Symbiotic unicellular cyanobacteria fix nitrogen in the Arctic Ocean.

Biological dinitrogen (N2) fixation is an important source of nitrogen (N) in low-latitude open oceans. The unusual N2-fixing unicellular cyanobacteria (UCYN-A)/haptophyte symbiosis has been found in an increasing number of unexpected environments, including northern waters of the Danish Straight and Bering and Chukchi Seas. We used nanoscale secondary ion mass spectrometry (nanoSIMS) to measure 15N2 uptake into UCYN-A/haptophyte symbiosis and found that UCYN-A strains identical to low-latitude strains are fixing N2 in the Bering and Chukchi Seas, at rates comparable to subtropical waters. These results show definitively that cyanobacterial N2 fixation is not constrained to subtropical waters, challenging paradigms and models of global N2 fixation. The Arctic is particularly sensitive to climate change, and N2 fixation may increase in Arctic waters under future climate scenarios

Pathogenic Acinetobacter species have a functional type I secretion system and contact-dependent inhibition systems

Pathogenic Acinetobacter species, including Acinetobacter baumannii and Acinetobacter nosocomialis, are opportunistic human pathogens of increasing relevance worldwide. Although their mechanisms of drug resistance are well studied, the virulence factors that governAcinetobacter pathogenesis are incompletely characterized. Here we define the complete secretome of A. nosocomialis strain M2 in minimal medium and demonstrate that pathogenicAcinetobacter species produce both a functional type I secretion system (T1SS) and a contact-dependent inhibition (CDI) system. Using bioinformatics, quantitative proteomics, and mutational analyses, we show that Acinetobacter uses its T1SS for exporting two putative T1SS effectors, an Repeatsin-Toxin (RTX)-serralysin-like toxin, and the biofilm-associated protein (Bap). Moreover, we found that mutation of any component of the T1SS system abrogated type VI secretion activity under nutrient-limited conditions, indicating a previously unrecognized cross-talk between these two systems. We also demonstrate that the Acinetobacter T1SS is required for biofilm formation. Last, we show that both A. nosocomialis and A. baumannii produce functioning CDI systems that mediate growth inhibition of sister cells lacking the cognate immunity protein. The Acinetobacter CDI systems are widely distributed across pathogenicAcinetobacter species, with manyA. baumannii isolates harboring two distinct CDI systems. Collectively, these data demonstrate the power of differential, quantitative proteomics approaches to study secreted proteins, define the role of previously uncharacterized protein export systems, and observe cross-talk between secretion systems in the pathobiology of medically relevant Acinetobacter speciesSubprograma Sara Borrell from the Instituto de Salud Carlos IIISubdirección General de Evaluación y Fomento de la InvestigaciónMinisterio de Economía y Competitividad de España CD14/0001

An evaluation into procalcitonin levels in full-term neonates managed for suspected early onset sepsis due to probable maternal intrapartum sepsis

Purpose: To investigate procalcitonin (PCT) levels in full-term neonates managed for suspected early onset sepsis (EOS) due to probable maternal intrapartum sepsis. Methods: Prospective longitudinal observational study at University Hospitals of Bristol NHS Foundation trust. Included were a total of 117 neonates managed for suspected EOS from June to October 2020. In addition to routine full-blood-counts and c-reactive protein (CRP) tests, serum PCT levels were also measured as part of the septic screen and follow-up blood tests. Placentas were sent for histopathology analysis. Neonatal parameters were used to categorize cases into: “high-suspicion bacterial sepsis (BS),” “equivocal BS” and “low-suspicion BS.” Statistical test Kruskal-Wallis compared categories with biomarker values and placental histopathology scores. Results: A higher percentage of PCT levels showed elevation in comparison to CRP levels in the initial testing (55.3% versus 5.9%) and follow-up testing (98.9% versus 35%). There was a significant difference between the “low-suspicion BS” and “high-suspicion BS” categories for both the initial and follow-up PCT results. 71.2% of placentas showed varying degrees of chorioamnionitis. Conclusion: This study provides evidence to the physiological rise in PCT during the first few days of life. The significant difference in PCT levels according to clinical severity shows that PCT could be utilized in calculating odds for EOS, but as a standalone test will have limited use

Multiscale modelling of drug transport and metabolism in liver spheroids

In early preclinical drug development, potential candidates are tested in the laboratory using isolated cells. These in vitro experiments traditionally involve cells cultured in a two-dimensional monolayer environment. However, cells cultured in three-dimensional spheroid systems have been shown to more closely resemble the functionality and morphology of cells in vivo. While the increasing usage of hepatic spheroid cultures allows for more relevant experimentation in a more realistic biological environment, the underlying physical processes of drug transport, uptake and metabolism contributing to the spatial distribution of drugs in these spheroids remain poorly understood. The development of a multiscale mathematical modelling framework describing the spatio-temporal dynamics of drugs in multicellular environments enables mechanistic insight into the behaviour of these systems. Here, our analysis of cell membrane permeation and porosity throughout the spheroid reveals the impact of these properties on drug penetration, with maximal disparity between zonal metabolism rates occurring for drugs of intermediate lipophilicity. Our research shows how mathematical models can be used to simulate the activity and transport of drugs in hepatic spheroids and in principle any organoid, with the ultimate aim of better informing experimentalists on how to regulate dosing and culture conditions to more effectively optimize drug delivery

Nuclear rupture at sites of high curvature compromises retention of DNA repair factors.

The nucleus is physically linked to the cytoskeleton, adhesions, and extracellular matrix-all of which sustain forces, but their relationships to DNA damage are obscure. We show that nuclear rupture with cytoplasmic mislocalization of multiple DNA repair factors correlates with high nuclear curvature imposed by an external probe or by cell attachment to either aligned collagen fibers or stiff matrix. Mislocalization is greatly enhanced by lamin A depletion, requires hours for nuclear reentry, and correlates with an increase in pan-nucleoplasmic foci of the DNA damage marker γH2AX. Excess DNA damage is rescued in ruptured nuclei by cooverexpression of multiple DNA repair factors as well as by soft matrix or inhibition of actomyosin tension. Increased contractility has the opposite effect, and stiff tumors with low lamin A indeed exhibit increased nuclear curvature, more frequent nuclear rupture, and excess DNA damage. Additional stresses likely play a role, but the data suggest high curvature promotes nuclear rupture, which compromises retention of DNA repair factors and favors sustained damage

Designing Health Information Technology Tools to Prevent Gaps in Public Health Insurance

Background: Changes in health insurance policies have increased coverage opportunities, but enrollees are required to annually reapply for benefits which, if not managed appropriately, can lead to insurance gaps. Electronic health records (EHRs) can automate processes for assisting patients with health insurance enrollment and re-enrollment.Objective: We describe community health centers' (CHC) workflow, documentation, and tracking needs for assisting families with insurance application processes, and the health information technology (IT) tool components that were developed to meet those needs.Method: We conducted a qualitative study using semi-structured interviews and observation of clinic operations and insurance application assistance processes. Data were analyzed using a grounded theory approach. We diagramed workflows and shared information with a team of developers who built the EHR-based tools.Results: Four steps to the insurance assistance workflow were common among CHCs: 1) Identifying patients for public health insurance application assistance; 2) Completing and submitting the public health insurance application when clinic staff met with patients to collect requisite information and helped them apply for benefits; 3) Tracking public health insurance approval to monitor for decisions; and 4) assisting with annual health insurance reapplication. We developed EHR-based tools to support clinical staff with each of these steps.Conclusion: CHCs are uniquely positioned to help patients and families with public health insurance applications. CHCs have invested in staff to assist patients with insurance applications and help prevent coverage gaps. To best assist patients and to foster efficiency, EHR based insurance tools need comprehensive, timely, and accurate health insurance information

The clustering of galaxies in the SDSS-III Baryon Oscillation Spectroscopic Survey: Baryon Acoustic Oscillations in the Data Release 9 Spectroscopic Galaxy Sample

We present measurements of galaxy clustering from the Baryon Oscillation Spectroscopic Survey (BOSS), which is part of the Sloan Digital Sky Survey III (SDSS-III). These use the Data Release 9 (DR9) CMASS sample, which contains 264,283 massive galaxies covering 3275 square degrees with an effective redshift z=0.57 and redshift range 0.43 < z < 0.7. Assuming a concordance Lambda-CDM cosmological model, this sample covers an effective volume of 2.2 Gpc^3, and represents the largest sample of the Universe ever surveyed at this density, n = 3 x 10^-4 h^-3 Mpc^3. We measure the angle-averaged galaxy correlation function and power spectrum, including density-field reconstruction of the baryon acoustic oscillation (BAO) feature. The acoustic features are detected at a significance of 5\sigma in both the correlation function and power spectrum. Combining with the SDSS-II Luminous Red Galaxy Sample, the detection significance increases to 6.7\sigma. Fitting for the position of the acoustic features measures the distance to z=0.57 relative to the sound horizon DV /rs = 13.67 +/- 0.22 at z=0.57. Assuming a fiducial sound horizon of 153.19 Mpc, which matches cosmic microwave background constraints, this corresponds to a distance DV(z=0.57) = 2094 +/- 34 Mpc. At 1.7 per cent, this is the most precise distance constraint ever obtained from a galaxy survey. We place this result alongside previous BAO measurements in a cosmological distance ladder and find excellent agreement with the current supernova measurements. We use these distance measurements to constrain various cosmological models, finding continuing support for a flat Universe with a cosmological constant.Comment: 33 page

The \u27Healthy Parks-Healthy People\u27 Movement in Canada: Progress, Challenges, and an Emerging Knowledge and Action Agenda

In this article, we outline progress and challenges in establishing effective health promotion tied to visitor experiences provided by protected and conserved areas in Canada. Despite an expanding global evidence base, case studies focused on aspects of health and well-being within Canada’s protected and conserved areas remain limited. Data pertaining to motivations, barriers and experiences of visitors are often not collected by governing agencies and, if collected, are not made generally available or reported on. There is an obvious, large gap in research and action focused on the needs and rights of groups facing systemic barriers related to a variety of issues including, but not limited to, access, nature experiences, and needs with respect to health and well-being outcomes. Activation of programmes at the site level continue to grow, and Park Prescription programmes, as well as changes to the Accessible Canada Act, represent significant, positive examples of recent cross-sector policy integration. Evaluations of outcomes associated with HPHP programmes have not yet occurred but will be important to adapting interventions and informing cross-sector capacity building. We conclude by providing an overview of gaps in evidence and practice that, if addressed, can lead to more effective human health promotion vis-à-vis nature contact in protected and conserved areas in Canada

A population of gamma-ray emitting globular clusters seen with the Fermi Large Area Telescope

Globular clusters with their large populations of millisecond pulsars (MSPs) are believed to be potential emitters of high-energy gamma-ray emission. Our goal is to constrain the millisecond pulsar populations in globular clusters from analysis of gamma-ray observations. We use 546 days of continuous sky-survey observations obtained with the Large Area Telescope aboard the Fermi Gamma-ray Space Telescope to study the gamma-ray emission towards 13 globular clusters. Steady point-like high-energy gamma-ray emission has been significantly detected towards 8 globular clusters. Five of them (47 Tucanae, Omega Cen, NGC 6388, Terzan 5, and M 28) show hard spectral power indices $(0.7 < \Gamma <1.4)$ and clear evidence for an exponential cut-off in the range 1.0-2.6 GeV, which is the characteristic signature of magnetospheric emission from MSPs. Three of them (M 62, NGC 6440 and NGC 6652) also show hard spectral indices $(1.0 < \Gamma < 1.7)$, however the presence of an exponential cut-off can not be unambiguously established. Three of them (Omega Cen, NGC 6388, NGC 6652) have no known radio or X-ray MSPs yet still exhibit MSP spectral properties. From the observed gamma-ray luminosities, we estimate the total number of MSPs that is expected to be present in these globular clusters. We show that our estimates of the MSP population correlate with the stellar encounter rate and we estimate 2600-4700 MSPs in Galactic globular clusters, commensurate with previous estimates. The observation of high-energy gamma-ray emission from a globular cluster thus provides a reliable independent method to assess their millisecond pulsar populations that can be used to make constraints on the original neutron star X-ray binary population, essential for understanding the importance of binary systems in slowing the inevitable core collapse of globular clusters.Comment: Accepted for publication in A&A. Corresponding authors: J. Kn\"odlseder, N. Webb, B. Pancraz

Disability and self-care living strategies among adults living with HIV during the COVID-19 pandemic

Background Events associated with the COVID-19 pandemic, such as physical distancing, closure of community services, postponement of health appointments, and loss of employment can lead to social isolation, financial uncertainty, and interruption of antiretroviral adherence, resulting in additional health-related challenges (disability) experienced among adults living with chronic illness such as HIV. ‘Living strategies’ is a concept derived from the perspectives of people living with HIV, defined as behaviors, attitudes and beliefs adopted by people living with HIV to help deal with disability associated with HIV and multi-morbidity. Our aim was to describe disability among adults living with HIV and self-care living strategies used during the COVID-19 pandemic. Methods Adults living with HIV in Toronto, Ontario, Canada, including some with pre-pandemic HIV Disability Questionnaire (HDQ) data, completed a cross-sectional web-based survey between June–August 2020. The survey included the HDQ and questions about self-care living strategy use during the pandemic. We compared disability (HDQ) scores prior to versus during the pandemic using paired t-tests. We reported the proportion of participants who engaged in various living strategies at least ‘a few times a week’ or ‘everyday’ during the pandemic. Results Of the 63 respondents, 84% were men, median age 57 years, and 62% lived alone. During the pandemic the greatest disability severity was in the uncertainty [median 30; Interquartile range (IQR): 16, 43] and mental-emotional (25; IQR: 14, 41) domains. Among the 51 participants with pre-pandemic data, HDQ severity scores were significantly greater (worse) during the pandemic (vs prior) in all domains. Greatest change from prior to during the pandemic was in the mental-emotional domain for presence (17.7; p  60%) reported engaging a ‘few times a week’ or ‘everyday’ in self-care strategies associated with maintaining sense of control and adopting positive attitudes and beliefs. Conclusions People living with HIV reported high levels of uncertainty and mental-emotional health challenges during the pandemic. Disability increased across all HDQ dimensions, with the greatest worsening in the mental-emotional health domain. Results provide an understanding of disability and self-care strategy use during the COVID-19 pandemic