The effect of water deprivation on signalling molecules that utilise cGMP in the Spinifex Hopping Mouse Notomys alexis

In mammals the natriuretic and guanylin peptides influence renal and intestinal fluid content and electrolyte transport by binding to and activating guanylyl cyclase (GC) receptors that in turn stimulate production of the intracellular second messenger guanosine 3':5'-cyclic monophospate
(cGMP). However, the role of natriuretic and guanylin peptides in desert mammals is not understood. The spinifex hopping-mouse (Notomys alexis), has a suite of behavioural and physiological mechanisms that permits survival for extended periods without access to free water. Because signalling molecules that generate cGMP are known to promote water excretion, it was predicted that natriuretic and guanylin peptide synthesis would be down regulated in water-deprived N. alexis, and thus reduce the amount of water lost in the urine and faeces. However, in the kidney ANP and GC-A mRNA levels were increased in water-deprived mice, but CNP and GC-B mRNA levels were decreased. Water deprivation increased guanylin and uroguanylin mRNA expression in the distal colon, but it remained unchanged in the kidney and proximal colon. The expression of GC-C mRNA increased in the proximal colon but not in the distal colon. This study shows that water deprivation differentially affects the expression of regulatory molecules that stimulate cGMP producti

The evolution of nitric oxide signalling in vertebrate blood vessels

Nitric oxide is one of the most important signalling molecules involved in the regulation of physiological function. It first came to prominence when it was discovered that the vascular endothelium of mammals synthesises and releases nitric oxide (NO) to mediate a potent vasodilation. Subsequently, it was shown that NO is synthesised in the endothelium by a specific isoform of nitric oxide synthase (NOS) called NOS3. Following this discovery, it was assumed that an endothelial NO/NOS3 system would be present in all vertebrate blood vessels. This review will discuss the latest genomic, anatomical and physiological evidence which demonstrates that an endothelial NO/NOS3 signalling is not ubiquitous in non-mammalian vertebrates, and that there have been key evolutionary steps that have led to the endothelial NO signalling system being a regulatory system found only in reptiles, birds and mammals. Furthermore, the emerging role of nitrite as an endocrine source of NO for vascular regulation is discussed.

Lipotoxicity: the obese and endurance-trained paradox

The potential lipotoxic effect of intramyocellular triglyceride (IMTG) accumulation has been suggested to be a major component in the development of insulin resistance. Increased levels of IMTGs correlate with insulin resistance in both obese and diabetic patients, but this relationship does not exist in endurance trained (ETr) subjects. This may be, in part, related to differences in the gene expression and activities of key enzymes involved in fatty acid transport and oxidation as well as in the perodixation status of the IMTGs in obese/diabetic patients as compared with ETr subjects. Disruptions in fat and lipid homeostasis in skeletal muscle have been shown to activate protein kinase C (PKC), which acts on several downstream signalling pathways, including the insulin and the IB kinase (IKK)/NFB signalling pathways. Additionally, an increased peroxidation of IMTGs may reduce insulin sensitivity by increasing TNF, which is known to increase the expression of suppressor of cytokine signalling proteins (SOCS). A common characteristic observed when activating both PKC and TNF/SOCS3 is the inhibition of tyrosine phosphorylation of IRS-1 and subsequently an inhibition of its activation of downstream signalling molecules. These may be important players in the development of insulin resistance and understanding their activation and expression in both obese and ETr humans should assist in understanding how and why IMTGs become lipotoxic.

UV induces resistance in Arabidopsis Thaliana to the Oomycete Pathogen Hyaloperonospora Parasitica

Owing to their sessile nature, plants have evolved mechanisms to minimise the damaging effects of abiotic and biotic stresses. Attack by pathogenic fungi, viruses and bacterium is a major type of biotic stress. To resist infection, plants recognise invading pathogens and induce disease resistance through multiple signal transduction pathways. In addition, appropriate stimulation can cause plants to increase their resistance to future pathogen attack. We have found that exposure to non-lethal doses of UV-C (254 nm) renders a normally susceptible ecotype of Arabidopsis thaliana resistant to the biotrophic Oomycete pathogen Hyaloperonospora parasitica. The UV treatment induces an incompatible response in a dose-dependent fashion, and is still effective upon pathogen inoculation up to seven days after UV exposure. The degree of resistance diminishes with time but higher doses result in greater levels of resistance, even after seven days. Furthermore, the effect is systemic, occurring in parts of the plant that have not been irradiated. Incubation in the dark post?irradiation and prior to infection reduces the UV dose required to generate a specific level of pathogen resistance without affecting the duration of resistance. These observations, plus the inability of plants to photoreactivate UV photoproducts in the dark, strongly suggest that DNA damage induces the resistance phenotype. Currently, we are assessing the influence of DNA repair defects on UV-induced resistance, following the expression of a number of defence?related genes post-UV-C irradiation, and assessing the effect of UV in plant mutants deficient in specific signalling molecules involved in resistance.

Inflammatory signaling in skeletal muscle cell growth

This thesis examines the potential beneficial role of inflammation in skeletal muscle tissue. This work establishes cyclooxygenase pathway derived prostaglandins as key anabolic signalling molecules regulating skeletal muscle cell growth and examines changes in circulating inflammatory lipid mediators and intramuscular anabolic signaling in response to acute resistance exercise in humans.

Hyperaccumulation of zinc by Noccaea caerulescens results in a cascade of stress responses and changes in the elemental profile

Noccaea caerulescens (J. & C. Presl) F. K. Meyer is a metal hyperaccumulating plant which can accumulate more than 2% zinc (Zn) dry tissue mass in its aerial tissues. At this concentration Zn is toxic to most plants due to inhibition of enzyme function, oxidative damage and mineral deficiencies. In this study the elemental and metabolite profiles of N. caerulescens plants grown in four different Zn concentrations were measured. This revealed broad changes in the metabolite and elemental profiles with the hyperaccumulation of Zn. The Zn treated plants exhibited no typical signs of stress such as chlorosis or reduced biomass, however, a range of metabolic stress responses, such as the modification of galactolipids and the major membrane lipids of plastids, and increases in oxylipins, which are precursors to the signalling molecules jasmonic and abscisic acids, as well as the increased synthesis of glucosinolates, was observed. Increases in particular organic acids and the ubiquitous metal cation chelator nicotianamine were also observed. The small molecule metabolite changes observed, however, did not account for the extreme Zn concentrations in the leaf tissue showing that the increase in nicotianamine production most likely negates Fe deficiency. The elemental analyses also revealed significant changes in other essential micronutrients, in particular, significantly lower Mn concentrations in the high Zn accumulating plants, yet higher Fe concentrations. This comprehensive elemental and metabolite analysis revealed novel metabolite responses to Zn and offers evidence against organic acids as metal-storage ligands in N. caerulescens. © 2014 The Royal Society of Chemistry.

Information signalling of common stock repurchase announcements: Australian evidence

Stock repurchases (or share buy-backs) have become increasingly popular among Australian companies. One of the main aims of announcing a stock repurchase by a listed company is signalling the market that its shares are currently underpriced. When market reacts to the signal, price of the shares is expected to increase immediately after the announcement. While there are several ways of repurchasing shares, 'on-market buy-backs' is the most popular method of stock repurchases in Australia. Australian listed companies have announced more than two hundred on-market share buy-backs over the past three years. The aim of this paper is to examine the information signalling effects of these on-market buy-back announcements. If the signal is considered positively (negatively) by the market, the price of the repurchasing company's shares should increase (decrease) immediately after the announcement. If there is no information content in the announcement, the price will remain the same. In this study, signalling effect of share buy-back announcements was examined using most recent Australian data. The total population of on-market buy-back announcements during the period from January 1, 2000 to March 10, 2003 was included. The abnormal market return over the short-run (announcement day and 9 trading days centred on the announcement date) was computed using the All Ordinaries Accumulation Index as the reference portfolio. The daily Abnormal Returns (AR) and Cumulative Abnormal Returns (CAR) during the event period were computed. The results strongly support the information-signalling hypothesis of share buy..backs. Australian market generally considers announcement of on~market share repurchases as signalling of insider information that shares are currently underpriced.

A dynamic ratio-based model for signalling corporate collapse

The recognition of behavioural elements in finance has caused major shifts in the analytic framework pertaining to ratio-based modeling of corporate collapse. The modeling approach so far has been based on the classical rational theory in behavioural economics, which assumes that the financial ratios (i.e., the predictors of collapse) are static over time. The paper argues that, in the absence of rational economic theory, a static model is flawed, and that a suitable model instead is one that reflects the heuristic behavioural framework, which is what characterises behavioural attributes of company directors and in turn influences the accounting numbers used in calculating the financial ratios. This calls for a dynamic model: dynamic in the sense that it does not rely on a coherent assortment of financial ratios for signaling corporate collapse over multiple time periods. This paper provides empirical evidence, using a data set of Australian publicly listed companies, to demonstrate that a dynamic model consistently outperforms its static counterpart in signaling the event of collapse. On average, the overall predictive power of the dynamic model is 86.83% compared to an average overall predictive power of 69.35% for the static model.

Store names information signalling : a credibility perspective

This study is about store names as brand signals. Using the framework of Erdem and Swait (1998), hypotheses are developed regarding the effects of store names on consumers' expected product utility. It is relevant to study store names as brand signals because store names can act as additional signals in the consumer purchase decision process. The study focuses in particular on the effects of store name credibility on perceived risk, information costs and perceived product quality. The hypotheses will be tested on data that are currently being collected in a survey among two hundred students.

Improved glusoce homeostasis and enhanced insulin signalling in Grb 14-deficient mice

Gene targeting was used to characterize the physiological role of growth factor receptor-bound (Grb)14, an adapter-type signalling protein that associates with the insulin receptor (IR). Adult male Grb14^-/- mice displayed improved glucose tolerance, lower circulating insulin levels, and increased incorporation of glucose into glycogen in the liver and skeletal muscle. In ex vivo studies, insulin-induced 2-deoxyglucose uptake was enhanced in soleus muscle, but not in epididymal adipose tissue. These metabolic effects correlated with tissue-specific alterations in insulin signalling. In the liver, despite lower IR autophosphorylation, enhanced insulin-induced tyrosine phosphorylation of insulin receptor substrate (IRS)-1 and activation of protein kinase B (PKB) was observed. In skeletal muscle, IR tyrosine phosphorylation was normal, but signalling via IRS-1 and PKB was increased. Finally, no effect of Grb14 ablation was observed on insulin signalling in white adipose tissue. These findings demonstrate that Grb14 functions in vivo as a tissue-specific modulator of insulin action, most likely via repression of IR-mediated IRS-1 tyrosine phosphorylation, and highlight this protein as a potential target for therapeutic intervention.

syn-Facial hetero-bridged [n]polynorbornanes : a new class of polarofacial framework molecules composed of fused 7-oxa- and 7-azanorbornanes

New oxygen-bridged norbornane-fused cyclobutene epoxides and bis-(cyclobutene epoxides) are described and shown to react stereoselectively with 7-azanorbornenes to produce syn-facial N,O-bridged polynorbornanes and stereorandomly with 7-oxanorbornenes to produce O,O-bridged polynorbornanes as mixtures of syn-facial and anti-facial products.[1] Polarofacial systems containing up to six syn-facial norbornane bridges are described, while systems with seven co-facial oxygen atoms have been prepared by incorporating terminal epoxide rings to O5-[5]polynorbornanes. Ester-substituted 1,3,4-oxadiazoles are shown to be useful reagents for coupling 7-oxanorbornanes and produce predominantly syn-facial O-bridged polarofacial systems together with their anti-facial isomers.

Natriuretic peptide signalling in the gills of freshwater and seawater fishes

The gills are considered major targets for cardiac natriuretic peptides with studies confirming natriuretic peptide receptor presence on vascular and sometimes epithelial tissues. Natriuretic peptide intracellular signalling is via guanylyl cyclase receptors and the cGMP pathway, and via inhibitory G-proteins linked to cyclic AMP pathways. Natriuretic peptides in the gills alter branchial blood flow and may also alter ion transport in various salinities. We present an overview of natriuretic peptide cGMP and cAMP signalling in fishes and consider the implications of the recent discovery of several CNPs and BNP in bony fishes on natriuretic peptide receptor studies.