Phytol-based novel adjuvants in vaccine formulation: 2. assessment of efficacy in the induction of protective immune responses to lethal bacterial infections in mice

BACKGROUND: Adjuvants are known to significantly enhance vaccine efficacy. However, commercial adjuvants often have limited use because of toxicity in humans. The objective of this study was to determine the comparative effectiveness of a diterpene alcohol, phytol and its hydrogenated derivative PHIS-01, relative to incomplete Freund's adjuvant (IFA), a commonly used adjuvant in augmenting protective immunity in mice against E. coli and S. aureus, and in terms of inflammatory cytokines. METHODS: Vaccines, consisting of heat-attenuated E. coli or S. aureus and either of the two phytol-based adjuvants or IFA, were tested in female BALB/c mice. The vaccines were administered intraperitoneally at 10-day intervals. The efficacy of the phytol and PHIS-01, as compared to IFA, was assessed by ELISA in terms of anti-bacterial antibody and inflammatory cytokines. We also examined the ability of the vaccines to induce specific protective immunity by challenging mice with different doses of live bacteria. RESULTS AND DISCUSSION: IFA, phytol, and PHIS-01 were equally efficient in evoking anti-E. coli antibody response and in providing protective immunity against live E. coli challenges. In contrast, the antibody response to S. aureus was significant when PHIS-01 was used as the adjuvant. However, in terms of the ability to induce protective immunity, phytol was most effective against S. aureus. Moreover, during challenges with live E. coli and S. aureus immune mice produced much less IL-6, the mediators of fatal septic shock syndromes. CONCLUSION: Our results show that vaccine formulations containing phytol and PHIS-01 as adjuvants confer a robust and protective immunity against both Gram-negative and Gram-positive bacteria without inducing adverse inflammatory cytokine due to IL-6

Evidence for Cold Accretion: Primitive Gas Flowing onto a Galaxy at z~0.274

We present UV and optical observations from the Cosmic Origins Spectrograph on the Hubble Space Telescope and Keck of a z= 0.27395 Lyman limit system (LLS) seen in absorption against the QSO PG1630+377. We detect H I absorption with log N(HI)=17.06\pm0.05 as well as Mg II, C III, Si III, and O VI in this system. The column densities are readily explained if this is a multi-phase system, with the intermediate and low ions arising in a very low metallicity ([Mg/ H] =-1.71 \pm 0.06) photoionized gas. We identify via Keck spectroscopy and Large Binocular Telescope imaging a 0.3 L_* star-forming galaxy projected 37 kpc from the QSO at nearly identical redshift (z=0.27406, \Delta v = -26 \kms) with near solar metallicity ([O/ H]=-0.20 \pm 0.15). The presence of very low metallicity gas in the proximity of a near-solar metallicity, sub-L_* galaxy strongly suggests that the LLS probes gas infalling onto the galaxy. A search of the literature reveals that such low metallicity LLSs are not uncommon. We found that 50% (4/8) of the well-studied z < 1 LLSs have metallicities similar to the present system and show sub-L_* galaxies with rho < 100 kpc in those fields where redshifts have been surveyed. We argue that the properties of these primitive LLSs and their host galaxies are consistent with those of cold mode accretion streams seen in galaxy simulations.Comment: Accepted for publication in the Astrophysical Journa

Evaluating the harmonisation potential of diverse cohort datasets

Data discovery, the ability to find datasets relevant to an analysis, increases scientific opportunity, improves rigour and accelerates activity. Rapid growth in the depth, breadth, quantity and availability of data provides unprecedented opportunities and challenges for data discovery. A potential tool for increasing the efficiency of data discovery, particularly across multiple datasets is data harmonisation.A set of 124 variables, identified as being of broad interest to neurodegeneration, were harmonised using the C-Surv data model. Harmonisation strategies used were simple calibration, algorithmic transformation and standardisation to the Z-distribution. Widely used data conventions, optimised for inclusiveness rather than aetiological precision, were used as harmonisation rules. The harmonisation scheme was applied to data from four diverse population cohorts.Of the 120 variables that were found in the datasets, correspondence between the harmonised data schema and cohort-specific data models was complete or close for 111 (93%). For the remainder, harmonisation was possible with a marginal a loss of granularity.Although harmonisation is not an exact science, sufficient comparability across datasets was achieved to enable data discovery with relatively little loss of informativeness. This provides a basis for further work extending harmonisation to a larger variable list, applying the harmonisation to further datasets, and incentivising the development of data discovery tools

An Introduction to Gas Accretion onto Galaxies

Evidence for gas accretion onto galaxies can be found throughout the universe. In this chapter, I summarize the direct and indirect signatures of this process and discuss the primary sources. The evidence for gas accretion includes the star formation rates and metallicities of galaxies, the evolution of the cold gas content of the universe with time, numerous indirect indicators for individual galaxies, and a few direct detections of inflow. The primary sources of gas accretion are the intergalactic medium, satellite gas and feedback material. There is support for each of these sources from observations and simulations, but the methods with which the fuel ultimately settles in to form stars remain murky.Comment: 14 pages, 5 figures, Invited review to appear in Gas Accretion onto Galaxies, Astrophysics and Space Science Library, eds. A. J. Fox & R. Dav\'e, to be published by Springe

Utilization and metabolism of palmityl and oleoyl fatty acids and alcohols in caecal enterocytes of Atlantic salmon (Salmo salar L.)

The substitution of fish oil with wax ester-rich calanoid copepod-derived oil in diets for carnivorous fish, such as Atlantic salmon, has previously indicated a lower lipid digestibility. This suggests that the fatty alcohols (FAlc) present in wax esters may be a poorer substrate for intestinal enzymes than the fatty acids (FA) in triacylglycerol, the major lipid in fish oil. The hypothesis tested was that the possible lower utilization of dietary FAlc by salmon enterocytes is at the level of uptake and that subsequent intracellular metabolism was identical to that of FA. A dual-labelled FAlc-FA metabolism assay was employed to determine simultaneous FAlc and FA uptake and relative utilisation in enterocytes isolated from pyloric caeca of Atlantic salmon fed either a diet supplemented with fish oil or wax ester-rich Calanus oil. The diets were fed for 10 weeks before caecal enterocytes from each dietary group were isolated and incubated with equimolar mixtures of either [1-14C]16:0 FA and [9,10(n)-3H]16:0 FAlc, or [1-14C]18:1n-9 FA and [9,10(n)-3H]18:1n-9 FAlc. Uptake was measured after 2 h with relative utilization of labelled FAlc and FA calculated as a percentage of uptake. Differences in uptake were observed, with FA showing higher uptake than FAlc, and 18:1 chains a higher uptake than 16:0. A proportion of unesterified FAlc was possibly recovered in the cells, but the majority of FALc was recovered in lipid classes such as triacylglycerol and phospholipids indicating substantial conversion of FAlc to FA followed by esterification. However, incorporation of FA and FAlc into esterified lipids was higher when derived from FA than from FAlc. Twenty-five to fifty percentage of the absorbed 16:0 FA was recovered in TAG fraction of the enterocytes compared with fifteen to seventy-five percentage of 18:1 FA. Twenty to thirty percentage of the absorbed 16:0 FA was recovered in the PC fraction of the enterocytes compared with only five to fifteen percentage of the 18:1 FA. Less than 15% of the fatty chains taken up by the cells was used for energy production, with significantly higher oxidation of 18:1 in enterocytes from fish fed the fish oil diet compared to the Calanus oil diet. However, overall, dietary copepod oil had little effect on FAlc and FA metabolism. Metabolic modification by elongation and/or desaturation was generally low at 1-5% of uptake. We conclude that our hypothesis was generally proved in that the uptake of FAlc by salmon enterocytes was lower than the uptake of FA and that subsequent intracellular metabolism of FAlc was similar to that of FA. However, unesterified FAlc was possibly recovered in the cells suggesting that the conversion to FA may not be concomitant with uptake

Building Community in the HIV Online Intervention Space: Lessons From the HealthMPowerment Intervention

Background: Mobile health platforms can facilitate social support and address HIV (human immunodeficiency virus) stigma but pose challenges for intervention design and participant engagement. Giddens’s structuration theory, that individuals are shaped by—and shape—their communities through rules and resources that give them power to operate within these environments, provides a useful analytic framework for exploring these dynamic intervention spaces. Method: Data were drawn from an online randomized controlled trial intervention (HealthMpowerment) for young Black men who have sex with men to reduce condomless anal intercourse. We applied a conversational analysis informed by structuration theory to 65 user-generated conversations that included stigma content. We aimed to understand how the interdependent relationship between the intervention space and participants’ contributions might contribute to behavior change. Results: Thirty five intervention participants contributed to the analyzed conversations. Our analysis identified three types of conversational processes that may underlie behavior change: (1) Through intervention engagement, participants established norms and expectations that shaped their discussions; (2) participants used anecdotes and anonymity to reinforce norms; and (3) intervention staff members sought to improve engagement and build knowledge by initiating discussions and correcting misinformation, thus playing an integral role in the online community. Conclusions: The lens of structuration theory usefully reveals potential behavior change mechanisms within the social interactions of an online intervention. Future design of these interventions to address HIV stigma should explicitly characterize the context in which individuals (study staff and participants) engage with one another in order to assess whether these processes are associated with improved intervention outcomes

Comment on "On the subtleties of searching for dark matter with liquid xenon detectors"

In a recent manuscript (arXiv:1208.5046) Peter Sorensen claims that XENON100's upper limits on spin-independent WIMP-nucleon cross sections for WIMP masses below 10 GeV "may be understated by one order of magnitude or more". Having performed a similar, though more detailed analysis prior to the submission of our new result (arXiv:1207.5988), we do not confirm these findings. We point out the rationale for not considering the described effect in our final analysis and list several potential problems with his study.Comment: 3 pages, no figure

The Allen Telescope Array Pi GHz Sky Survey I. Survey Description and Static Catalog Results for the Bootes Field

The Pi GHz Sky Survey (PiGSS) is a key project of the Allen Telescope Array. PiGSS is a 3.1 GHz survey of radio continuum emission in the extragalactic sky with an emphasis on synoptic observations that measure the static and time-variable properties of the sky. During the 2.5-year campaign, PiGSS will twice observe ~250,000 radio sources in the 10,000 deg^2 region of the sky with b > 30 deg to an rms sensitivity of ~1 mJy. Additionally, sub-regions of the sky will be observed multiple times to characterize variability on time scales of days to years. We present here observations of a 10 deg^2 region in the Bootes constellation overlapping the NOAO Deep Wide Field Survey field. The PiGSS image was constructed from 75 daily observations distributed over a 4-month period and has an rms flux density between 200 and 250 microJy. This represents a deeper image by a factor of 4 to 8 than we will achieve over the entire 10,000 deg^2. We provide flux densities, source sizes, and spectral indices for the 425 sources detected in the image. We identify ~100$ new flat spectrum radio sources; we project that when completed PiGSS will identify 10^4 flat spectrum sources. We identify one source that is a possible transient radio source. This survey provides new limits on faint radio transients and variables with characteristic durations of months.Comment: Accepted for publication in ApJ; revision submitted with extraneous figure remove