Using JERS-1 and a DEM for regional scale mapping of the wet tropics world heritage area, Australia

Proceedings of the 11th Australasian Remote Sensing and Photogrammetry Conference

Ascorbic acid induces an oxidative stress in CCRF cells activating the transcription factors AP-1 and NFRB

We have previously tested the effects of high dose AA supplements on human volunteers in terms of reducing DNA damage, as a possible mechanism of the vitamin’s proposed protective effect against cancer and detected a transient, pro-oxidant effect at high doses (500 mg/day). Herein, we present evidence of a pro-oxidant effect of the vitamin when added to CCRF cells at extracellular concentrations which mimic those present in human serum in vivo (50–150AM). The activation of the transcription factor AP-1 was optimal at 100 AM AA following 3h exposure at 37jC. A minimum dose of 50 AM of AA activated NFnB but there appeared to be no dose-dependent effect. Increases of 2–3 fold were observed for both transcription factors when cells were exposed to 100 AM AA for 3h, comparing well with the pro-oxidant effect of H2O2 at similar concentrations. In parallel experiments the activation of AP-1 (binding to DNA) was potentiated when cells were pre-incubated with AA prior to exposure with H2O2. Cycloheximide pretreatment (10 Ag/ml for 15min) caused a 50% inhibition of AP-1 binding to DNA suggesting that it was due to a combination of increasing the binding of pre-existing Fos and Jun and an increase in their de novo synthesis. Cellular localisation was confirmed by immunocytochemistry using antibodies specific for c-Fos and c-Jun proteins. These results suggest that extracellular AA can elicit an intracellular stress response resulting in the activation of the oxidative stress-responsive transcription factors AP-1 and NFnB. These transcription factors are involved in the induction of genes associated with an oxidative stress response, cell cycle arrest and DNA repair confirmed by our cDNA microarray analysis (Affymetrix). This may explain the abilty for AA to appear to inhibit 8-oxodG, yet simultaneously generate another oxidative stress biomarker, 8-oxo-dA. These results suggest a completely novel DNA repair action for AA. Whether this action is relevant to our in vivo findings will be the subject of our future research.

Pro-inflammatory cytokines IL6, TNF-α, IL1β, procalcitonin, lipopolysaccharide binding protein and C-reactive protein in infective endocarditis

Objective: To evaluate the serum levels and diagnostic value of cytokines and acute phase proteins in patients with infective endocarditis (IE). Patients and methods: Serum samples from 63 patients diagnosed with IE and 71 control patients were analysed for the following markers: interleukin-6 (IL6), tumour necrosis factor-α (TNF-α), interleukin 1-β (IL1β), procalcitonin (PCT), lipopolysaccharide binding protein (LBP) and C-reactive protein (CRP). Results: Serum levels of IL6, IL1β and CRP were significantly elevated in patients with IE as compared to controls. PCT, TNF-α and LBP were not elevated. Conclusion: Serum CRP and IL6 are elevated in IE. IL 6 may aid in establishing the diagnosis. There was no correlation between IL 6 levels and CRP, causative microorganism, echocardiographic features or outcome. © 2007 The British Infection Society.

Some aspects of the interaction of humic substances with metal ions

Humic substances are the major organic constituents of soils and sediments. They are heterogeneous, polyfunctional, polydisperse, macromolecular and have no accurately known chemical structure. Their interactions with radionuclides are particularly important since they provide leaching mechanisms from disposal sites. The central theme to this research is the interaction of heavy metal actinide analogues with humic materials. Studies described focus on selected aspects of the characteristics and properties of humic substances. Some novel approaches to experiments and data analysis are pursued. Several humic substances are studied; all but one are humic acids, and those used most extensively were obtained commercially. Some routine characterisation techniques are applied to samples in the first instance. Humic substances are coloured, but their ultra-violet and visible absorption spectra are featureless. Yet, they fluoresce over a wide range of wavelengths. Enhanced fluorescence in the presence of luminescent europium(III) ions is explained by energy transfer from irradiated humic acid to the metal ion in a photophysical model. Nuclear magnetic resonance spectroscopy is applied to the study of humic acids and their complexes with heavy metals. Proton and carbon-13 NMR provides some structural and functionality information; Paramagnetic lanthanide ions affect these spectra. Some heavy metals are studied as NMR nuclei, but measurements are restricted by their sensitivity. A humic acid is fractionated yielding a broad molecular weight distribution. Electrophoretic mobilities and particle radii determined by Laser Doppler Electrophoretic Light Scattering are sensitive to the conditions of the supporting media, and the concentration and particle size distribution of humic substances. In potentiometric titrations of humate dispersions, the organic matter responds slowly and the mineral acid addition is buffered. Proton concentration data is modelled and a mechanism is proposed involving two key stages, both resulting in proton release after some conformational changes.

Application of ERS-1 and Topex/Poseidon altimetry using precise orbits

The work described in this thesis concerns the application of radar altimetry, collected from the ERS-1 and TOPEX/POSEIDON missions, to precise satellite orbits computed at Aston University. The data is analysed in a long arc fashion to determine range biases, time tag biases, sea surface topographies and to assess the radial accuracy of the generated orbits through crossover analysis. A sea surface variability study is carried out for the North Sea using repeat altimeter profiles from ERS-1 and TOPEX/POSEIDON in order to verify two local U.K. models for ocean tide and storm surge effects. An on-side technique over the English Channel is performed to compute the ERS-1, TOPEX and POSEIDON altimeter range biases by using a combination of altimetry, precise orbits determined by short arc methods, tide gauge data, GPS measurements, geoid, ocean tide and storm surge models. The remaining part of the thesis presents some techniques for the short arc correction of long arc orbits. Validation of this model is achieved by way of comparison with actual SEASAT short arcs. Simulations are performed for the ERS-1 microwave tracking system, PRARE, using the range data to determine time dependent orbit corrections. Finally, a brief chapter is devoted to the recovery of errors in station coordinates by the use of multiple short arcs.

Structural characterization of CD81-Claudin-1 hepatitis C virus receptor complexes

Tetraspanins are thought to exert their biological function(s) by co-ordinating the lateral movement and trafficking of associated molecules into tetraspanin-enriched microdomains. A second four-TM (transmembrane) domain protein family, the Claudin superfamily, is the major structural component of cellular TJs (tight junctions). Although the Claudin family displays low sequence homology and appears to be evolutionarily distinct from the tetraspanins, CD81 and Claudin-1 are critical molecules defining HCV (hepatitis C virus) entry; we recently demonstrated that CD81-Claudin-1 complexes have an essential role in this process. To understand the molecular basis of CD81-Claudin-1 complex formation, we produced and purified milligram quantities of full-length CD81 and Claudin-1, alone and in complex, in both detergent and lipid contexts. Structural characterization of these purified proteins will allow us to define the mechanism(s) underlying virus-cell interactions and aid the design of therapeutic agents targeting early steps in the viral life cycle.

Extracellular loops 1 and 3 and their associated transmembrane regions of the calcitonin receptor-like receptor are needed for CGRP receptor function

The first and third extracellular loops (ECL) of G protein-coupled receptors (GPCRs) have been implicated in ligand binding and receptor function. This study describes the results of an alanine/leucine scan of ECLs 1 and 3 and loop-associated transmembrane (TM) domains of the secretin-like GPCR calcitonin receptor-like receptor which associates with receptor activity modifying protein 1 to form the CGRP receptor. Leu195Ala, Val198Ala and Ala199Leu at the top of TM2 all reduced aCGRP-mediated cAMP production and internalization; Leu195Ala and Ala199Leu also reduced aCGRP binding. These residues form a hydrophobic cluster within an area defined as the "minor groove" of rhodopsin-like GPCRs. Within ECL1, Ala203Leu and Ala206Leu influenced the ability of aCGRP to stimulate adenylate cyclase. In TM3, His219Ala, Leu220Ala and Leu222Ala have influences on aCGRP binding and cAMP production; they are likely to indirectly influence the binding site for aCGRP as well as having an involvement in signal transduction. On the exofacial surfaces of TMs 6 and 7, a number of residues were identified that reduced cell surface receptor expression, most noticeably Leu351Ala and Glu357Ala in TM6. The residues may contribute to the RAMP1 binding interface. Ile360Ala impaired aCGRP-mediated cAMP production. Ile360 is predicted to be located close to ECL2 and may facilitate receptor activation. Identification of several crucial functional loci gives further insight into the activation mechanism of this complex receptor system and may aid rational drug design.

Quantitative interpretation of diffusion-ordered NMR spectra:can we rationalize small molecule diffusion coefficients?

Appealingly simple: A new method is described that allows the diffusion coefficient of a small molecule to be estimated given only the molecular weight and the viscosity of the solvent used. This method makes possible the quantitative interpretation of the diffusion domain of diffusion-ordered NMR spectra (see picture). © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Predictors of maternal control of feeding at 1 and 2 years of age

Objective: To establish the best predictors of maternal use of controlling feeding practices at 1 and 2 years of age. Design: A longitudinal study from birth to 2 years. Participants: Sixty-two mothers of 2-year-old children. Measures: Infant weight at birth, 6, 12 and 24 months, breastfeeding history, infant temperament and feeding difficulties at 6 and 12 months, maternal demographics at 12 and 24 months, maternal mental health at 6 and 12 months, maternal controlling feeding practices at 12 and 24 months. Results: Controlling feeding practices at 1 year were predicted by perceptions of infant temperament at 6 months, birth weight, length of breastfeeding, mental health at 6 months, and mealtime negativity at 6 months. Parental control over feeding when their child reached 2 years was predicted by the mother's tendency to use that particular strategy at 1 year in combination with the perceptions of infant temperament and feeding problems at 1 year, weight at 1 year, length of breastfeeding in infancy, and/or maternal mental health at 1 year. Conclusions: Breastfeeding appears to promote subsequent monitoring, and is associated with reduced use of pressurising and restrictive feeding practices. Infant characteristics are important predictors of control at both 1 and 2 years of age. The use of controlling feeding practices is relatively stable from 1 to 2 years. © 2007 Nature Publishing Group All rights reserved.

Negative regulation of soluble Flt-1 and soluble endoglin release by heme oxygenase-1

Preeclampsia is characterized clinically by hypertension and proteinuria. Soluble Flt-1 (sFlt-1; also known as soluble vascular endothelial growth factor receptor-1 [VEGFR-1]) and soluble endoglin (sEng) are elevated in preeclampsia, and their administration to pregnant rats elicits preeclampsia-like symptoms. Heme oxygenase-1 (HO-1) and its metabolite carbon monoxide (CO) exert protective effects against oxidative stimuli. Thus, we hypothesized that HO-1 upregulation may offer protection against preeclampsia by inhibiting sFlt-1 and sEng release.

Nucleoside diphosphate kinase--a component of the [Na+1]- and [Cl-]-sensitive phosphorylation cascade in human and murine airway epithelium

We have shown that proteins within apically enriched fractions of human nasal respiratory epithelium vary their phosphohistidine content with ambient [Cl-] and other anion concentrations. This membrane-delimited phosphorylation cascade includes a multifunctional protein histidine kinase - nucleoside diphosphate kinase (NDPK). NDPK is itself a cascade component in both human and ovine airway, the self-phosphorylation of which is inhibited selectively by [Na+] in the presence of ATP (but not GTP). These findings led us to propose the existence of a dual anion-/cation-controlled phosphorylation-based "sensor" bound to the apical membrane. The present study showed that this cascade uses ATP to phosphorylate a group of proteins above 45 kDa (p45-group, identities unknown). Additionally, the Cl- dependence of ATP (but not GTP) phosphorylation is conditional on phosphatase activity and that interactions exist between the ATP- and GTP-phosphorylated components of the cascade under Cl--free conditions. As a prelude to studies in cystic fibrosis (CF) mice, we showed in the present study that NDPK is present and functionally active in normal murine airway. Since NDPK is essential for UTP synthesis and regulates fetal gut development, G proteins, K+channels, neutrophil-mediated inflammation and pancreatic secretion, the presence of ion-regulated NDPK protein in mouse airway epithelium might aid understanding of the pathogenesis of CF.

Sensor and software use for the glycaemic management of insulin-treated type 1 and type 2 diabetes patients

Lowering glucose levels, while avoiding hypoglycaemia, can be challenging in insulin-treated patients with diabetes. We evaluated the role of ambulatory glucose profile in optimising glycaemic control in this population. Insulin-treated patients with type 1 and type 2 diabetes were recruited into a prospective, multicentre, 100-day study and randomised to control (n = 28) or intervention (n = 59) groups. The intervention group used ambulatory glucose profile, generated by continuous glucose monitoring, to assess daily glucose levels, whereas the controls relied on capillary glucose testing. Patients were reviewed at days 30 and 45 by the health care professional to adjust insulin therapy. Comparing first and last 2 weeks of the study, ambulatory glucose profile-monitored type 2 diabetes patients (n = 28) showed increased time in euglycaemia (mean ± standard deviation) by 1.4 ± 3.5 h/day (p = 0.0427) associated with reduction in HbA1c from 77 ± 15 to 67 ± 13 mmol/mol (p = 0.0002) without increased hypoglycaemia. Type 1 diabetes patients (n = 25) showed reduction in hypoglycaemia from 1.4 ± 1.7 to 0.8 ± 0.8 h/day (p = 0.0472) associated with a marginal HbA1c decrease from 75 ± 10 to 72 ± 8 mmol/mol (p = 0.0508). Largely similar findings were observed comparing intervention and control groups at end of study. In conclusion, ambulatory glucose profile helps glycaemic management in insulin-treated diabetes patients by increasing time spent in euglycaemia and decreasing HbA1c in type 2 diabetes patients, while reducing hypoglycaemia in type 1 diabetes patients.

Serum procalcitonin, interleukin-6, soluble intercellular adhesin molecule-1 and IgG to short-chain exocellular lipoteichoic acid as predictors of infection in total joint prosthesis revision

The diagnosis of prosthetic joint infection and its differentiation from aseptic loosening remains problematic. The definitive laboratory diagnostic test is the recovery of identical infectious agents from multiple intraoperative tissue samples; however, interpretation of positive cultures is often complex as infection is frequently associated with low numbers of commensal microorganisms, in particular the coagulase-negative staphylococci (CNS). In this investigation, the value of serum procalcitonin (PCT), interleukin-6 (IL-6) and soluble intercellular adhesion molecule-1 (sICAM-1) as predictors of infection in revision hip replacement surgery is assessed. Furthermore, the diagnostic value of serum IgG to short-chain exocellular lipoteichoic acid (sce-LTA) is assessed in patients with infection due to CNS. Presurgical levels of conventional serum markers of infection including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and white blood cell count (WBC) is also established. Forty-six patients undergoing revision hip surgery were recruited with a presumptive clinical diagnosis of either septic (16 patients) or aseptic loosening (30 patients). The diagnosis was confirmed microbiologically and levels of serum markers were determined. Serum levels of IL-6 and sICAM-1 were significantly raised in patients with septic loosening (P=0.001 and P=0.0002, respectively). Serum IgG to sce-LTA was elevated in three out of four patients with infection due to CNS. In contrast, PCT was not found to be of value in differentiating septic and aseptic loosening. Furthermore, CRP, ESR and WBC were significantly higher (P=0.0001, P=0.0001 and P=0.003, respectively) in patients with septic loosening. Serum levels of IL-6, sICAM-1 and IgG to sce-LTA may provide additional information to facilitate the diagnosis of prosthetic joint infection.

Transcriptome Analysis Reveals New Insights into the Modulation of Endometrial Stromal Cell Receptive Phenotype by Embryo-Derived Signals Interleukin-1 and Human Chorionic Gonadotropin: Possible Involvement in Early Embryo Implantation

The presence of the conceptus in uterine cavity necessitates an elaborate network of interactions between the implanting embryo and a receptive endometrial tissue. We believe that embryo-derived signals play an important role in the remodeling and the extension of endometrial receptivity period. Our previous studies provided original evidence that human Chorionic Gonadotropin (hCG) modulates and potentiates endometrial epithelial as well as stromal cell responsiveness to interleukin 1 (IL1), one of the earliest embryonic signals, which may represent a novel pathway by which the embryo favors its own implantation and growth within the maternal endometrial host. The present study was designed to gain a broader understanding of hCG impact on the modulation of endometrial cell receptivity, and in particular, cell responsiveness to IL1 and the acquisition of growth-promoting phenotype capable of receiving, sustaining, and promoting early and crucial steps of embryonic development. Our results showed significant changes in the expression of genes involved in cell proliferation, immune modulation, tissue remodeling, apoptotic and angiogenic processes. This points to a relevant impact of these embryonic signals on the receptivity of the maternal endometrium, its adaptation to the implanting embryo and the creation of an environment that is favorable for the implantation and the growth of this latter within a new and likely hostile host tissue. Interestingly our data further identified a complex interaction between IL1 and hCG, which, despite a synergistic action on several significant endometrial target genes, may encompass a tight control of endogenous IL1 and extends to other IL1 family members.