Regulated Inositol‐Requiring Protein 1‐Dependent Decay as a Mechanism of Corin RNA and Protein Deficiency in Advanced Human Systolic Heart Failure

BACKGROUND: The compensatory actions of the endogenous natriuretic peptide system require adequate processing of natriuretic peptide pro‐hormones into biologically active, carboxyl‐terminal fragments. Natriuretic peptide pro‐peptide processing is accomplished by corin, a transmembrane serine protease expressed by cardiomyocytes. Brain natriuretic peptide (BNP) processing is inadequate in advanced heart failure and is independently associated with adverse outcomes; however, the molecular mechanisms causing impaired BNP processing are not understood. We hypothesized that the development of endoplasmic reticulum stress in cardiomyocytes in advanced heart failure triggers inositol‐requiring protein 1 (IRE1)‐dependent corin mRNA decay, which would favor a molecular substrate favoring impaired natriuretic peptide pro‐peptide processing. METHODS AND RESULTS: Two independent samples of hearts obtained from patients with advanced heart failure at transplant demonstrated that corin RNA was reduced as Atrial natriuretic peptide (ANP)/BNP RNA increased. Increases in spliced X‐box protein 1, a marker for IRE1‐endoribonuclease activity, were associated with decreased corin RNA. Moreover, ≈50% of the hearts demonstrated significant reductions in corin RNA and protein as compared to the nonfailing control sample. In vitro experiments demonstrated that induction of endoplasmic reticulum stress in cultured cardiomyocytes with thapsigargin activated IRE1s endoribonuclease activity and time‐dependent reductions in corin mRNA. In HL‐1 cells, overexpression of IRE1 activated IRE1 endoribonuclease activity and caused corin mRNA decay, whereas IRE1‐RNA interference with shRNA attenuated corin mRNA decay after induction of endoplasmic reticulum stress with thapsigargin. Pre‐treatment of cells with Actinomycin D to inhibit transcription did not alter the magnitude or time course of thapsigargin‐induced corin mRNA decline, supporting the hypothesis that this was the result of IRE1‐mediated corin mRNA degradation. CONCLUSIONS: These data support the hypothesis that endoplasmic reticulum stress‐mediated, IRE1‐dependent targeted corin mRNA decay is a mechanism leading to corin mRNA resulting in corresponding corin protein deficiency may contribute to the pathophysiology of impaired natriuretic peptide pro‐hormone processing in humans processing in humans with advanced systolic heart failure

Preservice Teachers’ Self-efficacy Through COVID-19: A Large Scale Survey of Students at a Regional University In Australia

Throughout 2020, the world was significantly impacted by the COVID-19 pandemic. In the context of higher education, the pandemic critically affected professional experience, a core component of teacher education. This paper shares data from a large-scale survey about teachers’ sense of self-efficacy and the impact of COVID-19 on professional experience. Findings showed that the disrupted context had a moderate effect of pre-service teachers’ self-efficacy in relation to their classroom management, instructional strategies, and student engagement. Qualitative results illuminated that the modes of learning, changing classroom contexts and communication between the pre-service teachers, school and their university were the underlying contextual factors that impacted pre-service teacher’s self-efficacy. Implications from these findings challenge universities to consider how to best support pre-service teachers’ progression in times of disruption and consider how Initial Teacher Education (ITE) programs prepare pre-service teachers to teach in disrupted classrooms

The Making of \u3ci\u3eAlways Coming Home\u3c/i\u3e

Transcript of panel discussion from 1988 Mythopoeic Conference. Author, illustrator, composer, and cartographer/ researcher discuss the genesis of Always Coming Home

Galaxy Pairs in the 2dF Survey I. Effects of Interactions in the Field

We study galaxy pairs in the field selected from the 100 K public release of the 2dF galaxy redshift survey. Our analysis provides a well defined sample of 1258 galaxy pairs, a large database suitable for statistical studies of galaxy interactions in the local universe, $z \le 0.1$. Galaxy pairs where selected by radial velocity ($\Delta V$) and projected separation ($r_{\rm p}$) criteria determined by analyzing the star formation activity within neighbours (abridged). The ratio between the fractions of star forming galaxies in pairs and in isolation is a useful tools to unveil the effects of having a close companion. We found that about fifty percent of galaxy pairs do not show signs of important star formation activity (independently of their luminosities) supporting the hypothesis that the internal properties of the galaxies play a crucial role in the triggering of star formation by interactions.Comment: 9 pages, 11 Postscript figures. Submitted to MNRAS. Revised versio

Integration of a failure monitoring within a hybrid dynamic simulation environment

The complexity and the size of the industrial chemical processes induce the monitoring of a growing number of process variables. Their knowledge is generally based on the measurements of system variables and on the physico-chemical models of the process. Nevertheless this information is imprecise because of process and measurement noise. So the research ways aim at developing new and more powerful techniques for the detection of process fault. In this work, we present a method for the fault detection based on the comparison between the real system and the reference model evolution generated by the extended Kalman filter. The reference model is simulated by the dynamic hybrid simulator, PrODHyS. It is a general object-oriented environment which provides common and reusable components designed for the development and the management of dynamic simulation of industrial systems. The use of this method is illustrated through a didactic example relating to the field of Chemical Process System Engineering

Analytic Metaphysics versus Naturalized Metaphysics: The Relevance of Applied Ontology

The relevance of analytic metaphysics has come under criticism: Ladyman & Ross, for instance, have suggested do discontinue the field. French & McKenzie have argued in defense of analytic metaphysics that it develops tools that could turn out to be useful for philosophy of physics. In this article, we show first that this heuristic defense of metaphysics can be extended to the scientific field of applied ontology, which uses constructs from analytic metaphysics. Second, we elaborate on a parallel by French & McKenzie between mathematics and metaphysics to show that the whole field of analytic metaphysics, being useful not only for philosophy but also for science, should continue to exist as a largely autonomous field

Métaphysique analytique, métaphysique naturalisée et ontologie appliquée

La pertinence de la métaphysique analytique a fait l'objet de critiques : Ladyman et Ross, par exemple, ont suggéré d'abandonner ce domaine. French et McKenzie ont défendu la métaphysique analytique en affirmant qu'elle développe des outils qui pourraient s'avérer utiles pour la philosophie de la physique. Dans cet article, nous montrons dans un premier temps que cette défense heuristique de la métaphysique peut être étendue au domaine scientifique de l'ontologie appliquée, qui utilise des théories et outils issus de la métaphysique analytique. Dans un deuxième temps, nous développons le parallèle que font French et McKenzie entre les mathématiques et la métaphysique pour montrer que l'ensemble du domaine de la métaphysique analytique, étant donné son utilité non seulement pour la philosophie mais également pour la science, devrait continuer à exister en tant que domaine largement autonome

Analytic Metaphysics versus Naturalized Metaphysics: The Relevance of Applied Ontology

The relevance of analytic metaphysics has come under criticism: Ladyman & Ross, for instance, have suggested do discontinue the field. French & McKenzie have argued in defense of analytic metaphysics that it develops tools that could turn out to be useful for philosophy of physics. In this article, we show first that this heuristic defense of metaphysics can be extended to the scientific field of applied ontology, which uses constructs from analytic metaphysics. Second, we elaborate on a parallel by French & McKenzie between mathematics and metaphysics to show that the whole field of analytic metaphysics, being useful not only for philosophy but also for science, should continue to exist as a largely autonomous field

Incorporating organic matter alters soil greenhouse gas emissions and increases grain yield in a semi-arid climate

© 2016 The Authors Increasing soil organic matter (OM) is promoted as a strategy for improving the resilience of coarse-textured cropping soils in semi-arid climates. While increasing soil OM can benefit crop productivity, it can also enhance nitrous oxide (N2O) emissions in temperate climates. Our objective was to investigate if increasing soil OM affected soil greenhouse gas (GHG) fluxes and grain production in a semi-arid region in south-western Australia. We firstly measured N2O and methane (CH4) fluxes from a free-draining sandy soil with contrasting soil OM content for 2.5 years using automated soil chambers. The randomized block design included two OM additions (no OM, plus OM) by two nitrogen (N) fertilizer rates (0, 0N; 100 kg N ha-1 yr-1, +N) by three replicate plots. Organic matter (chaff) had been applied to the plus OM treatments every three years since 2003, with 80 t OM ha-1applied in total. Secondly, we investigated the interaction between soil OM content and N fertilizer addition on grain yield for two growing seasons. The randomized split-plot design included two OM treatments by five N fertilizer rates (0, 25, 50, 75 and 100 kg N ha-1), by three replicates. Increasing soil OM increased grain yields and soil mineral N, but also enhanced soil N2O emissions. Nitrous oxide emissions were low by international standards (<0.12% of the N fertilizer applied), with total N2O emissions after two years ranked: plus OM (+N; 427 g N2O-N ha-1) > plus OM (0N; 194 g N2O-N ha-1) > no OM (+N; 41 g N2O-N ha-1) = no OM (0N; 14 g N2O-N ha-1). Increasing soil OM also decreased CH4uptake by 30%. Management practices that increase soil OM in sandy-textured rainfed, cropping soils in semi-arid regions should be encouraged as they can improve grain yield without substantial increases in soil N2O or CH4emissions

International students' perception of workplace experiences in Australian study programs: a large-scale survey

Across the globe there are increased numbers of students undertaking university level study in foreign countries. Many of the programs they enrol in, include a workplace experience (also known as work integrated learning, internship and/or practicum). The Work Placement for International Student Programs (WISP) project was conducted across Australia and aimed to identify current practices related to international students’ workplace experiences as well as develop resources to improve these experiences overall. This paper focuses on a large-scale survey distributed to international students (n=252) throughout Australia to explore their perception of their experience whilst on their required placement. Results showed that students rated their overall workplace experience highly however, their confidence in completing assessment items where reflection and self-evaluation were required was a concern. Students also rated their self-perception of employability as uncertain despite having positive experiences in the workplace context. Findings showed that there is a need for universities to better support international students in completing reflective and self-evaluative assessment. In addition, more work needs to be done to improve confidence levels of international students around employability