Stressful animal housing conditions and their potential effect on sympathetic neurotransmission in mice

Although the sympathetic nervous system (SNS) plays a major role in mediating the peripheral stress response, due consideration is not usually given to the effects of prolonged stress on the SNS. The present study examined changes in neurotransmission in the SNS after exposure of mice (BALB/c) to stressful housing conditions. Focal extracellular recording of excitatory junction currents (EJCs) was used as a relative measure of neurotransmitter release from different regions of large surface areas of the mouse vas deferens. Mice were either group housed (control), isolation housed (social deprivation), group housed in a room containing rats (rat odor stress), or isolation housed in a room containing rats (concurrent stress). Social deprivation and concurrent stressors induced an increase of 30 and 335% in EJC amplitude, respectively. The success rate of recording EJCs from sets of varicosities in the concurrent stressor group was greater compared with all other groups. The present study has shown that some common animal housing conditions act as stressors and induce significant changes in sympathetic neurotransmission.

Distribution of a nematocyst-bearing sponge in relation to potential coral donors

Haliclona sp. 628 (Demospongiae, Haplosclerida, Chalinidae), a sponge found on the reef slope below 5 in depth on the Great Barrier Reef, has two unusual characteristics. It contains a symbiotic dinoflagellate, Symbiodinium sp., similar in structure to the dinoflagellate found within Acropora nobilis (S. microadriaticum), and it contains coral nematocysts randomly distributed between the ectosome and endosome and usually undischarged in intact sponge tissue. Given the unusual occurrence of nematocysts in Haliclona sp. 628, the focus of this study was to determine the distribution of this species of sponge on the reef slope at Heron Island Reef in relation to the distribution of potential coral donors. A combination of line and belt transects was used to estimate the abundance of Halielona sp. 628 and a co-occurring congener, Haliclona sp. 1031, which does not contain nematocysts, at three widely separated sites on the reef slope at Heron Island Reef. The abundance of different types of substratum (sand, sand-covered coral rubble, dead A. nobilis, live A. nobilis, other live coral, and other dead coral) along the transects and the substratum to which each sponge colony was attached were also recorded. Despite the predominance of live A. nobilis and sand-covered rubble at all sites, between 30 and 55% of Haliclona sp. 628 colonies were attached to dead A. nobilis which comprised less than 8% of the available substratum along any transect. In contrast, Haliclona sp. 1031 was found significantly more frequently on other dead corals and less frequently on live A. nobilis than would be expected based on the availability of the different substrata in the sites. Potential explanations to account for the distribution of Haliclona sp. 628 in relation to potential coral donors are discussed.

The JK three-product cyclone - performance and potential applications

In spite of their wide application in comminution circuits, hydrocyclones have at least one significant disadvantage in that their operation inherently tends to return the fine denser liberated minerals to the grinding mill. This results in unnecessary overgrinding which adds to the milling cost and can adversely affect the efficiency of downstream processes. In an attempt to solve this problem, a three-product cyclone has been developed at the Julius Kruttschnitt Mineral Research Centre (JKMRC) to generate a second overflow in which the fine dense liberated minerals can be selectively concentrated for further treatment. In this paper, the design and operation of the three-product cyclone are described. The influence of the length of the second vortex finder on the performance of a 150-mm unit treating a mixture of magnetite and silica is investigated. Conventional cyclone tests were also conducted under similar conditions. Using the operational performance data of the three-product and conventional cyclones, it is shown that by optimising the length of the second vortex finder, the amount of fine dense mineral particles that reports to the three-product cyclone underflow can be reduced. In addition, the three-product cyclone can be used to generate middlings stream that may be more suitable for flash flotation than the conventional cyclone underflow, or alternatively, could be classified with a microscreen to separate the valuables from the gangue. At the same time, a fines stream having similar properties to those of the conventional overflow can be obtained. Hence, if the middlings stream was used as feed for flash flotation or microscreening, the fines stream could be used in lieu of the conventional overflow without compromising the feed requirements for the conventional flotation circuit. Some of the other potential applications of the new cyclone are described. (C) 2003 Elsevier Science B.V. All rights reserved.

Evaluation of potential biocontrol agents against Claviceps africana in vitro and in vivo

Undiluted culture filtrates of two commercial products of Trichoderma spp., Trichopel and Trichoflow, and two isolates of Penicillium citrinum completely inhibited the conidial germination of macroconidia of Claviceps africana , the cause of ergot or sugary disease of sorghum (Sorghum bicolor) in vitro . Similarly, Pseudomonas aeruginosa and Burkholderia cepacia completely inhibited macroconidial germination, with the former being more effective at high dilutions. In contrast, these bacterial isolates failed to inhibit infection in vivo in glasshouse tests with ergot-inoculated sorghum, but all fungal biocontrol agents (including an isolate of Epicoccum nigrum) reduced the severity of disease (percentage of infected spikelets per panicle), in some cases completely inhibiting the development of ergot. In a second glasshouse trial, optimum control was achieved when the biocontrol agents were applied 3-7 days before inoculation with conidia of C. africana .

Anaerobic ammonium oxidation by marine and freshwater planctomycete-like bacteria

Recently, two fresh water species, 'Candidatus Brocadia anammoxidans' and 'Candidatus Kuenenia stuttgartiensis', and one marine species, 'Candidatus Scalindua sorokinii', of planctomycete anammox bacteria have been identified. 'Candidatus Scalindua sorokinii' was discovered in the Black Sea, and contributed substantially to the loss of fixed nitrogen. All three species contain a unique organelle-the anammoxosome-in their cytoplasm. The anammoxosome contains the hydrazine/hydroxylamine oxidoreductase enzyme, and is thus the site of anammox catabolism. The anammoxosome is surrounded by a very dense membrane composed almost exclusively of linearly concatenated cyclobutane-containing lipids. These so-called 'ladderanes' are connected to the glycerol moiety via both ester and ether bonds. In natural and man-made ecosystems, anammox bacteria can cooperate with aerobic ammonium-oxidising bacteria, which protect them from harmful oxygen, and provide the necessary nitrite. The cooperation of these two groups of ammonium-oxidising bacteria is the microbial basis for a sustainable one reactor system, CANON (completely autotrophic nitrogen-removal over nitrite) to remove ammonia from high strength wastewater.

Estimates of global and regional potential health gains from reducing multiple major risk factors

Background Estimates of the disease burden due to multiple risk factors can show the potential gain from combined preventive measures. But few such investigations have been attempted, and none on a global scale. Our aim was to estimate the potential health benefits from removal of multiple major risk factors. Methods We assessed the burden of disease and injury attributable to the joint effects of 20 selected leading risk factors in 14 epidemiological subregions of the world. We estimated population attributable fractions, defined as the proportional reduction in disease or mortality that would occur if exposure to a risk factor were reduced to an alternative level, from data for risk factor prevalence and hazard size. For every disease, we estimated joint population attributable fractions, for multiple risk factors, by age and sex, from the direct contributions of individual risk factors. To obtain the direct hazards, we reviewed publications and re-analysed cohort data to account for that part of hazard that is mediated through other risks. Results Globally, an estimated 47% of premature deaths and 39% of total disease burden in 2000 resulted from the joint effects of the risk factors considered. These risks caused a substantial proportion of important diseases, including diarrhoea (92%-94%), lower respiratory infections (55-62%), lung cancer (72%), chronic obstructive pulmonary disease (60%), ischaemic heart disease (83-89%), and stroke (70-76%). Removal of these risks would have increased global healthy life expectancy by 9.3 years (17%) ranging from 4.4 years (6%) in the developed countries of the western Pacific to 16.1 years (43%) in parts of sub-Saharan Africa. Interpretation Removal of major risk factors would not only increase healthy life expectancy in every region, but also reduce some of the differences between regions, The potential for disease prevention and health gain from tackling major known risks simultaneously would be substantial.

Potential role of head lice, Pediculus humanus capitis, as vectors of Rickettsia prowazekii

Since the pioneering work of Charles Nicolle in 1909 [see Gross (1996) Proc Natl Acad Sci USA 93:10539-10540] most medical officers and scientists have assumed that body lice are the sole vectors of Rickettsia prowazekii, the aetiological agent of louse-borne epidemic typhus (LBET). Here we review the evidence for the axiom that head lice are not involved in epidemics of LBET. Laboratory experiments demonstrate the ability of head lice to transmit R. prowazekii, but evidence for this in the field has not been reported. However, the assumption that head lice do not transmit R. prowazekii has meant that head lice have not been examined for R. prowazekii during epidemics of LBET. The strong association between obvious (high) infestations of body lice and LBET has contributed to this perception, but this association does not preclude head lice as vectors of R. prowazekii. Indeed, where the prevalence and intensity of body louse infections may be high (e.g. during epidemics of LBET), the prevalence and intensity of head louse infestations is generally high as well. This review of the epidemiology of head louse and body louse infestations, and of LBET, indicates that head lice are potential vectors of R. prowazekii in the field. Simple observations in the field would reveal whether or not head lice are natural vectors of this major human pathogen.

Therapeutic potential of venom peptides

Venomous animals have evolved a vast array of peptide toxins for prey capture and defence. These peptides are directed against a wide variety of pharmacological targets, making them an invaluable source of ligands for studying the properties of these targets in different experimental paradigms. A number of these peptides have been used in vivo for proof-of-concept studies, with several having undergone preclinical or clinical development for the treatment of pain, diabetes, multiple sclerosis and cardiovascular diseases. Here we survey the pharmacology of venom peptides and assess their therapeutic prospects.

Assessing forest fire as a potential PCDD/F source in Queensland, Australia

Forest fires are suggested as a potential and significant source of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs), even though no studies to date provide sufficient evidence to confirm forest fires as a source of PCDD/Fs. Recent investigations in Gueensland, Australia have identified a widespread contamination of PCDDs (in particular OND) in soils and sediments in the coastal region from an unknown source of PCDD/Fs. Queensland is predominately rural; it has few known anthropogenic sources of PCDD/Fs, whereas forest fires are a frequent occurrence. This study was conducted to assess forest fires as a potential source of the unknown PCDD/F contamination in Queensland. A combustion experiment was designed to assess the overall mass of PCDD/Fs before and after a simulated forest fire. The results from this study did not identify an increase in Sigma-PCDD/Fs or OCDD after the combustion process. However, specific non-2,3,7,8 substituted lower chlorinated PCDD/Fs were elevated after the combustion process, suggesting formation from a precursor. The results from this study indicate that forest fires are unlikely to be the source of the unknown PCDD contamination in Gueensland, rather they are a key mechanism for the redistribution of PCDD/Fs from existing sources and precursors.

Subsoil nitrogen mineralisation and its potential to contribute to NH4 accumulation in a Vertosol

High concentrations of NH4+ (up to 270 kg N/ha) have been observed in a Vertosol below 1 m depth in south-east Queensland. This study examined the possibility that mineralisation associated with the removal of native vegetation (Acacia harpophylla) for cropping was responsible for the production of NH4+. Particularly, the potential contribution of decomposing root material and/or dissolved organic nitrogen (DON) leached into the subsoil after clearing was investigated. The amount of N that was contained within native vegetation root material was determined from an area of native vegetation adjacent to the cleared site containing elevated NH4+ concentrations. In addition, the amount of NH4+ that could be mineralised in the native vegetation soil was determined by monitoring NH4+ concentrations over 360 days in intact cores, and by conducting waterlogged incubations. To determine the rate at which a source of DON leached into the subsoil would mineralise, soil was amended with glutamic acid at a rate of 250 mg N/kg and placed under waterlogged incubation. The possibility that the acidic pH of the subsoil, or the lack of a significant subsoil microbial population, was inhibiting mineralisation was also examined by increasing soil pH from 4.4 to 7.0, and inoculating the subsoil with surface soil microorganisms during waterlogged incubations. Low concentrations of N, approximately 90 kg N/ha between 1.2 and 3 m, were found in the native vegetation root material. In addition, no net N mineralisation was observed in either the extended incubation of intact cores or in the control samples of the waterlogged incubations. Net N mineralisation was also not detected when the subsoil was amended with a source of organic N. Results indicate that this lack of mineralisation is largely due to pH inhibition of the microbial population. It is concluded that the mineralisation of either in situ organic material, or DON transported to the subsoil during leaching events, is unlikely to have significantly contributed to the subsoil NH4 accumulation at the study site.

Protein film voltammetry of Rhodobacter capsulatus xanthine dehydrogenase

Xanthine dehydrogenase (XDH) from the bacterium Rhodobacter capsulatus catalyzes the hydroxylation of xanthine to uric acid with NAD(+) as the electron acceptor. R. capsulatus XDH forms an (alphabeta)(2) heterotetramer and is highly homologous to homodimeric eukaryotic XDHs. The crystal structures of bovine XDH and R. capsulatus XDH showed that the two proteins have highly similar folds; however, R. capsulatus XDH is at least 5 times more active than bovine XDH and, unlike mammalian XDH, does not undergo the conversion to the oxidase form. Here we demonstrate electrocatalytic activity of the recombinant enzyme, expressed in Escherichia coli, while immobilized on an edge plane pyrolytic graphite working electrode. Furthermore, we have determined all redox potentials of the four cofactors (Mo-VI/V, Mo-V/IV, FAD/FADH, FADH/FADH(2) and two distinct [2Fe-2S](2+/+) clusters) using a combination of potentiometric and voltammetric methods. A novel feature identified in catalytic voltammetry of XDH concerns the potential for the onset of catalysis (ca. 400 mV), which is at least 600 mV more positive than that of the highest potential cofactor. This unusual observation is explained on the basis of a pterin-associated oxidative switch during voltammetry that precedes catalysis.

Potential for early involvement of CYP isoforms in aspects of human cadmium toxicity

This paper investigates the possible link between non-workplace cadmium (Cd) exposure, cytochrome P450 expression and hypertension. We present results of our investigation into the relationships between liver and kidney Cd burdens and the abundance of the CYP isoform 4A11. Our data show associations between non-workplace Cd exposure and changes in the abundance of hepatic and renal cortical CYP4A11. In liver the levels of immunochemically detectable CYP4A11 were positively correlated with tissue Cd content while in contrast CYP4A11 abundance was inversely correlated with kidney Cd burden. These differences are most likely related to the different Cd burden of the tissues. These observations suggest the potential for involvement of Cd as a mediator of CYP4A11 expression in kidney cortex and indicate that elevations in kidney Cd content may be involved in hypertension via alteration of the expression of this particular isoform. Potential mechanisms by which Cd may alter CYP4A11 expression are discussed briefly. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

Cytotoxic iron chelators: Characterization of the structure, solution chemistry and redox activity of ligands and iron complexes of the di-2-pyridyl ketone isonicotinoyl hydrazone (HPKIH) analogues

Di-2-pyridyl ketone isonicotinoyl hydrazone (HPKIH) and a range of its analogues comprise a series of monobasic acids that are capable of binding iron (Fe) as tridentate (N,N,O) ligands. Recently, we have shown that these chelators are highly cytotoxic, but show selective activity against cancer cells. Particularly interesting was the fact that cytotoxicity of the HPKIH analogues is maintained even after complexation with Fe. To understand the potent anti-tumor activity of these compounds, we have fully characterized their chemical properties. This included examination of the solution chemistry and X-ray crystal structures of both the ligands and Fe complexes from this class and the ability of these complexes to mediate redox reactions. Potentiometric titrations demonstrated that all chelators are present predominantly in their charge-neutral form at physiological pH (7.4), allowing access across biological membranes. Keto-enol tautomerism of the ligands was identified, with the tautomers exhibiting distinctly different protonation constants. Interestingly, the chelators form low-spin (diamagnetic) divalent Fe complexes in solution. The chelators form distorted octahedral complexes with Fe-II, with two tridentate ligands arranged in a meridional fashion. Electrochemistry of the Fe complexes in both aqueous and non-aqueous solutions revealed that the complexes are oxidized to their ferric form at relatively high potentials, but this oxidation is coupled to a rapid reaction with water to form a hydrated (carbinolamine) derivative, leading to irreversible electrochemistry. The Fe complexes of the HPKIH analogues caused marked DNA degradation in the presence of hydrogen peroxide. This observation confirms that Fe complexes from the HPKIH series mediate Fenton chemistry and do not repel DNA. Collectively, studies on the solution chemistry and structure of these HPKIH analogues indicate that they can bind cellular Fe and enhance its redox activity, resulting in oxidative damage to vital biomolecules.

Functionalized macrocyclic compounds: potential sensors of small molecules and ions

The potential applications of macrocycles in chemistry and at its interfaces with biology and physics continue to emerge, one of which is as receptors for small molecules and ions. This review illustrates these applications with examples from the last ten years employing complexation as the binding mechanism; some of the systems presented have already found real-world sensor applications. In any case, the challenges remain to design more selective and sensitive receptors for guests.