Agnogene Deletion in a Novel Pathogenic JC Virus Isolate Impairs VP1 Expression and Virion Production

Infection of glial cells by the human polyomavirus JC (JCV) causes progressive multifocal leukoencephalopathy (PML). JCV Encephalopathy (JCVE) is a newly identified disease characterized by JCV infection of cortical pyramidal neurons. The virus JCVCPN associated with JCVE contains a unique 143 base pair deletion in the agnogene. Contrary to most JCV brain isolates, JCVCPN has an archetype-like regulatory region (RR) usually found in kidney strains. This provided us with the unique opportunity to determine for the first time how each of these regions contributed to the phenotype of JCVCPN. We characterized the replication of JCVCPN compared to the prototype virus JCVMad-1 in kidney, glial and neuronal cell lines. We found that JCVCPN is capable of replicating viral DNA in all cell lines tested, but is unable to establish persistent infection seen with JCVMad-1. JCVCPN does not have an increased ability to replicate in the neuronal cell line tested. To determine whether this phenotype results from the archetype-like RR or the agnogene deletion, we generated chimeric viruses between JCVCPN of JCVMad-1. We found that the deletion in the agnogene is the predominant cause of the inability of the virus to maintain a persistent infection, with the introduction of a full length agnogene, either with or without agnoprotein expression, rescues the replication of JCVCPN. Studying this naturally occurring pathogenic variant of JCV provides a valuable tool for understanding the functions of the agnogene and RR form in JCV replication

Embodied Knowledge: Writing Researchers’ Bodies Into Qualitative Health Research

After more than a decade of postpositivist health care research and an increase in narrative writing practices, social scientific, qualitative health research remains largely disembodied. The erasure of researchers’ bodies from conventional accounts of research obscures the complexities of knowledge production and yields deceptively tidy accounts of research. Qualitative health research could benefit significantly from embodied writing that explores the discursive relationship between the body and the self and the semantic challenges of writing the body by incorporating bodily details and experiences into research accounts. Researchers can represent their bodies by incorporating autoethnographic narratives, drawing on all of their senses, interrogating the connections between their bodily signifiers and research processes, and experimenting with the semantics of self and body. The author illustrates opportunities for embodiment with excerpts from an ethnography of a geriatric oncology team and explores implications of embodied writing for the practice of qualitative health research

Towards W b bbar + j at NLO with an automatized approach to one-loop computations

We present results for the O(alpha_s) virtual corrections to q g -> W b bbar q' obtained with a new automatized approach to the evaluation of one-loop amplitudes in terms of Feynman diagrams. Together with the O(alpha_s) corrections to q q' -> W b bbar g, which can be obtained from our results by crossing symmetry, this represents the bulk of the next-to-leading order virtual QCD corrections to W b bbar + j and W b + j hadronic production, calculated in a fixed-flavor scheme with four light flavors. Furthermore, these corrections represent a well defined and independent subset of the 1-loop amplitudes needed for the NNLO calculation of W b bbar. Our approach was tested against several existing results for NLO amplitudes including selected O(alpha_s) one-loop corrections to W + 3 j hadronic production. We discuss the efficiency of our method both with respect to evaluation time and numerical stability.Comment: 14 pages, 3 figure

Quantum-limited optical time transfer for future geosynchronous links

The combination of optical time transfer and optical clocks opens up the possibility of large-scale free-space networks that connect both ground-based optical clocks and future space-based optical clocks. Such networks promise better tests of general relativity, dark matter searches, and gravitational wave detection. The ability to connect optical clocks to a distant satellite could enable space-based very long baseline interferometry (VLBI), advanced satellite navigation, clock-based geodesy, and thousand-fold improvements in intercontinental time dissemination. Thus far, only optical clocks have pushed towards quantum-limited performance. In contrast, optical time transfer has not operated at the analogous quantum limit set by the number of received photons. Here, we demonstrate time transfer with near quantum-limited acquisition and timing at 10,000 times lower received power than previous approaches. Over 300 km between mountaintops in Hawaii with launched powers as low as 40 $\mu$W, distant timescales are synchronized to 320 attoseconds. This nearly quantum-limited operation is critical for long-distance free-space links where photons are few and amplification costly -- at 4.0 mW transmit power, this approach can support 102 dB link loss, more than sufficient for future time transfer to geosynchronous orbits

Disaggregating the evidence linking biodiversity and ecosystem services

Ecosystem services (ES) are an increasingly popular policy framework for connecting biodiversity with human well-being. These efforts typically assume that biodiversity and ES covary, but the relationship between them remains remarkably unclear. Here we analyse \u3e500 recent papers and show that reported relationships differ among ES, methods of measuring biodiversity and ES, and three different approaches to linking them (spatial correlations, management comparisons and functional experiments). For spatial correlations, biodiversity relates more strongly to measures of ES supply than to resulting human benefits. For management comparisons, biodiversity of â € service providers\u27 predicts ES more often than biodiversity of functionally unrelated taxa, but the opposite is true for spatial correlations. Functional experiments occur at smaller spatial scales than management and spatial studies, which show contrasting responses to scale. Our results illuminate the varying dynamics relating biodiversity to ES, and show the importance of matching management efforts to the most relevant scientific evidence

Impact of disease, cognitive and behavioural factors on caregiver outcome in amyotrophic lateral sclerosis

Up to 50% of patients with amyotrophic lateral sclerosis (ALS) show mild to moderate cognitive-behavioural change alongside their progressive functional impairment. This study examines the relative impact of patients' disease symptoms, behavioural change and current executive function and social cognition abilities on psychosocial outcomes in spouse caregivers of people with ALS. Thirty-five spouse caregivers rated their own levels of depression and anxiety, subjective burden and marital satisfaction. Caregivers also rated their partner's everyday behaviour. The patients were assessed for disease severity and cognitive function, with composite scores derived for executive function and social cognition. Regression analyses revealed that caregiver burden was predicted by the severity of patients' limb involvement and behavioural problems. Depression was predicted by patients' limb involvement, while behavioural problems and patient age predicted caregiver anxiety. Current marital satisfaction was predicted by patient behavioural problems beyond the level of pre-illness marital satisfaction. In conclusion, the study highlights the potential impact of ALS patients' functional impairment and behavioural change on ALS caregivers' psychosocial functioning. Clinical communication with ALS families should emphasise both physical and psychological challenges presented by the disease

Are deprivation-specific cancer survival patterns similar according to individual- and area-based measures? A cohort study of patients diagnosed with five malignancies in England & Wales, 2008-2016

Objective: To investigate if measured inequalities in cancer survival differ when using individual- (‘person’) compared to area- (‘place’) based measures of deprivation for three socio-economic dimensions: income, deprivation and occupation Design: Cohort studySetting: Data from the Office for National Statistics (ONS) Longitudinal Study of England and Wales, UK, linked to the National Cancer Registration DatabaseParticipants: Patients diagnosed with cancers of the colorectum, breast, prostate, bladder or with Non-Hodgkin Lymphoma (NHL) during the period 2008-2016Primary and secondary outcome measures: Differentials in net survival between groups defined by individual wage, occupation and education compared to those obtained from corresponding area-level metrics using the English and Welsh Indices of Multiple Deprivation (IMD).Results: Survival was negatively associated with area-based deprivation irrespective of the type analysed, although a trend from least to most deprived was not always observed. Socio-economic differences were present according to individually-measured socio-economic groups although there was an absence of a consistent ‘gradient’ in survival. The magnitude of differentials was similar for area-based and individually-derived measures of deprivation, which was unexpected.Conclusion: These unique data suggest that the socio-economic influence of ‘person’ is different to that of ‘place’ with respect to cancer outcomes. This has implications for health policy aimed at reducing inequalities. Further research could further consider the separate and additional influence of area-based deprivation over individual-level characteristics (contextual effects) as well as investigate the geographic, socio-economic and healthcare related characteristics of areas with poor outcomes in order to inform policy intervention

Eavesdropping on the Arctic: Automated bioacoustics reveal dynamics in songbird breeding phenology

Bioacoustic networks could vastly expand the coverage of wildlife monitoring to complement satellite observations of climate and vegetation. This approach would enable global-scale understanding of how climate change influences phenomena such as migratory timing of avian species. The enormous data sets that autonomous recorders typically generate demand automated analyses that remain largely undeveloped. We devised automated signal processing and machine learning approaches to estimate dates on which songbird communities arrived at arctic breeding grounds. Acoustically estimated dates agreed well with those determined via traditional surveys and were strongly related to the landscape’s snow-free dates. We found that environmental conditions heavily influenced daily variation in songbird vocal activity, especially before egg laying. Our novel approaches demonstrate that variation in avian migratory arrival can be detected autonomously. Large-scale deployment of this innovation in wildlife monitoring would enable the coverage necessary to assess and forecast changes in bird migration in the face of climate change

Association between recent overdose and chronic pain among individuals in treatment for opioid use disorder

Chronic pain increases risk for opioid overdose among individuals with opioid use disorder. The purpose of this study is to evaluate the relationship between recent overdose and whether or not chronic pain is active. 3,577 individuals in treatment for opioid use disorder in 2017 or 2018 were surveyed regarding recent overdoses and chronic pain. Demographics from the 2017 Treatment Episode Data Set, which includes all U.S. facilities licensed or certified to provide substance use care, were used to evaluate the generalizability of the sample. χ2 tests and logistic regression models were used to compare associations between recent overdoses and chronic pain. Specifically, active chronic pain was associated with opioid overdose among people in treatment for opioid use disorder. Individuals with active chronic pain were more likely to have had a past month opioid overdose than those with no history chronic pain (adjusted OR = 1.55, 95% CI 1.16-2.08, p = 0.0003). In contrast, individuals with prior chronic pain, but no symptoms in the past 30 days, had a risk of past month opioid overdose similar to those with no history of chronic pain (adjusted OR = 0.88, 95% CI 0.66-1.17, p = 0.38). This suggests that the incorporation of treatment for chronic pain into treatment for opioid use disorder may reduce opioid overdoses

Jasmonate promotes auxin-induced adventitious rooting in dark-grown Arabidopsis thaliana seedlings and stem thin cell layers by a cross-talk with ethylene signalling and a modulation of xylogenesis

Background: Adventitious roots (ARs) are often necessary for plant survival, and essential for successful micropropagation. In Arabidopsis thaliana dark-grown seedlings AR-formation occurs from the hypocotyl and is enhanced by application of indole-3-butyric acid (IBA) combined with kinetin (Kin). The same IBA + Kin-treatment induces AR-formation in thin cell layers (TCLs). Auxin is the main inducer of AR-formation and xylogenesis in numerous species and experimental systems. Xylogenesis is competitive to AR-formation in Arabidopsis hypocotyls and TCLs. Jasmonates (JAs) negatively affect AR-formation in de-etiolated Arabidopsis seedlings, but positively affect both AR-formation and xylogenesis in tobacco dark-grown IBA + Kin TCLs. In Arabidopsis the interplay between JAs and auxin in AR-formation vs xylogenesis needs investigation. In de-etiolated Arabidopsis seedlings, the Auxin Response Factors ARF6 and ARF8 positively regulate AR-formation and ARF17 negatively affects the process, but their role in xylogenesis is unknown. The cross-talk between auxin and ethylene (ET) is also important for AR-formation and xylogenesis, occurring through EIN3/EIL1 signalling pathway. EIN3/EIL1 is the direct link for JA and ET-signalling. The research investigated JA role on AR-formation and xylogenesis in Arabidopsis dark-grown seedlings and TCLs, and the relationship with ET and auxin. The JA-donor methyl-jasmonate (MeJA), and/or the ET precursor 1-aminocyclopropane-1-carboxylic acid were applied, and the response of mutants in JA-synthesis and -signalling, and ET-signalling investigated. Endogenous levels of auxin, JA and JA-related compounds, and ARF6, ARF8 and ARF17 expression were monitored. Results: MeJA, at 0.01 μM, enhances AR-formation, when combined with IBA + Kin, and the response of the early-JA-biosynthesis mutant dde2–2 and the JA-signalling mutant coi1–16 confirmed this result. JA levels early change during TCL-culture, and JA/JA-Ile is immunolocalized in AR-tips and xylogenic cells. The high AR-response of the late JA-biosynthesis mutant opr3 suggests a positive action also of 12-oxophytodienoic acid on AR-formation. The crosstalk between JA and ET-signalling by EIN3/EIL1 is critical for AR-formation, and involves a competitive modulation of xylogenesis. Xylogenesis is enhanced by a MeJA concentration repressing AR-formation, and is positively related to ARF17 expression. Conclusions: The JA concentration-dependent role on AR-formation and xylogenesis, and the interaction with ET opens the way to applications in the micropropagation of recalcitrant species