Efferocytes release extracellular vesicles to resolve inflammation and tissue injury via prosaposin-GPR37 signaling.

Macrophages release soluble mediators following efferocytic clearance of apoptotic cells to facilitate intercellular communication and promote the resolution of inflammation. However, whether inflammation resolution is modulated by extracellular vesicles (EVs) and vesicular mediators released by efferocytes is not known. We report that efferocyte-derived EVs express prosaposin, which binds to macrophage GPR37 to increase expression of the efferocytosis receptor Tim4 via an ERK-AP1-dependent signaling axis, leading to increased macrophage efferocytosis efficiency and accelerated resolution of inflammation. Neutralization and knockdown of prosaposin or blocking GRP37 abrogates the pro-resolution effects of efferocyte-derived EVs in vivo. Administration of efferocyte-derived EVs in a murine model of atherosclerosis is associated with an increase in lesional macrophage efferocytosis efficiency and a decrease in plaque necrosis and lesional inflammation. Thus, we establish a critical role for efferocyte-derived vesicular mediators in increasing macrophage efferocytosis efficiency and accelerating the resolution of inflammation and tissue injury

WormPaths: Caenorhabditis elegans metabolic pathway annotation and visualization [preprint]

In our group, we aim to understand metabolism in the nematode Caenorhabditis elegans and its relationships with gene expression, physiology and the response to therapeutic drugs. On March 15, 2020, a stay-at-home order was put into effect in the state of Massachusetts, USA, to flatten the curve of the spread of the novel SARS-CoV2 virus that causes COVID-19. For biomedical researchers in our state, this meant putting a hold on experiments for nine weeks until May 18, 2020. To keep the lab engaged and productive, and to enhance communication and collaboration, we embarked on an in-lab project that we all found important but that we never had the time for: the detailed annotation and drawing of C. elegans metabolic pathways. As a result, we present WormPaths, which is composed of two parts: 1) the careful manual annotation of metabolic genes into pathways, categories and levels, and 2) 66 pathway maps that include metabolites, metabolite structures, genes, reactions, and pathway connections between maps. These maps are available on our WormFlux website. We show that WormPaths provides easy-to-navigate maps and that the different levels in WormPaths can be used for metabolic pathway enrichment analysis of transcriptomic data. In the unfortunate event of additional lockdowns, we envision further developing these maps to be more interactive, with an analogy of road maps that are available on mobile devices

Spectroscopic Mass and Host-star Metallicity Measurements for Newly Discovered Microlensing Planet OGLE-2018-BLG-0740Lb

We report the discovery of the microlensing planet OGLE-2018-BLG-0740Lb. The planet is detected with a very strong signal of $\Delta\chi^2\sim 4630$, but the interpretation of the signal suffers from two types of degeneracies. One type is caused by the previously known close/wide degeneracy, and the other is caused by an ambiguity between two solutions, in which one solution requires to incorporate finite-source effects, while the other solution is consistent with a point-source interpretation. Although difficult to be firmly resolved based on only the photometric data, the degeneracy is resolved in strong favor of the point-source solution with the additional external information obtained from astrometric and spectroscopic observations. The small astrometric offset between the source and baseline object supports that the blend is the lens and this interpretation is further secured by the consistency of the spectroscopic distance estimate of the blend with the lensing parameters of the point-source solution. The estimated mass of the host is $1.0\pm 0.1~M_\odot$ and the mass of the planet is $4.5\pm 0.6~M_{\rm J}$ (close solution) or $4.8\pm 0.6~M_{\rm J}$ (wide solution) and the lens is located at a distance of $3.2\pm 0.5$~kpc. The bright nature of the lens, with $I\sim 17.1$ ($V\sim 18.2$), combined with its dominance of the observed flux suggest that radial-velocity (RV) follow-up observations of the lens can be done using high-resolution spectrometers mounted on large telescopes, e.g., VLT/ESPRESSO, and this can potentially not only measure the period and eccentricity of the planet but also probe for close-in planets. We estimate that the expected RV amplitude would be $\sim 60\sin i ~{\rm m~s}^{-1}$.Comment: 12 pages, 11 figures, 4 table

Candidate Brown-dwarf Microlensing Events with Very Short Timescales and Small Angular Einstein Radii

Short-timescale microlensing events are likely to be produced by substellar brown dwarfs (BDs), but it is difficult to securely identify BD lenses based on only event timescales t_E because short-timescale events can also be produced by stellar lenses with high relative lens-source proper motions. In this paper, we report three strong candidate BD-lens events found from the search for lensing events not only with short timescales (t_E ≲ 6 days) but also with very small angular Einstein radii (θ_E ≲ 0.05 mas) among the events that have been found in the 2016–2019 observing seasons. These events include MOA-2017-BLG-147, MOA-2017-BLG-241, and MOA-2019-BLG-256, in which the first two events are produced by single lenses and the last event is produced by a binary lens. From the Monte Carlo simulations of Galactic events conducted with the combined t_E and θ_E constraint, it is estimated that the lens masses of the individual events are 0.051^(+0.100)_(−0.027) M⊙, 0.044^(+0.090)_(−0.023) M⊙, and 0.046^(+0.067)_(−0.023) M⊙/0.038^(+0.056)_(−0.019) M⊙ and the probability of the lens mass smaller than the lower limit of stars is ~80% for all events. We point out that routine lens mass measurements of short-timescale lensing events require survey-mode space-based observations

OGLE-2018-BLG-0022: First Prediction of an Astrometric Microlensing Signal from a Photometric Microlensing Event

In this work, we present the analysis of the binary microlensing event OGLE-2018-BLG-0022 that is detected toward the Galactic bulge field. The dense and continuous coverage with the high-quality photometry data from ground-based observations combined with the space-based {\it Spitzer} observations of this long time-scale event enables us to uniquely determine the masses $M_1=0.40 \pm 0.05~M_\odot$ and $M_2=0.13\pm 0.01~M_\odot$ of the individual lens components. Because the lens-source relative parallax and the vector lens-source relative proper motion are unambiguously determined, we can likewise unambiguously predict the astrometric offset between the light centroid of the magnified images (as observed by the {\it Gaia} satellite) and the true position of the source. This prediction can be tested when the individual-epoch {\it Gaia} astrometric measurements are released.Comment: 10 pages, 10 figures, 4 table

SpitzerSpitzer Parallax of OGLE-2018-BLG-0596: A Low-mass-ratio Planet around an M-dwarf

We report the discovery of a $Spitzer$ microlensing planet OGLE-2018-BLG-0596Lb, with preferred planet-host mass ratio $q \sim 2\times10^{-4}$. The planetary signal, which is characterized by a short $(\sim 1~{\rm day})$ "bump" on the rising side of the lensing light curve, was densely covered by ground-based surveys. We find that the signal can be explained by a bright source that fully envelops the planetary caustic, i.e., a "Hollywood" geometry. Combined with the source proper motion measured from $Gaia$, the $Spitzer$ satellite parallax measurement makes it possible to precisely constrain the lens physical parameters. The preferred solution, in which the planet perturbs the minor image due to lensing by the host, yields a Uranus-mass planet with a mass of $M_{\rm p} = 13.9\pm1.6~M_{\oplus}$ orbiting a mid M-dwarf with a mass of $M_{\rm h} = 0.23\pm0.03~M_{\odot}$. There is also a second possible solution that is substantially disfavored but cannot be ruled out, for which the planet perturbs the major image. The latter solution yields $M_{\rm p} = 1.2\pm0.2~M_{\oplus}$ and $M_{\rm h} = 0.15\pm0.02~M_{\odot}$. By combining the microlensing and $Gaia$ data together with a Galactic model, we find in either case that the lens lies on the near side of the Galactic bulge at a distance $D_{\rm L} \sim 6\pm1~{\rm kpc}$. Future adaptive optics observations may decisively resolve the major image/minor image degeneracy.Comment: 34 pages, 8 figures, Submitted to AAS journa

Developing the tissue viability seating guidelines

Background: Costs for the prevention and management of pressure ulcers have increased significantly with limited published advice from health and social care organisations on seating and preventing pressure ulcers. At the request of the UK Tissue Viability Society the aim of the publication was to develop a practical guide for people, carers and health and social care professionals on how the research and evidence base on pressure ulcer prevention and management can be applied to those who remain seated for extended periods of time. Methods and findings: The evidence base informing the guidelines was obtained by applying a triangulation of methods: a literature review, listening event and stakeholder group consultation. The purpose was to engage users and carers, academics, clinicians, inspectorate and charities, with an interest in seating, positioning and pressure management to: gather views, feedback, stories, and evidence of the current practices in the field to create a greater awareness of the issue. Conclusion: The new guidelines are inclusive of all people with short and long-term mobility issues to include all population groups. The document includes evidence on where pressure ulcers develop when seated, risk factors, best possible seated position and what seat adjustments are required, the ideal seating assessment, interventions, self-help suggestions and key seating outcomes. The updated TVS CPGs have been informed by the best available evidence, the insights and wisdom of experts, stakeholders and people who spend extended periods of time sitting

Serum-Dependent Selective Expression of EhTMKB1-9, a Member of Entamoeba histolytica B1 Family of Transmembrane Kinases

Entamoeba histolytica transmembrane kinases (EhTMKs) can be grouped into six distinct families on the basis of motifs and sequences. Analysis of the E. histolytica genome revealed the presence of 35 EhTMKB1 members on the basis of sequence identity (≥95%). Only six homologs were full length containing an extracellular domain, a transmembrane segment and an intracellular kinase domain. Reverse transcription followed by polymerase chain reaction (RT-PCR) of the kinase domain was used to generate a library of expressed sequences. Sequencing of randomly picked clones from this library revealed that about 95% of the clones were identical with a single member, EhTMKB1-9, in proliferating cells. On serum starvation, the relative number of EhTMKB1-9 derived sequences decreased with concomitant increase in the sequences derived from another member, EhTMKB1-18. The change in their relative expression was quantified by real time PCR. Northern analysis and RNase protection assay were used to study the temporal nature of EhTMKB1-9 expression after serum replenishment of starved cells. The results showed that the expression of EhTMKB1-9 was sinusoidal. Specific transcriptional induction of EhTMKB1-9 upon serum replenishment was further confirmed by reporter gene (luciferase) expression and the upstream sequence responsible for serum responsiveness was identified. EhTMKB1-9 is one of the first examples of an inducible gene in Entamoeba. The protein encoded by this member was functionally characterized. The recombinant kinase domain of EhTMKB1-9 displayed protein kinase activity. It is likely to have dual specificity as judged from its sensitivity to different kinase inhibitors. Immuno-localization showed EhTMKB1-9 to be a surface protein which decreased on serum starvation and got relocalized on serum replenishment. Cell lines expressing either EhTMKB1-9 without kinase domain, or EhTMKB1-9 antisense RNA, showed decreased cellular proliferation and target cell killing. Our results suggest that E. histolytica TMKs of B1 family are functional kinases likely to be involved in serum response and cellular proliferation