Indirect evidence of pathogen-associated altered oocyte production in queens of the invasive yellow crazy ant, Anoplolepis gracilipes, in Arnhem Land, Australia.

Anoplolepis gracilipes is one of the six most widespread and pestiferous invasive ant species. Populations of this invader in Arnhem Land, Australia have been observed to decline, but the reasons behind these declines are not known. We investigated if there is evidence of a pathogen that could be responsible for killing ant queens or affecting their reproductive output. We measured queen number per nest, fecundity and fat content of queens from A. gracilipes populations in various stages of decline or expansion. We found no significant difference in any of these variables among populations. However, 23% of queens were found to have melanized nodules, a cellular immune response, in their ovaries and fat bodies. The melanized nodules found in dissected queens are highly likely to indicate the presence of pathogens or parasites capable of infecting A. gracilipes. Queens with nodules had significantly fewer oocytes in their ovaries, but nodule presence was not associated with low ant population abundances. Although the microorganism responsible for the nodules is as yet unidentified, this is the first evidence of the presence of a pathogenic microorganism in the invasive ant A. gracilipes that may be affecting reproduction.

Density-Dependent Effects of an Invasive Ant on a Ground-Dwelling Arthropod Community.

It is frequently assumed that an invasive species that is ecologically or economically damaging in one region, will typically be so in other environments. The Argentine ant Linepithema humile (Mayr) is listed among the world's worst invaders. It commonly displaces resident ant species where it occurs at high population densities, and may also reduce densities of other ground-dwelling arthropods. We investigated the effect of varying Argentine ant abundance on resident ant and nonant arthropod species richness and abundance in seven cities across its range in New Zealand. Pitfall traps were used to compare an invaded and uninvaded site in each city. Invaded sites were selected based on natural varying abundance of Argentine ant populations. Argentine ant density had a significant negative effect on epigaeic ant abundance and species richness, but hypogaeic ant abundance and species richness was unaffected. We observed a significant decrease in Diplopoda abundance with increasing Argentine ant abundance, while Coleoptera abundance increased. The effect on Amphipoda and Isopoda depended strongly on climate. The severity of the impact on negatively affected taxa was reduced in areas where Argentine ant densities were low. Surprisingly, Argentine ants had no effect on the abundance of the other arthropod taxa examined. Morphospecies richness for all nonant arthropod taxa was unaffected by Argentine ant abundance. Species that are established as invasive in one location therefore cannot be assumed to be invasive in other locations based on presence alone. Appropriate management decisions should reflect this knowledge.

Standard virtual biological parts: a repository of modular modeling components for synthetic biology.

MOTIVATION: Fabrication of synthetic biological systems is greatly enhanced by incorporating engineering design principles and techniques such as computer-aided design. To this end, the ongoing standardization of biological parts presents an opportunity to develop libraries of standard virtual parts in the form of mathematical models that can be combined to inform system design. RESULTS: We present an online Repository, populated with a collection of standardized models that can readily be recombined to model different biological systems using the inherent modularity support of the CellML 1.1 model exchange format. The applicability of this approach is demonstrated by modeling gold-medal winning iGEM machines. AVAILABILITY AND IMPLEMENTATION: The Repository is available online as part of http://models.cellml.org. We hope to stimulate the worldwide community to reuse and extend the models therein, and contribute to the Repository of Standard Virtual Parts thus founded. Systems Model architecture information for the Systems Model described here, along with an additional example and a tutorial, is also available as Supplementary information. The example Systems Model from this manuscript can be found at http://models.cellml.org/workspace/bugbuster. The Template models used in the example can be found at http://models.cellml.org/workspace/SVP_Templates200906.

A method for visualizing CellML models.

MOTIVATION: The Physiome Project was established in 1997 to develop tools to facilitate international collaboration in the physiological sciences and the sharing of biological models and experimental data. The CellML language was developed to represent and exchange mathematical models of biological processes. CellML models can be very complicated, making it difficult to interpret the underlying physical and biological concepts and relationships captured/described in the mathematical model. RESULTS: To address this issue a set of ontologies was developed to explicitly annotate the biophysical concepts represented in the CellML models. This article presents a framework that combines a visual language, together with CellML ontologies, to support the visualization of the underlying physical and biological concepts described by the mathematical model and also their relationships with the CellML model. Automated CellML model visualization assists in the interpretation of model concepts and facilitates model communication and exchange between different communities.

Facilitating modularity and reuse: guidelines for structuring CellML 1.1 models by isolating common biophysical concepts.

The CellML language was developed in response to the need for a high-level language to represent and exchange mathematical models of biological processes. The flexible structure of CellML allows modellers to construct mathematical models of the same biological system in many different ways. However, some modelling styles do not naturally lead to clear abstractions of the biophysical concepts and produce CellML models that are hard to understand and from which it is difficult to isolate parts that may be useful for constructing other models. In this article, we advocate building CellML models which isolate common biophysical concepts and, using these, to build mathematical models of biological processes that provide a close correspondence between the CellML model and the underlying biological process. Subsequently, models of higher complexity can be constructed by reusing these modularized CellML models in part or in whole. Development of CellML models that best describe the underlying biophysical concepts thus avoids the need to code models from scratch and enhances the extensibility, reusability, consistency and interpretation of the models.

Modelling biological modularity with CellML.

In recent years advances in the construction of mathematical models of biological systems have yielded an array of valuable constructs. The authors seek to provide a 'leading practice' method for implementing modularised kinetic mass-action models in order to obtain a number of advantages in model construction, validation and derived insights. The authors advocate the consideration of 'accounting cycles' or 'chains' to define 'functional' components and the separate consideration of 'messenger' components for mobile or diffusive molecular species. From a conceptual modularisation the authors illustrate, with an example drawn from signal transduction, a component-based formulation in the model exchange format cellular modelling markup language (CellML) 1.1 - demonstrating loose coupling between functionally-focused reusable components. Finally, the authors discuss the dilemmas associated with modelling protein-to-protein interactions, and the vision for using future CellML enhancements to resolve potential duplications when combining independently developed models.

Best practices for the prevention and treatment of venous leg ulcers.

Chronic venous insufficiency is the most common cause of leg ulcers. Its incidence increases as the population ages. Managing venous leg ulcers involves treating the cause, optimizing local wound care, and addressing patient-centered concerns. The cornerstone of the diagnosis of chronic venous insufficiency includes demonstrating venous disease. The clinician must rule out significant coexisting arterial disease by performing a thorough clinical assessment and obtaining an ankle brachial pressure index. The most important aspect of treatment is resolving edema through high compression therapy for those individuals with an ankle brachial pressure index greater than or equal to 0.8. Other components of successful chronic venous insufficiency management include increasing mobility and medical management. Selected patients may respond to surgery, biologicals, adjunctive therapies, and lifestyle enhancements. Twelve recommendations are made incorporating current best clinical practices and expert opinion with available research. The approach to venous disease is best accomplished through a multidisciplinary team that revolves around the active participation of patients and their families. The authors' intent is to provide a practical, easy-to-follow guide to allow healthcare professionals to provide best clinical practices.

The role of Apligraf in the treatment of venous leg ulcers.

A cultured, allogeneic, bi-layered human skin equivalent has recently become available to help clinicians manage difficult-to-heal venous ulcers. This skin equivalent has an epidermis and dermis similar to human skin. Its living keratinocytes and fibroblasts are from cultured cell banks derived from human neonatal foreskin. Because the skin equivalent is made up of viable human cells, it cannot be terminally sterilized. Safety concerns, which have been addressed, include the risk of possible transmission of infection, immunogenicity, immunological graft rejection, and tumor formation. However, the maternal blood of the neonatal donor and the master cell banks are screened for infectious agents. Additionally, the human skin equivalent is produced under strict aseptic control, with sterility continuously monitored by the Good Manufacturing Processes. This paper reviews the characteristics of this human skin equivalent and provides practice guidelines.

Cardiovascular effects of the novel arteriovenous dilator agent, flosequinan in conscious dogs and cats.

1. Flosequinan (BTS 49 465, 7-fluoro-1-methyl-3-methylsulphinyl-4-quinolone) a novel arteriovenous dilator agent was orally effective in conscious renal hypertensive dogs and normotensive cats. The hypotensive potency of flosequinan was approximately ten times less than that of hydralazine in renal hypertensive dogs, 10 mg kg-1 and 20 mg kg-1 flosequinan causing similar falls in mean blood pressure to 1 mg kg-1 and 3 mg kg-1 hydralazine respectively. In normotensive cats, 5 mg kg-1 flosequinan caused similar falls to 0.5 and 1.0 mg kg-1 hydralazine. The onset of hypotensive effect after flosequinan appeared to be slightly slower than after hydralazine in the dog and slightly faster than hydralazine in the cat. 2. The degree of tachycardia and increase in plasma renin activity (PRA) for equivalent falls in mean blood pressure in both species was significantly less for flosequinan than for hydralazine (P less than 0.05). 3. In normotensive dogs, flosequinan, 10 and 20 mg kg-1 orally, caused a small but non-significant increase in sodium and chloride excretion and had little effect on urine volume whereas hydralazine, 1 and 3 mg kg-1 orally, caused a marked retention of sodium and chloride ions and a reduction in urine volume (P less than 0.01). 4. Neither flosequinan, 10 mg kg-1 orally, nor hydralazine 1 mg kg-1 orally, affected either glomerular filtration rate measured as creatinine clearance or effective renal plasma flow measured as p-aminohippuric acid clearance in normotensive dogs. 5. The lesser degree of tachycardia and increase in plasma renin activity together with a lack of sodium retaining activity associated with flosequinan suggest that this agent may have potential advantages over existing therapy as an antihypertensive in man.

Reduction of the effects of diuretics or sodium chloride loading in the conscious rat by inhibitors of prostaglandin synthesis.

In conscious rats pretreatment with indomethacin or flurbiprofen, two chemically unrelated inhibitors of prostaglandin synthesis, reduced urine volume and sodium excretion induced by four diuretics, acetazolamide, amiloride, bendrofluazide and frusemide, or oral sodium chloride loads. The maximum reduction in sodium excretion was limited to approximately 2 mmol/kg Na+ even when sodium excretion was greatly increased. In contrast these inhibitors did not appreciably affect potassium excretion. These results indicate that part of the natriuretic response in the rat to highly and moderately efficacious diuretics and to sodium chloride loading is modified by prostaglandins. We suggest that the lack of effects on potassium excretion indicate that the collecting tubule is the probable site of action.

BTS 39542, a dihydrophthalazin-1-ylacetic acid with high efficacy diuretic activity.

1 BTS 39542, a novel dihydrophthalazin-1-ylacetic acid, has high efficacy diuretic activity in mice, rats, rabbits and dogs. It is twice as potent as frusemide in mice and dogs, ten times as potent in rats and twenty times as potent in rabbits. 2 BTS 39542, like frusemide, exerts its major effects in the loop of Henle and increases renal blood flow but does not affect glomerular filtration rate in dogs. 3 The ratio of the excretion of the major cations (sodium plus potassium) to that of the major anion (chloride) after either BTS 39542 or frusemide varied with species. In rats and rabbits the ratio was approximately unity but in mice and dogs the ratio consistently exceeded unity. 4 A method for evaluating diuretics based on potency and relative potassium excretion is described.

An investigation of the sex difference in the diuretic response to ethacrynic acid in mice.

1. Female mice of the Hough/Porton and Tuck/TO strains were found to be more sensitive than male mice to the diuretic effects of oral and intravenous doses of ethacrynic acid. 2. The sensitivity of Hough/Porton male mice to ethacrynic acid was increased after pretreatment with stilboestrol and the sensitivity of female Hough/Porton mice decreased after pretreatment with testosterone. 3. There were no significant sex differences in the diuretic response to frusemide, acetazolamide, aminophylline, bendrofluazide, and Su 15049A although a small, but significant, increase in the sensitivity of male Tuck/TO mice to triamterene was noted. 4. The sex difference in diuretic response to ethacrynic acid may be related to an effect of sex hormone balance on its metabolism or on the sensitivity of its renal receptor.

Drinking behaviour in the cat induced by renin, angiotensin I, II and isoprenaline.

1. Angiotensin I, II and hog renin, infused into the lateral cerebral ventricles (I.C.V.) of water replete cats, each induced water drinking behaviour. 2. Intravenous infusion of high doses of angiotensin I or II also elicited a drinking response. The dipsogenic effect of I.V. renin was not marked. 3. Drinking in response to I.C.V. angiotensin II was abolished after autonomic ganglion blockade with I.V. hexamethonium or pempidine and was significantly reduced after I.V. atropine methonitrate. 4. The dipsogenic response to I.C.V. angiotensin II was unaffected by either peripheral adrenergic neurone blockade with I.V. bethanidine, alpha-adrenoceptor blockade with phentolamine or beta-adrenoceptor blockade with sotalol. 5. Atropine, atropine methonitrate, hexamethonium and pempidine given I.C.V did not inhibit the diposgenic response to I.C.V. angiotensin II. 6. Bethanidine I.C.V. produced a dose related reduction in the dipsogenic response to I.C.V. angiotensin II. 7. The alpha-adrenoceptor blocking agents tolazoline and phenoxybenzamine given I.C.V did not affect angiotensin induced drinking but the response was regularly inhibited by phentolamine I.C.V. 8. The beta-adrenoceptor blocking agents propranolol and practolol given I.C.V. each inhibited angiotensin induced drinking. The L-isomer of propranolol was a more effective blocker than the D-isomer. 9. Isoprenaline given I.C.V induced drinking in ten of sixteen cats. Subcutaneous administration of isoprenaline also elicited drinking but the onset of the response was delayed and the amount consumed slightly less than after I.C.V infusion.