collagen in fibrosis resolution. DISCUSSION/SIGNIFICANCE: These data suggest that the OGT/O-GlcNAc axis regulates collagen deposition in pulmonary fibrosis, and we show that O-GlcNAc is implicated in the pathogenesis of IPF. We identified OGT as a therapeutic target to overcome current drug limitations, opening new horizons for biomedical treatment.

The search for life in the Universe is a fundamental problem of astrobiology and modern science. The current progress in the detection of terrestrial-type exoplanets has opened a new avenue in the characterization of exoplanetary atmospheres and in the search for biosignatures of life with the upcoming ground-based and space missions. To specify the conditions favourable for the origin, development and sustainment of life as we know it in other worlds, we need to understand the nature of global (astrospheric), and local (atmospheric and surface) environments of exoplanets in the habitable zones (HZs) around G-K-M dwarf stars including our young Sun. Global environment is formed by propagated disturbances from the planet-hosting stars in the form of stellar flares, coronal mass ejections, energetic particles and winds collectively known as astrospheric space weather. Its characterization will help in understanding how an exoplanetary ecosystem interacts with its host star, as well as in the specification of the physical, chemical and biochemical conditions that can create favourable and/or detrimental conditions for planetary climate and habitability along with evolution of planetary internal dynamics over geological timescales. A key linkage of (astro)physical, chemical and geological processes can only be understood in the framework of interdisciplinary studies with the incorporation of progress in heliophysics, astrophysics, planetary and Earth sciences. The assessment of the impacts of host stars on the climate and habitability of terrestrial (exo)planets will significantly expand the current definition of the HZ to the biogenic zone and provide new observational strategies for searching for signatures of life. The major goal of this paper is to describe and discuss the current status and recent progress in this interdisciplinary field in light of presentations and discussions during the NASA Nexus for Exoplanetary System Science funded workshop ‘Exoplanetary Space Weather, Climate and Habitability’ and to provide a new roadmap for the future development of the emerging field of exoplanetary science and astrobiology.

Desiccation following prolonged air exposure challenges survival of aquatic plants during droughts, water drawdowns, and overland dispersal. To improve predictions of plant response to air exposure, we observed the viability of vegetative fragments of 10 aquatic plant species (Cabomba caroliniana, Ceratophyllum demersum, Elodea canadensis, Egeria densa, Myriophyllum aquaticum, Myriophyllum heterophyllum, Myriophyllum spicatum, Potamogeton crispus, Potamogeton richardsonii, and Hydrilla verticillata) following desiccation. We recorded mass loss, desiccation rate, and plant fragment survival across a range of air exposures. Mass loss accurately predicted viability of aquatic plant fragments upon reintroduction to water. However, similar periods of air exposure differentially affected viability between species. Understanding viability following desiccation can contribute to predicting dispersal, improving eradication protocols, and disposing of aquatic plants following removal from invaded lakes or contaminated equipment.

The aim of this study was to compare patterns of cognitive decline in older Latinos and non-Latinos. At annual intervals for a mean of 5.7 years, older Latino (n=104) and non-Latino (n=104) persons of equivalent age, education, and race completed a battery of 17 cognitive tests from which previously established composite measures of episodic memory, semantic memory, working memory, perceptual speed, and visuospatial ability were derived. In analyses adjusted for age, sex, and education, performance declined over time in each cognitive domain, but there were no ethnic group differences in initial level of function or annual rate of decline. There was evidence of retest learning following the baseline evaluation, but neither the magnitude nor duration of the effect was related to Latino ethnicity, and eliminating the first two evaluations, during which much of retest learning occurred, did not affect ethnic group comparisons. Compared to the non-Latino group, the Latino group had more diabetes (38.5% vs. 25.0; χ2[1]=4.4; p=.037), fewer histories of smoking (24.0% vs. 39.4%, χ2[1]=5.7; p=.017), and lower childhood household socioeconomic level (−0.410 vs. −0.045, t[185.0]=3.1; p=.002), but controlling for these factors did not affect results. Trajectories of cognitive aging in different abilities are similar in Latino and non-Latino individuals of equivalent age, education, and race. (JINS, 2016, 22, 58–65)

The Murchison Widefield Array is a Square Kilometre Array Precursor. The telescope is located at the Murchison Radio–astronomy Observatory in Western Australia. The MWA consists of 4 096 dipoles arranged into 128 dual polarisation aperture arrays forming a connected element interferometer that cross-correlates signals from all 256 inputs. A hybrid approach to the correlation task is employed, with some processing stages being performed by bespoke hardware, based on Field Programmable Gate Arrays, and others by Graphics Processing Units housed in general purpose rack mounted servers. The correlation capability required is approximately 8 tera floating point operations per second. The MWA has commenced operations and the correlator is generating 8.3 TB day−1 of correlation products, that are subsequently transferred 700 km from the MRO to Perth (WA) in real-time for storage and offline processing. In this paper, we outline the correlator design, signal path, and processing elements and present the data format for the internal and external interfaces.

The Murchison Widefield Array (MWA) is one of three Square Kilometre Array Precursor telescopes and is located at the Murchison Radio-astronomy Observatory in the Murchison Shire of the mid-west of Western Australia, a location chosen for its extremely low levels of radio frequency interference. The MWA operates at low radio frequencies, 80–300 MHz, with a processed bandwidth of 30.72 MHz for both linear polarisations, and consists of 128 aperture arrays (known as tiles) distributed over a ~3-km diameter area. Novel hybrid hardware/software correlation and a real-time imaging and calibration systems comprise the MWA signal processing backend. In this paper, the as-built MWA is described both at a system and sub-system level, the expected performance of the array is presented, and the science goals of the instrument are summarised.

There is increasing epidemiological evidence linking sub-optimal vitamin D status with overweight and obesity. Although increasing BMI and adiposity have also been negatively associated with the change in vitamin D status following supplementation, results have been equivocal. The aim of this randomised, placebo-controlled study was to investigate the associations between anthropometric measures of adiposity and the wintertime serum 25-hydroxycholecalciferol (25(OH)D) response to 15 μg cholecalciferol per d in healthy young and older Irish adults. A total of 110 young adults (20–40 years) and 102 older adults ( ≥ 64 years) completed the 22-week intervention with >85 % compliance. The change in 25(OH)D from baseline was calculated. Anthropometric measures of adiposity taken at baseline included height, weight and waist circumference (WC), along with skinfold thickness measurements to estimate fat mass (FM). FM was subsequently expressed as FM (kg), FM (%), FM index (FMI (FM kg/height m2)) and as a percentage ratio to fat-free mass (FFM). In older adults, vitamin D status was inversely associated with BMI (kg/m2), WC (cm), FM (kg and %), FMI (kg/m2) and FM:FFM (%) at baseline (r − 0·33, − 0·36, − 0·33, − 0·30, − 0·33 and − 0·27, respectively, all P values < 0·01). BMI in older adults was also negatively associated with the change in 25(OH)D following supplementation (β − 1·27, CI − 2·37, − 0·16, P = 0·026); however, no such associations were apparent in younger adults. Results suggest that adiposity may need to be taken into account when determining an adequate wintertime dietary vitamin D intake for healthy older adults residing at higher latitudes.

The number of elephants living in the forests of Gabon was estimated by a stratified dung survey. The forest zone was stratified according to the distribution of the human population. The density of dung-piles was estimated for each stratum by the line-transect method. The total number of dung-piles in the forests of Gabon was estimated to be 52.43 × 106 ± 13.25 × 106. This gave an elephant estimate of 61,800 ±20,200. This survey shows Gabon to have one of the largest elephant populations on the continent.

Previous work on the evolution of weak double layers in a hydrogen plasma has been extended to include H+ and O+ with relative drift. It has been shown (Bergmann & Lotko 1986) that the relative drift between hydrogen and oxygen ions due to a quasistatic parallel electric field gives rise to a strong linear fluid instability which dominates the ion acoustic mode at the bottom of the auroral acceleration region. This ion–ion instability can modify ion distributions at lower altitudes and the subsequent nonlinear evolution of weak double layers at higher altitudes in the ion acoustic regime. We have found that ion hole formation can occur for smaller relative electron-ion drifts than seen in previous simulations, due to the hydrogen-oxygen two-stream instability. This results in local modification of the ion distributions in phase space, and a partial filling of the valley between the hydrogen and oxygen peaks, which would be expected at higher altitudes on auroral field lines. It is shown that the observed velocity diffusion does not necessarily preclude ion hole and double layer formation in hydrogen in the ion acoustic regime. These simulation results are consistent with the experimentally measured persistence of separate hydrogen and oxygen peaks, and the observation of weak double layers above an altitude of 3000 km on auroral field lines.