Tumor site immune markers associated with risk for subsequent basal cell carcinomas.

BackgroundBasal cell carcinoma (BCC) tumors are the most common skin cancer and are highly immunogenic.ObjectiveThe goal of this study was to assess how immune-cell related gene expression in an initial BCC tumor biopsy was related to the appearance of subsequent BCC tumors.Materials and methodsLevels of mRNA for CD3ε (a T-cell receptor marker), CD25 (the alpha chain of the interleukin (IL)-2 receptor expressed on activated T-cells and B-cells), CD68 (a marker for monocytes/macrophages), the cell surface glycoprotein intercellular adhesion molecule-1 (ICAM-1), the cytokine interferon-γ (IFN-γ) and the anti-inflammatory cytokine IL-10 were measured in BCC tumor biopsies from 138 patients using real-time PCR.ResultsThe median follow-up was 26.6 months, and 61% of subjects were free of new BCCs two years post-initial biopsy. Patients with low CD3ε CD25, CD68, and ICAM-1 mRNA levels had significantly shorter times before new tumors were detected (p = 0.03, p = 0.02, p = 0.003, and p = 0.08, respectively). Furthermore, older age diminished the association of mRNA levels with the appearance of subsequent tumors.ConclusionsOur results show that levels of CD3ε, CD25, CD68, and ICAM-1 mRNA in BCC biopsies may predict risk for new BCC tumors

Bringing bioinformatics to schools with the 4273pi project

The work was supported by the Science and Technology Facilities Council (STFC) under Grants STFC ST/R000328/1 (including salary to S.A.B., D.B., H.P., T.R.M. and non-salary costs) and STFC ST/T000872/1 (including salary to S.A.B., D.B., K.C., T.R.M. and non-salary costs), the Darwin Trust of Edinburgh (https://darwintrust.bio.ed.ac.uk; including salary to S.A.B. and H.P. and non-salary costs), the Wellcome Trust-University of Edinburgh Institutional Strategic Support Fund under Wellcome Trust Grant number 204804/Z/16/Z (salary to H.P.), a Public Engagement with Genetics Tier 2 Grant from the Genetics Society (https://genetics.org.uk; non-salary costs), the Natural Environment Research Council (NERC) under Grant NE/P000592/1 (including salary to N.C. and M.G.R. and non-salary costs), the Biotechnology and Biological Sciences Research Council (BBSRC) under Grant BB/S018506/1 (including salary to F.A. and non-salary costs), the School of Biological Sciences at the University of Edinburgh (https://www.ed.ac.uk/biology; including salary to S.A.B. and H.P. and non-salary costs) and its Institute of Evolutionary Biology (https://www.ed.ac.uk/biology/evolutionary-biology; non-salary costs), the Access for Rural Communities project (ARC) at University of St Andrews (https://www.st-andrews.ac.uk/study/access/projects/arc; non-salary costs) and the Engineering and Physical Sciences Research Council (EPSRC) under Grant EP/V52038X/1 (including salary to S.A.B. and non-salary costs). E.W.J.W. is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society [208779/Z/17/Z] (including salary to E.W.J.W.).Over the last few decades, the nature of life sciences research has changed enormously, generating a need for a workforce with a variety of computational skills such as those required to store, manage, and analyse the large biological datasets produced by next-generation sequencing. Those with such expertise are increasingly in demand for employment in both research and industry. Despite this, bioinformatics education has failed to keep pace with advances in research. At secondary school level, computing is often taught in isolation from other sciences, and its importance in biological research is not fully realised, leaving pupils unprepared for the computational component of Higher Education and, subsequently, research in the life sciences. The 4273pi Bioinformatics at School project (https://4273pi.org) aims to address this issue by designing and delivering curriculum-linked, hands-on bioinformatics workshops for secondary school biology pupils, with an emphasis on equitable access. So far, we have reached over 180 schools across Scotland through visits or teacher events, and our open education resources are used internationally. Here, we describe our project, our aims and motivations, and the practical lessons we have learned from implementing a successful bioinformatics education project over the last 5 years.Publisher PDFPeer reviewe

Lung injury-induced skeletal muscle wasting in aged mice is linked to alterations in long chain fatty acid metabolism

Older patients are more likely to acquire and die from acute respiratory distress syndrome (ARDS) and muscle weakness may be more clinically significant in older persons. Recent data implicate muscle ring finger protein 1 (MuRF1) in lung injury-induced skeletal muscle atrophy in young mice and identify an alternative role for MuRF1 in cardiac metabolism regulation through inhibition of fatty acid oxidation

Social effects on age-related and sex-specific immune cell profiles in a wild mammal

Evidence for age-related changes in innate and adaptive immune responses is increasing in wild populations. Such changes have been linked to fitness, and knowledge of the factors driving immune response variation is important for understanding the evolution of immunity. Age-related changes in immune profiles may be owing to factors such as immune system development, sex-specific behaviour and responses to environmental conditions. Social environments may also contribute to variation in immunological responses, for example, through transmission of pathogens and stress arising from resource and mate competition. Yet, the impact of the social environment on age-related changes in immune cell profiles is currently understudied in the wild. Here, we tested the relationship between leukocyte cell composition (proportion of neutrophils and lymphocytes [innate and adaptive immunity, respectively] that were lymphocytes) and age, sex and group size in a wild population of European badgers (Meles meles). We found that the proportion of lymphocytes in early life was greater in males in smaller groups compared to larger groups, but with a faster age-related decline in smaller groups. By contrast, the proportion of lymphocytes in females was not significantly related to age or group size. Our results provide evidence of sex-specific age-related changes in immune cell profiles in a wild mammal, which are influenced by the social environment

Continuous Equilibrium in Affine and Information-Based Capital Asset Pricing Models

We consider a class of generalized capital asset pricing models in continuous time with a finite number of agents and tradable securities. The securities may not be sufficient to span all sources of uncertainty. If the agents have exponential utility functions and the individual endowments are spanned by the securities, an equilibrium exists and the agents' optimal trading strategies are constant. Affine processes, and the theory of information-based asset pricing are used to model the endogenous asset price dynamics and the terminal payoff. The derived semi-explicit pricing formulae are applied to numerically analyze the impact of the agents' risk aversion on the implied volatility of simultaneously-traded European-style options.Comment: 24 pages, 4 figure

Shear-Mediated Dilation of the Internal Carotid Artery Occurs Independent of Hypercapnia.

Evidence for shear stress as a regulator of carotid artery dilation in response to increased arterial carbon dioxide was recently demonstrated in humans during sustained elevations in CO2 (hypercapnia); however, the relative contributions of CO2 and shear stress to this response remains unclear. We examined the hypothesis that, following a 30-second transient increase in arterial CO2 tension and consequent increase in internal carotid artery shear stress, internal carotid artery diameter would increase, indicating shear-mediated dilation, in the absence of concurrent hypercapnia. In 27 healthy participants the partial pressures of end-tidal O2 and CO2, ventilation (pneumotachography), blood pressure (finger-photoplethysmography), heart-rate (electrocardiogram), internal carotid artery flow, diameter and shear stress (high resolution duplex ultrasound) and middle cerebral artery blood velocity (transcranial Doppler) were measured during 4-minute steady state and transient 30-second hypercapnic tests (both +9mmHg CO2). Internal carotid artery dilation was lower in the transient, compared to the steady state hypercapnia (3.3±1.9% vs. 5.3±2.9%, respectively; P<0.03). Increases in internal carotid artery shear stress preceded increases in diameter in both the transient (time: 16.8±13.2s vs. 59.4±60.3s; P<0.01) and steady state (time: 18.2±14.2s vs. 110.3±79.6s; P<0.01) tests. Internal carotid artery dilation was positively correlated with shear rate area under the curve in the transient (r(2)=0.44; P<0.01), but not steady state (r(2)=0.02; P=0.53) trial. Collectively, these results suggest that hypercapnia induces shear-mediated dilation of the internal carotid artery in humans. This study further promotes the application and development of hypercapnia as a clinical strategy for the assessment of cerebrovascular vasodilatory function and health in humans

Rapid mechanosensitive migration and dispersal of newly divided mesenchymal cells aid their recruitment into dermal condensates

Embryonic mesenchymal cells are dispersed within an extracellular matrix but can coalesce to form condensates with key developmental roles. Cells within condensates undergo fate and morphological changes and induce cell fate changes in nearby epithelia to produce structures including hair follicles, feathers, or intestinal villi. Here, by imaging mouse and chicken embryonic skin, we find that mesenchymal cells undergo much of their dispersal in early interphase, in a stereotyped process of displacement driven by 3 hours of rapid and persistent migration followed by a long period of low motility. The cell division plane and the elevated migration speed and persistence of newly born mesenchymal cells are mechanosensitive, aligning with tissue tension, and are reliant on active WNT secretion. This behaviour disperses mesenchymal cells and allows daughters of recent divisions to travel long distances to enter dermal condensates, demonstrating an unanticipated effect of cell cycle subphase on core mesenchymal behaviour

Notes towards a history of Khoi literature

This article puts forward a revisionist history of Khoi literature, and also presents a number of translated Khoi narratives that have not been available in English before. Compared to the large volume of Bushman literature and scholarship, there has been very little Khoi literature and engagement with it, and an argument is presented to account for this gap in South African cultural history. Until now, the major source of Khoi literature was Wilhelm Bleek’s Reynard the Fox in South Africa (1864), and this text is critically interrogated as a limiting version of Khoi orature. An alternative corpus of Khoi narratives is presented that was originally published in Leonard Schultze’s Aus Namaland und Kalahari (1907).Web of Scienc

Reference Intervals in Healthy Adult Ugandan Blood Donors and Their Impact on Conducting International Vaccine Trials

BACKGROUND: Clinical trials are increasingly being conducted internationally. In order to ensure enrollment of healthy participants and proper safety evaluation of vaccine candidates, established reference intervals for clinical tests are required in the target population. METHODOLOGY/PRINCIPAL FINDINGS: We report a reference range study conducted in Ugandan adult blood bank donors establishing reference intervals for hematology and clinical chemistry parameters. Several differences were observed when compared to previously established values from the United States, most notably in neutrophils and eosinophils. CONCLUSIONS/SIGNIFICANCE: In a recently conducted vaccine trial in Uganda, 31 percent (n = 69) of volunteers screened (n = 223) were excluded due to hematologic abnormalities. If local reference ranges had been employed, 83% of those screened out due to these abnormalities could have been included in the study, drastically reducing workload and cost associated with the screening process. In addition, toxicity tables used in vaccine and drug trial safety evaluations may need adjustment as some clinical reference ranges determined in this study overlap with grade 1 and grade 2 adverse events