The central conserved region (CCR) of respiratory syncytial virus (RSV) G protein modulates host miRNA expression and alters the cellular response to infection

Respiratory Syncytial Virus (RSV) infects respiratory epithelial cells and deregulates host gene expression by many mechanisms including expression of RSV G protein (RSV G). RSV G protein encodes a central conserved region (CCR) containing a CX3C motif that functions as a fractalkine mimic. Disruption of the CX3C motif (a.a. 182–186) located in the CCR of the G protein has been shown to affect G protein function in vitro and the severity of RSV disease pathogenesis in vivo. We show that infection of polarized Calu3 respiratory cells with recombinant RSV having point mutations in Cys173 and 176 (C173/176S) (rA2-GC12), or Cys186 (C186S) (rA2-GC4) is associated with a decline in the integrity of polarized Calu-3 cultures and decreased virus production. This is accompanied with downregulation of miRNAs let-7f and miR-24 and upregulation of interferon lambda (IFNλ), a primary antiviral cytokine for RSV in rA2-GC12/rA2-GC4 infected cells. These results suggest that residues in the cysteine noose region of RSV G protein can modulate IFN λ expression accompanied by downregulation of miRNAs, and are important for RSV G protein function and targeting

Changing environment at the Late Upper Palaeolithic ite of Lynx Cave, North Wales

Lynx Cave is one of a handful of locations in North Wales that provide evidence of Late Upper Palaeolithic huntergatherers at the end of the last ice-age. With the region being recolonized at a time of rapid environmental change there is a need to develop on-site palaeoenvironmental records that are directly linked to the archaeology in order to further understanding of the environments and landscapes that these hunter-gatherer groups experienced. Through carbon (δ13C), nitrogen (δ15N) and sulphur (δ34S) stable isotope analysis of animal bones we explore the environmental conditions during the human occupation of Lynx Cave. Analysis of the data indicates the faunal isotope results cluster into three distinct groupings, which when considered in light of the species composition, radiocarbon dates, sample layer provenance and known temporal patterns in herbivore isotope data from Northern Europe, are likely to relate to GI-1cba (the Allerød period) around 13,700-13,000 cal BP, GI-1cba/GS-1 (the Late Allerød/ early Younger Dryas period) around 13,100-12,800 cal BP, and the Bronze Age. The isotope data indicates that the Late Upper Palaeolithic or Late Palaeolithic occupations occurred in an open landscape in which soils were undergoing changing hydrological conditions linked to ice sheet melt and permafrost thaw process and subsequent recovery. The evidence of butchery marks on the faunal remains from both Late Glacial isotope clusters, along with the disparate radiocarbon dates and the presence of three hearths, support the idea of very short-term episodic use of the cave over an extended time period

Radiocarbon chronology and environmental context of Last Glacial Maximum human occupation in Switzerland

Central Europe during the Last Glacial Maximum (LGM) was dominated by polar desert and steppe-tundra biomes. Despite this, a human presence during this time period is evident at several locations across the region, including in Switzerland, less than 50 km from the Alpine ice sheet margin. It has been hypothesised that such human activity may have been restricted to brief periods of climatic warming within the LGM, but chronological information from many of these sites are currently too poorly resolved to corroborate this. Here we present a revised chronology of LGM human occupation in Switzerland. AMS radiocarbon dating of cut-marked reindeer (Rangifer tarandus) bones from the sites of Kastelhöhle-Nord and Y-Höhle indicates human occupation of Switzerland was most likely restricted to between 23,400 and 22,800 cal. BP. This timeframe corresponds to Greenland Interstadial 2, a brief warming phase, supporting the hypothesis that human presence was facilitated by favourable climatic episodes. Carbon, nitrogen and sulphur stable isotope analysis of the fauna provides palaeoenvironmental information for this time period. These findings contribute to our understanding of human activity in ice-marginal environments and have implications for understanding cultural connections across central Europe during the LGM

Testing Models of Intrinsic Brightness Variations in Type Ia Supernovae, and their Impact on Measuring Cosmological Parameters

For spectroscopically confirmed Type Ia supernovae we evaluate models of intrinsic brightness variations with detailed data/Monte Carlo comparisons of the dispersion in the following quantities: Hubble-diagram scatter, color difference (B-V-c) between the true B-V color and the fitted color (c) from the SALT-II light curve model, and photometric redshift residual. The data sample includes 251 ugriz light curves from the 3-season Sloan Digital Sky Survey-II, and 191 griz light curves from the Supernova Legacy Survey 3-year data release. We find that the simplest model of a wavelength-independent (coherent) scatter is not adequate, and that to describe the data the intrinsic scatter model must have wavelength-dependent variations. We use Monte Carlo simulations to examine the standard approach of adding a coherent scatter term in quadrature to the distance-modulus uncertainty in order to bring the reduced chi2 to unity when fitting a Hubble diagram. If the light curve fits include model uncertainties with the correct wavelength dependence of the scatter, we find that the bias on the dark energy equation of state parameter $w$ is negligible. However, incorrect model uncertainties can lead to a significant bias on the distance moduli, with up to ~0.05 mag redshift-dependent variation. For the recent SNLS3 cosmology results we estimate that this effect introduces an additional systematic uncertainty on $w$ of ~0.02, well below the total uncertainty. However, this uncertainty depends on the samples used, and thus this small $w$-uncertainty is not guaranteed in future cosmology results.Comment: accepted by Ap

An Empirical Characterization of Extended Cool Gas Around Galaxies Using MgII Absorption Features

We report results from a survey of MgII absorbers in the spectra of background QSOs that are within close angular distances to a foreground galaxy at z<0.5, using the Magellan Echellette Spectrograph. We have established a spectroscopic sample of 94 galaxies at a median redshift of = 0.24 in fields around 70 distant background QSOs (z_QSO>0.6), 71 of which are in an 'isolated' environment with no known companions and located at rho <~ 120 h^-1 kpc from the line of sight of a background QSO. The rest-frame absolute B-band magnitudes span a range from M_B-5log h=-16.4 to M_B-5log h=-21.4 and rest-frame B_AB-R_AB colors range from B_AB-R_AB~0 to B_AB-R_AB~1.5. Of these 'isolated' galaxies, we find that 47 have corresponding MgII absorbers in the spectra of background QSOs and rest-frame absorption equivalent width W_r(2796)=0.1-2.34 A, and 24 do not give rise to MgII absorption to sensitive upper limits. Our analysis shows that (1) Wr(2796) declines with increasing distance from 'isolated' galaxies but shows no clear trend in 'group' environments; (2) more luminous galaxies possess more extended MgII absorbing halos with the gaseous radius scaled by B-band luminosity according to R_gas=75x(L_B/L_B*)^(0.35+/-0.03) h^{-1} kpc; (3) there is little dependence between the observed absorber strength and galaxy intrinsic colors; and (4) within R_gas, we find a mean covering fraction of ~70% for absorbers of Wr(2796)>=0.3 A and ~80% for absorbers of Wr(2796)>=0.1 A. The lack of correlation between Wr(2796) and galaxy colors suggests a lack of physical connection between the origin of extended MgII halos and recent star formation history of the galaxies. Finally, we discuss the total gas mass in galactic halos as traced by MgII absorbers. We also compare our results with previous studies.Comment: 20 pages, 13 figures; to appear in the Astrophysical Journal 2010 May 10 issue; a version with higher resolution figures can be found at http://lambda.uchicago.edu/public/tmp/mage_apj.pd

Nitrogen palaeo-isoscapes: changing spatial gradients of faunal δ15N in late Pleistocene and early Holocene Europe

Nitrogen isotope ratio analysis (δ15N) of animal tissue is widely used in archaeology and palaeoecology to investigate diet and ecological niche. Data interpretations require an understanding of nitrogen isotope compositions at the base of the food web (baseline δ15N). Significant variation in animal δ15N has been recognised at various spatiotemporal scales and related to changes both in baseline δ15N, linked to environmental and climatic influence on the terrestrial nitrogen cycle, and animal ecology. Isoscapes (models of isotope spatial variation) have proved a useful tool for investigating spatial variability in biogeochemical cycles in present-day marine and terrestrial ecosystems, but so far, their application to palaeo-data has been more limited. Here, we present time-sliced nitrogen isoscapes for late Pleistocene and early Holocene Europe (c. 50,000 to 10,000 years BP) using herbivore collagen δ15N data. This period covers the Last Glacial-Interglacial Transition, during which significant variation in the terrestrial nitrogen cycle occurred. We use generalized linear mixed modelling approaches for interpolation and test models which both include and exclude climate covariate data. Our results show clear changes in spatial gradients of δ15N through time. Prediction of the lowest faunal δ15N values in northern latitudes after, rather than during, the Last Glacial Maximum is consistent with the Late Glacial Nitrogen Excursion (LGNE). We find that including climatic covariate data does not significantly improve model performance. These findings have implications for investigating the drivers of the LGNE, which has been linked to increased landscape moisture and permafrost thaw, and for understanding changing isotopic baselines, which are fundamental for studies investigating diets, niche partitioning, and migration of higher trophic level animals

The Subluminous Type Ia Supernova 1998de in NGC 252

We present spectroscopic and extensive photometric observations of supernova (SN) 1998de in the S0 galaxy NGC 252, discovered during the course of the Lick Observatory Supernova Search. These data, which span a time period of 8 days before to 76 days after $B$-band maximum, unambigously establish SN 1998de as a peculiar and subluminous SN Ia with strong similarities to SN 1991bg, the prototype of these intrinsically dim SNe Ia. We find that subluminous SNe Ia with the same Delta m_{15}(B) can have slightly different light curves at longer wavelengths. The notable spectroscopic similarities between SN 1998de and SN 1991bg are the wide Ti II trough at 4100-4500 A, the strong Ca II features, and the early onset of the nebular phase. We observe that spectroscopic deviations of SN 1998de from SN 1991bg increase toward redder wavelenghts. These deviations include the absence of the conspicuous Na I D absorption found in SN 1991 at 5700 A, and the evolution of a region (6800-7600 A) from featureless to feature-rich. Several lines of evidence suggest that SN 1998de was a slightly more powerful explosion than SN 1991bg. We discuss the implications of our observations for progenitor models and the explosion mechanism of peculiar, subluminous SNe Ia. The extensive photometric data make SN 1998de a better template than SN 1991bg for calibrating the low-luminosity end of the luminosity vs. decline-rate relationship.Comment: 15 pages, 10 figures, AASTeX V5.0, to appear in PAS

Production of Potent Fully Human Polyclonal Antibodies against Ebola Zaire Virus in Transchromosomal Cattle

Polyclonal antibodies, derived from humans or hyperimmunized animals, have been used prophylactically or therapeutically as countermeasures for a variety of infectious diseases. SAB Biotherapeutics has successfully developed a transchromosomic (Tc) bovine platform technology that can produce fully human immunoglobulins rapidly, and in substantial quantities, against a variety of disease targets. In this study, two Tc bovines expressing high levels of fully human IgG were hyperimmunized with a recombinant glycoprotein (GP) vaccine consisting of the 2014 Ebola virus (EBOV) Makona isolate. Serum collected from these hyperimmunized Tc bovines contained high titers of human IgG against EBOV GP as determined by GP specific ELISA, surface plasmon resonance (SPR), and virus neutralization assays. Fully human polyclonal antibodies against EBOV were purified and evaluated in a mouse challenge model using mouse adapted Ebola virus (maEBOV). Intraperitoneal administration of the purified anti-EBOV IgG (100 mg/kg) to BALB/c mice one day after lethal challenge with maEBOV resulted in 90% protection; whereas 100% of the control animals succumbed. The results show that hyperimmunization of Tc bovines with EBOV GP can elicit protective and potent neutralizing fully human IgG antibodies rapidly and in commercially viable quantities

Deglacial landscapes and the Late Upper Palaeolithic of Switzerland

The presence of people in Switzerland in recently deglaciated landscapes after the Last Glacial Maximum represents human utilisation of newly available environments. Understanding these landscapes and the resources available to the people who exploited them is key to understanding not only Late Upper Palaeolithic settlement in Switzerland, but more broadly human behavioural ecology in newly inhabited environmental settings. By applying bone collagen stable isotope analysis (δ13C, δ15N and δ34S) to faunal remains from Late Upper Palaeolithic localities in Switzerland, we investigate animal ecology and environmental conditions during periods of human occupation. High and relatively uniform δ34S values indicate that landscapes north of the Jura Mountains provided comparatively stable environmental conditions, while lower and more variable δ34S values on the Swiss Plateau suggest a dynamic landscape with diverse hydrological and pedological conditions, potentially linked to regionally different patterns of permafrost thaw. This contrasts with the archaeological record that appears relatively uniform between the two regions, suggesting people were employing similar subsistence behaviours across a range of environmental settings. The pattern of change in δ15N across the deglacial period appears consistent between areas that remained ice-free throughout the LGM and those that were glaciated. Most notable is a period of exclusively low δ15N values between 15,200 and 14,800 cal. BP, which could relate a regional expansion of floral biomass in response to environmental change

Magdalenian and Epimagdalenian chronology and palaeoenvironments at Kůlna Cave, Moravia, Czech Republic

Kůlna Cave is the only site in Moravia, Czech Republic, from which large assemblages of both Magdalenian and Epimagdalenian archaeological materials have been excavated from relatively secure stratified deposits. The site therefore offers the unrivalled opportunity to explore the relationship between these two archaeological phases. In this study, we undertake radiocarbon, stable isotope (carbon, nitrogen and sulphur), and ZooMS analysis of the archaeological faunal assemblage to explore the chronological and environmental context of the Magdalenian and Epimagdalenian deposits. Our results show that the Magdalenian and Epimagdalenian deposits can be understood as discrete units from one another, dating to the Late Glacial between c. 15,630 cal. BP and 14,610 cal. BP, and c. 14,140 cal. BP and 12,680 cal. BP, respectively. Stable isotope results (δ13C, δ15N, δ34S) indicate that Magdalenian and Epimagdalenian activity at Kůlna Cave occurred in very different environmental settings. Magdalenian occupation took place within a nutrient-poor landscape that was experiencing rapid changes to environmental moisture, potentially linked to permafrost thaw. In contrast, Epimagdalenian occupation occurred in a relatively stable, temperate environment composed of a mosaic of woodland and grassland habitats. The potential chronological gap between the two phases, and their associations with very different environmental conditions, calls into question whether the Epimagdalenian should be seen as a local, gradual development of the Magdalenian. It also raises the question of whether the gap in occupation at Kůlna Cave could represent a change in settlement dynamics and/or behavioural adaptations to changing environmental conditions