Benefits to Australia from ACIAR-funded Research

Research and Development/Tech Change/Emerging Technologies,

Developments in mental health service provision: views of service users and carers

This paper reports on a study in two NHS Mental Health Trusts in England in 2008-2009. Data were collected from staff, service users and carers to inform service and workforce developments. The findings reported relate to service users and carers and concur with staff views. They relate to modernisation of services, the challenges of a multiplicity of stakeholders and organisations, as well as the need to involve users and carers in developments. The findings resonate with national and local policy with a move away from traditional psychiatric care to integrated person-centred community care with a focus on recovery, rehabilitation and self care

The utility of HepG2 cells to identify direct mitochondrial dysfunction in the absence of cell death.

Drug-induced mitochondrial dysfunction has been hypothesized to be an important determining factor in the onset of drug-induced liver injury. It is essential to develop robust screens with which to identify drug-induced mitochondrial toxicity and to dissect its role in hepatotoxicity. In this study we have characterised a mechanistically refined HepG2 model, using a panel of selected hepatotoxicants and non-hepatotoxicants. We have demonstrated that acute metabolic modification, via glucose-deprivation over a 4 h period immediately prior to compound addition, is sufficient to allow the identification of drugs which induce mitochondrial dysfunction, in the absence of cell death over a short exposure (2 – 8 h) using a plate-based screen to measure cellular ATP content and cytotoxicity. These effects were verified by measuring changes in cellular respiration, via oxygen consumption and extracellular acidification rates. Overall, these studies demonstrate the utility of HepG2 cells for the identification of mitochondrial toxins which act directly on the electron transport chain and that the dual assessment of ATP content alongside cytotoxicity provides an enhanced mechanistic understanding of the causes of toxicity

IJRTP Volume 10(iv) Table of Contents

Special Issue : Pilgrimage as a Multi-Faceted Diamond, containing papers from Sacred Journeys 9th Global Conference at the University of Primorska’s Department of Tourism, in Portoroz and Piran, Slovenia, from July 6-8, 202

Cortical gene transcription response patterns to water maze training in aged mice

<p>Abstract</p> <p>Background</p> <p>The hippocampus mediates the acquisition of spatial memory, but the memory trace is eventually transferred to the cortex. We have investigated transcriptional activation of pathways related to cognitive function in the cortex of the aged mouse by analyzing gene expression following water maze training.</p> <p>Results</p> <p>We identified genes that were differentially responsive in aged mice with accurate spatial performance during probe trials or repeated swimming sessions, relative to home cage conditions. Effective learners exhibited significantly greater activation of several pathways, such as the mitogen-activated protein kinase and insulin receptor signaling pathways, relative to swimmers. The genes encoding activity-related cytoskeletal protein (Arc) and brain-derived neurotrophic factor (BDNF) were upregulated in proficient learners, relative to swimmers and home cage controls, while the gene encoding Rho GTPase activating protein 32 (GRIT) was downregulated. We explored the regulation of Arc, BDNF, and GRIT expression in greater morphological detail using in situ hybridization. Recall during probe trials enhanced Arc expression across multiple cortical regions involved in the cognitive component of water maze learning, while BDNF expression was more homogeneously upregulated across cortical regions involved in the associational and sensorimotor aspects of water maze training. In contrast, levels of GRIT expression were uniformly reduced across all cortical regions examined.</p> <p>Conclusions</p> <p>These results suggest that cortical gene transcription is responsive to learning in aged mice that exhibit behavioral proficiency, and support a distributed hypothesis of memory storage across multiple cortical compartments.</p

Non-Destructive Technologies for Detecting Insect Infestation in Fruits and Vegetables under Postharvest Conditions: A Critical Review

In the last two decades, food scientists have attempted to develop new technologies that can improve the detection of insect infestation in fruits and vegetables under postharvest conditions using a multitude of non-destructive technologies. While consumers\u27 expectations for higher nutritive and sensorial value of fresh produce has increased over time, they have also become more critical on using insecticides or synthetic chemicals to preserve food quality from insects\u27 attacks or enhance the quality attributes of minimally processed fresh produce. In addition, the increasingly stringent quarantine measures by regulatory agencies for commercial import-export of fresh produce needs more reliable technologies for quickly detecting insect infestation in fruits and vegetables before their commercialization. For these reasons, the food industry investigates alternative and non-destructive means to improve food quality. Several studies have been conducted on the development of rapid, accurate, and reliable insect infestation monitoring systems to replace invasive and subjective methods that are often inefficient. There are still major limitations to the effective in-field, as well as postharvest on-line, monitoring applications. This review presents a general overview of current non-destructive techniques for the detection of insect damage in fruits and vegetables and discusses basic principles and applications. The paper also elaborates on the specific post-harvest fruit infestation detection methods, which include principles, protocols, specific application examples, merits, and limitations. The methods reviewed include those based on spectroscopy, imaging, acoustic sensing, and chemical interactions, with greater emphasis on the noninvasive methods. This review also discusses the current research gaps as well as the future research directions for non-destructive methods\u27 application in the detection and classification of insect infestation in fruits and vegetables

Minimal Peroxide Exposure of Neuronal Cells Induces Multifaceted Adaptive Responses

Oxidative exposure of cells occurs naturally and may be associated with cellular damage and dysfunction. Protracted low level oxidative exposure can induce accumulated cell disruption, affecting multiple cellular functions. Accumulated oxidative exposure has also been proposed as one of the potential hallmarks of the physiological/pathophysiological aging process. We investigated the multifactorial effects of long-term minimal peroxide exposure upon SH-SY5Y neural cells to understand how they respond to the continued presence of oxidative stressors. We show that minimal protracted oxidative stresses induce complex molecular and physiological alterations in cell functionality. Upon chronic exposure to minimal doses of hydrogen peroxide, SH-SY5Y cells displayed a multifactorial response to the stressor. To fully appreciate the peroxide-mediated cellular effects, we assessed these adaptive effects at the genomic, proteomic and cellular signal processing level. Combined analyses of these multiple levels of investigation revealed a complex cellular adaptive response to the protracted peroxide exposure. This adaptive response involved changes in cytoskeletal structure, energy metabolic shifts towards glycolysis and selective alterations in transmembrane receptor activity. Our analyses of the global responses to chronic stressor exposure, at multiple biological levels, revealed a viable neural phenotype in-part reminiscent of aged or damaged neural tissue. Our paradigm indicates how cellular physiology can subtly change in different contexts and potentially aid the appreciation of stress response adaptations

VENNTURE–A Novel Venn Diagram Investigational Tool for Multiple Pharmacological Dataset Analysis

As pharmacological data sets become increasingly large and complex, new visual analysis and filtering programs are needed to aid their appreciation. One of the most commonly used methods for visualizing biological data is the Venn diagram. Currently used Venn analysis software often presents multiple problems to biological scientists, in that only a limited number of simultaneous data sets can be analyzed. An improved appreciation of the connectivity between multiple, highly-complex datasets is crucial for the next generation of data analysis of genomic and proteomic data streams. We describe the development of VENNTURE, a program that facilitates visualization of up to six datasets in a user-friendly manner. This program includes versatile output features, where grouped data points can be easily exported into a spreadsheet. To demonstrate its unique experimental utility we applied VENNTURE to a highly complex parallel paradigm, i.e. comparison of multiple G protein-coupled receptor drug dose phosphoproteomic data, in multiple cellular physiological contexts. VENNTURE was able to reliably and simply dissect six complex data sets into easily identifiable groups for straightforward analysis and data output. Applied to complex pharmacological datasets, VENNTURE’s improved features and ease of analysis are much improved over currently available Venn diagram programs. VENNTURE enabled the delineation of highly complex patterns of dose-dependent G protein-coupled receptor activity and its dependence on physiological cellular contexts. This study highlights the potential for such a program in fields such as pharmacology, genomics, and bioinformatics

Acute Metabolic Switch Assay Using Glucose/Galactose Medium in HepaRG Cells to Detect Mitochondrial Toxicity.

Using galactose instead of glucose in the culture medium of hepatoma cell lines, such as HepG2 cells, has been utilized for a decade to unmask the mitochondrial liability of chemical compounds. A modified glucose-galactose assay on HepG2 cells, reducing the experimental period for screening of mitochondrial toxicity to 2 to 4 hr, has been previously reported. HepaRG cells are one of the few cell lines that retain some of the important characteristics of human hepatocytes, offering advantages of working with a cell line, therefore, are considered an alternative for HepG2 cells in drug toxicity screening. A method is described here using HepaRG cells in an acute metabolic switch assay utilizing specific glucose/galactose media, a combined ATP-protein-LDH assay measuring three endpoints from one 96-well plate, and a criteria to label a compound as a mitochondrial toxin. © 2019 by John Wiley & Sons, Inc

Multiple Oxygen Tension Environments Reveal Diverse Patterns of Transcriptional Regulation in Primary Astrocytes

The central nervous system normally functions at O2 levels which would be regarded as hypoxic by most other tissues. However, most in vitro studies of neurons and astrocytes are conducted under hyperoxic conditions without consideration of O2-dependent cellular adaptation. We analyzed the reactivity of astrocytes to 1, 4 and 9% O2 tensions compared to the cell culture standard of 20% O2, to investigate their ability to sense and translate this O2 information to transcriptional activity. Variance of ambient O2 tension for rat astrocytes resulted in profound changes in ribosomal activity, cytoskeletal and energy-regulatory mechanisms and cytokine-related signaling. Clustering of transcriptional regulation patterns revealed four distinct response pattern groups that directionally pivoted around the 4% O2 tension, or demonstrated coherent ascending/decreasing gene expression patterns in response to diverse oxygen tensions. Immune response and cell cycle/cancer-related signaling pathway transcriptomic subsets were significantly activated with increasing hypoxia, whilst hemostatic and cardiovascular signaling mechanisms were attenuated with increasing hypoxia. Our data indicate that variant O2 tensions induce specific and physiologically-focused transcript regulation patterns that may underpin important physiological mechanisms that connect higher neurological activity to astrocytic function and ambient oxygen environments. These strongly defined patterns demonstrate a strong bias for physiological transcript programs to pivot around the 4% O2 tension, while uni-modal programs that do not, appear more related to pathological actions. The functional interaction of these transcriptional ‘programs’ may serve to regulate the dynamic vascular responsivity of the central nervous system during periods of stress or heightened activity