Immune responses to IAV infection and the roles of L-selectin and ADAM17 in lymphocyte homing

Influenza A virus (IAV) infection is a global public health burden causing up to 650,000 deaths per year. Yearly vaccination programmes and anti-viral drugs currently have limited benefits; therefore, research into IAV is fundamental. Leukocyte trafficking is a crucial process which orchestrates the immune response to infection to protect the host. It involves several homing molecules and receptors on both blood vessels and leukocytes. A key mediator of this process is the transmembrane glycoprotein L-selectin, which binds to vascular addressins on blood vessel endothelial cells. L-selectin classically mediates homing of naïve and central memory lymphocytes to lymph nodes via high endothelial venules (HEVs). Recent studies have found that L-selectin is essential for homing of activated CD8+ T cells to influenza-infected lungs and reduction in virus load. A disintegrin and metalloproteinase 17 (ADAM17) is the primary regulator of cell surface levels of L-selectin. Understanding the mechanisms that regulate these two proteins are central to comprehending recruitment of T cells to sites of IAV infection. This review summarises the immune response to IAV infection in humans and mice and discusses the roles of L-selectin and ADAM17 in T lymphocyte homing during IAV infectio

New constraints on Lyman-α opacity with a sample of 62 quasars at z > 5.7

We present measurements of the mean and scatter of the IGM Lyman-{\alpha} opacity at 4.9 5.7, the largest sample assembled at these redshifts to date by a factor of two. The sample size enables us to sample cosmic variance at these redshifts more robustly than ever before. The spectra used here were obtained by the SDSS, DES-VHS and SHELLQs collaborations, drawn from the ESI and X-Shooter archives, reused from previous studies or observed specifically for this work. We measure the effective optical depth of Lyman-{\alpha} in bins of 10, 30, 50 and 70 cMpc h-1, construct cumulative distribution functions under two treatments of upper limits on flux and explore an empirical analytic fit to residual Lyman-{\alpha} transmission. We verify the consistency of our results with those of previous studies via bootstrap re-sampling and confirm the existence of tails towards high values in the opacity distributions, which may persist down to z = 5.2. Comparing our results with predictions from cosmological simulations, we find further strong evidence against models that include a spatially uniform ionizing background and temperature-density relation. We also compare to IGM models that include either a fluctuating UVB dominated by rare quasars or temperature fluctuations due to patchy reionization. Although both models produce better agreement with the observations, neither fully captures the observed scatter in IGM opacity. Our sample of 62 z > 5.7 quasar spectra opens many avenues for future study of the reionisation epoch

Peatland core domain sets: building consensus on what should be measured in research and monitoring

It is often difficult to compile and synthesise evidence across multiple studies to inform policy and practice because different outcomes have been measured in different ways or datasets and models have not been fully or consistently reported. In the case of peatlands, a critical terrestrial carbon store, this lack of consistency hampers the evidence-based decisions in policy and practice that are needed to support effective restoration and conservation. This study adapted methods pioneered in the medical community to reach consensus over peatland outcomes that could be consistently measured and reported to improve the synthesis of data and reduce research waste. Here we report on a methodological framework for identifying, evaluating and prioritising the outcomes that should be measured. We discuss the subsequent steps to standardise methods for measuring and reporting outcomes in peatland research and monitoring. The framework was used to identify and prioritise sets of key variables (known as core domain sets) for UK blanket and raised bogs, and for tropical peat swamps. Peatland experts took part in a structured elicitation and prioritisation process, comprising two workshops and questionnaires, that focused on climate (32 and 18 unique outcomes for UK and tropical peats, respectively), hydrology (26 UK and 16 tropical outcomes), biodiversity (8 UK and 22 tropical outcomes) and fire-related outcomes (13, for tropical peatlands only). Future research is needed to tackle the challenges of standardising methods for data collection, management, analysis, reporting and re-use, and to extend the approach to other types of peatland. The process reported here is a first step towards creating datasets that can be synthesised to inform evidence-based policy and practice, and contribute towards the conservation, restoration and sustainable management of this globally significant carbon store. evidence-based policy and practice, evidence synthesis, outcomes, standardisationpublishedVersio

GA-NIFS: Black hole and host galaxy properties of two z≃\simeq6.8 quasars from the NIRSpec IFU

Integral Field Spectroscopy (IFS) with JWST NIRSpec will significantly improve our understanding of the first quasars, by providing spatially resolved, infrared spectroscopic capabilities which cover key rest-frame optical emission lines that have been previously unobservable. Here we present our results from the first two z>6 quasars observed as a part of the Galaxy Assembly with NIRSpec IFS (GA-NIFS) GTO program, DELS J0411-0907 at z=6.82 and VDES J0020-3653 at z=6.86. By observing the H$\beta$, [OIII], and H$\alpha$ emission lines in these high-z quasars for the first time, we measure accurate black hole masses, $M_{\rm{BH}}=1.85e9$ and $2.9e9$M$_\odot$, corresponding to Eddington ratios of $\lambda_{\rm{Edd}}=0.8$ and 0.4 for DELS J0411-0907 and VDES J0020-3653 respectively. These provide a key comparison for existing estimates from the more uncertain MgII line. We perform quasar-host decomposition using models of the quasars' broad lines to measure the underlying host galaxies. We also discover multiple emission line regions surrounding each of the host galaxies, which are likely companion galaxies undergoing mergers with these hosts. We measure the star formation rates, excitation mechanisms, and dynamical masses of the hosts and companions, measuring the $M_{\rm{BH}}/M_{\rm{dyn}}$ ratios at high-z using these estimators for the first time. DELS J0411-0907 and VDES J0020-3653 both lie above the local black hole--host mass relation, and are consistent with the existing observations of $z\gtrsim6$ quasar host galaxies with ALMA. We detect ionized outflows in [OIII] and H$\beta$ from both quasars, with mass outflow rates of 58 and 525 M$_{\odot}$/yr for DELS J0411-0907 and VDES J0020-3653, much larger than their host star formation rates of <33 and <54 M$_\odot$/yr. This work highlights the exceptional capabilities of the JWST NIRSpec IFU for observing quasars in the early Universe.Comment: 27 pages, 10 figures. Resubmitted to A&A after significant revisions. If you have cited values from our first version, please check this version and update accordingly, as many values have changed slightly thanks to improvements in our analysi

L-selectin enhanced T cells improve the efficacy of cancer immunotherapy

The T cell homing molecule, L-selectin (CD62L), is commonly used as a marker of T cell activation, as expression of L-selectin is downregulated following engagement of the T cell receptor. Furthermore, it is used to distinguish “central memory” T cells (TCM) from, “effector memory” T cells (TEM). It has been reported that CD8+ T cells with a CD62L+ TCM phenotype are better able to control tumour growth than CD62L- TEM CD8+ T cells, while L-selectin knockout T cells are poor at controlling tumour growth. Here, we test the hypothesis that T cells expressing a genetically modified form of L-selectin that is not downregulated following T cell activation (L-selectin enhanced T cells) are better able to control tumour growth than wild type T cells. Using mouse models of solid and disseminated tumours, we show that L-selectin enhancement improves the efficacy of CD8+ T cells in controlling tumour growth. Longitudinal tracking of Zirconium-89 (89Zr) labelled T cells using PET-CT showed that transferred T cells localised to tumours within 24 hours. Early T cell recruitment into tumours was not dependent on L-selectin, however, upregulation of the early activation marker CD69 was higher on L-selectin expressing T cells both inside tumours and in secondary lymphoid organs. Reduced growth of tumours by L-selectin enhanced T cells correlated with increased frequency of CD8+ tumour infiltrating T cells 21 days after commencing therapy. Ex vivo analysis showed that clonal expansion of L-selectin enhanced T cells was slower, and that L-selectin was linked to expression of the proliferation marker Ki67. Together these findings indicate that maintaining L-selectin expression on tumour-specific T cells offers an advantage in mouse models of cancer immunotherapy. The beneficial role of L-selectin may be unrelated to its’ well-known role in T cell homing and instead linked to activation, clonal expansion and retention of therapeutic T cells. These findings have implications both for the selection of T cell subsets for adoptive transfer immunotherapy, and for possible modifications of transgenic chimeric antigen receptor (CAR) T cells to broaden the clinical scope of these therapies

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

A well-kept treasure at depth: precious red coral rediscovered in Atlantic deep coral gardens (SW Portugal) after 300 years

The highly valuable red coral Corallium rubrum is listed in several Mediterranean Conventions for species protection and management since the 1980s. Yet, the lack of data about its Atlantic distribution has hindered its protection there. This culminated in the recent discovery of poaching activities harvesting tens of kg of coral per day from deep rocky reefs off SW Portugal. Red coral was irregularly exploited in Portugal between the 1200s and 1700s, until the fishery collapsed. Its occurrence has not been reported for the last 300 years.info:eu-repo/semantics/publishedVersio