Islands of non-essential genes, including a DNA translocation operon, in the genome of bacteriophage 0305ϕ8-36

We investigate genes of lytic, Bacillus thuringiensis bacteriophage 0305ϕ8-36 that are non-essential for laboratory propagation, but might have a function in the wild. We isolate deletion mutants to identify these genes. The non-permutation of the genome (218.948 Kb, with a 6.479 Kb terminal repeat and 247 identified orfs) simplifies isolation of deletion mutants. We find two islands of non-essential genes. The first island (3.01% of the genomic DNA) has an informatically identified DNA translocation operon. Deletion causes no detectable growth defect during propagation in a dilute agarose overlay. Identification of the DNA translocation operon begins with a DNA relaxase and continues with a translocase and membrane-binding anchor proteins. The relaxase is in a family, first identified here, with homologs in other bacteriophages. The second deleted island (3.71% of the genome) has genes for two metallo-protein chaperonins and two tRNAs. Deletion causes a significant growth defect. In addition, (1) we find by “in situ” (in-plaque) single-particle fluorescence microscopy that adsorption to the host occurs at the tip of the 486 nm long tail, (2) we develop a procedure of 0305ϕ8-36 purification that does not cause tail contraction, and (3) we then find by electron microscopy that 0305ϕ8-36 undergoes tail tip-tail tip dimerization that potentially blocks adsorption to host cells, presumably with effectiveness that increases as the bacteriophage particle concentration increases. These observations provide an explanation of the previous observation that 0305ϕ8-36 does not lyse liquid cultures, even though 0305ϕ8-36 is genomically lytic

Valuing Patients' Experiences of Healthcare Processes::Towards broader applications of existing methods

Healthcare policy leaders internationally recognise that people's experiences of healthcare delivery are important, and invest significant resources to monitor and improve them. However, the value of particular aspects of experiences of healthcare delivery - relative to each other and to other healthcare outcomes - is unclear. This paper considers how economic techniques have been and might be used to generate quantitative estimates of the value of particular experiences of healthcare delivery. A recently published conceptual map of patients' experiences served to guide the scope and focus of the enquiry. The map represented both what health services and staff are like and do and what individual patients can feel like, be and do (while they are using services and subsequently). We conducted a systematic search for applications of economic techniques to healthcare delivery. We found that these techniques have been quite widely used to estimate the value of features of healthcare systems and processes (e.g. of care delivery by a nurse rather than a doctor, or of a consultation of 10 minutes rather than 15 minutes), but much less to estimate the value of the implications of these features for patients personally. To inform future research relating to the valuation of experiences of healthcare delivery, we organised a workshop for key stakeholders. Participants undertook and discussed 'exercises' that explored the use of different economic techniques to value descriptions of healthcare delivery that linked processes to what patients felt like and were able to be and do. The workshop identified a number of methodological issues that need careful attention, and highlighted some important concerns about the ways in which quantitative estimates of the value of experiences of healthcare delivery might be used. However the workshop confirmed enthusiasm for efforts to attend directly to the implications of healthcare delivery from patients' perspectives, including in terms of their capabilities

Prayer and psychological health: a study among sixth-form pupils attending Catholic and Protestant schools in Northern Ireland

Eysenck's dimensional model of personality includes two indicators of psychological health, defined as neuroticism and psychoticism. In order to examine the association between psychological health and prayer, two samples of sixth-form pupils in Northern Ireland (16- to 18-year-olds) attending Catholic (N = 1246) and Protestant (N = 1060) schools completed the abbreviated Revised Eysenck Personality Questionnaire alongside a simple measure of prayer frequency. The data demonstrated a positive association between prayer frequency and better levels of psychological health as assessed by Eysenck's notion of psychoticism. Among pupils attending both Catholic and Protestant schools, higher levels of prayer were associated with lower psychoticism scores. Among pupils attending Catholic schools, however, higher levels of prayer were also associated with higher neuroticism scores

Carbon ionization at Gbar pressures: an ab initio perspective on astrophysical high-density plasmas

A realistic description of partially-ionized matter in extreme thermodynamic states is critical to model the interior and evolution of the multiplicity of high-density astrophysical objects. Current predictions of its essential property, the ionization degree, rely widely on analytical approximations that have been challenged recently by a series of experiments. Here, we propose a novel ab initio approach to calculate the ionization degree directly from the dynamic electrical conductivity using the Thomas-Reiche-Kuhn sum rule. This Density Functional Theory framework captures genuinely the condensed matter nature and quantum effects typical for strongly-correlated plasmas. We demonstrate this new capability for carbon and hydrocarbon, which most notably serve as ablator materials in inertial confinement fusion experiments aiming at recreating stellar conditions. We find a significantly higher carbon ionization degree than predicted by commonly used models, yet validating the qualitative behavior of the average atom model Purgatorio. Additionally, we find the carbon ionization state to remain unchanged in the environment of fully-ionized hydrogen. Our results will not only serve as benchmark for traditional models, but more importantly provide an experimentally accessible quantity in the form of the electrical conductivity.Comment: accepted for publication in Physical Review Researc

Dynamic Interstitial Cell Response during Myocardial Infarction Predicts Resilience to Rupture in Genetically Diverse Mice.

Cardiac ischemia leads to the loss of myocardial tissue and the activation of a repair process that culminates in the formation of a scar whose structural characteristics dictate propensity to favorable healing or detrimental cardiac wall rupture. To elucidate the cellular processes underlying scar formation, here we perform unbiased single-cell mRNA sequencing of interstitial cells isolated from infarcted mouse hearts carrying a genetic tracer that labels epicardial-derived cells. Sixteen interstitial cell clusters are revealed, five of which were of epicardial origin. Focusing on stromal cells, we define 11 sub-clusters, including diverse cell states of epicardial- and endocardial-derived fibroblasts. Comparing transcript profiles from post-infarction hearts in C57BL/6J and 129S1/SvImJ inbred mice, which displays a marked divergence in the frequency of cardiac rupture, uncovers an early increase in activated myofibroblasts, enhanced collagen deposition, and persistent acute phase response in 129S1/SvImJ mouse hearts, defining a crucial time window of pathological remodeling that predicts disease outcome

Behind the curtain of the "Ultimate Empathy Machine"

Virtual Reality nonfiction (VRNF) is an emerging form of immersive media experience created for consumption using panoramic “Virtual Reality" headsets. VRNF promises nonfiction content producers the potential to create new ways for audiences to experience “the real"; allowing viewers to transition from passive spectators to active participants. Our current project is exploring VRNF through a series of ethnographic and experimental studies. In order to document the content available, we embarked on an analysis of VR documentaries produced to date. In this paper, we present an analysis of a representative sample of 150 VRNF titles released between 2012-2018. We identify and quantify 64 characteristics of the medium over this period, discuss how producers are exploiting the affordances of VR, and shed light on new audience roles. Our findings provide insight into the current state of the art in VRNF and provide a digital resource for other researchers in this area

Inhibition of histone deacetylase 6 (HDAC6) protects against vincristine-induced peripheral neuropathies and inhibits tumor growth

As cancer is becoming more and more a chronic disease, a large proportion of patients is confronted with devastating side effects of certain anti-cancer drugs. The most common neurological complications are painful peripheral neuropathies. Chemotherapeutics that interfere with microtubules, including plant-derived vinca-alkaloids such as vincristine, can cause these chemotherapy-induced peripheral neuropathies (CIPN). Available treatments focus on symptom alleviation and pain reduction rather than prevention of the neuropathy. The aim of this study was to investigate the potential of specific histone deacetylase 6 (HDAC6) inhibitors as a preventive therapy for CIPN using multiple rodent models for vincristine-induced peripheral neuropathies (VIPN). HDAC6 inhibition increased the level of acetylated α-tubulin in tissues of rodents undergoing vincristine-based chemotherapy, which correlates to a reduced severity of the neurological symptoms, both at the electrophysiological and the behavioral level. Mechanistically, disturbances in axonal transport of mitochondria is considered as an important contributing factor in the pathophysiology of VIPN. As vincristine interferes with the polymerization of microtubules, we investigated whether disturbances in axonal transport could contribute to VIPN. We observed that increasing α-tubulin acetylation through HDAC6 inhibition restores vincristine-induced defects of axonal transport in cultured dorsal root ganglion neurons. Finally, we assured that HDAC6-inhibition offers neuroprotection without interfering with the anti-cancer efficacy of vincristine using a mouse model for acute lymphoblastic leukemia. Taken together, our results emphasize the therapeutic potential of HDAC6 inhibitors with beneficial effects both on vincristine-induced neurotoxicity, as well as on tumor proliferation. ispartof: Neurobiology of Disease vol:111 pages:59-69 ispartof: location:United States status: publishe