Quantifying cellular dynamics in mice using a novel fluorescent division reporter system

The dynamics of cell populations are frequently studied in vivo using pulse-chase DNA labeling techniques. When combined with mathematical models, the kinetic of label uptake and loss within a population of interest then allows one to estimate rates of cell production and turnover through death or onward differentiation. Here we explore an alternative method of quantifying cellular dynamics, using a cell fate-mapping mouse model in which dividing cells can be induced to constitutively express a fluorescent protein, using a Ki67 reporter construct. We use a pulse-chase approach with this reporter mouse system to measure the lifespans and division rates of naive CD4 and CD8 T cells using a variety of modeling approaches, and show that they are all consistent with estimates derived from other published methods. However we propose that to obtain unbiased parameter estimates and full measures of their uncertainty one should simultaneously model the timecourses of the frequencies of labeled cells within both the population of interest and its precursor. We conclude that Ki67 reporter mice provide a promising system for modeling cellular dynamics

Current Fertility Status Does Not Predict Sociosexual Attitudes and Desires in Normally Ovulating Women

Previous research has found that women at peak fertility show greater interest in extra-pair sex. However, recent replications have failed to detect this effect. In this study, we add to this ongoing debate by testing whether sociosexuality (the willingness to have sex in the absence of commitment) is higher in women who are at peak fertility. A sample of normally ovulating women (N = 773) completed a measure of sociosexuality and had their current fertility status estimated using the backward counting method. Contrary to our hypothesis, current fertility was unrelated to sociosexual attitudes and desires, even when relationship status was included as a moderator. These findings raise further doubts about the association between fertility and desire for extra-pair sex

Socio-legal studies and the humanities – law, interdisciplinarity and integrity

publication-status: Publishedtypes: ArticleInaugural lecture delivered at the SLSA Socio-Legal Studies and the Humanities Conference, at the Institute of Advanced Legal Studies, London, 5 November 2008.Published version; Published online by Cambridge University Press. Copyright © Cambridge University Press, 2009. Available online at http://journals.cambridge.org/This paper was delivered as a plenary lecture, designed to respond to the one-day special conference focus upon links between socio-legal studies and the humanities. The paper focuses in particular upon the relationship between law and the humanities. It may be argued that the role of empirically sourced socio-legal research is well accepted, given its tangible utility in terms of producing hard data which can inform and transform policy perspectives. However, scholarly speculation about the relationship between law and the humanities ranges from the indulgent to the hostile. In particular, legal scholars aligning themselves as ‘black letter’ commentators express strong opinions about such links, suggesting that scholarship purporting to establish links between the two fields is essentially spurious, bearing in mind the purposive role of law as a problem-solving mechanism. The paper sets out to challenge such assertions, indicating the natural connections between the two fields and the philosophical necessity of continued interaction, given the fact that certain aspects of human experience and nature cannot be plumbed by doctrine or empiricism or even by combinations of the two. Law must be understood to stand at the nexus of human experience, in a relationship of integrity, where the word is understood to mean both morally principled and culturally integrated. In particular, the development of human qualities, of character and moral sensibility informing normative values – and, ultimately, engagement with the world of law – is a process of subtle cultural as well as psychological significance, and may benefit from interrogation deriving from the wider fields of human discourse

Choice of resident costimulatory molecule can influence cell fate in human naïve CD4+ T cell differentiation

With antigen stimulation, naïve CD4+ T cells differentiate to several effector or memory cell populations, and cytokines contribute to differentiation outcome. Several proteins on these cells receive costimulatory signals, but a systematic comparison of their differential effects on naïve T cell differentiation has not been conducted. Two costimulatory proteins, CD28 and ICAM-1, resident on human naïve CD4+ T cells were compared for participation in differentiation. Under controlled conditions, and with no added cytokines, costimulation through either CD3+CD28 or CD3+ICAM-1 induced differentiation to T effector and T memory cells. In contrast, costimulation through CD3+ICAM-1 induced differentiation to Treg cells whereas costimulation through CD3+CD28 did not

The Nature of the Strong 24 micron Spitzer Source J222557+601148: Not a Young Galactic Supernova Remnant

The nebula J222557+601148, tentatively identified by Morris et al. (2006) as a young Galactic supernova remnant (SNR) from Spitzer Galactic First Look Survey images and a follow-up mid-infrared spectrum, is unlikely to be a SNR remnant based on Halpha, [O III], [S II] images and low dispersion optical spectra. The object is seen in Halpha and [O III] 5007 images as a faint, roughly circular ring nebula with dimensions matching that seen in 24 micron Spitzer images. Low-dispersion optical spectra show it to have narrow Halpha and [N II] 6548, 6583 line emissions with no evidence of broad or high-velocity (v > 300 km/s) line emissions. The absence of any high-velocity optical features, the presence of relatively strong [N II] emissions, a lack of detected [S II] emission which would indicate the presence of shock-heated gas, plus no coincident X-ray or nonthermal radio emissions indicate the nebula is unlikely to be a SNR, young or old. Instead, it is likely a faint, high-excitation planetary nebula (PN) as its elliptical morphology would suggest, lying at a distance of approximately 2 - 3 kpc with unusual but not extraordinary mid-IR colors and spectrum. We have identified a m_r' = 22.4 +/- 0.2 star as a PN central star candidate.Comment: 6 pages, 3 figures, accepted to The Astronomical Journa

Vertical structure and physical processes of the Madden-Julian oscillation: synthesis and summary

The "Vertical structure and physical processes of the Madden-Julian oscillation (MJO)" project comprises three experiments, designed to evaluate comprehensively the heating, moistening and momentum associated with tropical convection in general circulation models (GCMs). We consider here only those GCMs that performed all experiments. Some models display relatively higher or lower MJO fidelity in both initialized hindcasts and climate simulations, while others show considerable variations in fidelity between experiments. Fidelity in hindcasts and climate simulations are not meaningfully correlated. The analysis of each experiment led to the development of process-oriented diagnostics, some of which distinguished between GCMs with higher or lower fidelity in that experiment. We select the most discriminating diagnostics and apply them to data from all experiments, where possible, to determine if correlations with MJO fidelity hold across scales and GCM states. While normalized gross moist stability had a small but statistically significant correlation with MJO fidelity in climate simulations, we find no link with fidelity in medium-range hindcasts. Similarly, there is no association between timestep-to-timestep rainfall variability, identified from short hindcasts, and fidelity in medium-range hindcasts or climate simulations. Two metrics that relate precipitation to free-tropospheric moisture--the relative humidity for extreme daily precipitation, and variations in the height and amplitude of moistening with rain rate--successfully distinguish between higher- and lower-fidelity GCMs in hindcasts and climate simulations. To improve the MJO, developers should focus on relationships between convection and both total moisture and its rate of change. We conclude by offering recommendations for further experiments

It\u27s safe to move! A protocol for a randomised controlled trial investigating the effect of a video designed to increase people\u27s confidence becoming more active despite back pain

Introduction Social media provide promising contemporary platforms for sharing public health information with a broad audience. Before implementation, testing social media campaigns that are intended to engage audiences and initiate behaviour change is necessary. This trial aims to investigate the effectiveness of a public health campaign to increase people\u27s confidence in becoming more active despite low back pain in comparison with no intervention. Methods and analysis This is an online randomised controlled trial with two intervention groups and one control group in a 1:1:1 allocation. People over 18 years of age and fluent in English will be recruited via social media advertising. We developed a social media-based public health campaign to support recommendations for managing low back pain. The interventions are two videos. Participants in the control group will be asked questions about low back pain but will not view either video intervention. The primary outcome will be item 10 of the Pain Self-Efficacy Questionnaire, which asks participants to rate how confident they would feel to gradually become more active despite pain ranging from 0 (not at all confident) to 6 (completely confident). This outcome will be measured immediately in all participant groups. We will compare group mean of the three arms of the trial using univariate analyses of variance. Ethics and dissemination This trial has been prospectively registered with the Australian New Zealand Clinical Trials Registry. We obtained ethical approval from our institutions Human Research Ethics Committee before data collection. We will publish the results in a peer-reviewed medical journal and on institution websites

Quantifying cellular dynamics in mice using a novel fluorescent division reporter system

The dynamics of cell populations are frequently studied in vivo using pulse-chase DNA labeling techniques. When combined with mathematical models, the kinetic of label uptake and loss within a population of interest then allows one to estimate rates of cell production and turnover through death or onward differentiation. Here we explore an alternative method of quantifying cellular dynamics, using a cell fate-mapping mouse model in which dividing cells can be induced to constitutively express a fluorescent protein, using a Ki67 reporter construct. We use a pulse-chase approach with this reporter mouse system to measure the lifespans and division rates of naive CD4 and CD8 T cells using a variety of modeling approaches, and show that they are all consistent with estimates derived from other published methods. However we propose that to obtain unbiased parameter estimates and full measures of their uncertainty one should simultaneously model the timecourses of the frequencies of labeled cells within both the population of interest and its precursor. We conclude that Ki67 reporter mice provide a promising system for modeling cellular dynamics

A regime analysis of Atlantic winter jet variability applied to evaluate HadGEM3-GC2

The behaviour of the eddy-driven jet over the Atlantic sector during the winter season is analyzed for the ERA-Interim reanalysis and the coupled and atmosphere-only configuration of HadGEM3-GC2—the climate model in use at the Met Office. The trimodal distribution that characterizes the jet-stream structure in terms of its preferred locations is reproduced with good accuracy by the model, although a distinct bias towards the high-latitude position is observed. Two different scenarios are found to contribute to this bias. One occurs when the jet shifts from its southern regime, whereby it settles too far north and for too long compared with the reanalysis. The other is associated with the exit from the central latitude regime, with too many events shifting poleward rather than equatorward. Excessively large lower tropospheric eddy heat fluxes during these transitions may account for the jet errors, even though the heat fluxes do not exhibit a climatological bias. Interestingly, these biases are weaker when the atmosphere model is forced with observed sea-surface temperatures (SSTs), suggesting that either it is vital to have the correct SST distribution or ocean–atmosphere coupling plays a key role in the biases. Additional analysis revealed that the Pacific jet exit is biased south in the coupled model and that this contributes to the Atlantic bias. Anomalously warm SSTs in the Gulf Stream region may be acting together with the Pacific bias in fostering anomalous activity in low-level eddy heat fluxes