92 research outputs found
Gene expression drives the evolution of dominance.
Dominance is a fundamental concept in molecular genetics and has implications for understanding patterns of genetic variation, evolution, and complex traits. However, despite its importance, the degree of dominance in natural populations is poorly quantified. Here, we leverage multiple mating systems in natural populations of Arabidopsis to co-estimate the distribution of fitness effects and dominance coefficients of new amino acid changing mutations. We find that more deleterious mutations are more likely to be recessive than less deleterious mutations. Further, this pattern holds across gene categories, but varies with the connectivity and expression patterns of genes. Our work argues that dominance arises as a consequence of the functional importance of genes and their optimal expression levels
Spatial-temporal patterns of ambient fine particulate matter (PM2.5) and black carbon (BC) pollution in Accra
Background: Sub-Saharan Africa (SSA) is rapidly urbanizing, and ambient air pollution has emerged as a major environmental health concern in SSA cities. Yet, effective air quality management is hindered by limited data. We deployed robust, low-cost and low-power devices in a large-scale measurement campaign and characterized within-city variations in fine particulate matter (PM2.5) and black carbon (BC) pollution in Accra, Ghana. Methods: Between April 2019 and June 2020, we measured weekly gravimetric (filter-based) and minute-by-minute PM2.5 concentrations at 146 unique locations, comprising of 10 fixed (~1-year) and 136 rotating (7-day) sites covering a range of land-use and source influences. Filters were weighed for mass, and light absorbance (10β5mβ1) of the filters was used as proxy for BC concentration. Year-long data at four fixed sites that were monitored in a previous study (2006-2007) were compared to assess change in PM2.5 concentrations. Results: The mean annual PM2.5 across the fixed sites ranged from 26 ΞΌg/m3 at a peri-urban site to 40 ΞΌg/m3 at commercial, business, and industrial (CBI) areas. CBI areas had the highest PM2.5 levels (mean: 37 ΞΌg/m3), followed by high-density residential neighborhoods (mean: 36 ΞΌg/m3), while peri-urban areas recorded the lowest (mean: 26 ΞΌg/m3). Both PM2.5 and BC levels were highest during the dry dusty Harmattan period (mean PM2.5: 89 ΞΌg/m3) compared to non-Harmattan season (mean PM2.5: 23 ΞΌg/m3). PM2.5 at all sites peaked at dawn and dusk, coinciding with morning and evening heavy traffic. We found about a ~50% reduction (71 vs 37 ΞΌg/m3) in mean annual PM2.5 concentrations when compared to measurements in 2006-2007 in Accra. Conclusion: Ambient PM2.5 concentrations in Accra may have plateaued at levels lower than those seen in large Asian megacities. However, levels are still 2- to 4-fold higher than the WHO guideline. Effective and equitable policies are needed to reduce pollution levels and protect public health
A dosimetric comparison of real-time adaptive and non-adaptive radiotherapy: A multi-institutional study encompassing robotic, gimbaled, multileaf collimator and couch tracking
AbstractPurposeA study of real-time adaptive radiotherapy systems was performed to test the hypothesis that, across delivery systems and institutions, the dosimetric accuracy is improved with adaptive treatments over non-adaptive radiotherapy in the presence of patient-measured tumor motion.Methods and materialsTen institutions with robotic(2), gimbaled(2), MLC(4) or couch tracking(2) used common materials including CT and structure sets, motion traces and planning protocols to create a lung and a prostate plan. For each motion trace, the plan was delivered twice to a moving dosimeter; with and without real-time adaptation. Each measurement was compared to a static measurement and the percentage of failed points for Ξ³-tests recorded.ResultsFor all lung traces all measurement sets show improved dose accuracy with a mean 2%/2mm Ξ³-fail rate of 1.6% with adaptation and 15.2% without adaptation (p<0.001). For all prostate the mean 2%/2mm Ξ³-fail rate was 1.4% with adaptation and 17.3% without adaptation (p<0.001). The difference between the four systems was small with an average 2%/2mm Ξ³-fail rate of <3% for all systems with adaptation for lung and prostate.ConclusionsThe investigated systems all accounted for realistic tumor motion accurately and performed to a similar high standard, with real-time adaptation significantly outperforming non-adaptive delivery methods
Accurate masses and radii of normal stars: modern results and applications
This paper presents and discusses a critical compilation of accurate,
fundamental determinations of stellar masses and radii. We have identified 95
detached binary systems containing 190 stars (94 eclipsing systems, and alpha
Centauri) that satisfy our criterion that the mass and radius of both stars be
known to 3% or better. To these we add interstellar reddening, effective
temperature, metal abundance, rotational velocity and apsidal motion
determinations when available, and we compute a number of other physical
parameters, notably luminosity and distance. We discuss the use of this
information for testing models of stellar evolution. The amount and quality of
the data also allow us to analyse the tidal evolution of the systems in
considerable depth, testing prescriptions of rotational synchronisation and
orbital circularisation in greater detail than possible before. The new data
also enable us to derive empirical calibrations of M and R for single (post-)
main-sequence stars above 0.6 M(Sun). Simple, polynomial functions of T(eff),
log g and [Fe/H] yield M and R with errors of 6% and 3%, respectively.
Excellent agreement is found with independent determinations for host stars of
transiting extrasolar planets, and good agreement with determinations of M and
R from stellar models as constrained by trigonometric parallaxes and
spectroscopic values of T(eff) and [Fe/H]. Finally, we list a set of 23
interferometric binaries with masses known to better than 3%, but without
fundamental radius determinations (except alpha Aur). We discuss the prospects
for improving these and other stellar parameters in the near future.Comment: 56 pages including figures and tables. To appear in The Astronomy and
Astrophysics Review. Ascii versions of the tables will appear in the online
version of the articl
A cluster randomised feasibility study of an adolescent incentive intervention to increase uptake of HPV vaccination.
BACKGROUND: Uptake of human papillomavirus (HPV) vaccination is suboptimal among some groups. We aimed to determine the feasibility of undertaking a cluster randomised controlled trial (RCT) of incentives to improve HPV vaccination uptake by increasing consent form return. METHODS: An equal-allocation, two-arm cluster RCT design was used. We invited 60 London schools to participate. Those agreeing were randomised to either a standard invitation or incentive intervention arm, in which Year 8 girls had the chance to win a Β£50 shopping voucher if they returned a vaccination consent form, regardless of whether consent was provided. We collected data on school and parent participation rates and questionnaire response rates. Analyses were descriptive. RESULTS: Six schools completed the trial and only 3% of parents opted out. The response rate was 70% for the girls' questionnaire and 17% for the parents'. In the intervention arm, 87% of girls returned a consent form compared with 67% in the standard invitation arm. The proportion of girls whose parents gave consent for vaccination was higher in the intervention arm (76%) than the standard invitation arm (61%). CONCLUSIONS: An RCT of an incentive intervention is feasible. The intervention may improve vaccination uptake but a fully powered RCT is needed.British Journal of Cancer advance online publication: 22 August 2017; doi:10.1038/bjc.2017.284 www.bjcancer.com
Group B <em>Streptococcus </em>engages an inhibitory siglec through sialic acid mimicry to blunt innate immune and inflammatory responses <em>in vivo</em>
Group B Streptococcus (GBS) is a common agent of bacterial sepsis and meningitis in newborns. The GBS surface capsule contains sialic acids (Sia) that engage Sia-binding immunoglobulin-like lectins (Siglecs) on leukocytes. Here we use mice lacking Siglec-E, an inhibitory Siglec of myelomonocytic cells, to study the significance of GBS Siglec engagement during in vivo infection. We found GBS bound to Siglec-E in a Sia-specific fashion to blunt NF-ΞΊB and MAPK activation. As a consequence, Siglec-E-deficient macrophages had enhanced pro-inflammatory cytokine secretion, phagocytosis and bactericidal activity against the pathogen. Following pulmonary or low-dose intravenous GBS challenge, Siglec-E KO mice produced more pro-inflammatory cytokines and exhibited reduced GBS invasion of the central nervous system. In contrast, upon high dose lethal challenges, cytokine storm in Siglec-E KO mice was associated with accelerated mortality. We conclude that GBS Sia mimicry influences host innate immune and inflammatory responses in vivo through engagement of an inhibitory Siglec, with the ultimate outcome of the host response varying depending upon the site, stage and magnitude of infection
Characteristics of the Mesophotic Megabenthic Assemblages of the Vercelli Seamount (North Tyrrhenian Sea)
The biodiversity of the megabenthic assemblages of the mesophotic zone of a Tyrrhenian seamount (Vercelli Seamount) is described using Remotely Operated Vehicle (ROV) video imaging from 100 m depth to the top of the mount around 61 m depth. This pinnacle hosts a rich coralligenous community characterized by three different assemblages: (i) the top shows a dense covering of the kelp Laminaria rodriguezii; (ii) the southern side biocoenosis is mainly dominated by the octocorals Paramuricea clavata and Eunicella cavolinii; while (iii) the northern side of the seamount assemblage is colonized by active filter-feeding organisms such as sponges (sometimes covering 100% of the surface) with numerous colonies of the ascidian Diazona violacea, and the polychaete Sabella pavonina. This study highlights, also for a Mediterranean seamount, the potential role of an isolated rocky peak penetrating the euphotic zone, to work as an aggregating structure, hosting abundant benthic communities dominated by suspension feeders, whose distribution may vary in accordance to the geomorphology of the area and the different local hydrodynamic conditions
Development of two novel high-throughput assays to quantify ubiquitylated proteins in cell lysates: application to screening of new anti-malarials
Epigenetic regulation of prostate cancer
Prostate cancer is a commonly diagnosed cancer in men and a leading cause of cancer deaths. Whilst the underlying mechanisms leading to prostate cancer are still to be determined, it is evident that both genetic and epigenetic changes contribute to the development and progression of this disease. Epigenetic changes involving DNA hypo- and hypermethylation, altered histone modifications and more recently changes in microRNA expression have been detected at a range of genes associated with prostate cancer. Furthermore, there is evidence that particular epigenetic changes are associated with different stages of the disease. Whilst early detection can lead to effective treatment, and androgen deprivation therapy has a high response rate, many tumours develop towards hormone-refractory prostate cancer, for which there is no successful treatment. Reliable markers for early detection and more effective treatment strategies are, therefore, needed. Consequently, there is a considerable interest in the potential of epigenetic changes as markers or targets for therapy in prostate cancer. Epigenetic modifiers that demethylate DNA and inhibit histone deacetylases have recently been explored to reactivate silenced gene expression in cancer. However, further understanding of the mechanisms and the effects of chromatin modulation in prostate cancer are required. In this review, we examine the current literature on epigenetic changes associated with prostate cancer and discuss the potential use of epigenetic modifiers for treatment of this disease
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