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

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.

The miscibility of poly(d,l-lactide-co-glycolide) with amphiphilic molecules and the interaction of their mixtures with DNA at air/water interface

The miscibility of poly(d,l-lactide-co-glycolide) (PLG) with three amphiphilic molecules and the interaction of the PLG/surfactant mixtures with DNA at air/water interface are investigated by π-A isotherms, Brewster angle microscopy (BAM) and atomic force microscopy (AFM) techniques. The π-A isotherms of the PLG mixtures with cationic C12AzoC6PyBr, and C12AzoC6N(CH3)3Br, are quite different from the π-A isotherm of pure PLG on water subphase. In contrast to the case, the π-A isotherm of PLG mixed with nonionic C12AzoC6OPy is almost identical to the pure PLG except some increasing of molecular area. Similar phenomena are observed on DNA subphase. The in situ BAM and ex situ AFM observations demonstrate that the dispersion of PLG at air/water interface becomes good when it mixes with the two cationic surfactants, whereas quite poor due to the phase separation when it mixes with the nonionic amphiphilic molecule. Based on these results we conclude that the cationic surfactants can affect the conformation change of PLG at air/water interface and figure a well miscibility with polymer whereas the nonionic amphiphilic molecule presents poor miscibility. In addition, the even mixing of the PLG and the cationic surfactants is favorable for the adsorption to DNA more effectively.

Attachment of magnetic molecules on a nanoSQUID

A novel procedure combining monolayer self-assembly with electron beam lithography has been developed for attaching ferritin nanoparticles to a submicron thin-film SQUID (superconducting quantum interference device). After opening a window in the PMMA (polymethylmethacrylate) resist, organic linker molecules are used to attach ferritin to the exposed parts of the gold overlayer of a Nb nanoSQUID. This allows the magnetic nanoparticles to be located optimally as far as magnetic coupling to the nanoSQUID is concerned.

Therapeutic molecules

The present invention relates generally to a ligand for a protein associated with modulating obesity, diabetes and metabolic energy levels in animals including humans. More particularly, the present invention provides a ligand of the protein, Beacon, and its homologs. The identification of a Beacon ligand permits the identification of agents which agonize or antagonize the Beacon-ligand interaction and, hence, the development of therapeutic molecules useful in modulating obesity, diabetes and/or energy imbalance.

THERAPEUTIC MOLECULES

The present invention relates generally to a ligand for a protein associated with modulating obesity, diabetes and metabolic energy levels in animals including humans. More particularly, the present invention provides a ligand of the protein, Beacon, and its homologs. The identification of a Beacon ligand permits the identification of agents which agonize or antagonize the Beacon-ligand interaction and, hence, the development of therapeutic molecules useful in modulating obesity, diabetes and/or energy imbalance.

THERAPEUTIC MOLECULES

The present invention relates generally to a ligand for a protein associated with modulating obesity, diabetes and metabolic energy levels in animals including humans. More particularly, the present invention provides a ligand of the protein, Beacon, and its homologs. The identification of a Beacon ligand permits the identification of agents which agonize or antagonize the Beacon-ligand interaction and, hence, the development of therapeutic molecules useful in modulating obesity, diabetes and/or energy imbalance.

THERAPEUTIC MOLECULES

The present invention relates generally to a ligand for a protein associated with modulating obesity, diabetes and metabolic energy levels in animals including humans. More particularly, the present invention provides a ligand of the protein, Beacon, and its homologs. The identification of a Beacon ligand permits the identification of agents which agonize or antagonize the Beacon-ligand interaction and, hence, the development of therapeutic molecules useful in modulating obesity, diabetes and/or energy imbalance.

Therapeutic molecules

The present invention relates generally to a ligand for a protein associated with modulating obesity, diabetes and metabolic energy levels in animals including humans. More particularly, the present invention provides a ligand of the protein, Beacon, and its homologs. The identification of a Beacon ligand permits the identification of agents which agonize or antagonize the Beacon-ligand interaction and, hence, the development of therapeutic molecules useful in modulating obesity, diabetes and/or energy imbalance.

THERAPEUTIC MOLECULES

The present invention relates generally to a ligand for a protein associated with modulating obesity, diabetes and metabolic energy levels in animals including humans. More particularly, the present invention provides a ligand of the protein, Beacon, and its homologs. The identification of a Beacon ligand permits the identification of agents which agonize or antagonize the Beacon-ligand interaction and, hence, the development of therapeutic molecules useful in modulating obesity, diabetes and/or energy imbalance.

Enhancing the chemiluminescence determination of biologically and forensically important molecules

This thesis describes a systematic approach to the design, evaluation and optimisation of novel flow-cells for liquid-phase chemiluminescence detection. Various approaches were employed for improving the sensitivity of several analytically important reactions utilised for the determination of biologically significant thiols and disulfides as well as forensically important opiate alkaloids.

Role of increased CD8/CD28null T cells and alternative co-stimulatory molecules in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease; it is a leading cause of death and existing treatments have no proven disease-modifying effect. The mechanisms underlying this resistance are largely unknown, but suggest the presence of some self-maintaining pathogenic process, possibly initiated by cigarette smoking, that prevents the normal resolution of inflammation. We have previously reported increased production of proinflammatory cytokines and granzyme b by CD8⁺ T cells in COPD; costimulatory receptor/ligand interactions required include CD80:86/CD28, B7-1/CTLA4, 4-1BB/1BBL and OX40/OX40L. We hypothesized that a dysregulated expression/function of these molecules may play a role in inflammatory/autoimmune components of COPD. We analysed T cell co-stimulatory molecules in blood from 34 controls, 15 smokers and 48 COPD subjects. We assessed the potential functional relevance of CD8/CD28^null cells in COPD by measuring their production of proinflammatory cytokines, co-stimulatory molecules, granzyme and perforin. A smoke-exposed murine model was applied to investigate the relative expression of CD8/CD28^null T cells in blood, lung tissue and airway. CD8/CD28^null cells were increased in both current- and ex-smoker COPD groups; these cells expressed significantly more interferon (IFN)-γ, OX40, 4-1BB, CTLA4, granzyme and perforin when stimulated than CD8/CD28⁺ T cells. There were no changes in CD4/CD28^null T cells. In mice exposed to cigarette smoke for 12 weeks, CD8/CD28^null T cells were significantly increased in the airway with a trend for an increase in lung tissue and blood. Increased production of proinflammatory cytokines and expression of alternative co-stimulatory molecules by CD8/CD28^null T cells may play a role in inflammatory or autoimmune responses in COPD and identify therapeutic targets.