Ks1, an epithelial cell-specific gene, responds to early signals of head formation in Hydra

As a molecular marker for head specification in Hydra, we have cloned an epithelial cell-specific gene which responds to early signals of head formation. The gene, designated ks1, encodes a 217-amino acid protein lacking significant sequence similarity to any known protein. KS1 contains a N-terminal signal sequence and is rich in charged residues which are clustered in several domains. ks1 is expressed in tentacle-specific epithelial cells (battery cells) as well as in a small fraction of ectodermal epithelial cells in the gastric region subjacent to the tentacles. Treatment with the protein kinase C activator 12-O-tetradecanoylphorbol-13- acetate (TPA) causes a rapid increase in the level of ks1 mRNA in head-specific epithelial cells and also induces ectopic ks1 expression in cells of the gastric region. Sequence elements in the 5 ¢-flanking region of ks1 that are related to TPA-responsive elements may mediate the TPA inducibility of ks1 expression. The pattern of expression of ks1 suggests that a ligand-activated diacylglycerol second messenger system is involved in head-specific differentiation

Isospectral deformations of closed Riemannian manifolds with different scalar curvature

We construct the first examples of continuous families of isospectral Riemannian metrics that are not locally isometric on closed manifolds, more precisely, on $S^n\times T^m$, where $T^m$ is a torus of dimension $m\ge 2$ and $S^n$ is a sphere of dimension $n\ge 4$. These metrics are not locally homogeneous; in particular, the scalar curvature of each metric is nonconstant. For some of the deformations, the maximum scalar curvature changes during the deformation.Comment: amstex, 10 pages, no figure

Characterising the tumour morphological response to therapeutic intervention:an ex vivo model

In cancer, morphological assessment of histological tissue samples is a fundamental part of both diagnosis and prognosis. Image analysis offers opportunities to support that assessment through quantitative metrics of morphology. Generally, morphometric analysis is carried out on two dimensional tissue section data and so only represents a small fraction of any tumour. We present a novel application of three-dimensional (3D) morphometrics for 3D imaging data obtained from tumours grown in a culture model. Minkowski functionals, a set of measures that characterise geometry and topology in n-dimensional space, are used to quantify tumour topology in the absence of and in response to therapeutic intervention. These measures are used to stratify the morphological response of tumours to therapeutic intervention. Breast tumours are characterised by estrogen receptor (ER) status, human epidermal growth factor receptor (HER)2 status and tumour grade. Previously, we have shown that ER status is associated with tumour volume in response to tamoxifen treatment ex vivo. Here, HER2 status is found to predict the changes in morphology other than volume as a result of tamoxifen treatment ex vivo. Finally, we show the extent to which Minkowski functionals might be used to predict tumour grade.Minkowski functionals are generalisable to any 3D data set, including in vivo and cellular systems. This quantitative topological analysis can provide a valuable link among biomarkers, drug intervention and tumour morphology that is complementary to existing, non-morphological measures of tumour response to intervention and could ultimately inform patient treatment

Pilus distribution among lineages of group b <i>streptococcus</i>: an evolutionary and clinical perspective

&lt;b&gt;Background&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Group B Streptococcus (GBS) is an opportunistic pathogen in both humans and bovines. Epidemiological and phylogenetic analyses have found strains belonging to certain phylogenetic lineages to be more frequently associated with invasive newborn disease, asymptomatic maternal colonization, and subclinical bovine mastitis. Pilus structures in GBS facilitate colonization and invasion of host tissues and play a role in biofilm formation, though few large-scale studies have estimated the frequency and diversity of the three pilus islands (PIs) across diverse genotypes. Here, we examined the distribution of pilus islands (PI) 1, 2a and 2b among 295 GBS strains representing 73 multilocus sequence types (STs) belonging to eight clonal complexes. PCR-based RFLP was also used to evaluate variation in the genes encoding pilus backbone proteins of PI-2a and PI-2b.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt;&lt;p&gt;&lt;/p&gt; All 295 strains harbored one of the PI-2 variants and most human-derived strains contained PI-1. Bovine-derived strains lacked PI-1 and possessed a unique PI-2b backbone protein allele. Neonatal strains more frequently had PI-1 and a PI-2 variant than maternal colonizing strains, and most CC-17 strains had PI-1 and PI-2b with a distinct backbone protein allele. Furthermore, we present evidence for the frequent gain and loss of genes encoding certain pilus types.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt;&lt;p&gt;&lt;/p&gt; These data suggest that pilus combinations impact host specificity and disease presentation and that diversification often involves the loss or acquisition of PIs. Such findings have implications for the development of GBS vaccines that target the three pilus islands

Detecting Solar System Analogs through Joint Radial Velocity/Astrometric Surveys

Earth-mass exoplanets on year-long orbits and cool gas giants (CGG) on decade-long orbits lie at the edge of current detection limits. The Terra Hunting Experiment (THE) will take nightly radial velocity (RV) observations on HARPS3 of at least 40 bright nearby G and K dwarfs for 10 years, with a target 1$\sigma$ measurement error of $\sim$0.3 m/s, in search of exoplanets that are Earth-like in mass and temperature. However, RV observations can only provide minimum mass estimates, due to the mass-inclination degeneracy. Astrometric observations of these same stars, with sufficient precision, could break this degeneracy. Gaia will soon release $\sim$100-200 astrometric observations of the THE stars with a 10 year baseline and $\sim$34.2 $\mu$as 1$\sigma$ along-scan measurement error. The Nancy Grace Roman Space Telescope will be capable of precision astrometry using its wide field imager (target $\sim$5-20 $\mu$as 1$\sigma$ measurement error for bright stars) and could extend the astrometric observational baseline to $\sim$25 years. We simulate and model an observing program that combines data from these three telescopes. We find that (1) THE RVs and Gaia astrometry can detect Earth-like and CGG-like exoplanets around bright Sun-like stars at 10 parsecs and that (2) adding Roman astrometry improves the detection precision for CGG masses and periods by a factor up to $\sim$10 and $\sim$4, respectively. Such a survey could provide insight into the prevalence of Solar System analogs, exoplanet architectures reminiscent of the mass and orbital separation hierarchy of our Solar System, for the nearest Sun-like stars.Comment: 21 pages, 10 figures. Revised based on comments from anonymous reviewer at AAS Journals. Code available at https://github.com/dyahalomi/rv_and_astrometr

Prevalence of liver fluke (Fasciola hepatica) in wild Red Deer (Cervus elaphus): coproantigen ELISA is a practicable alternative to faecal egg counting for surveillance in remote populations

Red deer (Cervus elaphus) are hosts of liver fluke (Fasciola hepatica); yet, prevalence is rarely quantified in wild populations. Testing fresh samples from remote regions by faecal examination (FE) can be logistically challenging; hence, we appraise frozen storage and the use of a coproantigen ELISA (cELISA) for F. hepatica surveillance. We also present cELISA surveillance data for red deer from the Highlands of Scotland. Diagnoses in faecal samples (207 frozen, 146 fresh) were compared using a cELISA and by FE. For each storage method (frozen or fresh), agreement between the two diagnostics was estimated at individual and population levels, where population prevalence was stratified into cohorts (e.g., by sampling location). To approximate sensitivity and specificity, 65 post-slaughter whole liver examinations were used as a reference. At the individual level, FE and cELISA diagnoses agreed moderately (κfrozen = 0.46; κfresh = 0.51), a likely reflection of their underlying principles. At the population level, FE and cELISA cohort prevalence correlated strongly (Pearson’s R = 0.89, p &lt; 0.0001), reflecting good agreement on relative differences between cohort prevalence. In frozen samples, prevalence by cELISA exceeded FE overall (42.8% vs. 25.8%) and in 9/12 cohorts, alluding to differences in sensitivity; though, in fresh samples, no significant difference was found. In 959 deer tested by cELISA across the Scottish Highlands, infection prevalence ranged from 9.6% to 53% by sampling location. We highlight two key advantages of cELISA over FE: i) the ability to store samples long term (frozen) without apparent loss in diagnostic power; and ii) reduced labour and the ability to process large batches. Further evaluation of cELISA sensitivity in red deer, where a range of fluke burdens can be obtained, is desirable. In the interim, the cELISA is a practicable diagnostic for F. hepatica surveillance in red deer, and its application here has revealed considerable geographic, temporal, sex and age related differences in F. hepatica prevalence in wild Scottish Highland red deer

Informed consent in palliative care clinical trials: challenging but possible

Obtaining informed consent is a key protection that should be afforded universally to people using health services and the basis around which any participation in clinical trials is built. Randomized controlled effectiveness studies are necessary to answer key questions in hospice and palliative care, in order to help systematically improve the quality of care. In order to be properly generalizable, such trials need to have broad inclusion criteria to reflect the population most likely to be affected by the condition. The inclusion of patients who are seriously ill, and therefore potentially vulnerable, requires careful exploration of ethical and legal principles that underpin informed consent. Specific challenges in obtaining informed consent for randomised clinical trials (RCTs) in clinically unstable populations such as hospice and palliative care include higher rates of people with impaired cognitive capacity as well as interventional studies in clinical situations which may present as a sudden change in condition. None of these challenges is unique to hospice and palliative care research, but the combination and frequency with which they are encountered require systematic and considered solutions. This article outlines five different ethically valid consent approaches and discusses their applicability to hospice and palliative care research trials. These include: consent by the patient (at the time of enrolment, in advance of the study, or delayed until after the study has commenced); a proxy (or legally authorised representative); or a consent waiver. Increased use of the less traditional modes of informed consent may lead to greater participation rates in hospice and palliative care trials, thereby improving the evidence base more rapidly in part by better reflecting the population served and hence improving generalizability

Events in Early Life are Associated with Female Reproductive Ageing: A UK Biobank Study.

The available oocyte pool is determined before birth, with the majority of oocytes lost before puberty. We hypothesised that events occurring before birth, in childhood or in adolescence ('early-life risk factors') could influence the size of the oocyte pool and thus the timing of menopause. We included cross-sectional data from 273,474 women from the UK Biobank, recruited in 2006-2010 from across the UK. We analysed the association of early menopause with events occurring before adulthood in 11,781 cases (menopause aged under 45) and 173,641 controls (menopause/pre-menopausal at ≥ 45 years), in models controlling for potential confounding variables. Being part of a multiple birth was strongly associated with early menopause (odds ratio = 1.42, confidence interval: 1.11, 1.82, P = 8.0 × 10(-9), fully-adjusted model). Earlier age at menarche (odds ratio = 1.03, confidence interval: 1.01, 1.06, P = 2.5 × 10(-6)) and earlier year of birth were also associated with EM (odds ratio = 1.02, confidence interval: 1.00, 1.04, P = 8.0 × 10(-6)). We also confirmed previously reported associations with smoking, drinking alcohol, educational level and number of births. We identified an association between multiple births and early menopause, which connects events pre-birth, when the oocyte pool is formed, with reproductive ageing in later life.This research has been conducted using the UK Biobank Resource. This work was generously supported by a Wellcome Trust Institutional Strategic Support Award [WT097835MF to University of Exeter].This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/srep2471

Debating the effectiveness of marine protected areas

Increasing the size and number of marine protected areas (MPAs) is widely seen as a way to meet ambitious biodiversity and sustainable development goals. Yet, debate still exists on the effectiveness of MPAs in achieving ecological and societal objectives. Although the literature provides significant evidence of the ecological effects of MPAs within their boundaries, much remains to be learned about the ecological and social effects of MPAs on regional and seascape scales. Key to improving the effectiveness of MPAs, and ensuring that they achieve desired outcomes, will be better monitoring that includes ecological and social data collected inside and outside of MPAs. This can lead to more conclusive evidence about what is working, what is not, and why. Eight authors were asked to write about their experiences with MPA effectiveness. The authors were instructed to clearly define “effectiveness” and discuss the degree to which they felt MPAs had achieved or failed to be effective. Essays were exchanged among authors and each was invited to write a shorter “counterpoint.” The exercise shows that, while experiences are diverse, many authors found common ground regarding the role of MPAs in achieving conservation targets. This exchange of perspectives is intended to promote reflection, analysis, and dialogue as a means for improving MPA design, assessment, and integration with other conservation tools