Oxovanadium(IV)-based near-IR PDT agents: design to biological evaluation

An oxovanadium(IV) complex of dipyridophenazine, as a potent metal-based PDT agent, shows efficient DNA photocleavage activity at near-IR region and high photocytotoxicity in both UV-A and visible light in HeLa cells.

In vivo positive contrast IRON sequence and quantitative T2* measurement confirms inflammatory burden in a patient with asymptomatic carotid atheroma after USPIO-enhanced MR Imaging

The authors report an in vivo human examination of carotid atheroma by using the inversion-recovery ON resonance (IRON) sequence, which is able to produce positive contrast after the infusion of an ultrasmall super paramagnetic iron oxide (USPIO) contrast medium. This technique provides a method of potentially identifying inflammatory burden within carotid atheroma. This may be particularly useful in patients who currently do not meet criteria for intervention (ie, moderate symptomatic stenosis or <70% asymptomatic stenosis) to further risk-stratify this important patient cohort. A 63-year-old man was imaged at 1.5 T before and 36 hours after USPIO infusion by using the IRON sequence. Regions of interest showing profound signal loss at T2*-weighted imaging corresponded well with regions of positive contrast at IRON imaging after the administration of USPIO. These regions also showed a profound decrease in T2* measurements after USPIO infusion, whereas surrounding tissue did not. It has been shown that such strong signal loss on T2*-weighted images after USPIO infusion is indicative of USPIO uptake.

Shared common variants in prostate cancer and blood lipids

Background Epidemiological and clinical studies suggest comorbidity between prostate cancer (PCA) and cardiovascular disease (CVD) risk factors. However, the relationship between these two phenotypes is still not well understood. Here we sought to identify shared genetic loci between PCA and CVD risk factors. Methods We applied a genetic epidemiology method based on conjunction false discovery rate (FDR) that combines summary statistics from different genome-wide association studies (GWAS), and allows identification of genetic overlap between two phenotypes. We evaluated summary statistics from large, multi-centre GWA studies of PCA (n = 50 000) and CVD risk factors (n = 200 000) [triglycerides (TG), low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol, systolic blood pressure, body mass index, waist-hip ratio and type 2 diabetes (T2D)]. Enrichment of single nucleotide polymorphisms (SNPs) associated with PCA and CVD risk factors was assessed with conditional quantile-quantile plots and the Anderson-Darling test. Moreover, we pinpointed shared loci using conjunction FDR. Results We found the strongest enrichment of P-values in PCA was conditional on LDL and conditional on TG. In contrast, we found only weak enrichment conditional on HDL or conditional on the other traits investigated. Conjunction FDR identified altogether 17 loci; 10 loci were associated with PCA and LDL, 3 loci were associated with PCA and TG and additionally 4 loci were associated with PCA, LDL and TG jointly (conjunction FDR < 0.01). For T2D, we detected one locus adjacent to HNF1B. Conclusions We found polygenic overlap between PCA predisposition and blood lipids, in particular LDL and TG, and identified 17 pleiotropic gene loci between PCA and LDL, and PCA and TG, respectively. These findings provide novel pathobiological insights and may have implications for trials using targeting lipid-lowering agents in a prevention or cancer setting.

GABAAα1 and GABAAρ1 subunits are expressed in cultured human RPE cells and GABAA receptor agents modify the intracellular calcium concentration.

Purpose: Gamma-aminobutyric acid A (GABAA) receptors (GABAARs), which are ionotropic receptors involving chloride channels, have been identified in various neural (e.g., mouse retinal ganglion cells) and nonneural cells (e.g., mouse lens epithelial cells) regulating the intracellular calcium concentration ([Ca(2+)]i). GABAAR β-subunit protein has been isolated in the cultured human and rat RPE, and GABAAα1 and GABAAρ1 mRNAs and proteins are present in the chick RPE. The purpose of this study was to investigate the expression of GABAAα1 and GABAAρ1, two important subunits in forming functional GABAARs, in the cultured human RPE, and further to explore whether altering receptor activation modifies [Ca(2+)]i. Methods: Human RPE cells were separately cultured from five donor eye cups. Real-time PCR, western blots, and immunofluorescence were used to test for GABAAα1 and GABAAρ1 mRNAs and proteins. The effects of the GABAAR agonist muscimol, antagonist picrotoxin, or the specific GABAAρ antagonist 1,2,5,6-tetrahydropyridin-4-yl) methylphosphinic acid (TPMPA) on [Ca(2+)]i in cultured human RPE were demonstrated using Fluo3-AM. Results: Both GABAAα1 and GABAAρ1 mRNAs and proteins were identified in cultured human RPE cells; antibody staining was mainly localized to the cell membrane and was also present in the cytoplasm but not in the nucleus. Muscimol (100 μM) caused a transient increase of the [Ca(2+)]i in RPE cells regardless of whether Ca(2+) was added to the buffer. Muscimol-induced increases in the [Ca(2+)]i were inhibited by pretreatment with picrotoxin (300 μM) or TPMPA (500 μM). Conclusions: GABAAα1 and GABAAρ1 are expressed in cultured human RPE cells, and GABAA agents can modify [Ca(2+)]i.

Climatic-requirements models of cat's claw creeper Macfadyena unguis-cati (Bignoniaceae) to prioritise areas for exploration and release of biological control agents

Climate matching software (CLIMEX) was used to prioritise areas to explore for biological control agents in the native range of cat's claw creeper Macfadyena unguis-cati (Bignoniaceae), and to prioritise areas to release the agents in the introduced ranges of the plant. The native distribution of cat's claw creeper was used to predict the potential range of climatically suitable habitats for cat's claw creeper in its introduced ranges. A Composite Match Index (CMI) of cat's claw creeper was determined with the 'Match Climates' function in order to match the ranges in Australia and South Africa where the plant is introduced with its native range in South and Central America. This information was used to determine which areas might yield climatically-adapted agents. Locations in northern Argentina had CMI values which best matched sites with cat's claw creeper infestations in Australia and South Africa. None of the sites from where three currently prioritised biological control agents for cat's claw creeper were collected had CMI values higher than 0.8. The analysis showed that central and eastern Argentina, south Brazil, Uruguay and parts of Bolivia and Paraguay should be prioritised for exploration for new biological control agents for cat's claw creeper to be used in Australia and South Africa.

Pain in juvenile idiopathic arthritis : parents and children as agents of disease management

Juvenile idiopathic arthritis (JIA) is a severe childhood disease usually characterized by long-term morbidity, unpredictable course, pain, and limitations in daily activities and social participation. The disease affects not only the child but also the whole family. The family is expected to adhere to an often very laborious regimen over a long period of time. However, the parental role is incoherently conceptualized in the research field. Pain in JIA is of somatic origin, but psychosocial factors, such as mood and self-efficacy, are critical in the perception of pain and in its impact on functioning. This study examined the factors correlating and possibly explaining pain in JIA, with a special emphasis on the mutual relations between parent- and patient-driven variables. In this patient series pain was not associated with the disease activity. The degree of pain was on average fairly low in children with JIA. When the children were clustered according to age, anxiety and depression, four distinguishable cluster groups significantly associated with pain emerged. One of the groups was described by concept vulnerability because of unfavorable variable associations. Parental depressive and anxiety symptoms accompanied by illness management had a predictive power in discriminating groups of children with varying distress levels. The parent’s and child’s perception of a child’s functional capability, distress, and somatic self-efficacy had independent explanatory power predicting the child’s pain. Of special interest in the current study was self-efficacy, which refers to the belief of an individual that he/she has the ability to engage in the behavior required for tackling the disease. In children with JIA, strong self-efficacy was related to lower levels of pain, depressive symptoms and trait anxiety. This suggests strengthening a child’s sense of self-efficacy, when helping the child to cope with his or her disease. Pain experienced by a child with JIA needs to be viewed in a multidimensional bio-psycho-social context that covers biological, environmental and cognitive behavioral mechanisms. The relations between the parent-child variables are complex and affect pain both directly and indirectly. Developing pain-treatment modalities that recognize the family as a system is also warranted.

Prioritising potential guilds of specialist herbivores as biological control agents for prickly acacia through simulated herbivory

Understanding plant response to herbivory facilitates the prioritisation of guilds of specialist herbivores as biological control agents based on their potential impacts. Prickly acacia (Acacia nilotica ssp. indica) is a weed of national significance in Australia and is a target for biological control. Information on the susceptibility of prickly acacia to herbivory is limited, and there is no information available on the plant organ (i.e. leaf, shoot and root in isolation or in combination) most susceptible to herbivory. We evaluated the ability of prickly acacia seedlings, to respond to different types of simulated herbivory (defoliation, shoot damage, root damage and combinations), at varying frequencies (no herbivory, single, two and three events of herbivory) to identify the type and frequency of herbivory that will be required to reduce the growth and vigour. Defoliation and shoot damage, individually, had a significant negative impact on prickly acacia seedlings. For the defoliation to be effective, more than two defoliation events were required, whereas a single bout of shoot damage was enough to cause a significant reduction in plant vigour. A combination of defoliation + shoot damage had the greatest negative impact. The study highlights the need to prioritise specialist leaf and shoot herbivores as potential biological control agents for prickly acacia.

Factors influencing the release and establishment of weed biological control agents

Mike Day and colleagues recently published their paper 'Factors influencing the release and establishment of weed biocontrol agents' in Proceedings of the 16th Australian Weeds Conference. The CRC for Australian Weed Management facilitated an investigation into the factors influencing the release and establishment of weed biological control agents on a wide variety of Australian weeds. The investigation improved the understanding of post-release ecology of biocontrol agents and generated recommendations for best practice. Factors affecting successful establishment on the weed include host plant characteristics, size of releases, dispersal power of the agent, predation and parasitism, and climate. A best practice guide was produced by the CRC to assist practitioners in designing robust release strategies to increase rates of establishment.

Maximising the contribution of native-range studies towards the identification and prioritisation of weed biocontrol agents

Effective study in the native range to identify potential agents underpins all efforts in classical biological control of weeds. Good agents that demonstrate both a high degree of host specificity and the potential to be damaging are a very limited resource and must therefore be carefully studied and considered. The overseas component is often operationally difficult and expensive but can contribute considerably more than a list of herbivores attacking a particular target. While the principles underlying this foreign component have been understood for some time, recently developed technologies and methods can make very significant contributions to foreign studies. Molecular and genetic characterisations of both target weed and agent organism can be increasingly employed to more accurately define the identity and phylogeny of them. Climate matching and modelling software is now available and can be utilised to better select agents for particular regions of concern. Relational databases can store collection information for analysis and future enquiry while quantification of sampling effort, employment of statistical survey methods and analysis by techniques such as rarefaction curves contribute to efficient and effective searching. Obtaining good and timely identifications for discovered agent organisms is perhaps the most serious issue confronting the modern explorer. The diminishing numbers of specialist taxonomists employed at the major museums while international and national protocols demand higher standards of identity exacerbates the issue. Genetic barcoding may provide a very useful tool to overcome this problem. Native-range work also offers under-exploited opportunities for contributing towards predicting safety, abundance and efficacy of potential agents in their target environment.

Review of approaches to evaluate the effectiveness of weed biological control agents

We review key issues, available approaches and analyses to encourage and assist practitioners to develop sound plans to evaluate the effectiveness of weed biological control agents at various phases throughout a program. Assessing the effectiveness of prospective agents before release assists the selection process, while post-release evaluation aims to determine the extent that agents are alleviating the ecological, social and economic impacts of the weeds. Information gathered on weed impacts prior to the initiation of a biological control program is necessary to provide baseline data and devise performance targets against which the program can subsequently be evaluated. Detailed data on weed populations, associated plant communities and, in some instances ecosystem processes collected at representative sites in the introduced range several years before the release of agents can be compared with similar data collected later to assess agent effectiveness. Laboratory, glasshouse and field studies are typically used to assess agent effectiveness. While some approaches used for field studies may be influenced by confounding factors, manipulative experiments where agents are excluded (or included) using chemicals or cages are more robust but time-consuming and expensive to implement. Demographic modeling and benefit–cost analyses are increasingly being used to complement other studies. There is an obvious need for more investment in long-term post-release evaluation of agent effectiveness to rigorously document outcomes of biological control programs.

Calculating the Fickian diffusivity for a lattice-based random walk with agents and obstacles of different shapes and sizes

Random walk models are often used to interpret experimental observations of the motion of biological cells and molecules. A key aim in applying a random walk model to mimic an in vitro experiment is to estimate the Fickian diffusivity (or Fickian diffusion coefficient),D. However, many in vivo experiments are complicated by the fact that the motion of cells and molecules is hindered by the presence of obstacles. Crowded transport processes have been modeled using repeated stochastic simulations in which a motile agent undergoes a random walk on a lattice that is populated by immobile obstacles. Early studies considered the most straightforward case in which the motile agent and the obstacles are the same size. More recent studies considered stochastic random walk simulations describing the motion of an agent through an environment populated by obstacles of different shapes and sizes. Here, we build on previous simulation studies by analyzing a general class of lattice-based random walk models with agents and obstacles of various shapes and sizes. Our analysis provides exact calculations of the Fickian diffusivity, allowing us to draw conclusions about the role of the size, shape and density of the obstacles, as well as examining the role of the size and shape of the motile agent. Since our analysis is exact, we calculateDdirectly without the need for random walk simulations. In summary, we find that the shape, size and density of obstacles has a major influence on the exact Fickian diffusivity. Furthermore, our results indicate that the difference in diffusivity for symmetric and asymmetric obstacles is significant.

Use of CLIMEX modelling to identify prospective areas for exploration to find new biological control agents for prickly acacia

Selection of biocontrol agents that are adapted to the climates in areas of intended release demands a thorough analysis of the climates of the source and release sites. We present a case study that demonstrates how use of the CLIMEX software can improve decision making in relation to the identification of prospective areas for exploration for agents to control the woody weed, prickly acacia Acacia nilotica ssp. indica in the arid areas of north Queensland.

The effect of data sources and quality on the predictive capacity of CLIMEX models: an assessment of Teleonemia scrupulosa and Octotoma scabripennis for the biocontrol of Lantana camara in Australia

Understanding the effects of different types and quality of data on bioclimatic modeling predictions is vital to ascertaining the value of existing models, and to improving future models. Bioclimatic models were constructed using the CLIMEX program, using different data types – seasonal dynamics, geographic (overseas) distribution, and a combination of the two – for two biological control agents for the major weed Lantana camara L. in Australia. The models for one agent, Teleonemia scrupulosa Stål (Hemiptera:Tingidae) were based on a higher quality and quantity of data than the models for the other agent, Octotoma scabripennis Guérin-Méneville (Coleoptera: Chrysomelidae). Predictions of the geographic distribution for Australia showed that T. scrupulosa models exhibited greater accuracy with a progressive improvement from seasonal dynamics data, to the model based on overseas distribution, and finally the model combining the two data types. In contrast, O. scabripennis models were of low accuracy, and showed no clear trends across the various model types. These case studies demonstrate the importance of high quality data for developing models, and of supplementing distributional data with species seasonal dynamics data wherever possible. Seasonal dynamics data allows the modeller to focus on the species response to climatic trends, while distributional data enables easier fitting of stress parameters by restricting the species envelope to the described distribution. It is apparent that CLIMEX models based on low quality seasonal dynamics data, together with a small quantity of distributional data, are of minimal value in predicting the spatial extent of species distribution.