Structure and Dynamics of Metalloproteins in Live Cells

X-ray absorption spectroscopy (XAS) has emerged as one of the premier tools for investigating the structure and dynamic properties of metals in cells and in metal containing biomolecules. Utilizing the high flux and broad energy range of X-rays supplied by synchrotron light sources, one can selectively excite core electronic transitions in each metal. Spectroscopic signals from these electronic transitions can be used to dissect the chemical architecture of metals in cells, in cellular components and in biomolecules at varying degrees of structural resolution. With the development of ever-brighter X-ray sources, X-ray methods have grown into applications that can be utilized to provide both a cellular image of relative distribution of metals throughout the cell as well as a high-resolution picture of the structure of the metal. As these techniques continue to grow in their capabilities and ease of use, so to does the demand for their application by chemists and biochemists interested in studying the structure and dynamics of metals in cells, in cellular organelles and in metalloproteins

Acute rotator cuff tendinopathy: does ice, low load isometric exercise, or a combination of the two produce an analgaesic effect?

This document is the Accepted Manuscript version of the following article: Parle PJ, Riddiford-Harland DL, Howitt CD, et al. 'Acute rotator cuff tendinopathy: does ice, low load isometric exercise, or a combination of the two produce an analgaesic effect?.' Br J Sports Med 2017;51:208-209, doi: http://dx.doi.org/10.1136/bjsports-2016-096107.Rotator cuff tendinopathies are the most commonly diagnosed musculoskeletal shoulder conditions and are associated with pain, weakness and loss of function.1 Tendon swelling may be associated with tendinopathy and may result from acute overload.2–3 An increase in tendon cells (tenocytes) and upregulation of large molecular weight proteoglycans, such as aggrecan, may increase tendon water content.2 There is uncertainty as to whether the swelling is related to the pain or is instead an observed but unrelated phenomenon. Weakness detected clinically may be due to pain inhibition.4–5 Early treatment of acute rotator cuff tendinopathy involves patient education and relative rest, and may include non-steroidal anti-inflammatory drugs (NSAIDs) to reduce pain, swelling and inflammation. Subacromial corticosteroid injections are also used to achieve the same purpose. These techniques show low to moderate evidence of reducing short-term pain but they do not improve function.6 The medications have side effects such as gastrointestinal tract complaints,7 and corticosteroids may damage tendon tissue.8 Identifying alternative ways to control pain and inflammation may be warranted. Two clinical procedures to manage RC tendinopathy include ice wraps and isometric exercise, however, there are no empirical data supporting their use. This pilot study, conducted at the Illawarra Sports Medicine Clinic, NSW, Australia, was designed to test (1) the short term analgaesic effect of these interventions and (2) the feasibility of a larger clinical trial for adults diagnosed with acute rotator cuff tendinopathy (<12 weeks).Peer reviewe

Self-Assembly and Disassembly of the SNARE Complex: Examined Using Circular Dichroism and Atomic Force Microscopy

In this study, we report for the first time that both t-SNAREs and v-SNARE and their complexes in buffered suspension, exhibit defined peaks at CD signals of 208 and 222 nm wavelengths, consistent with a higher degree of helical secondary structure. Surprisingly, when incorporated in lipid membrane, both SNAREs and their complexes exhibit reduced folding. In presence of NSF-ATP, the SNARE complex disassembles, as reflected from the CD signals demonstrating elimination of α-helices within the structure

Regional seasonality of fire size and fire weather conditions across Australia's northern savanna

Australia's northern savannas have among the highest fire frequencies in the world. The climate is monsoonal, with a long, dry season of up to 9 months, during which most fires occur. The Australian Government's Emissions Reduction Fund allows land managers to generate carbon credits by abating the direct emissions of CO2 equivalent gases via prescribed burning that shifts the fire regime from predominantly large, high-intensity late dry season fires to a more benign, early dry season fire regime. However, the Australian savannas are vast and there is significant variation in weather conditions and seasonality, which is likely to result in spatial and temporal variations in the commencement and length of late dry season conditions. Here, we assess the temporal and spatial consistency of the commencement of late dry season conditions, defined as those months that maximise fire size and where the most extreme fire weather conditions exist. The results demonstrate that significant yearly, seasonal and spatial variations in fire size and fire weather conditions exist, both within and between bioregions. The effective start of late dry season conditions, as defined by those months that maximise fire size and where the most extreme fire weather variables exist, is variable across the savannas

The Structure and Function of Frataxin

Frataxin, a highly conserved protein found in prokaryotes and eukaryotes, is required for efficient regulation of cellular iron homeostasis. Humans with a frataxin deficiency have the cardio- and neurodegenerative disorder Friedreich’s ataxia, commonly resulting from a GAA trinucleotide repeat expansion in the frataxin gene. While frataxin’s specific function remains a point of controversy, a general consensus is the protein assists in controlling cellular iron homeostasis by directly binding iron. This review focuses on the structural and biochemical aspects of iron binding by the frataxin orthologs and outlines molecular attributes that may help explain the protein’s role in different cellular pathways

A Review of Critical Infrastructure Protection Approaches: Improving Security through Responsiveness to the Dynamic Modelling Landscape

As new technologies such as the Internet of Things (IoT) are integrated into Critical National Infrastructures (CNI), new cybersecurity threats emerge that require specific security solutions. Approaches used for analysis include the modelling and simulation of critical infrastructure systems using attributes, functionalities, operations, and behaviours to support various security analysis viewpoints, recognising and appropriately managing associated security risks. With several critical infrastructure protection approaches available, the question of how to effectively model the complex behaviour of interconnected CNI elements and to configure their protection as a system-of-systems remains a challenge. Using a systematic review approach, existing critical infrastructure protection approaches (tools and techniques) are examined to determine their suitability given trends like IoT, and effective security modelling and analysis issues. It is found that empirical-based, agent-based, system dynamics-based, and network-based modelling are more commonly applied than economic-based and equation-based techniques, and empirical-based modelling is the most widely used. The energy and transportation critical infrastructure sectors reflect the most responsive sectors, and no one Critical Infrastructure Protection (CIP) approach – tool, technique, methodology or framework – provides a ‘fit-for-all’ capacity for all-round attribute modelling and simulation of security risks. Typically, deciding factors for CIP choices to adopt are often dominated by trade-offs between ‘complexity of use’ and ‘popularity of approach’, as well as between ‘specificity’ and ‘generality’ of application in sectors. Improved security modelling is feasible via; appropriate tweaking of CIP approaches to include a wider scope of security risk management, functional responsiveness to interdependency, resilience and policy formulation requirements, and collaborative information sharing between public and private sectors

Rectal Swabs as an Alternative Sample Collection Method to Bulk Stool for the Real-Time PCR Detection of \u3ci\u3eGiardia duodenalis\u3c/i\u3e

Though bulk stool remains the gold standard specimen type for enteropathogen diagnosis, rectal swabs may offer comparable sensitivity with greater ease of collection for select pathogens. This study sought to evaluate the validity and reproducibility of rectal swabs as a sample collection method for the molecular diagnosis of Giardia duodenalis. Paired rectal swab and bulk stool samples were collected from 86 children ages 0–4 years living in southwest Niger, with duplicate samples collected among a subset of 50 children. Infection was detected using a previously validated real-time PCR diagnostic targeting the small subunit ribosomal RNA gene. Giardia duodenalis was detected in 65.5% (55/84) of bulk stool samples and 44.0% (37/84) of swab samples. The kappa evaluating test agreement was 0.81 (95% CI: 0.54–1.00) among duplicate stool samples (N = 49) and 0.75 (95% CI: 0.47–1.00) among duplicate rectal swabs (N = 48). Diagnostic sensitivity was 93% (95% CI: 84–98) by bulk stool and 63% (95% CI: 49–75) by rectal swabs. When restricting to the lowest three quartiles of bulk stool quantitation cycle values (an indication of relatively high parasite load), sensitivity by rectal swabs increased to 78.0% (95% CI: 64–89, P \u3c 0.0001). These findings suggest that rectal swabs provide less sensitive and reproducible results than bulk stool for the real-time PCR diagnosis of G. duodenalis. However, their fair sensitivity for higher parasite loads suggests that swabs may be a useful tool for detecting higher burden infections when stool collection is excessively expensive or logistically challenging

ICON 2019: International Scientific Tendinopathy Symposium Consensus: Clinical Terminology

© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.Background Persistent tendon pain that impairs function has inconsistent medical terms that can influence choice of treatment.1 When a person is told they have tendinopathy by clinician A or tendinitis by clinician B, they might feel confused or be alarmed at receiving what they might perceive as two different diagnoses. This may lead to loss of confidence in their health professional and likely adds to uncertainty if they were to search for information about their condition. Clear and uniform terminology also assists inter-professional communication. Inconsistency in terminology for painful tendon disorders is a problem at numerous anatomical sites. Historically, the term ‘tendinitis’ was first used to describe tendon pain, thickening and impaired function (online supplementary figure S1). The term ‘tendinosis’ has also been used in a small number of publications, some of which were very influential.2 3 Subsequently, ‘tendinopathy’ emerged as the most common term for persistent tendon pain.4 5 To our knowledge, experts (clinicians and researchers) or patients have never engaged in a formal process to discuss the terminology we use. We believe that health professionals have not yet agreed on the appropriate terminology for painful tendon conditions.Peer reviewedFinal Accepted Versio