Targeted disruption of the heat shock protein 20–phosphodiesterase 4D (PDE4D) interaction protects against pathological cardiac remodelling in a mouse model of hypertrophy

Phosphorylated heat shock protein 20 (HSP20) is cardioprotective. Using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and a mouse model of pressure overload mediated hypertrophy, we show that peptide disruption of the HSP20–phosphodiesterase 4D (PDE4D) complex results in attenuation of action potential prolongation and protection against adverse cardiac remodelling. The later was evidenced by improved contractility, decreased heart weight to body weight ratio, and reduced interstitial and perivascular fibrosis. This study demonstrates that disruption of the specific HSP20–PDE4D interaction leads to attenuation of pathological cardiac remodelling

Application and Assessment of a Rapid Riparian Creek Assessment Tool in Ku-ring-gai Council, Sydney, Australia

Abstract Urbanisation is the principal cause of physical and ecological degradation in urban stream systems around the world. In Australia, legislation centred on the ideals of Ecologically Sustainable Development require local governments to protect and maintain the environment and conduct regular environmental auditing via State of the Environment reporting procedures. In order to achieve these aims effectively, a thorough understanding of local stream processes and potential intervention methods is required, an often very complex task for systems situated within urban landscapes. To assist in these legislative requirements, Macquarie University and Ku-ring-gai Council (Sydney) have developed a prototype method for assessing the biophysical condition of urban riparian zones, referred to as the Rapid Riparian Assessment (RRA). Multiple, independent data sets comprised of significant riparian features and processes such as weed density, water quality and percent impervious surface cover will be compared to RRA scores to verify how effectively the tool reflects the true condition and health of the stream-reach

Orchestration of Adaptive T Cell Responses by Neutrophil Granule Contents

Neutrophils are the most abundant leukocytes in peripheral blood and respond rapidly to danger, infiltrating tissues within minutes of infectious or sterile injury. Neutrophils were long thought of as simple killers, but now we recognise them as responsive cells able to adapt to inflammation and orchestrate subsequent events with some sophistication. Here, we discuss how these rapid responders release mediators which influence later adaptive T cell immunity through influences on DC priming and directly on the T cells themselves. We consider how the release of granule contents by neutrophils—through NETosis or degranulation—is one way in which the innate immune system directs the phenotype of the adaptive immune response

Declaration of medical writing assistance in international peer-reviewed publications

Medical researchers have an ethical and scientific obligation to publish, but between one third and two thirds of research may remain unpublished. A major reason for nonpublication is lack of time, which may lead researchers to seek medical writing assistance. Guidelines from journal editors and medical writers encourage authors to acknowledge medical writers. We quantified the proportion of articles from international, peer-reviewed, high-ranking journals that reported medical writing assistance

Cyclic AMP-specific phosphodiesterase, PDE8A1, is activated by protein kinase A-mediated phosphorylation

The cyclic AMP-specific phosphodiesterase PDE8 has been shown to play a pivotal role in important processes such as steroidogenesis, T cell adhesion, regulation of heart beat and chemotaxis. However, no information exists on how the activity of this enzyme is regulated. We show that under elevated cAMP conditions, PKA acts to phosphorylate PDE8A on serine 359 and this action serves to enhance the activity of the enzyme. This is the first indication that PDE8 activity can be modulated by a kinase, and we propose that this mechanism forms a feedback loop that results in the restoration of basal cAMP levels. (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserve

cAMP-phosphodiesterase 4D7 (PDE4D7) forms a cAMP signalosome complex with DHX9 and is implicated in prostate cancer progression

A robust body of work has demonstrated that a reduction in cAMP-specific 3′,5′-cyclic phosphodiesterase 4D isoform 7 (PDE4D7) is linked with negative prostate cancer outcomes; however, the exact molecular mechanism that underpins this relationship is unknown. Epigenetic profiling has shown that the PDE4D gene can be hyper-methylated in transmembrane serine protease 2 (TMPRSS2)–ETS transcriptional regulator ERG (ERG) gene-fusion-positive prostate cancer (PCa) tumours, and this inhibits messenger RNA (mRNA) expression, leading to a paucity of cellular PDE4D7 protein. In an attempt to understand how the resulting aberrant cAMP signalling drives PCa growth, we immunopurified PDE4D7 and identified binding proteins by mass spectrometry. We used peptide array technology and proximity ligation assay to confirm binding between PDE4D7 and ATP-dependent RNA helicase A (DHX9), and in the design of a novel cell-permeable disruptor peptide that mimics the DHX9-binding region on PDE4D7. We discovered that PDE4D7 forms a signalling complex with the DExD/H-box RNA helicase DHX9. Importantly, disruption of the PDE4D7–DHX9 complex reduced proliferation of LNCaP cells, suggesting the complex is pro-tumorigenic. Additionally, we have identified a novel protein kinase A (PKA) phosphorylation site on DHX9 that is regulated by PDE4D7 association. In summary, we report the existence of a newly identified PDE4D7–DHX9 signalling complex that may be crucial in PCa pathogenesis and could represent a potential therapeutic target

Post-prandial effects of a meal rich in long-chain omega-3 fatty acids on indicators of cardiovascular risk

Funding was provided through a joint funding initiative from the Institute for Health & Welfare Research at RGU and QMUIntroduction Evidence from epidemiological studies indicates that the regular consumption of oily fish may be protective against the risk of cardiovascular disease. The benefits appear to be related to the content of long-chain omega-3 fatty acids (LC n-3 PUFA), specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Current UK dietary guidelines therefore recommend the consumption of two portions of fish per week, one of which should be oily (1), which equates to 0.45g LC n-3 PUFA per day. Although there is limited information about intakes of EPA and DHA in Scotland, recent studies show that they are consistently below recommendations (2). Further review of the dietary intake data indicates that the consumption of oily fish is sporadic and inconsistent (3) despite attempts to promote regular intake. Several of the mechanisms involved in the development of cardiovascular disease (CVD) involve endothelial function. Post-prandial hyperlipidaemia has been linked to an increased risk of CVD (4), which is largely attributed to the transient (2-6 hour) decrease in endothelial function (5). Changes in endothelial function have also been shown to be associated with superoxide production (6), implicating oxidative stress as a possible mechanism for endothelial dysfunction. The long-term effects of LC n-3 PUFA on oxidative stress and inflammation are well established, however little is known about their immediate post-prandial effects. Identifying the possible benefits of consumption of a single meal rich in LC n-3 PUFA may provide a new perspective on which to promote dietary changes. The aim of this pilot project was therefore to identify post-prandial changes in markers of cardiovascular risk, assessed by measurement of arterial compliance, whole blood fatty acid profile, plasma glucose and insulin, markers of endothelial dysfunction, oxidative stress and antioxidant status in response a test meal naturally rich LC n-3 PUFA compared with a control meal.sch_dieunpub2825unpu

Mapping the links between gender, status and genre in Shakespeare’s plays

The AHRC-funded Encyclopedia of Shakespeare’s Language (ESL) project has produced a resource allowing users to explore Shakespeare’s plays in a variety of (semi-automatic) ways, via a web-based corpus query processor interface (CQPweb) hosted by Lancaster University. It enables users, for example, to interrogate a corpus of Shakespeare’s plays using queries restricted by dramatic genre, gender and/or social status of characters, and to target and explore the language of the plays not only at the word level, but also at the grammatical and semantic levels (by querying part-of-speech or semantic categories). Using keyword techniques, we examine how female and male language varies in general, by social status (high or low), and by genre (comedy, history and tragedy). Among our findings, we note differences in the use of pronouns and references to male authority (female overuse of ‘I’ and ‘husband’; male overuse of ‘we’ and ‘king’). We also observe that high-status males in comedies (as opposed to histories and tragedies) are characterised by polite requests (‘please you’) and sharp-minded ‘wit’. Despite many similarities between female and male usage of gendered forms of language (‘woman’), male characters alone use terms such as ‘womanish’ in a disparaging way

Clinical Oncology Society of Australia: Position statement on cancer-related malnutrition and sarcopenia

© 2020 The Authors. Nutrition & Dietetics published by John Wiley & Sons Australia, Ltd on behalf of Dietitians Australia. This position statement describes the recommendations of the Clinical Oncology Society of Australia (COSA) regarding management of cancer-related malnutrition and sarcopenia. A multidisciplinary working group completed a review of the literature, focused on evidence-based guidelines, systematic reviews and meta-analyses, to develop recommendations for the position statement. National consultation of the position statement content was undertaken through COSA members. All people with cancer should be screened for malnutrition and sarcopenia in all health settings at diagnosis and as the clinical situation changes throughout treatment and recovery. People identified as “at risk” of malnutrition or with a high-risk cancer diagnosis or treatment plan should have a comprehensive nutrition assessment; people identified as “at risk” of sarcopenia should have a comprehensive evaluation of muscle status using a combination of assessments for muscle mass, muscle strength and function. All people with cancer-related malnutrition and sarcopenia should have access to the core components of treatment, including medical nutrition therapy, targeted exercise prescription and physical and psychological symptom management. Treatment for cancer-related malnutrition and sarcopenia should be individualised, in collaboration with the multidisciplinary team (MDT), and tailored to meet needs at each stage of cancer treatment. Health services should ensure a broad range of health care professionals across the MDT have the skills and confidence to recognise malnutrition and sarcopenia to facilitate timely referrals and treatment. The position statement is expected to provide guidance at a national level to improve the multidisciplinary management of cancer-related malnutrition and sarcopenia