Striated muscle activator of Rho signalling (STARS) is a PGC-1α/oestrogen-related receptor-α target gene and is upregulated in human skeletal muscle after endurance exercise

Exercise improves the ability of skeletal muscle to metabolise fats and sugars. For these improvements to occur the muscle detects a signal caused by exercise, resulting in changes in genes and proteins that control metabolism. We show that endurance exercise increases the amount of a protein called striated muscle activator of Rho signalling (STARS) as well as several other proteins influenced by STARS.We also show that the amount of STARS can be increased by signals directed from proteins called peroxisome proliferator-activated receptor gamma co-activator 1-α (PGC-1α) and oestrogen-related receptor-α (ERRα). We also observed that when we reduce the amount of STARS in muscle cells, we block the ability of PGC-1α/ERRα to increase a gene called carnitine palmitoyltransferase-1β (CPT-1β), which is important for fat metabolism. Our study has shown that the STARS pathway is regulated by endurance exercise. STARS may also play a role in fat metabolism in muscle.

Glutathione : a novel treatment target in psychiatry

There is accumulating evidence for oxidative stress mechanisms as common pathophysiological pathways in diverse psychiatric disorders, which offers novel treatment targets in oxidation biology systems. Of these the glutathione system has the most favourable theoretical foundation, given its dominance as the most generic of cellular antioxidants. Clinically, this hypothesis has been supported by several recently published studies that have reported on the efficacy of N-acetylcysteine, a glutathione precursor, in the treatment of various psychiatric disorders. This article outlines the multidimensional evidence that currently exists for oxidative stress mechanisms in psychiatric disorders and specifically discusses glutathione as a promising novel therapeutic target.

Oxidative pathways as a drug target for the treatment of autism

Importance of the field: Autism is a severe, pervasive developmental disorder, the aetiology of which is poorly understood. Current pharmacological treatment options for autism are often focused on addressing comorbid behavioural problems, rather than core features of the disorder. Investigation of a new treatment approach is needed.

Areas covered in this review: Recent research has indicated a possible role of abnormalities in oxidative homeostasis in the pathophysiology of autism, based on reports that a range of oxidative biomarkers are significantly altered in people with autism. This article reviews the current findings on oxidative stress in autism, including genetic links to oxidative pathways, changes in antioxidant levels and other oxidative stress markers. We conducted a search of the literature up to June 2010, using Medline, Pubmed, PsycINFO, CINAHL PLUS and BIOSIS Previews.

What the reader will gain: This review provides an overview of the current understanding of the role of oxidative stress in autism. This will assist in highlighting areas of future therapeutic targets and potential underlying pathophysiology of this disorder.

Take home message: Abnormalities in oxidative homeostasis may play a role in the pathophysiology of autism. Antioxidant treatment may form a potential therapeutic pathway for this complex disorder.

Target will mean new approach

The Bradley report argues that we need a more "sophisticated approach" to equity. This includes a joined-up approach to TAFE and higher education. We need to think in terms of a tertiary system and to examine the pathways between them for their equity consequences.

Regulation of human pregnane X receptor and its target gene cytochrome P450 3A4 by Chinese herbal compounds and a molecular docking study

1. The pregnane X receptor (PXR) plays a critical role in the regulation of human cytochrome P450 3A4 (CYP3A4) gene. In this study, we investigated the effect of an array of compounds isolated from Chinese herbal medicines on the activity of PXR using a luciferase reporter gene assay in transiently transfected HepG2 and Huh7 cells and on the expression of PXR and CYP3A4 in LS174T cells. Furthermore, molecular docking was performed to investigate the binding modes of herbal compounds with PXR.

2. Praeruptorin A and C, salvianolic acid B, sodium danshensu, protocatechuic aldehyde, cryptotanshinone, emodin, morin, and tanshinone IIA significantly transactivated the CYP3A4 reporter gene construct in either HepG2 or Huh7 cells. The PXR mRNA expression in LS174T cells was significantly induced by physcion, protocatechuic aldehyde, salvianolic acid B, and sodium danshensu. However, epifriedelanol, morin, praeruptorin D, mulberroside A, tanshinone I, and tanshinone IIA significantly down-regulated the expression of PXR mRNA in LS174T cells.

3. All the herbal compounds tested can be readily docked into the ligand-binding cavity of PXR mainly through hydrogen bond and aromatic interactions with Ser247, Gln285, His407, and Arg401.

4. These findings suggest that herbal medicines can significantly regulate PXR and CYP3A4 and this has important implication in herb–drug interactions.

Arrow hitting wooden target (two takes- centred & L-C pan)

A sound design that animates elves working in an office processing Christmas orders.

Arrow hitting target SFX X2

A sound effect of an arrow whooshing past and hitting its target X 2.

Disease costing methodology used in the Disease Costs and Impact Study 1993–94

Describes in detail the methodology used by the Australian Institute of Health and Welfare to measure health services use and expenditure for specific diseases and disease groups in Australia in 1993-94. A companion report, Health System Costs of Diseases and Injury in Australia 1993-94, provides estimates of the health system costs for each disease and injury group and area of expenditure. Other reports will provide detailed estimates for specific National Health Priority Areas - cancer, cardiovascular disease, injury, mental health and diabetes.

Do drivers intentionally target wildlife on roads?

Despite frequent reliance on surveys to document public attitudes towards conservation issues (such as invasive-species control), only rarely do researchers assess the validity of statements made by the public in response to such surveys. Therefore, how well responses match actual behaviour remains an open question. We conducted a survey asking drivers if they had seen and/or run over (intentionally or not) snakes, native frogs or invasive cane toads (Rhinella marina) on roads in the Northern Territory of Australia. To compare actual driver behaviour to the survey responses, we also carried out field experiments where we quantified the rates at which model snakes, frogs and toads (and controls) were run over on a rural highway. Our results show a discrepancy between survey responses and driver behaviour: for example, 25% of the people we surveyed indicated that they intentionally run over cane toads, yet field experiments showed that model toads were run over no more frequently than expected by chance, or than any other type of model.

Lipid membrane : a novel target for viral and bacterial pathogens

Abstracts: Lipid rafts are defined as specialized, dynamic microdomains that can be found in plasma membrane, and they are enriched with cholesterol and sphingolipids. Since lipid rafts’ first debut in the mid 1990’s, their existence, function and biological relevance have been a subject of intense scrutiny within the scientific community. Throughout this debate, we have learned a great deal regarding how cargos (both pathogens and cellular factors) are transported into and out of the cell through raft-dependent or raft-independent pathways. It is now apparent that a number of toxins, bacterial-, and viral-pathogens are able to exploit cholesterol and/or lipid rafts to gain a foot hold in their target hosts. The objective of this review is to describe our current appreciation on how selected pathogens utilise cholesterol and/or lipid rafts to support their propagation and to speculate on how some of these observations can be explored for the development of novel strategies that target plasma membrane lipids to control the spread of these viral- and bacterial-pathogens.

Early events of HIV-1 infection : can signalling be the next therapeutic target?

Intracellular signaling events are signposts of biological processes, which govern the direction and action of biological activities. Through millions of years of evolution, pathogens, such as viruses, have evolved to hijack host cell machinery to infect their targets and are therefore dependent on host cell signaling for replication. This review will detail our current understanding of the signaling events that are important for the early steps of HIV-1 replication. More specifically, the therapeutic potential of signaling events associated with chemokine coreceptors, virus entry, viral synapses, and post-entry processes will be discussed. We argue that these pathways may represent novel targets for antiviral therapy.

Potent nonnucleoside reverse transcriptase inhibitors target HIV-1 gag-pol

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) target HIV-1 reverse transcriptase (RT) by binding to a pocket in RT that is close to, but distinct, from the DNA polymerase active site and prevent the synthesis of viral cDNA. NNRTIs, in particular, those that are potent inhibitors of RT polymerase activity, can also act as chemical enhancers of the enzyme's inter-subunit interactions. However, the consequences of this chemical enhancement effect on HIV-1 replication are not understood. Here, we show that the potent NNRTIs efavirenz, TMC120, and TMC125, but not nevirapine or delavirdine, inhibit the late stages of HIV-1 replication. These potent NNRTIs enhanced the intracellular processing of Gag and Gag-Pol polyproteins, and this was associated with a decrease in viral particle production from HIV-1-transfected cells. The increased polyprotein processing is consistent with premature activation of the HIV-1 protease by NNRTI-enhanced Gag-Pol multimerization through the embedded RT sequence. These findings support the view that Gag-Pol multimerization is an important step in viral assembly and demonstrate that regulation of Gag-Pol/Gag-Pol interactions is a novel target for small molecule inhibitors of HIV-1 production. Furthermore, these drugs can serve as useful probes to further understand processes involved in HIV-1 particle assembly and maturation.