The Phagocyte Oxidase Controls Tolerance to Mycobacterium tuberculosis infection. [preprint]

Protection from infectious disease relies on two distinct mechanisms. \u27Antimicrobial resistance\u27 directly inhibits pathogen growth, whereas \u27infection tolerance\u27 controls tissue damage. A single immune-mediator can differentially contribute to these mechanisms in distinct contexts, confounding our understanding of protection to different pathogens. For example, the NADPH-dependent phagocyte oxidase complex (Phox) produces anti-microbial superoxides and protects from tuberculosis in humans. However, Phox-deficient mice do not display the expected defect in resistance to M. tuberculosis leaving the role of this complex unclear. We re-examined the mechanisms by which Phox contributes to protection from TB and found that mice lacking the Cybb subunit of Phox suffered from a specific defect in tolerance, which was due to unregulated Caspase1 activation, IL-1β production, and neutrophil influx into the lung. These studies demonstrate that Phox-derived superoxide protect against TB by promoting tolerance to persistent infection, and highlight a central role for Caspase1 in regulating TB disease progression

When do Anisotropic Magnetic Susceptibilities Lead to Large NMR Shifts? Exploring Particle Shape Effects in the Battery Electrode Material LiFePO4.

Materials used as electrodes in energy storage devices have been extensively studied with solid-state NMR spectroscopy. Due to the almost ubiquitous presence of transition metals, these systems are also often magnetic. While it is well known that the presence of anisotropic bulk magnetic susceptibility (ABMS) leads to broadening of resonances under MAS, we show that for mono-disperse and non-spherical particle morphologies, the ABMS can also lead to considerable shifts, which vary substantially as a function of particle shape. This, on one hand, complicates the interpretation of the NMR spectrum and the ability to compare the measured shift of different samples of the same system. On the other hand the ABMS shift provides a mechanism with which to derive the particle shape from the NMR spectrum. In this work, we present a methodology to model the ABMS shift, and relate it to the shape of the studied particles. The approach is tested on the $^7$Li NMR spectra of single crystals and powders of LiFePO$_4$. The results show that the ABMS shift can be a major contribution to the total NMR shift in systems with large magnetic anisotropies and small hyperfine shifts, $^7$Li shifts for typical LiFePO$_4$ morphologies varying by as much as 100 ppm. The results are generalised to demonstrate that the approach can be used as a means with which to probe the aspect ratio of particles. The work has implications for the analysis of NMR spectra of all materials with anisotropic magnetic susceptibilities, including diamagnetic materials such as graphite

Group-based pulmonary telerehabilitation is feasible, safe, beneficial and well-received in patients that have been hospitalised with Covid-19

Introduction Covid-19 has caused worldwide mass hospitalisation. The need for multi-disciplinary post-hospitalisation rehabilitation is becoming increasingly apparent and telerehabilitation has been endorsed. The aim of study was to investigate the feasibility and efficacy of pulmonary telerehabilitation for Covid-19 survivors.Methods A single centre, mixed-methods, fast-track (wait-list), randomised controlled trial of telerehabilitation for patients who have been hospitalised with Covid-19.Participants Forty patients discharged from two University Teaching Hospitals in the North of England. Interventions: Telerehabilitation consisted of twelve exercise classes, six education events and opportunity for peer support. Patients commenced telerehabilitation 14 days after randomisation in the fast-track group and 56 days after randomisation in the wait-list group.Outcome measures and results Descriptive and statistical improvements were noted is several clinical outcome measures. Exercise capacity increased from a median (Q1–Q3) 20 (14–24) sit-to-stand repetitions in one-minute at baseline to 25 (24–30) post-telerehabilitation. Breathlessness rated using the MRC changed from 3.5 (3–4) at baseline to 2 (1.5–3) post-telerehabilitation, with additional favourable outcomes noted in respiratory symptoms measured using numerical rating scales and visual analogue scales (VAS). Quality of life measured using the EQ-VAS improved from 55 (60–70) units at baseline to 70 (55–80) units following telerehabilitation. Improvements in fatigue (FACIT-F) and mood (HADS-D) were also observed. Natural recovery was observed in the wait-list group prior to receiving telerehabilitation, however, improvements were accelerated by early telerehabilitation in the fast-track group.Conclusions We have shown that group-based telerehabilitation is feasible, safe, beneficial and well-received in this population

Cyanobacterial endobionts within a major marine, planktonic, calcifier (Globigerina bulloides, Foraminifera) revealed by 16S rRNA metabarcoding

We investigated the possibility of bacterial symbiosis in Globigerina bulloides, a palaeoceanographically important, planktonic foraminifer. This marine protist is commonly used in micropalaeontological investigations of climatically sensitive subpolar and temperate water masses as well as wind-driven upwelling regions of the world's oceans. G. bulloides is unusual because it lacks the protist algal symbionts that are often found in other spinose species. In addition, it has a large offset in its stable carbon and oxygen isotopic compositions compared to other planktonic foraminifer species, and also that predicted from seawater equilibrium. This is suggestive of novel differences in ecology and life history of G. bulloides, making it a good candidate for investigating the potential for bacterial symbiosis as a contributory factor influencing shell calcification. Such information is essential to evaluate fully the potential response of G. bulloides to ocean acidification and climate change. To investigate possible ecological interactions between G. bulloides and marine bacteria, 18S rRNA gene sequencing, fluorescence microscopy, 16SrRNA gene metabarcoding and transmission electron microscopy (TEM) were performed on individual specimens ofG. bulloides(type IId) collected from two locations in the California Current. Intracellular DNA extracted from fiveG. bulloidesspecimens was subjected to 16S rRNA gene metabarcoding and, remarkably, 37–87 % of all 16S rRNA gene sequences recovered were assigned to operational taxonomic units (OTUs) from the picocyanobacterium Synechococcus. This finding was supported by TEM observations of intact Synechococcus cells in both the cytoplasm and vacuoles of G. bulloides. Their concentrations were up to 4 orders of magnitude greater inside the foraminifera than those reported for the California Current water column and approximately 5 % of the intracellular Synechococcus cells observed were undergoing cell division. This suggests that Synechococcus is an endobiont of G. bulloides type IId, which is the first report of a bacterial endobiont in the planktonic foraminifera. We consider the potential roles of Synechococcus and G. bulloides within the relationship and the need to determine how widespread the association is within the widely distributed G. bulloides morphospecies. The possible influence of Synechococcus respiration on G. bulloides shell geochemistry is also explored

First in-situ monitoring of sponge response and recovery to an industrial sedimentation event

Assessment of risks to seabed habitats from industrial activities is based on the resilience and potential for recovery. Increased sedimentation, a key impact of many offshore industries, results in burial and smothering of benthic organisms. Sponges are particularly vulnerable to increases in suspended and deposited sediment, but response and recovery have not been observed in-situ. We quantified the impact of sedimentation from offshore hydrocarbon drilling over ∼5 days on a lamellate demosponge, and its recovery in-situ over ∼40 days using hourly time-lapse photographs with measurements of backscatter (a proxy of suspended sediment) and current speed. Sediment accumulated on the sponge then cleared largely gradually but occasionally sharply, though it did not return to the initial state. This partial recovery likely involved a combination of active and passive removal. We discuss the use of in-situ observing, which is critical to monitoring impacts in remote habitats, and need for calibration to laboratory conditions

Telerehabilitation for patients who have been hospitalised with covid-19: a qualitative study

PurposeThe aim of this qualitative study was to explore the views of participants of a group-based, supervised, telerehabilitation programme, following discharge from hospital with Covid-19. This study was part of a single-centre, fast-track (wait-list), randomised, mixed-methods, feasibility trial of telerehabilitation (Registration: Clinicaltrials.gov reference:285205).MethodsSemi-structured interviews were conducted over a virtual teleconference platform with 10 participants who took part in a telerehabilitation programme following Covid-19 after discharge from an acute hospital. Data were transcribed verbatim and analysed using thematic analysis.ResultsFive themes were important from the participant perspective: telerehabilitation programme as part of the Covid-19 journey; the telerehabilitation programme design and delivery; peer aspects; the role of the instructor; and the role of technology and online delivery.ConclusionsOverall, the telerehabilitation programme was a positive experience for participants. The instructors were central to this positive view as was the group nature of the programme. The group aspect was particularly important in supporting the broader perceived wellbeing gains, such as the sense of enjoyment and reduced social isolation. Several participants would have liked to have continued with the exercises beyond the six-week intervention indicating that the programme could be a way to help people sustain a physically active lifestyle.IMPLICATIONS FOR REHABILITATIONParticipants who were recovering from Covid-19 following hospital admission perceived the telerehabilitation to be a positive experience overall.The group aspect of the telerehabilitation programme was important in supporting the broader perceived wellbeing gains such as the sense of enjoyment and reduced social isolation.Telerehabilitation programmes for Covid-19 may need to include pathways for participants to continue to engage in exercise beyond the time-limited six-week intervention to support ongoing self-management

Closing the Coverage Gaps: Reducing Health Insurance Disparities in Massachusetts

Massachusetts has been exemplary in developing health insurance coverage policies to cover its residents. By 2019, the state's uninsurance rate was 3.0 percent, the lowest rate in the nation, representing about 204,000 uninsured residents. While the state's overall uninsured rate at a given point in time is low, more than twice as many people - 503,000, or 7.3 percent of the population - experienced a gap in coverage over the previous twelve months. And importantly, not all groups benefit equally. People who are Black or Hispanic, or who have lower incomes, experience significantly higher rates of uninsurance than the state population overall. As a result, these groups are more likely to face access barriers and financial insecurity associated with being uninsured.The purpose of this report is to begin charting a course toward closing the coverage gaps in Massachusetts, with a particular focus on creating a more racially and ethnically equitable system of coverage. The report and accompanying infographics describe the people in Massachusetts without health insurance and the barriers to coverage they face, including affordability, administrative complexity, and immigration, language, and cultural barriers. It then proposes a menu of policy options that address the specific circumstances in Massachusetts. The proposed options are meant to inform a statewide conversation about the best approaches to closing the remaining coverage gaps in Massachusetts and removing structural barriers that result in racial and ethnic disparities in health insurance coverage

Genomics Virtual Laboratory: a practical bioinformatics workbench for the cloud

Analyzing high throughput genomics data is a complex and compute intensive task, generally requiring numerous software tools and large reference data sets, tied together in successive stages of data transformation and visualisation. A computational platform enabling best practice genomics analysis ideally meets a number of requirements, including: a wide range of analysis and visualisation tools, closely linked to large user and reference data sets ; workflow platform(s) enabling accessible, reproducible, portable analyses, through a flexible set of interfaces ; highly available, scalable computational resources ; and flexibility and versatility in the use of these resources to meet demands and expertise of a variety of users. Access to an appropriate computational platform can be a significant barrier to researchers, as establishing such a platform requires a large upfront investment in hardware, experience, and expertise