332 research outputs found
Flyglow: Single-fly observations of simultaneous molecular and behavioural circadian oscillations in controls and an Alzheimer's model.
Circadian rhythms are essential for health and are frequently disturbed in disease. A full understanding of the causal relationships between behavioural and molecular circadian rhythms requires simultaneous longitudinal observations over time in individual organisms. Current experimental paradigms require the measurement of each rhythm separately across distinct populations of experimental organisms, rendering the comparability of the resulting datasets uncertain. We therefore developed FLYGLOW, an assay using clock gene controlled luciferase expression detected by exquisitely sensitive EM-CCD imaging, to enable simultaneous quantification of parameters including locomotor, sleep consolidation and molecular rhythms in single flies over days/weeks. FLYGLOW combines all the strengths of existing techniques, and also allows powerful multiparametric paired statistics. We found the age-related transition from rhythmicity to arrhythmicity for each parameter occurs unpredictably, with some flies showing loss of one or more rhythms during middle-age. Using single-fly correlation analysis of rhythm robustness and period we demonstrated the independence of the peripheral clock from circadian behaviours in wild type flies as well as in an Alzheimer's model. FLYGLOW is a useful tool for investigating the deterioration of behavioural and molecular rhythms in ageing and neurodegeneration. This approach may be applied more broadly within behavioural neurogenetics research
Stellar winds from Massive Stars
We review the various techniques through which wind properties of massive
stars - O stars, AB supergiants, Luminous Blue Variables (LBVs), Wolf-Rayet
(WR) stars and cool supergiants - are derived. The wind momentum-luminosity
relation (e.g. Kudritzki et al. 1999) provides a method of predicting mass-loss
rates of O stars and blue supergiants which is superior to previous
parameterizations. Assuming the theoretical sqrt(Z) metallicity dependence,
Magellanic Cloud O star mass-loss rates are typically matched to within a
factor of two for various calibrations. Stellar winds from LBVs are typically
denser and slower than equivalent B supergiants, with exceptional mass-loss
rates during giant eruptions Mdot=10^-3 .. 10^-1 Mo/yr (Drissen et al. 2001).
Recent mass-loss rates for Galactic WR stars indicate a downward revision of
2-4 relative to previous calibrations due to clumping (e.g. Schmutz 1997),
although evidence for a metallicity dependence remains inconclusive (Crowther
2000). Mass-loss properties of luminous (> 10^5 Lo) yellow and red supergiants
from alternative techniques remain highly contradictory. Recent Galactic and
LMC results for RSG reveal a large scatter such that typical mass-loss rates
lie in the range 10^-6 .. 10^-4 Mo/yr, with a few cases exhibiting 10^-3 Mo/yr.Comment: 16 pages, 2 figures, Review paper to appear in Proc `The influence of
binaries on stellar population studies', Brussels, Aug 2000 (D. Vanbeveren
ed.), Kluwe
Eta Carinae and the Luminous Blue Variables
We evaluate the place of Eta Carinae amongst the class of luminous blue
variables (LBVs) and show that the LBV phenomenon is not restricted to
extremely luminous objects like Eta Car, but extends luminosities as low as
log(L/Lsun) = 5.4 - corresponding to initial masses ~25 Msun, and final masses
as low as ~10-15 Msun. We present a census of S Doradus variability, and
discuss basic LBV properties, their mass-loss behaviour, and whether at maximum
light they form pseudo-photospheres. We argue that those objects that exhibit
giant Eta Car-type eruptions are most likely related to the more common type of
S Doradus variability. Alternative atmospheric models as well as
sub-photospheric models for the instability are presented, but the true nature
of the LBV phenomenon remains as yet elusive. We end with a discussion on the
evolutionary status of LBVs - highlighting recent indications that some LBVs
may be in a direct pre-supernova state, in contradiction to the standard
paradigm for massive star evolution.Comment: 27 pages, 6 figures, Review Chapter in "Eta Carinae and the supernova
imposters" (eds R. Humphreys and K. Davidson) new version submitted to
Springe
Conservative management versus open reduction and internal fixation for mid-shaft clavicle fractures in adults - The Clavicle Trial: Study protocol for a multicentre randomized controlled trial
Background: Clavicle fractures account for around 4% of all fractures and up to 44% of fractures of the shoulder girdle. Fractures of the middle third (or mid-shaft) account for approximately 80% of all clavicle fractures. Management of this group of fractures is often challenging and the outcome can be unsatisfactory. In particular it is not clear whether surgery produces better outcomes than non-surgical management. Currently there is much variation in the use of surgery and a lack of good quality evidence to inform our decision.Methods/Design: We aim to undertake a multicentre randomised controlled trial evaluating the effectiveness and safety of conservative management versus open reduction and internal fixation for displaced mid-shaft clavicle fractures in adults. Surgical treatment will be performed using the Acumed clavicle fixation system. Conservative management will consist of immobilisation in a sling at the side in internal rotation for 6 weeks or until clinical or radiological union. We aim to recruit 300 patients. These patients will be followed-up for at least 9 months. The primary endpoint will be the rate of non-union at 3 months following treatment. Secondary endpoints will be limb function measured using the Constant-Murley Score and the Disabilities of the Arm, Shoulder and Hand (DASH) Score at 3 and 9 months post-operatively.Discussion: This article presents the protocol for a multicentre randomised controlled trial. It gives extensive details of, and the basis for, the chosen methods, and describes the key measures taken to avoid bias and to ensure validity.Trial Registration: United Kingdom Clinical Research Network ID: 8665. The date of registration of the trial is 07/09/2006. The date the first patient was recruited is 18/12/2007. © 2011 Longo et al; licensee BioMed Central Ltd
Patent Human Infections with the Whipworm, Trichuris trichiura, Are Not Associated with Alterations in the Faecal Microbiota
Background: The soil-transmitted helminth (STH), Trichuris trichiura colonises the human large intestine where it may
modify inflammatory responses, an effect possibly mediated through alterations in the intestinal microbiota. We
hypothesised that patent T. trichiura infections would be associated with altered faecal microbiota and that anthelmintic treatment would induce a microbiota resembling more closely that observed in uninfected individuals.
Materials and Methods: School children in Ecuador were screened for STH infections and allocated to 3 groups: uninfected, T. trichiura only, and mixed infections with T. trichiura and Ascaris lumbricoides. A sample of uninfected children and those with T. trichiura infections only were given anthelmintic treatment. Bacterial community profiles in faecal samples were studied by 454 pyrosequencing of 16 S rRNA genes.
Results: Microbiota analyses of faeces were done for 97 children: 30 were uninfected, 17 were infected with T. trichiura, and 50 with T. trichiura and A. lumbricoides. Post-treatment samples were analyzed for 14 children initially infected with T. trichiura alone and for 21 uninfected children. Treatment resulted in 100% cure of STH infections. Comparisons of the microbiota at different taxonomic levels showed no statistically significant differences in composition between uninfected
children and those with T. trichiura infections. We observed a decreased proportional abundance of a few bacterial genera from the Clostridia class of Firmicutes and a reduced bacterial diversity among children with mixed infections compared to the other two groups, indicating a possible specific effect of A. lumbricoides infection. Anthelmintic treatment of children with T. trichiura did not alter faecal microbiota composition.
Discussion: Our data indicate that patent human infections with T. trichiura may have no effect on faecal microbiota but that A. lumbricoides colonisation might be associated with a disturbed microbiota. Our results also catalogue the microbiota of rural Ecuadorians and indicate differences with individuals from more urban industrialised societies
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The influence of soil communities on the temperature sensitivity of soil respiration
Soil respiration represents a major carbon flux between terrestrial ecosystems and the atmosphere, and is expected to accelerate under climate warming. Despite its importance in climate change forecasts, however, our understanding of the effects of temperature on soil respiration (RS) is incomplete. Using a metabolic ecology approach we link soil biota metabolism, community composition and heterotrophic activity, to predict RS rates across five biomes. We find that accounting for the ecological mechanisms underpinning decomposition processes predicts climatological RS variations observed in an independent dataset (n = 312). The importance of community composition is evident because without it RS is substantially underestimated. With increasing temperature, we predict a latitudinal increase in RS temperature sensitivity, with Q10 values ranging between 2.33 ±0.01 in tropical forests to 2.72 ±0.03 in tundra. This global trend has been widely observed, but has not previously been linked to soil communities
Long gamma-ray bursts and core-collapse supernovae have different environments
When massive stars exhaust their fuel they collapse and often produce the
extraordinarily bright explosions known as core-collapse supernovae. On
occasion, this stellar collapse also powers an even more brilliant relativistic
explosion known as a long-duration gamma-ray burst. One would then expect that
long gamma-ray bursts and core-collapse supernovae should be found in similar
galactic environments. Here we show that this expectation is wrong. We find
that the long gamma-ray bursts are far more concentrated on the very brightest
regions of their host galaxies than are the core-collapse supernovae.
Furthermore, the host galaxies of the long gamma-ray bursts are significantly
fainter and more irregular than the hosts of the core-collapse supernovae.
Together these results suggest that long-duration gamma-ray bursts are
associated with the most massive stars and may be restricted to galaxies of
limited chemical evolution. Our results directly imply that long gamma-ray
bursts are relatively rare in galaxies such as our own Milky Way.Comment: 27 pages, 4 figures, submitted to Nature on 22 August 2005, revised 9
February 2006, online publication 10 May 2006. Supplementary material
referred to in the text can be found at
http://www.stsci.edu/~fruchter/GRB/locations/supplement.pdf . This new
version contains minor changes to match the final published versio
Supernovae from rotating stars
The present paper discusses the main physical effects produced by stellar
rotation on presupernovae, as well as observations which confirm these effects
and their consequences for presupernova models. Rotation critically influences
the mass of the exploding cores, the mass and chemical composition of the
envelopes and the types of supernovae, as well as the properties of the
remnants and the chemical yields. In the formation of gamma-ray bursts,
rotation and the properties of rotating stars appear as the key factor. In
binaries, the interaction between axial rotation and tidal effects often leads
to interesting and unexpected results. Rotation plays a key role in shaping the
evolution and nucleosynthesis in massive stars with very low metallicities
(metallicity below about the Small Magellanic Cloud metallicity down to
Population III stars). At solar and higher metallicities, the effects of
rotation compete with those of stellar winds. In close binaries, the
synchronisation process can lock the star at a high rotation rate despite
strong mass loss and thus both effects, rotation and stellar winds, have a
strong impact. In conclusion, rotation is a key physical ingredient of the
stellar models and of presupernova stages, and the evolution both of single
stars and close binaries. Moreover, important effects are expected along the
whole cosmic history.Comment: 36 pages, 15 figures, published in Handbook of Supernovae, A.W.
Alsabti and P. Murdin (eds), Springe
Neoantigen-reactive CD8+ T cells affect clinical outcome of adoptive transfer with tumor-infiltrating lymphocytes in melanoma
BACKGROUND: Neoantigen-driven recognition and T cell-mediated killing contribute to tumor clearance following adoptive cell therapy (ACT) with Tumor-Infiltrating Lymphocytes (TILs). Yet, how diversity, frequency, and persistence of expanded neoepitope-specific CD8+ T cells derived from TIL infusion products affect patient outcome is not fully determined. METHODS: Using barcoded pMHC multimers, we provide a comprehensive mapping of CD8+ T cells recognizing neoepitopes in TIL infusion products and blood samples from 26 metastatic mela-noma patients who received ACT. RESULTS: We identified 106 neoepitopes within TIL infusion products corresponding to 1.8% of all predicted neoepitopes. We observed neoepitope-specific recognition to be virtually devoid in TIL infusion products given to patients with progressive disease outcome. Moreover, we found that the frequency of neoepitope-specific CD8+ T cells in TIL infusion products correlated with in-creased survival, and that detection of engrafted CD8+ T cells in post-treatment (i.e. originating from the TIL infusion product) were unique to responders of TIL-ACT. Finally, we found that a transcriptional signature for lymphocyte activity within the tumor microenvironment was associated with a higher frequency of neoepitope-specific CD8+ T cells in the infusion product. CONCLUSIONS: These data support previous case studies of neoepitope-specific CD8+ T cells in melanoma, and indicate that successful TIL-ACT is associated with an expansion of neoepitope-specific CD8+ T cells. FUNDING: NEYE Foundation; European Research Council; Lundbeck Foundation Fellowship; Carlsberg Foundation
The R136 star cluster dissected with Hubble Space Telescope/STIS. I. Far-ultraviolet spectroscopic census and the origin of He II lambda 1640 in young star clusters
We introduce a Hubble Space Telescope (HST)/Space Telescope Imaging Spectrograph (STIS) stellar census of R136a, the central ionizing star cluster of 30 Doradus. We present low resolution far-ultraviolet STIS spectroscopy of R136 using 17 contiguous 52 arcsec × 0.2 arcsec slits which together provide complete coverage of the central 0.85 parsec (3.4 arcsec). We provide spectral types of 90 per cent of the 57 sources brighter than mF555W = 16.0 mag within a radius of 0.5 parsec of R136a1, plus 8 additional nearby sources including R136b (O4 If/WN8). We measure wind velocities for 52 early-type stars from C IVλλ1548–51, including 16 O2–3 stars. For the first time, we spectroscopically classify all Weigelt and Baier members of R136a, which comprise three WN5 stars (a1–a3), two O supergiants (a5–a6) and three early O dwarfs (a4, a7, a8). A complete Hertzsprung–Russell diagram for the most massive O stars in R136 is provided, from which we obtain a cluster age of 1.5
+0.3−0.7
−0.7+0.3
Myr. In addition, we discuss the integrated ultraviolet spectrum of R136, and highlight the central role played by the most luminous stars in producing the prominent He II λ1640 emission line. This emission is totally dominated by very massive stars with initial masses above ∼100 M⊙. The presence of strong He II λ1640 emission in the integrated light of very young star clusters (e.g. A1 in NGC 3125) favours an initial mass function extending well beyond a conventional upper limit of 100 M⊙. We include montages of ultraviolet spectroscopy for Large Magellanic Cloud O stars in the appendix. Future studies in this series will focus on optical STIS medium resolution observations
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