Challenging perspectives on the cellular origins of lymphoma.

Both B and T lymphocytes have signature traits that set them apart from other cell types. They actively and repeatedly rearrange their DNA in order to produce a unique and functional antigen receptor, they have potential for massive clonal expansion upon encountering antigen via this receptor or its precursor, and they have the capacity to be extremely long lived as 'memory' cells. All three of these traits are fundamental to their ability to function as the adaptive immune response to infectious agents, but concurrently render these cells vulnerable to transformation. Thus, it is classically considered that lymphomas arise at a relatively late stage in a lymphocyte's development during the process of modifying diversity within antigen receptors, and when the cell is capable of responding to stimulus via its receptor. Attempts to understand the aetiology of lymphoma have reinforced this notion, as the most notable advances to date have shown chronic stimulation of the antigen receptor by infectious agents or self-antigens to be key drivers of these diseases. Despite this, there is still uncertainty about the cell of origin in some lymphomas, and increasing evidence that a subset arises in a more immature cell. Specifically, a recent study indicates that T-cell lymphoma, in particular nucleophosmin-anaplastic lymphoma kinase-driven anaplastic large cell lymphoma, may originate in T-cell progenitors in the thymus.T.I.M.M. was supported by a Bloodwise Gordon Piller Studentship.This is the final version of the article. It first appeared from The Royal Society via https://doi.org/10.1098/rsob.16023

A collective action approach to improving attitudes and self-efficacy towards gender equality among male STEM academics

Despite the implementation of equality interventions within higher education, progress towards gender parity in science, technology, engineering, and mathematics (STEM) remains slow. Male educators often exhibit poorer engagement with diversity initiatives, potentially contributing to persisting gender disparities in STEM given men’s longstanding dominance in these programs. Two experiments investigate how equality interventions should be designed to maximize support from male educators. Experiment 1 (N = 72; Mage = 39.72, SDage = 12.33) used virtual reality to manipulate 2 factors among male academics: (1) exposure to gender inequality and (2) virtually taking the perspective of a female scientist. Using self-report and behavioral measures, viewing an empirical presentation outlining the prevalence of gender issues in STEM yielded the greatest support for equality initiatives following successful perspective-taking. Experiment 2 (N = 120; Mage = 32.48, SDage = 10.36) varied two additional factors among male academics: (1) evidence-based methods to reduce gender biases in STEM (i.e., promoting self-efficacy) and (2) blaming male academics for gender inequalities. Promoting self-efficacy and blaming men for disparities led to greater confidence in male academics’ ability to address gender inequalities in their field. Notably, higher self-efficacy accounted for greater support for equality initiatives and internal motives to engage with diversity programs. Findings provide an empirical framework and high-tech training tools for promoting engagement with diversity initiatives among male educators, informing development of interventions within higher education to improve student and faculty experiences in STEM

The Cosmic Lens All-Sky Survey: statistical strong lensing, cosmological parameters, and global properties of galaxy populations

Extensive analyses of statistical strong gravitational lensing are performed based on the final Cosmic Lens All Sky Survey (CLASS) well-defined statistical sample of flat spectrum radio sources and current estimates of galaxy luminosity functions per morphological type. The analyses are done under the assumption that galactic lenses are well-approximated by singular isothermal ellipsoids and early-type galaxies evolved passively since redshift $z \sim 1$. Depending on how the late-type galaxy population is treated (i.e., whether its characteristic velocity dispersion is constrained or not), we find for a flat universe with a cosmological constant that the present matter fraction of the present critical density $\Omega_{\rm m} = 0.31^{+0.27}_{-0.14}$ (68%) for the unconstrained case or $0.40^{+0.28}_{-0.16}$ (68%) for the constrained case, with an additional systematic uncertainty of $\approx 0.11$ arising from the present uncertainty in the distribution of CLASS sources in redshift and flux density. For a flat universe with a constant equation of state for dark energy w = $p_x$(pressure)/$\rho_x$(energy density), we find that $w < -0.55^{+0.18}_{-0.11}$ (68%) for the unconstrained case or $w < -0.41^{+0.28}_{-0.16}$ (68%) for the constrained case. For the equal frequencies of oblates and prolates, we find that $\sigma_{*}^{(e)} = 198^{+22}_{-18}$ km s$^{-1}$ (68%) for a `steep' $\alpha^{(e)}=-1$ or $\sigma_{*}^{(e)} = 181^{+18}_{-15}$ km s$^{-1}$ (68%) for a `shallow' $\alpha^{(e)}=-0.54$. Finally, from the relative frequencies of doubly-imaged sources and quadruply-imaged sources, we find that a mean projected mass ellipticity of early-type galaxies $\bar{\epsilon}_{\rm mass} = 0.42$ with a 68% lower limit of 0.28. (Abridged)Comment: 31 pages, 12figures, 6 tables, to appear in MNRAS (referee comments incorporated, a section on future prospects added

Brn3a and Islet1 Act Epistatically to Regulate the Gene Expression Program of Sensory Differentiation

The combinatorial expression of transcription factors frequently marks cellular identity in the nervous system, yet how these factors interact to determine specific neuronal phenotypes is not well understood. Sensory neurons of the trigeminal ganglion (TG) and dorsal root ganglia (DRG) coexpress the homeodomain transcription factors Brn3a and Islet1, and past work has revealed partially overlapping programs of gene expression downstream of these factors. Here we examine sensory development in Brn3a/Islet1 double knock-out (DKO) mice. Sensory neurogenesis and the formation of the TG and DRG occur in DKO embryos, but the DRG are dorsally displaced, and the peripheral projections of the ganglia are markedly disturbed. Sensory neurons in DKO embryos show a profound loss of all early markers of sensory subtypes, including the Ntrk neurotrophin receptors, and the runt-family transcription factors Runx1 and Runx3. Examination of global gene expression in the E12.5 DRG of single and double mutant embryos shows that Brn3a and Islet1 are together required for nearly all aspects of sensory-specific gene expression, including several newly identified sensory markers. On a majority of targets, Brn3a and Islet1 exhibit negative epistasis, in which the effects of the individual knock-out alleles are less than additive in the DKO. Smaller subsets of targets exhibit positive epistasis, or are regulated exclusively by one factor. Brn3a/Islet1 double mutants also fail to developmentally repress neurogenic bHLH genes, and in vivo chromatin immunoprecipitation shows that Islet1 binds to a known Brn3a-regulated enhancer in the neurod4 gene, suggesting a mechanism of interaction between these genes

A candidate tolerance gene identified in a natural population of field voles (Microtus agrestis)

The animal immune response has hitherto been viewed primarily in the context of resistance only. However, individuals, can also employ a tolerance strategy to maintain good health in the face of on-going infection. To shed light on the genetic and physiological basis of tolerance, we use a natural population of field voles, Microtus agrestis, to search for an association between the expression of the transcription factor Gata3, previously identified as a marker of tolerance in this system, and polymorphism in 84 immune and non-immune genes. Our results show clear evidence for an association between Gata3 expression and polymorphism in the Fcer1a gene, with the explanatory power of this polymorphism being comparable to that of other non-genetic variables previously identified as important predictors of Gata3 expression. We also uncover the possible mechanism behind this association using an existing protein-protein interaction network for the mouse model rodent, Mus musculus, which we validate using our own expression network for M. agrestis. Our results suggest that the polymorphism in question may be working at the transcriptional level, leading to changes in the expression of the Th2-related genes, Tyrosine-protein kinase BTK and Tyrosine-protein kinase TXK, and hence potentially altering the strength of the Th2 response, of which Gata3 is a mediator. We believe our work has implications for both treatment and control of infectious disease

Passive ground-based remote sensing of radiation fog

Accurate boundary layer temperature and humidity profiles are crucial for successful forecasting of fog, and accurate retrievals of liquid water path are important for understanding the climatological significance of fog. Passive ground-based remote sensing systems such as microwave radiometers (MWRs) and infrared spectrometers like the Atmospheric Emitted Radiance Interferometer (AERI), which measures spectrally resolved infrared radiation (3.3 to 19.2 µm), can retrieve both thermodynamic profiles and liquid water path. Both instruments are capable of long-term unattended operation and have the potential to support operational forecasting. Here we compare physical retrievals of boundary layer thermodynamic profiles and liquid water path during 12 cases of thin (LWP<40 g m−2) supercooled radiation fog from an MWR and an AERI collocated in central Greenland. We compare both sets of retrievals to in-situ measurements from radiosondes and surface-based temperature and humidity sensors. The retrievals based on AERI observations accurately capture shallow surface-based temperature inversions (0–10 m a.g.l.) with lapse rates of up to −1.2 ∘C m−1, whereas the strength of the surface-based temperature inversions retrieved from MWR observations alone are uncorrelated with in-situ measurements, highlighting the importance of constraining MWR thermodynamic profile retrievals with accurate surface meteorological data. The retrievals based on AERI observations detect fog onset (defined by a threshold in liquid water path) earlier than those based on MWR observations by 25 to 185 min. We propose that, due to the high sensitivity of the AERI instrument to near-surface temperature and small changes in liquid water path, the AERI (or an equivalent infrared spectrometer) could be a useful instrument for improving fog monitoring and nowcasting, particularly for cases of thin radiation fog under otherwise clear skies, which can have important radiative impacts at the surface

The impact of lens galaxy environments on the image separation distribution

We study the impact of lens galaxy environments on the image separation distribution of lensed quasars. We account for both environmental convergence and shear, using a joint distribution derived from galaxy formation models calibrated by galaxy-galaxy lensing data and number counts of massive elliptical galaxies. We find that the external field enhances lensing probabilities, particularly at large image separations; the increase is ~30% at \theta=3'' and ~200% at \theta=5'', when we adopt a power-law source luminosity function \Phi(L) \propto L^-2.1. The enhancement is mainly driven by convergence, which boosts both the image separation and magnification bias (for a fixed lens galaxy mass). These effects have been neglected in previous studies of lens statistics. Turning the problem around, we derive the posterior convergence and shear distributions and point out that they are strong functions of image separation; lens systems with larger image separations are more likely to lie in dense environments.Comment: 8 pages, 10 figures, accepted for publication in MNRA

High Energy Neutrinos from Quasars

We review and clarify the assumptions of our basic model for neutrino production in the cores of quasars, as well as those modifications to the model subsequently made by other workers. We also present a revised estimate of the neutrino background flux and spectrum obtained using more recent empirical studies of quasars and their evolution. We compare our results with other thoeretical calculations and experimental upper limits on the AGN neutrino background flux. We also estimate possible neutrino fluxes from the jets of blazars detected recently by the EGRET experiment on the Compton Gamma Ray Observatory. We discuss the theoretical implications of these estimates.Comment: 14 pg., ps file (includes figures), To be published in Space Science Review

The Impacts of Work-Life-Balance (WLB) Challenges on Social Sustainability: The Experience of Nigerian Female Medical Doctors

Purpose: The purpose of this paper is to examine the implications of work-life-balance (WLB) challenges for Nigerian female medical doctors. This study focusses on Nigeria, which its peculiar socio-cultural, institutional and professional realities constitute WLB as well as social sustainability (SS) challenge for female medical doctors. Design/methodology/approach: Relying on qualitative, interpretivist approach and informed by institutional theory, this study explores how Nigeria's institutional environment and workplace realities engender WLB challenges, which consequently impact SS for female doctors. In total, 43 semi-structured interviews and focus group session involving eight participants were utilised for empirical analysis. Findings: The study reveals that factors such as work pressure, cultural expectations, unsupportive relationships, challenging work environment, gender role challenges, lack of voice/participation, and high stress level moderate the ability of female medical doctors to manage WLB and SS. It also identifies that socio-cultural and institutional demands on women show that these challenges, while common to female physicians in other countries, are different and more intense in Nigeria because of their unique professional, socio-cultural and institutional frameworks. Research limitations/implications: The implications of the WLB and SS requires scholarship to deepen as well as extend knowledge on contextual disparities in understanding these concepts from developing countries perspective, which is understudied. Originality/value: This study offers fresh insights into the WLB and SS concepts from the non-western context, such as Nigeria, highlighting the previously understudied challenges of WLB and SS and their implications for female doctors. © 2018, Emerald Publishing Limited