School of Biomedical Sciences Publications - UQ eSpace

Binding and internalization of the melanocyte stimulating hormone receptor ligand [Nle(4), D-Phe(7)]alpha-MSH in B16 melanoma cells

Wong, WS og Minchin, RF — 2007-08-13T00:00:00Z

The current study aims to ascertain the fate of the melanocyte stimulating hormone (MSH) receptor and its ligand [Nle(4), D-Phe(7)]alpha-MsH (NDP-MSH) following binding to murine B16 melanoma cells. Cells were incubated with [I-125]-NDP-MSH for up to 180 min and binding, internalization and degradation determined. Intracellular trafficking of the radiolabel was assessed !using Percoll density gradient centrifugation of homogenized cells. Receptor down-regulation and receptor mRNA levels were also measured over 96 hr after exposure to 1 mu M ligand. NDP-MSH accumulation increased with time in a temperature-dependent manner and was inhibited by excess peptide. The ligand was rapidly internalized and translocated to the lysosomal compartment where it was degraded. Internalization was accompanied by a loss or down-regulation of cell surface receptors, suggesting internalization of the NDP-MSH-receptor complex. No recycling of the receptors between the plasma membrane and intracellular compartments could be detected in this cell-hue. Approximately 15% of the surface receptors were resistant to down-regulation, possibly indicating receptor heterogeneity. Down-regulation persisted ibr up to 96 hr and was accompanied by a decrease in MSH receptor mRNA levels 48 hr after treatment. However, before this time, transcript levels were the same in treated and control cells. In contrast to what was seen with NDP-MSH, cell surface receptors removed with trypsin wc:re rapidly replaced. These results show that NDP-MSH not only induced MSH receptor :internalization but also inhibited receptor turnover, resulting in a prolonged down-regulation. It is concluded that, in B16 cells, the MSH receptor undergoes ligand-dependent internalization, resulting in a prolonged down-regulation. Copyright (C) 1996 Elsevier Science Ltd

Binocular rivalry and perceptual coherence

2008-06-10T00:00:00Z

Bioactivation of tamoxifen by recombinant human cytochrome P450 enzymes

2007-08-24T00:00:00Z

Bioactivation of tamoxifen by recombinant human cytochrome P450 enzymes

2007-08-14T00:00:00Z

Tamoxifen is a major drug used for adjuvant chemotherapy of breast cancer; however, its use has been associated with a small but significant increase in risk of endometrial cancer. In rats, tamoxifen is a hepatocarcinogen, and DNA adducts have been observed in both rat and human tissues. Tamoxifen has been shown previously to be metabolized to reactive products that have the potential to form protein and DNA adducts. Previous studies have suggested a role for P450 3A4 in protein adduct formation in human liver microsomes, via a catechol intermediate; however, no clear correlation was seen between P450 3A4 content of human liver microsomes and adduct formation. In the present study, we investigated the P450 forms responsible for covalent drug-protein adduct formation and the possibility that covalent adduct formation might occur via alternative pathways to catechol formation. Recombinant P450 3A4 catalyzed adduct formation, and this correlated with the level of uncoupling in the P450 incubation, consistent with a role of reactive oxygen species in potentiating adduct formation after enzymatic formation of the catechol metabolite. Whereas P450s 1AI, 2D6, and 3A5 generated catechol metabolite, no covalent adduct formation was observed with these forms. By contrast, P450 2136, 2C19, and rat liver microsomes catalyzed drug-protein adduct formation but not catechol formation. Drug protein adducts formed specifically with P450 3A4 in incubations using membranes isolated from bacteria expressing P450 3A4 and reductase, as well as in reconstitutions of purified 3A4, suggesting that the electrophilic species reacted preferentially with the P450 enzymes concerned.

Biochemical requirements of virus wrapping by the endoplasmic reticulum: Involvement of ATP and endoplasmic reticulum calcium store during envelopment of African swine fever virus

2009-12-22T00:00:00Z

Enwrapment by membrane cisternae has emerged recently as a mechanism of envelopment for large enveloped DNA viruses, such as herpesviruses, poxviruses, and African swine fever (ASF) virus. For both ASF virus and the poxviruses, wrapping is a multistage process initiated by the recruitment of capsid proteins onto membrane cisternae of the endoplasmic reticulum (ER) or associated ER-Golgi intermediate membrane compartments. Capsid assembly induces progressive bending of membrane cisternae into the characteristic shape of viral particles, and envelopment provides virions with two membranes in one step. We have used biochemical assays for ASF virus capsid recruitment, assembly, and envelopment to define the cellular processes important for the enwrapment of viruses by membrane cisternae. Capsid assembly on the ER membrane, and envelopment by ER cisternae, were inhibited when cells were depleted of ATP or depleted of calcium by incubation with A23187 and EDTA or the ER calcium ATPase inhibitor, thapsigargin. Electron microscopy analysis showed that cells depleted of calcium were unable to assemble icosahedral particles. Instead, assembly sites contained crescent-shaped and bulbous structures and, in rare cases, empty closed five-sided particles. Interestingly, recruitment of the capsid protein from the cytosol onto the ER membrane did not require ATP or an intact ER calcium store. The results show that following recruitment of the virus capsid protein onto the ER membrane, subsequent stages of capsid assembly and enwrapment are dependent on ATP and are regulated by the calcium gradients present across the ER membrane cisternae.

Biochemistry of lipid and myoglobin oxidation in post-mortem muscle and processed meat products - effects on rancidity

Trout, Graham — 2006-04-20T00:00:00Z

Biocompatible properties of surgical mesh using an animal model

2007-08-15T00:00:00Z

To study the biocompatibility of surgical meshes for use in pelvic reconstructive surgery using an animal model. Eight different types of mesh: Atrium, Dexon, Gynemesh, IVS tape, Prolene, SPARC tape, TVT tape and Vypro II, were implanted into the abdominal walls of rats for 3 months' duration. Explanted meshes were assessed, using light microscopy, for parameters of rejection and incorporation. Type 1 (Atrium, Gynemesh, Prolene, SPARC and TVT) and type 3 (Vypro II, Dexon and IVS) meshes demonstrated different biocompatible properties. Inflammatory cellular response and fibrosis at the interface of mesh and host tissue was most marked with Vypro II and IVS. All type 1 meshes displayed similar cellular responses despite markedly different mesh architecture. The inflammatory response and fibrous reaction in the non-absorbable type 3 meshes tested (IVS and Vypro II) was more marked than the type 1 meshes. The increased inflammatory and fibrotic response may be because of the multifilamentous polypropylene components of these meshes. Material and filament composition of mesh is the main factor in determining cellular response.

Biogeographic origins of primate higher taxa

2011-10-21T00:00:00Z

Biohorizons - An eConference to assess human biology in large, first-year classes

2008-02-18T00:00:00Z

We detail the design, implementation and evaluation of an eConference entitled "Biohorizons", using a presage-process-product model to describe the development,of an eLearning community. Biohorizons was a summative learning and assessment task aiming to introduce large classes of first-year Human Biology students to the practices of professional scientists. It was implemented in semester 1 for students enrolled in Pharmacy and Human Movement Studies degree programs, and in semester 2, for Science students. Pairs of students selected a topic of interest in Human Biology, registered into on-line clusters, then developed and wrote a short scientific paper and accompanying PowerPoint presentation. They then individually participated in an online Discussion. All three tasks were assessed using standards-referenced assessment rubrics. Learning was supported by eTutors, working in asynchronous mode. Biohorizons was evaluated by analyzing student achievement data, surveys and focus group interviews. Most students were able to achieve high academic standards (global mean scores for semester 1, 85-96%; semester 2, 81-90%). Student evaluations support: 1) the successful integration of eLearning into large classes of Human Biology, 2) the engagement of first-year students through collaborative learning, and 3) the fostering of learning through challenging assessment relevant to the core practices of professional scientists.

BIOL 76-Investigations of agonist-receptor cation-pi interactions in cys-loop ligand gated ion channels

2010-06-20T00:00:00Z

Biological and diurnal variation in glucocorticoid sensitivity detected with a sensitive in vitro dexamethasone suppression of cytokine production assay

2011-10-19T00:00:00Z

Biologically active conformer of the effector region of human C5a and modulatory effects of N-terminal receptor binding determinants on activity

2007-08-13T00:00:00Z

A conformationally biased decapeptide agonist of human C5a (C5a(65-74)Y65,F67,P69,P71,D-Ala73 or YSFKPMPLaR) was used as a functional probe of the C5a receptor (C5aR) in order to understand the conformational features in the C-terminal effector region of C5a that are important for C5aR binding and signal transduction. YSFKPMPLaR was a potent, full agonist of C5a, but at higher concentrations had a superefficacious effect compared to the natural factor. The maximal efficacy of this analogue was 216 +/- 56% that of C5a in stimulating the release of beta-glucuronidase from human neutrophils. C5aR activation and binding curves both occurred in the same concentration range with YSFKPMPLaR, characteristics not observed with natural C5a or more conformationally flexible C-terminal agonists. YSFKPMPLaR was then used as a C-terminal effector template onto which was synthesized various C5aR binding determinants from the N-terminal core domain of the natural factor. In general, the presence of N-terminal binding determinants had little effect on either potency or binding affinity when the C-terminal effector region was presented to the C5aR in this biologically active conformation. However, one peptide, C5a(12-20)-Ahx-YSFKPMPLaR, expressed a 100-fold increase in affinity for the neutrophil C5aR and a 6-fold increase in potency relative to YSFKPMPLaR. These analyses showed that the peptides used in this study have up to 25% of the potency of C5a in human fetal artery and up to 5% of the activity of C5a in the PMN enzyme release assay.

Biological monitoring and Biological Limit Values (BLV): The strategy of the European Union

Bolt, H. M. og Thier, R. — 2007-08-14T00:00:00Z

Biological monitoring and Biological Limit Values (BLV): The strategy of the European Union

Bolt, H. M. og Thier, R. — 2007-08-15T00:00:00Z

Occupational standards concerning allowable concentrations of chemical compounds in the ambient air of workplaces have been established in several countries worldwide. With the integration of the European Union (EU), there has been a need of establishing harmonised Occupational Exposure Limits (OEL). The European Commission Directive 95/320/EC of 12 July 1995 has given the tasks to a Scientific Committee for Occupational Exposure Limits (SCOEL) to propose, based on scientific data and where appropriate, occupational limit values which may include the 8-h time-weighted average (TWA), short-term limits/excursion limits (STEL) and Biological Limit Values (BLVs). In 2000, the European Union issued a list of 62 chemical substances with Occupational Exposure Limits. Of these, 25 substances received a skin notation, indicating that toxicologically significant amounts may be taken up via the skin. For such substances, monitoring of concentrations in ambient air may not be sufficient, and biological monitoring strategies appear of potential importance in the medical surveillance of exposed workers. Recent progress has been made with respect to formulation of a strategy related to health-based BLVs. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

Biological monitoring in workers in a nitrobenzene reduction plant: haemoglobin versus serum albumin adducts

2008-03-28T00:00:00Z

The high priority of monitoring workers exposed to nitrobenzene is a consequence of clear findings of experimental carcinogenicity of nitrobenzene and the associated evaluations by the International Agency for Research on Cancer. Eighty male employees of a nitrobenzene reduction plant, with potential skin contact with nitrobenzene and aniline, participated in a current medical surveillance programme. Blood samples were routinely taken and analysed for aniline, 4-aminodiphenyl (4-ADP) and benzidine adducts of haemoglobin (Hb) and human serum albumin (HSA). Also, levels of methaemoglobin (Met-Hb) and of carbon monoxide haemoglobin (CO-Hb) were monitored. Effects of smoking were straightforward. Using the rank sum test of Wilcoxon, we found that very clear-cut and statistically significant smoking effects (about 3-fold increases) were apparent on CO-Hb (P = 0.00085) and on the Hb adduct of 4-ADP (P = 0.0006). The mean 'aniline-Hb adduct level in smokers was 1.5 times higher than in non-smokers; the significance (P = 0.05375) was close to the 5% level. The strongest correlation was evident between the Hb and HSA adducts of aniline (r(s) = 0.846). Less pronounced correlations (but with P values < 0.02) appeared between aniline-Hb and 4-ADP-Hb adducts (r(s) = 0.388), between 4-ADP and 4-ADP-HSA adducts (r(s) = 0.373), and between 4-ADP-Hb and aniline-HSA adducts (r(s) = 0.275). In view of the proposal for additional use of the aniline-HSA adduct for biological monitoring, particularly in cases of acute overexposures or poisonings, the strong correlation of the Hb and HSA conjugates is noteworthy; the ratio aniline-HSA:aniline-Hb was 1:42 for the entire cohort.

Biological polarized light reflectors in stomatopod crustaceans

2007-08-23T00:00:00Z

Body parts that can reflect highly polarized light have been found in several species of stomatopod crustaceans (mantis shrimps). These polarized light reflectors can be grossly divided into two major types. The first type, usually red or pink in color to the human visual system, is located within an animal’s cuticle. Reflectors of the second type, showing iridescent blue, are located beneath the exoskeleton and thus are unaffected by the molt cycle. We used reflection spectropolarimetry and transmission electron microscopy (TEM) to study the reflective properties and the structures that reflect highly polarized light in stomatopods. For the first type of reflector, the degree of polarization usually changes dramatically, from less than 20% to over 70%, with a change in viewing angle. TEM examination indicates that the polarization reflection is generated by multilayer thin-film interference. The second type of reflector, the blue colored ones, reflects highly polarized light to all viewing angles. However, these reflectors show a slight chromatic change with different viewing angles. TEM sections have revealed that streams of oval-shaped vesicles might be responsible for the production of the polarized light reflection. In all the reflectors we have examined so far, the reflected light is always maximally polarized at around 500 nm, which is close to the wavelength best transmitted by sea water. This suggests that the polarized light reflectors found in stomatopods are well adapted to the underwater environment. We also found that most reflectors produce polarized light with a horizontal e-vector. How these polarized light reflectors are used in stomatopod signaling remains unknown.

Biology, ecology and conservation of the Mobulidae

2012-05-14T21:27:43Z

Biomechanical properties of raw meshes used in pelvic floor reconstruction

2009-03-18T00:00:00Z

Female urinary incontinence and pelvic organ prolapse are common conditions. The aim of this study was to assess the biomechanical properties of raw meshes commonly used in pelvic floor surgery, particularly the effects of cyclical loading on these meshes. The material properties of nine different types of surgical meshes were examined using uniaxial tensile tests. The strength and extensibility of the mesh designs differed considerably. Most mesh types exhibited curvilinear loading curves. Cyclical loading of mesh samples produced significant permanent deformation in all mesh designs. This non-recoverable extension ranged from about 8.5% to 19% strain. Hysteresis also varied considerably between materials from 30% to 85%. All mesh groups tested for their biomechanical properties displayed differences in results for failure load, stiffness, non-recoverable extension and hysteresis.

Birth in marsupials

Gemmell, R. T. og Veitch, C. og Nelson, J. — 2007-08-14T00:00:00Z

Birth in the bandicoot, Isoodon macrourus

Veitch, C. og Gemmell, R. T. og Nelson, J. — 2008-06-06T00:00:00Z

Birth in the brushtail possum Trichosurus vulpecula

Veitch, C. og Gemmell, R. T. — 2008-06-06T00:00:00Z

Birth in the brushtail possum, Trichosurus vulpecular (Marsupialia: Phalangeridae)

Veitch, C. og Nelson, J. og Gemmell, R. T. — 2008-06-10T00:00:00Z

Birth in the marsupial quoll, Dasyurus hallucatus.

Nelson, J. og Gemmell, R. T. — 2007-08-24T00:00:00Z

Birth in the northern quoll, Dasyurus hallucatus (Marsupialia : Dasyuridae)

Nelson, John E. og Gemmell, Robert T. — 2007-08-14T00:00:00Z

Birth has been observed in a number of marsupial species and, in the studies to date, the newborn have crawled up to or across to the pouch. The method of birth in the quoll, a dasyurid, differs greatly from that observed in other marsupials. Births were recorded at normal speed using hand-held digital video cameras. Birth was heralded by a release of about 1 mL of watery fluid from the urogenital sinus followed by gelatinous material contained in either one or two tubes emanating from the sinus. The newborn, still encased in their placental membranes, were in the gelatinous material within a column. To exit this column, they had to grasp a hair and wriggle about 1 cm across to the pouch. In the pouch the newborn young had to compete for a teat. Although the quolls possessed 8 teats, the number of young in the pouch immediately after birth was 17, 16, 6, 16, 13 and 11 for each of the 6 quolls filmed. While birth has been described previously in another two dasyurids, the observers did not describe birth as reported here for the quoll. Nevertheless the movement of the newborn from the sinus to the pouch is so quick that this could have previously been missed. Filming birth from beneath and from the side allowed for a greater understanding of the birth process. Further studies are required to determine whether this use of a gelatinous material is part of the birth process in all dasyurids.

Birth of a metabolic gene cluster in yeast by adaptive gene relocation

Wong, S og Wolfe, KH — 2008-01-25T00:00:00Z

Although most eukaryotic genomes lack operons, they contain some physical clusters of genes that are related in function despite being unrelated in sequence(1-5). How these clusters are formed during evolution is unknown. The DAL cluster is the largest metabolic gene cluster in yeast and consists of six adjacent genes encoding proteins that enable Saccharomyces cerevisiae to use allantoin as a nitrogen source(6). We show here that the DAL cluster was assembled, quite recently in evolutionary terms, through a set of genomic rearrangements that happened almost simultaneously. Six of the eight genes involved in allantoin degradation, which were previously scattered around the genome, became relocated to a single subtelomeric site in an ancestor of S. cerevisiae and Saccharomyces castellii. These genomic rearrangements coincided with a biochemical reorganization of the purine degradation pathway, which switched to importing allantoin instead of urate. This change eliminated urate oxidase, one of several oxygen- consuming enzymes that were lost by yeasts that can grow vigorously in anaerobic conditions. The DAL cluster is located in a domain of modified chromatin involving both H2A. Z histone exchange and Hst1- Sum1 - mediated histone deacetylation, and it may be a coadapted gene complex formed by epistatic selection.

Bi-sensory, striped representations: comparative insights from owl and platypus

Pettigrew, JD — 2007-08-15T00:00:00Z

Bi-sensory striped arrays are described in owl and platypus that share some similarities with the other variant of bi-sensory striped array found in primate and carnivore striate cortex: ocular dominance columns. Like ocular dominance columns, the owl and platypus striped systems each involve two different topographic arrays that are cut into parallel stripes, and interdigitated, so that higher-order neurons can integrate across both arrays. Unlike ocular dominance stripes, which have a separate array for each eye, the striped array in the middle third of the owl tectum has a separate array for each cerebral hemisphere. Binocular neurons send outputs from both hemispheres to the striped array where they are segregated into parallel stripes according to hemisphere of origin. In platypus primary somatosensory cortex (SI), the two arrays of interdigitated stripes are derived from separate sensory systems in the bill, 40,000 electroreceptors and 60,000 mechanoreceptors. The stripes in platypus SI cortex produce bimodal electrosensory-mechanosensory neurons with specificity for the time-of-arrival difference between the two systems. This thunder-and-lightning system would allow the platypus to estimate the distance of the prey using time disparities generated at the bill between the earlier electrical wave and the later mechanical wave caused by the motion of benthic prey. The functional significance of parallel, striped arrays is not clear, even for the highly-studied ocular dominance system, but a general strategy is proposed here that is based on the detection of temporal disparities between the two arrays that can be used to estimate distance. (C) 2004 Elsevier Ltd. All rights reserved.

Bisphosphonates are associated with microdamage accumulation at clinically relevant skeletal sites in beagles

2008-06-06T00:00:00Z

Bisphosphonate treatment delays stress fracture remodeling in the rat ulna

2012-01-01T00:00:00Z

Because bisphosphonates (BPs) are potent inhibitors of bone resorption, we hypothesized that they would retard direct remodeling of stress fractures. The aim of this study was to determine the effect of risedronate on direct remodeling and woven bone callus formation following stress fracture formation in the rat ulna. In 135 adult female Wistar rats, cyclic loading of the ulna created stress fractures. Rats were treated daily with oral saline, or risedronate at 0.1 or 1.0 mg/kg. From each bone, histomorphometry was performed on sections stained with toluidine blue at a standard level along the fracture. The high dose of risedronate caused a significant decrease in the percentage of repaired stress fracture and bone resorption along the stress fracture line at 6 and 10 weeks after loading (p < 0.05). At this dose, intracortical resorption was significantly reduced at 10 weeks after loading and intracortical new bone area was significantly reduced at 6 and 10 weeks. Woven bone formation and consolidation phases of stress fracture repair were not affected by low or high doses of risedronate. In conclusion, high dose bisphosphonate treatment impaired healing of a large stress fracture line by reducing the volume of bone resorbed and replaced during remodeling. We also confirmed that periosteal callus formation was not adversely affected by risedronate treatment.

Blockade of C5a receptors reduces astroglial inflammation in a rat SOD1G93A model of amyotrophic lateral sclerosis

2009-09-14T00:00:00Z

Amyotrophic lateral sclerosis (ALS), the most common form of motor neuron disease, is a fatal neurodegenerative disorder characterized by the progressive loss of both upper and lower motor neurons leading to muscle paralysis and eventual death. It remains a disease that is largely untouched by current therapeutics. Transgenic animals harboring mutant human SOD1G93A enzyme found in familial cases of ALS, develop similar pathology to the human condition, and are thus used as an animal model to test out new therapeutics. Several years ago, our laboratory developed a series of potent drugs (C5a receptor antagonists) which block the action of the complement factor C5a. We have previously demonstrated that SOD1 transgenic rats treated with one of these drugs (hydrocinnamate-[OPdChaWR]; PMX205), was able to improve survival (127 ± 4 days vs. 144 ± 8 days) and reduce end-stage motor deficits. The present study aimed to examine these effects further using immunohistochemical techniques. Lumbar spinal cord tissue from wild-type, untreated SOD1, and PMX205-treated SOD1 transgenic rats were immuno-stained with antibodies for motor neurons, astrocytes, microglia and C5a receptors. We observed a significant upregulation of both astrocytes and microglia in SOD1G93A rats (34-fold and 21-fold increase, respectively), corresponding with motor neuron loss in these same regions. Interestingly, we found C5a receptors to be strongly expressed on these proliferating astrocytes, but not on microglia. C5a receptors were also found on motor neurons in both wild-type and SOD1G93A rats. PMX205 treatment was found to significantly reduce the degree of astrocyte proliferation in end-stage SOD1G93A rats, but treatment had no effect on microglial proliferation. This study indicates that PMX205 may exert its protective effect in the SOD1G93A rat by reducing astroglial inflammation. Inhibitors of C5a may therefore serve as potential novel therapeutics to treat this disease. Copyright © 2009 Elsevier Ltd. All rights reserved

Blockade of the C5a receptor fails to protect against experimental autoimmune encephalomyelitis in rats

2007-08-15T00:00:00Z

Complement activation contributes to inflammation and tissue damage in human demyelinating diseases and in rodent models of demyelination. Inhibitors of complement activation ameliorate disease in the rat model antibody-dependent experimental autoimmune encephalomyelitis and rats unable to generate the membrane attack complex of complement develop inflammation without demyelination. The role of the highly active chemotactic and anaphylactic complement-derived peptide C5a in driving inflammation and pathology in rodent models of demyelination has been little explored. Here we have used a small molecule C5a receptor antagonist, AcF-[OPdChaWR], to examine the effects of C5a receptor blockade in rat models of brain inflammation and demyelination. C5a receptor antagonist therapy completely blocked neutrophil response to C5a in vivo but had no effect on clinical disease or resultant pathology in either inflammatory or demyelinating rat models. We conclude that C5a is not required for disease induction or perpetuation in these strongly complement-dependent disease models.

Blockade of vascular smooth muscle cell proliferation and intimal thickening after balloon injury by the sulfated oligosaccharide PI-88: Phosphomannopentaose sulfate directly binds FGF-2, blocks cellular signaling, and inhibits proliferation

2007-08-13T00:00:00Z

Percutaneous transluminal coronary angioplasty is a frequently used interventional technique to reopen arteries that have narrowed because of atherosclerosis. Restenosis, or renarrowing of the artery shortly after angioplasty, is a major limitation to the success of the procedure and is due mainly to smooth muscle cell accumulation in the artery wall at the site of balloon injury. In the present study, we demonstrate that the antiangiogenic sulfated oligosaccharide, PI-88, inhibits primary vascular smooth muscle cell proliferation and reduces intimal thickening 14 days after balloon angioplasty of rat and rabbit arteries. PI-88 reduced heparan sulfate content in the injured artery wall and prevented change in smooth muscle phenotype. However, the mechanism of PI-88 inhibition was not merely confined to the antiheparanase activity of this compound. PI-88 blocked extracellular signal-regulated kinase-1/2 (ERK1/2) activity within minutes of smooth muscle cell injury. It facilitated FGF-2 release from uninjured smooth muscle cells in vitro, and super-released FGF-2 after injury while inhibiting ERK1/2 activation. PI-88 inhibited the decrease in levels of FGF-2 protein in the rat artery wall within 8 minutes of injury. PI-88 also blocked injury-inducible ERK phosphorylation, without altering the clotting time in these animals. Optical biosensor studies revealed that PI-88 potently inhibited (K-i 10.3 nmol/L) the interaction of FGF-2 with heparan sulfate. These findings show for the first time the capacity of this sulfated oligosaccharide to directly bind FGF-2, block cellular signaling and proliferation in vitro, and inhibit injury-induced smooth muscle cell hyperplasia in two animal models. As such, this study demonstrates a new role for PI-88 as an inhibitor of intimal thickening after balloon angioplasty. The full text of this article is available online at http://www.circresaha.org.

Blood pressure and renal function in adult sheep treated prenatally with glucocorticoids: effects of a high salt diet

2008-07-29T00:00:00Z

No abstract

Blue and yellow signal cleaning behaviour in coral reef fishes

2010-01-05T00:00:00Z

Marine cleaning symbioses are classic examples of mutualism: cleaners remove and consume ectoparasites from‘‘client’’ fish, while clients benefit from a reduction in ectoparasites[1, 2]. However, how clients recognize cleaners and decide not to eat them is unclear. Color and body pattern are thought to be important in signaling cleaning services to coral reef fish [1, 3, 4]; in this study, we tested the longheld belief that cleaner fish display a blue ‘‘guild’’ coloration [5–7]. Via color analytical techniques and phylogenetic comparisons, we show that cleaner fish are more likely to display a blue coloration, in addition to a yellow coloration,compared to noncleaner fish. Via theoretical vision models,we show that, from the perspective of potential signal receivers, blue is the most spectrally contrasting color against coral reef backgrounds, whereas yellow is most contrasting against blue water backgrounds or against black lateral stripes. Finally, behavioral experiments confirm that blue within the cleaner fish pattern attracts more client reef fish to cleaning stations. Cleaner fish have evolved some of the most conspicuous combinations of colors and patterns in the marine environment, and this is likely to underpin the success of the cleaner-client relationship on the reef.

Blue light special in a red light district

Schwab, I. R. og Marshall, J. — 2007-08-15T00:00:00Z

Blunted sodium excretion in response to a saline load in 5 year old female sheep following fetal uninephrectomy

2012-12-02T00:56:22Z

BOC, brother of CDO, is a dorsoventral axon-guidance molecule in the embryonic vertebrate brain

2007-08-15T00:00:00Z

The early axon scaffolding in the embryonic vertebrate brain consists of a series of ventrally projecting axon tracts that grow into a single major longitudinal pathway connected across the midline by commissures. We have investigated the role of Brother of CDO (BOC), an immunoglobulin (Ig) superfamily member distantly related to the Roundabout (Robo) family of axon-guidance receptors, in the development of this embryonic template of axon tracts in the zebrafish brain. A zebrafish homologue of BOC was isolated and shown to be expressed predominantly in the developing neural plate and later in the neural tube and developing brain. Zebrafish boc was initially highly localized to discrete bands in the mid- and hindbrain, but, as the major brain subdivisions emerged, it became more evenly expressed along the rostrocaudal axis, particularly in dorsal regions. The function of zebrafish boc was examined by a loss-of-function approach. Analysis of embryos injected with antisense morpholinos designed against boc revealed highly selective defects in the development of dorsoventrally projecting axon tracts. Loss of boc caused ventrally projecting axons, particularly those arising from the presumptive telencephalon, to follow aberrant trajectories. These data indicate that boc is an axon-guidance molecule playing a fundamental role in pathfinding during the early patterning of the axon scaffold in the embryonic vertebrate brain. (c) 2005 Wiley-Liss, Inc.

Body composition and muscle strength as predictors of bone mineral density in Crohn's disease

2009-11-25T00:00:00Z

Compromised skeletal status is a frequent finding in patients with Crohn’s disease (CD), leading to increased fracture risk. Low body weight is associated with bone mineral density (BMD) in CD, although the relative importance of its components, lean and fat mass, is unclear. Muscle strength is also a predictor of BMD in nondiseased populations; however, its association with bone in CD is unknown. We examined the independent effects of body composition and muscle strength on regional and whole-body BMD in a cohort of CD patients. Sixty men and women, aged 22–72 years, with disease duration of 13 ± 7 years, underwent scanning of the spine, hip, forearm, and whole-body BMD by dual-energy X-ray absorptiometry (DXA). Lean tissue, appendicular muscle mass (AMM), and fat mass were derived by DXA and grip strength by dynamometry. Medical history, medication usage, clinical variables, and nutritional intake were obtained by questionnaire. Prevalence of osteopenia and osteoporosis was 32 and 17%, respectively, with osteopenia more common at the hip and osteoporosis more common at the spine. In multiple regression analyses, AMM was an independent predictor of whole-body and regional BMD whereas lean mass was an independent predictor at the hip. Neither grip strength nor fat mass was independently associated with BMD. Of the components of body composition, muscle mass was strongly associated with regional and whole-body BMD. Preserving or augmenting muscle mass in this population may be a useful strategy to preserve BMD and thereby reduce fracture risk.

Body fluid volume regulation in elasmobranch fish

2008-06-05T00:00:00Z

This review addresses an often overlooked aspect of elasmobranch osmoregulation, i.e., control of body fluid volume. More specifically the review addresses the impact of changes in blood volume in elasmobranchs exposed to different environmental salinities. Measurement of blood volume in the European lesser-spotted dogfish, Scyliorhinus canicula, following acute and chronic exposure to 80% and 120% seawater (SW) is reported. In 80%, 100% and 120% SW-adapted S. canicula, blood volume was 6.3 ± 0.2, 5.6 ± 0.2 and 4.6 ± 0.2 mL 100 g− 1 body mass, respectively. Blood volume was significantly higher and lower in 80% and 120% SW-acclimated animals compared to 100% SW controls. Comparisons are made between these results and previously published data. The role of drinking and volume regulation in elasmobranchs is discussed. For the first time measured water reabsorption rates and solute flux rates across the elasmobranch intestinal epithelia are presented. Water reabsorption rates did not differ between 100% SW-adapted bamboo shark, Chiloscyllium plagiosum, and fish acutely transferred to 140% SW. For the most part net solute flux rates and direction for both the 100% and 140% SW groups were the same with the exception of a net efflux of chloride and potassium in the 140% group and influx of these ions in the 100% adapted group. The significance of the intestine as part of the overall elasmobranch osmoregulatory strategy is discussed as is the role of the kidneys, rectal gland and gills in the regulation of body fluid volume in this class of vertebrates.

Bone marrow chimeric mice reveal a role for CX3CR1 in maintenance of the monocyte-derived cell population in the olfactory neuroepithelium

2011-01-09T00:00:00Z

Bone remodelling in osteoarthritic cancellous bone: A molecular histomorphometric study

2008-06-06T00:00:00Z

Bone-Specific Heparan Sulfates Induce Osteoblast Growth Arrest and Downregulation of Retinoblastoma Protein

2007-08-15T00:00:00Z

Botulinum neurotoxins: from paralysis to recovery of functional neuromuscular transmission

Meunier, FA og Schiavo, G og Molgo, J — 2007-10-17T00:00:00Z

The neuromuscular junction is one of the most accessible mammalian synapses which offers a useful model to study long-term synaptic modifications occurring throughout life. It is also the natural target of botulinum neurotoxins (BoNTs) causing a selective blockade of the regulated exocytosis of acetylcholine thereby triggering a profound albeit transitory muscular paralysis. The scope of this review is to describe the principal steps implicated in botulinum toxin intoxication from the early events leading to a paralysis to the cellular response implementing an impressive synaptic remodelling culminating in the functional recovery of neuromuscular transmission. BoNT/A treatment promotes extensive sprouting emanating from intoxicated motor nerve terminals and the distal portion of motor axons. The current view is that sprouts have the ability to form functional synapses as they display a number of key proteins required for exocytosis: SNAP-25, VANIP/synaptobrevin, syntaxin-1, synaptotagmin-II, synaptophysin, and voltage-activated Na+, Ca2+ and Ca2+-activated K+ channels. Exo-endocytosis was demonstrated (using the styryl dye FM1-43) to occur only in the sprouts in vivo, at the time of functional recovery emphasising the direct role of nerve terminal outgrowth in implementing the restoration of functional neurotransmitter release (at a time when nerve stimulation again elicited muscle contraction). Interestingly, sprouts are only transitory since a second distinct phase of the rehabilitation process occurs with a return of synaptic activity to the original nerve terminals. This is accompanied by the elimination of the dispensable sprouts. The growth or elimination of these nerve processes appears to be strongly correlated with the level of synaptic activity at the parent terminal. The BoNT/A-induced extension and later removal of "functional" sprouts indicate their fundamental importance in the rehabilitation of paralysed endplates, a finding with ramifications for the vital process of nerve regeneration. (C) 2002 Elsevier Science Ltd. All rights reserved.

Brain morphology and sensory specialisation in elasmobranchs

Lisney, T. J. og Collin, S. P. — 2009-01-23T00:00:00Z

Brain morphology in large pelagic fishes: A comparison between sharks and teleosts

Lisney, T. J. og Collin, S. P. — 2007-08-15T00:00:00Z

A quantitative comparison was made of both relative brain size (encephalization) and the relative development of five brain area of pelagic sharks and teleosts. Two integration areas (the telencephalon and the corpus cerebellum) and three sensory brain areas (the olfactory bulbs, optic tectum and octavolateralis area, which receive primary projections from the olfactory epithelium, eye and octavolateralis senses, respectively), in four species of pelagic shark and six species of pelagic teleost were investigated. The relative proportions of the three sensory brain areas were assessed as a proportion of the total 'sensory brain', while the two integration areas were assessed relative to the sensory brain. The allometric analysis of relative brain size revealed that pelagic sharks had larger brains than pelagic teleosts. The volume of the telencephalon was significantly larger in the sharks, while the corpus cerebellum was also larger and more heavily foliated in these animals. There were also significant differences in the relative development of the sensory brain areas between the two groups, with the sharks having larger olfactory bulbs and octavolateralis areas, whilst the teleosts had larger optic tecta. Cluster analysis performed on the sensory brain areas data confirmed the differences in the composition of the sensory brain in sharks and teleosts and indicated that these two groups of pelagic fishes had evolved different sensory strategies to cope with the demands of life in the open ocean.

Branchial vascular pathways in two species of Tetraodontiformes and the concept of secondary vessels and nutrient arteries

Skov, P. V. og Bennett, M. B. — 2007-08-15T00:00:00Z

The vascular organisation of the branchial basket was examined in two Tetraodontiform fishes; the three-barred porcupinefish, Dicotylichthys punctulatus and the banded toadfish, Marylina pleurosticta by scanning electron microscopy of vascular casts and standard histological approaches. In D. punctulatus, interarterial anastomoses (iaas) originated at high densities from the efferent filamental and branchial arteries, subsequently re-anastomosing to form progressively larger secondary vessels. Small branches of this system entered the filament body, where it was interspersed between the intrafilamental vessels. Large-bore secondary vessels ran parallel with the efferent branchial arteries, and were found to constitute an additional arterio-arterial pathway, in that these vessels exited the branchial basket in company with the mandibular, the carotid and the afferent and efferent branchial arteries, from where they gave rise to capillary beds after exit. Secondary vessels were not found to supply filament muscle; rather these tissues were supplied by single specialised vessels running in parallel between the efferent and afferent branchial arteries in both species examined. Although the branchial vascular anatomy was generally fairly similar for the two species examined, iaas were not found to originate from any branchial component in the banded toadfish, M. pleurosticta, which instead showed a moderate frequency of iaas on other vessels in the cephalic region. It is proposed that four independent vascular pathways may be present within the teleostean gill filament, the conventional arterio-arterial pathway across the respiratory lamellae; an arterio-arterial system of secondary vessels supplying the filament and non-branchial tissues; a system of vessels supplying the filament musculature; and the intrafilamental vessels (central venous sinus). The present study demonstrates that phylogenetic differences in the arrangement of the branchial vascular system occur between species of the same taxon.

Bridging the gap between teaching and research in a research-intensive university

2010-08-18T00:00:00Z

Broth recycling to reduce process noise resulting from concentrated substrate addition in fed-batch cultivation of Escherichaa coli

Johnston, W. A. og Cooney, M. J. — 2008-03-28T00:00:00Z

In this work feed hardware for fed-batch cultivation is presented (broth recycle feed injection system or BRFIS). BRFIS proved superior to conventional submerged or dripped feed systems in reducing dissolved oxygen (DO) oscillations during Escherichia coli fed-batch cultivation (5 min coefficient of variation of 0.7% for BRFIS as compared to 26% or greater for conventional feeding hardware in a 2 L test reactor). Hence, BRFIS is useful for fed-batch cultivation systems where the DO signal is used in measurement or control.

Building a new heart from old parts: stem cell turnover in the aging heart

Porrello, Enzo R. og Olson, Eric N. — 2012-09-21T00:00:00Z

Burkholderia cepacia complex epidemiology in persons with cystic fibrosis from Australia and New Zealand

2009-09-03T00:00:00Z

The Burkholderia cepacia complex (Bcc) is a group of significant opportunistic respiratory pathogens which affect people with cystic fibrosis. In this study, we sought to ascertain the epidemiology and geographic species distribution of 116 Bcc isolates collected from people with CF in Australia and New Zealand. We performed a combination of recA-based PCR, amplified rDNA restriction analysis (ARDRA), pulsed-field gel electrophoresis and repetitive extragenic palindromic PCR on each isolate. Each Burkholderia cenocepacia isolate was also screened by PCR for the presence of the B. cepacia epidemic strain marker. One hundred and fourteen isolates were assigned to a species using recA-based PCR and ARDRA. B. cenocepacia, B. multivorans and B. cepacia accounted for 45.7%, 29.3% and 11.2% of the isolates, respectively. Strain analysis of B. cenocepacia revealed that 85.3% of the isolates were unrelated. One related B. cenocepacia strain was identified amongst 15 people. Whilst full details of person-to-person contact was not available, all patients attended CF centres in Queensland (Qld) and New South Wales (NSW). Although person-to-person transmission of B. cenocepacia strains has occurred in Australia, the majority of CF-related Bcc infections in Australia and New Zealand are most likely acquired from the environment. Copyright © 2009 Elsevier Masson SAS. All rights reserved

cADP-ribose and agonist-induced Ca2e oscillations in mouse pancreatic acinar cells are dependent on a ryanodine receptor

2011-03-10T00:00:00Z