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Tryptophan metabolism and its relationship with immune activation, depression, and neurocognitive impairment among HIV-infected individuals
Ecological and genetic determinants of plasmid distribution in Escherichia coli.
Bacterial plasmids are important carriers of virulence and antibiotic resistance genes. Nevertheless, little is known of the determinants of plasmid distribution in bacterial populations. Here the factors affecting the diversity and distribution of the large plasmids of Escherichia coli were explored in cattle grazing on semi-natural grassland, a set of populations with low frequencies of antibiotic resistance genes. Critically, the population genetic structure of bacterial hosts was chararacterized. This revealed structured E. coli populations with high diversity between sites and individuals but low diversity within cattle hosts. Plasmid profiles, however, varied considerably within the same E. coli genotype. Both ecological and genetic factors affected plasmid distribution: plasmid profiles were affected by site, E. coli diversity, E. coli genotype and the presence of other large plasmids. Notably 3/26 E. coli serotypes accounted for half the observed plasmid-free isolates indicating that within species variation can substantially affect carriage of the major conjugative plasmids. The observed population structure suggest that most of the opportunities for within species plasmid transfer occur between different individuals of the same genotype and support recent experimental work indicating that plasmid-host coevolution, and epistatic interactions on fitness costs are likely to be important in determining occupancy.FM was supported by a joint Royal Holloway and Animal Health and Veterinary Laboratories Agency studentship, BR by a NERC Advanced Research fellowship
z ∼ 2–9 Galaxies Magnified by the Hubble Frontier Field Clusters. II. Luminosity Functions and Constraints on a Faint-end Turnover
We present new determinations of the rest-UV luminosity functions (LFs) at z = 2–9 to extremely low luminosities (>−14 mag) from a sample of >2500 lensed galaxies found behind the Hubble Frontier Fields (HFF) clusters. For the first time, we present faint-end slope results from lensed samples that are fully consistent with blank-field results over the redshift range z = 2–9, while reaching to much lower luminosities than possible from the blank-field studies. Combining the deep lensed sample with the large blank-field samples allows us to set tight constraints on the faint-end slope α of the z = 2–9 UV LFs and its evolution. We find a smooth flattening in α from −2.28 ± 0.10 (z = 9) to −1.53 ± 0.03 (z = 2) with cosmic time (dα/dz = −0.11 ± 0.01), fully consistent with dark matter halo buildup. We utilize these new results to present new measurements of the evolution in the UV luminosity density ρ
UV
brighter than −13 mag from z ∼ 9 to z ∼ 2. Accounting for the star formation rate (SFR) densities to faint luminosities implied by our LF results, we find that unobscured star formation dominates the SFR density at z ≳ 4, with obscured star formation dominant thereafter. Having shown we can quantify the faint-end slope α of the LF accurately with our lensed HFF samples, we also quantify the apparent curvature in the shape of the UV LF through a curvature parameter δ. The constraints on the curvature δ strongly rule out the presence of a turn-over brighter than −13.1 mag at z ∼ 3, −14.3 mag at z ∼ 6, and −15.5 mag at all other redshifts between z ∼ 9 and z ∼ 2
Blockade of Immunosuppressive Cytokines Restores NK Cell Antiviral Function in Chronic Hepatitis B Virus Infection
NK cells are enriched in the liver, constituting around a third of intrahepatic lymphocytes. We have previously demonstrated that they upregulate the death ligand TRAIL in patients with chronic hepatitis B virus infection (CHB), allowing them to kill hepatocytes bearing TRAIL receptors. In this study we investigated whether, in addition to their pathogenic role, NK cells have antiviral potential in CHB. We characterised NK cell subsets and effector function in 64 patients with CHB compared to 31 healthy controls. We found that, in contrast to their upregulated TRAIL expression and maintenance of cytolytic function, NK cells had a markedly impaired capacity to produce IFN-gamma in CHB. This functional dichotomy of NK cells could be recapitulated in vitro by exposure to the immunosuppressive cytokine IL-10, which was induced in patients with active CHB. IL-10 selectively suppressed NK cell IFN-gamma production without altering cytotoxicity or death ligand expression. Potent antiviral therapy reduced TRAIL-expressing CD56 bright NK cells, consistent with the reduction in liver inflammation it induced; however, it was not able to normalise IL-10 levels or the capacity of NK cells to produce the antiviral cytokine IFN-gamma. Blockade of IL-10 +/- TGF-beta restored the capacity of NK cells from both the periphery and liver of patients with CHB to produce IFN-gamma, thereby enhancing their non-cytolytic antiviral capacity. In conclusion, NK cells may be driven to a state of partial functional tolerance by the immunosuppressive cytokine environment in CHB. Their defective capacity to produce the antiviral cytokine IFN-gamma persists in patients on antiviral therapy but can be corrected in vitro by IL-10+/- TGF-beta blockade
Mean Hα+[N ii]+[S ii] EW inferred for star-forming galaxies at z ∼ 5.1–5.4 using high-quality Spitzer /IRAC photometry
Recent Spitzer/InfraRed Array Camera (IRAC) photometric observations have revealed that rest-frame optical emission lines contribute significantly to the broad-band fluxes of high-redshift galaxies. Specifically, in the narrow redshift range z ∼ 5.1–5.4 the [3.6]–[4.5] colour is expected to be very red, due to contamination of the 4.5 μm band by the dominant Hα line, while the 3.6 μm filter is free of nebular emission lines. We take advantage of new reductions of deep Spitzer/IRAC imaging over the Great Observatories Origins Deep Survey-North+South fields (Labbé et al. 2015) to obtain a clean measurement of the mean Hα equivalent width (EW) from the [3.6]–[4.5] colour in the redshift range z = 5.1–5.4. The selected sources either have measured spectroscopic redshifts (13 sources) or lie very confidently in the redshift range z = 5.1–5.4 based on the photometric redshift likelihood intervals (11 sources). Our zphot = 5.1–5.4 sample and zspec = 5.10–5.40 spectroscopic sample have a mean [3.6]–[4.5] colour of 0.31 ± 0.05 and 0.35 ± 0.07 mag, implying a rest-frame EW (Hα+[N II]+[S II]) of 665 ± 53 and 707 ± 74 Å, respectively, for sources in these samples. These values are consistent albeit slightly higher than derived by Stark et al. at z ∼ 4, suggesting an evolution to higher values of the Hα+[N II]+[S II] EW at z > 2. Using the 3.6 μm band, which is free of emission line contamination, we perform robust spectral energy distribution fitting and find a median specific star formation rate of sSFR = 17+2−517−5+2 Gyr−1, 7+1−2×7−2+1× higher than at z ∼ 2. We find no strong correlation (<2σ) between the Hα+[N II]+[S II] EW and the stellar mass of sources. Before the advent of JWST, improvements in these results will come through an expansion of current spectroscopic samples and deeper Spitzer/IRAC measurements
Phenomenology and Cosmology of an Electroweak Pseudo-Dilaton and Electroweak Baryons
In many strongly-interacting models of electroweak symmetry breaking the
lowest-lying observable particle is a pseudo-Goldstone boson of approximate
scale symmetry, the pseudo-dilaton. Its interactions with Standard Model
particles can be described using a low-energy effective nonlinear chiral
Lagrangian supplemented by terms that restore approximate scale symmetry,
yielding couplings of the pseudo-dilaton that differ from those of a Standard
Model Higgs boson by fixed factors. We review the experimental constraints on
such a pseudo-dilaton in light of new data from the LHC and elsewhere. The
effective nonlinear chiral Lagrangian has Skyrmion solutions that may be
identified with the `electroweak baryons' of the underlying
strongly-interacting theory, whose nature may be revealed by the properties of
the Skyrmions. We discuss the finite-temperature electroweak phase transition
in the low-energy effective theory, finding that the possibility of a
first-order electroweak phase transition is resurrected. We discuss the
evolution of the Universe during this transition and derive an
order-of-magnitude lower limit on the abundance of electroweak baryons in the
absence of a cosmological asymmetry, which suggests that such an asymmetry
would be necessary if the electroweak baryons are to provide the cosmological
density of dark matter. We revisit estimates of the corresponding
spin-independent dark matter scattering cross section, with a view to direct
detection experiments.Comment: 34 pages, 4 figures, additional references adde
Mass extinctions and supernova explosions
A nearby supernova (SN) explosion could have negatively influenced life on
Earth, maybe even been responsible for mass extinctions. Mass extinction poses
a significant extinction of numerous species on Earth, as recorded in the
paleontologic, paleoclimatic, and geological record of our planet. Depending on
the distance between the Sun and the SN, different types of threats have to be
considered, such as ozone depletion on Earth, causing increased exposure to the
Sun's ultraviolet radiation, or the direct exposure of lethal x-rays. Another
indirect effect is cloud formation, induced by cosmic rays in the atmosphere
which result in a drop in the Earth's temperature, causing major glaciations of
the Earth. The discovery of highly intensive gamma ray bursts (GRBs), which
could be connected to SNe, initiated further discussions on possible
life-threatening events in Earth's history. The probability that GRBs hit the
Earth is very low. Nevertheless, a past interaction of Earth with GRBs and/or
SNe cannot be excluded and might even have been responsible for past extinction
events.Comment: Chapter for forthcoming book: Handbook of Supernovae, P. Murdin and
A. Alsabeti (eds.), Springer International Publishing (in press
Reproductive Care of Childhood and Adolescent Cancer Survivors: A 12-Year Evaluation
Background: Reproductive complications for cancer survivors are identified as one of the top unmet needs in the survivorship period. However, current models of cancer care do not routinely incorporate reproductive follow-up for pediatric or adolescent cancer patients. The Kids Cancer Centre has had a one-stop survivorship clinic that includes the attendance of a gynecologist and fertility specialist for the last 12 years. Methodology: To inform the future development of our reproductive survivorship care, we reviewed the reproductive care our survivorship clinic has provided over a 12-year period, specifically reviewing the electronic and patient records to collect information on the demographics of the patients who used the service and their gonadotoxic risk and associated fertility treatment, their documented reproductive needs and concerns, and information provided on preventative reproductive advice and screening. Main Results: Two hundred seventy-eight patients were seen (397 consultations) for advice and management of reproductive issues, including 189 female patients (68.0%). Survivors' median age at follow-up was 25.0 years (range = 6-50), on average 19.2 years from their primary diagnosis (range = 3-46). The reviewed data had five overarching themes (fertility care, hormone dysfunction, sexual dysfunction, fertility-related psychological distress due to reproductive concerns, and preventative health care), although each theme had a number of components. Patients had on average 2.5 reproductive concerns documented per consultation (range 1-5). The three most commonly documented symptoms or concerns at the initial consultation related to fertility status (43.9%), endocrine dysfunction (35.3%), and contraception advice (32.4%). In patients younger than 25 years, documented discussions were predominately about endocrine dysfunction, fertility status, and contraception, while dominant themes for 26-35-year olds were fertility status, reproductive-related health prevention strategies, contraception, and endocrine dysfunction. Survivors 36-45 years of age prioritized fertility status, pregnancy, and contraception. Fertility preservation (FP) (p = 0.05), preventative health strategies (p = 0.001), and contraception advice (p < 0.001) were more commonly discussed by females than males. Conclusion: Young cancer survivors have multiple ongoing reproductive concerns that change over time. Assessing survivors' reproductive potential following cancer treatment is important as it gives patients who have not completed their family planning an opportunity to explore a possible window to FP or Assisted Reproductive Treatment. Our data can assist in informing the model of care for a reproductive survivorship clinic
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