To correlate the variable clinical features of oestrogen-receptor-positive breast cancer with somatic alterations, we studied pretreatment tumour biopsies accrued from patients in two studies of ...neoadjuvant aromatase inhibitor therapy by massively parallel sequencing and analysis. Eighteen significantly mutated genes were identified, including five genes (RUNX1, CBFB, MYH9, MLL3 and SF3B1) previously linked to haematopoietic disorders. Mutant MAP3K1 was associated with luminal A status, low-grade histology and low proliferation rates, whereas mutant TP53 was associated with the opposite pattern. Moreover, mutant GATA3 correlated with suppression of proliferation upon aromatase inhibitor treatment. Pathway analysis demonstrated that mutations in MAP2K4, a MAP3K1 substrate, produced similar perturbations as MAP3K1 loss. Distinct phenotypes in oestrogen-receptor-positive breast cancer are associated with specific patterns of somatic mutations that map into cellular pathways linked to tumour biology, but most recurrent mutations are relatively infrequent. Prospective clinical trials based on these findings will require comprehensive genome sequencing.
Plant-insect interactions are common and important in basic and applied biology. Trait and genetic variation can affect the outcome and evolution of these interactions, but the relative contributions ...of plant and insect genetic variation and how these interact remain unclear and are rarely subject to assessment in the same experimental context. Here, we address this knowledge gap using a recent host-range expansion onto alfalfa by the Melissa blue butterfly. Common garden rearing experiments and genomic data show that caterpillar performance depends on plant and insect genetic variation, with insect genetics contributing to performance earlier in development and plant genetics later. Our models of performance based on caterpillar genetics retained predictive power when applied to a second common garden. Much of the plant genetic effect could be explained by heritable variation in plant phytochemicals, especially saponins, peptides, and phosphatidyl cholines, providing a possible mechanistic understanding of variation in the species interaction. We find evidence of polygenic, mostly additive effects within and between species, with consistent effects of plant genotype on growth and development across multiple butterfly species. Our results inform theories of plant-insect coevolution and the evolution of diet breadth in herbivorous insects and other host-specific parasites.
Using a sample of 123 X-ray clusters and groups drawn from the XMM Cluster Survey first data release, we investigate the interplay between the brightest cluster galaxy (BCG), its black hole and the ...intracluster/group medium (ICM). It appears that for groups and clusters with a BCG likely to host significant active galactic nuclei (AGN) feedback, gas cooling dominates in those with T
X > 2 keV while AGN feedback dominates below. This may be understood through the subunity exponent found in the scaling relation we derive between the BCG mass and cluster mass over the halo mass range 1013 < M
500 < 1015 M⊙ and the lack of correlation between radio luminosity and cluster mass, such that BCG AGN in groups can have relatively more energetic influence on the ICM. The L
X-T
X relation for systems with the most massive BCGs, or those with BCGs co-located with the peak of the ICM emission, is steeper than that for those with the least massive and most offset, which instead follows self-similarity. This is evidence that a combination of central gas cooling and powerful, well fuelled AGN causes the departure of the ICM from pure gravitational heating, with the steepened relation crossing self-similarity at T
X= 2 keV. Importantly, regardless of their black hole mass, BCGs are more likely to host radio-loud AGN if they are in a massive cluster (T
X≳ 2 keV) and again co-located with an effective fuel supply of dense, cooling gas. This demonstrates that the most massive black holes appear to know more about their host cluster than they do about their host galaxy. The results lead us to propose a physically motivated, empirical definition of 'cluster' and 'group', delineated at 2 keV.
Wildlife surveys are central to the conservation and restoration management of wetland habitats; however, the often laborious and costly nature of traditional survey methods can constrain the spatial ...and temporal extent and replication of survey efforts.
Environmental DNA (eDNA) technologies now provide the opportunity to reduce some of these limitations, but applications in temporary and permanent freshwater marshes and meadows (herein referred to as ‘wetland habitats’) remain limited. This study investigates the performance of single‐time‐point eDNA surveys for characterizing fish, amphibian and bird assemblages of wetland habitats in south‐eastern Australia. Comparisons were made between coastal and inland wetlands, between wetlands of varying condition and between eDNA and traditional surveys.
Findings show that eDNA surveys can provide comprehensive descriptions of faunal assemblages associated with wetland habitats, with resolution similar to that provided by traditional survey approaches. Analyses also revealed significant differences in patterns of biodiversity between wetland types (coastal vs. inland) but not between wetland habitats varying in condition.
Overall, this study confirms that eDNA surveys provide a reliable option for undertaking wetland biodiversity assessments aimed at improving biodiversity data coverage for otherwise data deficient wetlands.
Herbivorous insects can defend themselves against pathogens via an immune response, which is influenced by the nutritional quality and phytochemistry of the host plant. However, it is unclear how ...these aspects of diet interact to influence the insect immune response and what role is played by ingested foliar microbes. We examined dietary protein, phytochemistry, and the caterpillar microbiome to understand variation in immune response of the Melissa blue butterfly, Lycaeides melissa. We also asked if these factors have host plant-specific effects by measuring L. melissa immune response when reared on a recently colonized exotic host plant (Medicago sativa) as compared to the immune response on an ancestral, native host (Astragalus canadensis). L. melissa did not experience immunological benefits directly related to consumption of the novel plant M. sativa. However, we did find negative, direct effects of phytochemical diversity and negative, direct effects of diet-derived microbial diversity on constitutive immune response for caterpillars fed M. sativa, as measured by phenoloxidase activity. Foliar protein did not directly influence the immune response, but did do so indirectly by increasing weight gain. Our results highlight the important effects of host diet on caterpillar physiology and raise the possibility that foliar microbiota, despite being rapidly passed through the gut, can affect the caterpillar immune response.
Background. A vaccine against Epstein-Barr virus (EBV) infection is in clinical trials. Up-to-date information on risk factors for EBV infection and infectious mononucleosis (IM) among young adults ...is required to inform a vaccination strategy. Methods. We carried out a prospective study on a cohort of university students. All EBV-seronegative students were asked to report symptoms of IM and were followed up 3 years later to undergo repeat EBV testing and to complete a lifestyle questionnaire. EBV typing was performed for these subjects, as well as for students who were EBV seropositive at enrollment and for additional students with IM. Results. A total of 510 students (25%) who took part in the study were EBV seronegative when they entered the university; 110 (46%) of these experienced seroconversion while at the university, 27 (25%) of whom developed IM. Penetrative sexual intercourse was a risk factor for EBV seroconversion (P = .004), but neither condom use nor oral sex significantly altered the rate of seroconversion. EBV type 1 was significantly overrepresented in IM, compared with silent seroconversion (P = .001). Conclusions. Our findings suggest that acquisition of EBV is enhanced by penetrative sexual intercourse, although transmission could occur through related sexual behaviors, such as “deep kissing.” We also found that EBV type 1 infection is significantly more likely to result in IM. Overall, the results suggest that a large EBV type 1 load acquired during sexual intercourse can rapidly colonize the B cell population and induce the exaggerated T cell response that causes IM. Thus, IM could, perhaps, be prevented with a vaccine that reduces the viral load without necessarily inducing sterile immunity.
The XMM Cluster Survey: X-ray analysis methodology Lloyd-Davies, E. J.; Romer, A. Kathy; Mehrtens, Nicola ...
Monthly notices of the Royal Astronomical Society,
November 2011, Letnik:
418, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The XMM Cluster Survey (XCS) is a serendipitous search for galaxy clusters using all publicly available data in the XMM-Newton Science Archive. Its main aims are to measure cosmological parameters ...and trace the evolution of X-ray scaling relations. In this paper we describe the data processing methodology applied to the 5776 XMM observations used to construct the current XCS source catalogue. A total of 3675 > 4σ cluster candidates with >50 background-subtracted X-ray counts are extracted from a total non-overlapping area suitable for cluster searching of 410 deg2. Of these, 993 candidates are detected with >300 background-subtracted X-ray photon counts, and we demonstrate that robust temperature measurements can be obtained down to this count limit. We describe in detail the automated pipelines used to perform the spectral and surface brightness fitting for these candidates, as well as to estimate redshifts from the X-ray data alone. A total of 587 (122) X-ray temperatures to a typical accuracy of <40 (<10) per cent have been measured to date. We also present the methodology adopted for determining the selection function of the survey, and show that the extended source detection algorithm is robust to a range of cluster morphologies by inserting mock clusters derived from hydrodynamical simulations into real XMMimages. These tests show that the simple isothermal β-profiles is sufficient to capture the essential details of the cluster population detected in the archival XMM observations. The redshift follow-up of the XCS cluster sample is presented in a companion paper, together with a first data release of 503 optically confirmed clusters.
The XMM Cluster Survey (XCS) is a serendipitous search for galaxy clusters using all publicly available data in the XMM-Newton Science Archive. Its main aims are to measure cosmological parameters ...and trace the evolution of X-ray scaling relations. In this paper we present the first data release from the XMM Cluster Survey (XCS-DR1). This consists of 503 optically confirmed, serendipitously detected, X-ray clusters. Of these clusters, 256 are new to the literature and 357 are new X-ray discoveries. We present 463 clusters with a redshift estimate (0.06 < z < 1.46), including 261 clusters with spectroscopic redshifts. The remainder have photometric redshifts. In addition, we have measured X-ray temperatures (T
X) for 401 clusters (0.4 < T
X < 14.7 keV). We highlight seven interesting subsamples of XCS-DR1 clusters: (i) 10 clusters at high redshift (z > 1.0, including a new spectroscopically confirmed cluster at z= 1.01); (ii) 66 clusters with high T
X (>5 keV); (iii) 130 clusters/groups with low T
X (<2 keV); (iv) 27 clusters with measured T
X values in the Sloan Digital Sky Survey (SDSS) 'Stripe 82' co-add region; (v) 77 clusters with measured T
X values in the Dark Energy Survey region; (vi) 40 clusters detected with sufficient counts to permit mass measurements (under the assumption of hydrostatic equilibrium); (vii) 104 clusters that can be used for applications such as the derivation of cosmological parameters and the measurement of cluster scaling relations. The X-ray analysis methodology used to construct and analyse the XCS-DR1 cluster sample has been presented in a companion paper, Lloyd-Davies et al.
Background
Long‐term follow‐up for clinician–scientist training programs is sparse. We describe the outcomes of clinician–scientist scholars in the National Heart Lung and Blood Institute (NHLBI) K12 ...program in emergency care research up to 8.7 years after matriculation in the program.
Methods
This was a cohort study of faculty clinician–scientist scholars enrolled in a NHLBI K12 research training program at 6 sites across the US, with median follow‐up 7.7 years (range 5.7–8.7 years) from the date of matriculation. Scholars completed electronic surveys in 2017 and 2019, with the 2019 survey collecting information for their current work setting, percent time for research, and grant funding from all sources. We used NIH RePorter and online resources to verify federal grants through March 2021. The primary outcome was a funded career development award (CDA) or research project grant (RPG) where the scholar was principal investigator. We included funding from all federal sources and national foundations.
Results
There were 43 scholars, including 16 (37%) women. Over the follow‐up period, 32 (74%) received an individual CDA or RPG, with a median of 36 months (range 9–83 months) after entering the program. Of the 43 scholars, 23 (54%) received a CDA and 22 (51%) received an RPG, 7 (16%) of which were R01s. Of the 23 scholars who received a CDA, 13 (56%) subsequently had an RPG funded. Time to CDA or RPG did not differ by sex (women vs. men log‐rank test p = 0.27) or specialty training (emergency medicine versus other specialties, p = 0.59).
Conclusions
After 7 years of follow‐up for this NHLBI K12 emergency care research training program, three quarters of clinician–scientist scholars had obtained CDA or RPG funding, with no notable differences by sex or clinical training.
The degree of influence that the environment and mass have on the stellar populations of early-type galaxies is uncertain. In this paper, we present the results of a spectroscopic analysis of the ...stellar populations of early-type galaxies aimed at addressing this question. The sample of galaxies is drawn from four clusters, with 〈z〉= 0.04, and their surrounding structure extending to ∼10R
vir. We find that the distributions of the absorption-line strengths and the stellar population parameters, age, metallicity and α-element abundance ratio, do not differ significantly between the clusters and their outskirts, but the tight correlations found between these quantities and the velocity dispersion within the clusters are weaker in their outskirts. All three stellar population parameters of cluster galaxies are positively correlated with the velocity dispersion. Galaxies in clusters form a homogeneous class of objects that have similar distributions of line-strengths and stellar population parameters, and follow similar scaling relations, regardless of the cluster richness or morphology. We estimate the intrinsic scatter of the Gaussian distribution of metallicities to be 0.3 dex, while that of the α-element abundance ratio is 0.07 dex. The e-folding time of the exponential distribution of galaxy ages is estimated to be 900 Myr. The intrinsic scatters of the metallicity and α-element abundance ratio distributions can almost entirely be accounted for by the correlations with the velocity dispersion and the intrinsic scatter about these relations. This implies that the galaxy mass plays a major role in determining its stellar population.
PDF
