Androgen receptor-dependent and independent functions of ARIP4

Androgen receptor (AR) is necessary for normal male phenotype development and essential for spermatogenesis. AR is a classical steroid receptor mediating actions of male sex steroids testosterone and 5-alpha-dihydrotestosterone. Numerous coregulators interact with the receptor and regulate AR activity on target genes. This study deals with the characterization of androgen receptor-interacting protein 4 (ARIP4). ARIP4 binds DNA, interacts with AR in vitro and in cultured yeast and mammalian cells, and modulates AR-dependent transactivation. ARIP4 is an active DNA-dependent ATPase, and this enzymatic activity is essential for the ability of ARIP4 to modulate AR function. On the basis of sequence homology in its ATPase domain, ARIP4 belongs to the SNF2 family of proteins involved in chromatin remodeling, DNA repair, and homologous recombination. Similar to its closest homologs ATRX and Rad54, ARIP4 does not seem to be a classical chromatin remodeling protein in that it does not appear to form large protein complexes in vivo or remodel mononucleosomes in vitro. However, ARIP4 is able to generate superhelical torsion on linear DNA fragments. ARIP4 is covalently modified by SUMO-1, and mutation of six potential SUMO attachment sites abolishes the ability of ARIP4 to bind DNA, hydrolyze ATP, and activate AR function. ARIP4 expression starts in early embryonic development. In mouse embryo ARIP4 is present mainly in the neural tube and limb buds. In adult mouse tissues ARIP4 expression is virtually ubiquitous. In mouse testis ARIP4 is expressed in the nuclei of Sertoli cells in a stage-dependent manner. ARIP4 is also present in the nuclei of Leydig cells, spermatogonia, pachytene and diplotene spermatocytes. Testicular expression pattern of ARIP4 does not differ significantly in wild-type, FSHRKO, and LuRKO mice. In the testis of hpg mice, ARIP4 is found mainly in interstitial cells and has very low, if any, expression in Sertoli and germ cells. Heterozygous Arip4+/ mice are fertile and appear normal; however, they are haploinsufficient with regard to androgen action in Sertoli cells. In contrast, Arip4 / embryos are not viable. They have significantly reduced body size at E9.5 and die by E11.5. Compared to wild-type littermates, Arip4 / embryos possess a higher percentage of apoptotic cells at E9.5 and E10.5. Fibroblasts derived from Arip4 / embryos cease growing after 2-3 passages and exhibit a significantly increased apoptosis and decreased proliferation rate than cells from wild-type embryos. Our findings demonstrate that ARIP4 plays an essential role in mouse embryonic development. In addition, testicular expression and AR coregulatory activity of ARIP4 suggest a role of ARIP4-AR interaction in the somatic cells of the testis.

Environment characterization as an aid to wheat improvement: interpreting genotype-environment interactions by modelling water-deficit patterns in North-Eastern Australia.

Genotype-environment interactions (GEI) limit genetic gain for complex traits such as tolerance to drought. Characterization of the crop environment is an important step in understanding GEI. A modelling approach is proposed here to characterize broadly (large geographic area, long-term period) and locally (field experiment) drought-related environmental stresses, which enables breeders to analyse their experimental trials with regard to the broad population of environments that they target. Water-deficit patterns experienced by wheat crops were determined for drought-prone north-eastern Australia, using the APSIM crop model to account for the interactions of crops with their environment (e.g. feedback of plant growth on water depletion). Simulations based on more than 100 years of historical climate data were conducted for representative locations, soils, and management systems, for a check cultivar, Hartog. The three main environment types identified differed in their patterns of simulated water stress around flowering and during grain-filling. Over the entire region, the terminal drought-stress pattern was most common (50% of production environments) followed by a flowering stress (24%), although the frequencies of occurrence of the three types varied greatly across regions, years, and management. This environment classification was applied to 16 trials relevant to late stages testing of a breeding programme. The incorporation of the independently-determined environment types in a statistical analysis assisted interpretation of the GEI for yield among the 18 representative genotypes by reducing the relative effect of GEI compared with genotypic variance, and helped to identify opportunities to improve breeding and germplasm-testing strategies for this region.

Commercial application of polychaete sand filters for wastewater remediation and broodstock feeds

Summary Prototype sand-worm filtration beds were constructed at two prawn farms and one fish farm to assess and demonstrate their polychaete (marine worm) production and wastewater remediation capacities at semi-commercial scale. Wastewater treatment properties were monitored and worms produced were assessed and either sold for bait or used by the farms’ hatcheries as broodstock (prawn or fish breeder) feed. More than 34 megalitres of prawn- and fish-pond water was beneficially treated in the 116-319-d trial. The design of the polychaete-assisted sand filters (PASFs) constructed at each farm affected their water handling rates, which on average ranged from 315 to 1000 L m-2 d-1 at the three farms. A low profile design incorporating shallow bunded ponds made from polyethylene liner and timber stakes provided the easiest method of construction. This simple design applied at broad scale facilitated the highest quantities of treated water and the greatest worm production. Designs with higher sides increased the head pressure above the sand bed surface, thus increasing the amount of water that could be treated each day. Most water qualities were affected in a similar way to that demonstrated in the previous tank trials: dissolved oxygen, pH, total suspended solids and chlorophyll a levels were all consistently significantly lowered as pond water percolated through the sand bed, and dissolved forms of nitrogen and phosphorus were marginally increased on several occasions. However, unlike the previous smaller-scale tank trials, total nitrogen (TN) and total phosphorus (TP) levels were both significantly lowered by these larger-scale PASFs. The reasons for this are still unclear and require further research. Maximum TN and TP removals detected in the trial were 48.8% and 67.5%, respectively, and average removals (in unfed beds) at the three farms ranged from 20.0 to 27.7% for TN and from 22.8 to 40.8% for TP. Collectively, these results demonstrate the best suspended solids, chlorophyll and macronutrient removal capacities so far reported for any mariculture wastewater treatment methodology to date. Supplemental feeding of PASFs with fish meal was also investigated at one farm as a potential means of increasing their polychaete biomass production. Whilst fed beds produced higher biomass (152 ± 35 g m-2) compared with unfed beds (89 ± 17 g m-2) after 3.7 months of operation, the low number of replicates (2) prevented statistically significant differences from being demonstrated for either growth or survival. At harvest several months later, worm biomass production was estimated to be similar to, or in slight excess of, previously reported production levels (300-400 g m-2). Several qualities of filtered water appear to have been affected by supplemental feeding: it appeared to marginally lower dissolved oxygen and pH levels, and increased the TN and TP levels though not so much to eliminate significant beneficial water treatment effects. Periodic sampling during an artificial-tide demonstrated the tendency for treated-water quality changes during the first hour of filtration. Total nitrogen and ammonia peaked early in the tidal flow and then fell to more stable levels for the remainder of the filtration period. Other dissolved nutrients also showed signs of this sand-bed-flushing pattern, and dissolved oxygen tended to climb during the first hour and become more stable thereafter. These patterns suggest that the routine sampling of treated water undertaken at mid-inflow during the majority of the wider study would likely have overestimated the levels of TN and dissolved nutrients discharged from the beds, and hence underestimated the PASFs treatment efficacies in this regard. Analyses of polychaete biomass collected from each bed in the study revealed that the worms were free from contamination with the main prawn viruses that would create concerns for their feeding to commercial prawn broodstock in Australia. Their documented proximal and nutritional contents also provide a guide for hatchery operators when using live or frozen stock. Their dry matter content ranged from 18.3 to 22.3%, ash ranged from 10.2 to 14.0%, gross energy from 20.2 to 21.5 MJ kg-1, and fat from 5.0 to 9.2%. Their cholesterol levels ranged from 0.86 to 1.03% of dry matter, whilst total phospholipids range from 0.41 to 0.72%. Thirty-one different fatty acids were present at detectable (≥0.005% of dry matter) levels in the sampled worm biomass. Palmitic acid was by far the most prevalent fatty acid detected (1.21 ± 0.18%), followed by eicosapentaenoic (EPA) (0.48 ± 0.03%), stearic (0.46 ± 0.04%), vaccenic (0.38 ± 0.05%), adrenic (0.35 ± 0.02%), docosadienoic (0.28 ± 0.02%), arachidonic (AA) (0.22 ± 0.01%), palmitoleic (0.20 ± 0.04%) and 23 other fatty acids with average contents of less than 0.2% of dry matter. Supplemental feeding with fish meal at one farm appeared to increase the docosahexaenoic acid (DHA) content of the worms considerably, and modify the average AA : EPA : DHA from 1.0 : 2.7 : 0.3 to 1.0 : 2.0 : 1.1. Consistent with previous results, the three most heavily represented amino acids in the dry matter of sampled worms were glutamic acid (8.5 ± 0.2%), aspartic acid (5.5 ± 0.1%) and glycine (4.9 ± 0.5%). These biomass content results suggest that worms produced in PASF systems are well suited to feeding to prawn and fish broodstock, and provide further strong evidence of the potential to modify their contents for specific nutritional uses. The falling wild-fishery production of marine bloodworms in Queensland is typical of diminishing polychaete resources world-wide and demonstrates the need to develop sustainable production methods here and overseas. PASF systems offer the dual benefits of wastewater treatment for environmental management and increased productivity through a valuable secondary crop grown exclusively on waste nutrients.

Wastewater remediation options for prawn farms - Aquaculture Industry Development Initiative 2002-04.

There are many potential bioremediation approaches that may be suitable for prawn farms in Queensland. Although most share generally accepted bioremediation principles, advocacy for different methods tends to vary widely. This diversity of approach is particularly driven by the availability and knowledge of functional species at different localities around the world. In Australia, little is known about the abilities of many native species in this regard, and translocation and biosecurity issues prevent the use of exotic species that have shown potential in other countries. Species selected must be tolerant of eutrophic conditions and ecological shifts, because prawn pond nutrient levels and pathways can vary with different assemblages of autotrophic and heterotrophic organisms. Generally, they would be included in a constructed ecosystem because of their functional contributions to nutrient cycling and uptake, and to create nutrient sinks in forms of harvestable biomass. Wide salinity, temperature and water quality tolerances are also valuable attributes for selected species due to the sometimes-pronounced effects of environmental extremes, and to provide over-wintering options and adequate safety margins in avoiding mass mortalities. To practically achieve these bioremediation polycultures on a large scale, and in concert with the operations of a prawn farm, methods involving seed production, stock management, and a range of other farm engineering and product handling systems need to be reliably achievable and economically viable. Research funding provided by the Queensland Government through the Aquaculture Industry Development Initiative (AIDI) 2002-04 has enabled a number of technical studies into biological systems to treat prawn farm effluent for recirculation and improved environmental sustainability. AIDI bioremediation research in southern Queensland was based at the Bribie Island Aquaculture Research Centre (BIARC), and was conducted in conjunction with AIDI genetics and selection research, and a Natural Heritage Trust (NHT) funded program (Coast and Clean Seas Project No.717757). This report compilation provides a summary of some of the work conducted within these programs.

Estimating and influencing the duration of weed eradication programmes

1. Weed eradication efforts often must be sustained for long periods owing to the existence of persistent seed banks, among other factors. Decision makers need to consider both the amount of investment required and the period over which investment must be maintained when determining whether to commit to (or continue) an eradication programme. However, a basis for estimating eradication programme duration based on simple data has been lacking. Here, we present a stochastic dynamic model that can provide such estimates. 2. The model is based upon the rates of progression of infestations from the active to the monitoring state (i.e. no plants detected for at least 12 months), rates of reversion of infestations from monitoring to the active state and the frequency distribution of time since last detection for all infestations. Isoquants that illustrate the combinations of progression and reversion parameters corresponding to eradication within different time frames are generated. 3. The model is applied to ongoing eradication programmes targeting branched broomrape Orobanche ramosa and chromolaena Chromolaena odorata. The minimum periods in which eradication could potentially be achieved were 22 and 23 years, respectively. On the basis of programme performance until 2008, however, eradication is predicted to take considerably longer for both species (on average, 62 and 248 years, respectively). Performance of the branched broomrape programme could be best improved through reducing rates of reversion to the active state; for chromolaena, boosting rates of progression to the monitoring state is more important. 4. Synthesis and applications. Our model for estimating weed eradication programme duration, which captures critical transitions between a limited number of states, is readily applicable to any weed.Aparticular strength of the method lies in its minimal data requirements. These comprise estimates of maximum seed persistence and infested area, plus consistent annual records of the detection (or otherwise) of the weed in each infestation. This work provides a framework for identifying where improvements in management are needed and a basis for testing the effectiveness of alternative tactics. If adopted, our approach should help improve decision making with regard to eradication as a management strategy.

Associations among Emdogain®, human oral carcinoma cells and oral proteolytic enzymes

The Enamel matrix derivative Emdogain® (EMD) is a commercially available tissue extract preparation of porcine enamel origin. Studies have shown EMD to be clinically useful in promoting periodontal regeneration. EMD has been widely used in periodontal therapy for over ten years, but the mechanism of its action and the exact composition are not completely clear. EMD is predominantly amelogenin (>90%). However, unlike amelogenin, EMD has a number of growth factor-like effects and it has been shown to enhance the proliferation, migration and other cellular functions of periodontal ligament fibroblasts and osteoblasts. In contrast, the effects of EMD on epithelial cell lines and in particular on oral malignant cells have not been adequately studied. In addition, EMD has effects on the production of cytokines by several oral cell lines and the product is in constant interaction with different oral enzymes. Regardless of the various unknown properties of EMD, it is said to be clinically safe in regenerative procedures, also in medically compromised patients. The aim of the study was to examine whether gingival crevicular fluid (GCF), which contains several different proteolysis enzymes, could degrade EMD and alter its biological functions. In addition, the objective was to study the effects of EMD on carcinogenesis-related factors, in particular MMPs, using in vitro and in vivo models. This study also aimed to contribute to the understanding of the composition of EMD. GCF was capable of degrading EMD, depending on the periodontal status, with markedly more degradation in all states of periodontal disease compared to healthy controls. EMD was observed to stimulate the migration of periodontal ligament fibroblasts (PLF), whereas EMD together with GCF could not stimulate this proliferation. In addition, recombinant amelogenin, the main component of EMD, decreased the migration of PLFs. A comparison of changes induced by EMD and TGF-β1 in the gene profiles of carcinoma cells showed TGF-β1 to regulate a greater number of genes than EMD. However, both of the study reagents enhanced the expression of MMP-10 and MMP-9. Furthermore, EMD was found to induce several factors closely related to carcinogenesis on gene, protein, cell and in vivo levels. EMD enhanced the production of MMP-2, MMP-9 and MMP-10 proteins by cultured carcinoma cells. In addition, EMD stimulated the migration and in vitro wound closure of carcinoma cells. EMD was also capable of promoting metastasis formation in mice. In conclusion, the diseased GCF, containing various proteases, causes degradation of EMD and decreased proliferation of PLFs. Thus, this in vitro study suggests that the regenerative effect of EMD may decrease due to proteases present in periodontal tissues during the inflammation and healing of the tissues in vivo. Furthermore, EMD was observed to enhance several carcinoma-related factors and in particular the production of MMPs by benign and malignant cell lines. These findings suggest that the clinical safety of EMD with regard to dysplastic mucosal lesions should be further investigated.

Modulation of arginine decarboxylase activity in cucumber (Cucumis sativus) cotyledons in short-term organ culture

Among the various amines administered to excisedCucumis sativus cotyledons in short-term organ culture, agmatine (AGM) inhibited arginine decarboxylase (ADC) activity to around 50%, and putrescine was the most potent entity in this regard. Homoarginine (HARG) dramatically stimulated (3- to 4-fold) the enzyme activity. Both AGM inhibition and HARG stimulation of ADC were transient, the maximum response being elicited at 12 h of culture. Mixing experiments ruled out involvement of a macromolecular effector in the observed modulation of ADC. HARG-stimulated ADC activity was completely abolished by cycloheximide, whereas AGM-mediated inhibition was unaffected. Half-life of the enzyme did not alter on treatment with either HARG or AGM. The observed alterations in ADC activity are accompanied by change in Km of the enzyme. HARG-stimulated ADC activity is additive to that induced by benzyladenine (BA) whereas in presence of KCl, HARG failed to enhance ADC activity, thus demonstrating the overriding influence of K+ on amine metabolism.

On the axiomatic approach to the maximum entropy principle of inference

Recent axiomatic derivations of the maximum entropy principle from consistency conditions are critically examined. We show that proper application of consistency conditions alone allows a wider class of functionals, essentially of the form ∝ dx p(x)[p(x)/g(x)] s , for some real numbers, to be used for inductive inference and the commonly used form − ∝ dx p(x)ln[p(x)/g(x)] is only a particular case. The role of the prior densityg(x) is clarified. It is possible to regard it as a geometric factor, describing the coordinate system used and it does not represent information of the same kind as obtained by measurements on the system in the form of expectation values.

Anthropometric measures of obesity-their association with type 2 diabetes and hypertension across ethnic groups

Clinical trials have shown that weight reduction with lifestyles can delay or prevent diabetes and reduce blood pressure. An appropriate definition of obesity using anthropometric measures is useful in predicting diabetes and hypertension at the population level. However, there is debate on which of the measures of obesity is best or most strongly associated with diabetes and hypertension and on what are the optimal cut-off values for body mass index (BMI) and waist circumference (WC) in this regard. The aims of the study were 1) to compare the strength of the association for undiagnosed or newly diagnosed diabetes (or hypertension) with anthropometric measures of obesity in people of Asian origin, 2) to detect ethnic differences in the association of undiagnosed diabetes with obesity, 3) to identify ethnic- and sex-specific change point values of BMI and WC for changes in the prevalence of diabetes and 4) to evaluate the ethnic-specific WC cutoff values proposed by the International Diabetes Federation (IDF) in 2005 for central obesity. The study population comprised 28 435 men and 35 198 women, ≥ 25 years of age, from 39 cohorts participating in the DECODA and DECODE studies, including 5 Asian Indian (n = 13 537), 3 Mauritian Indian (n = 4505) and Mauritian Creole (n = 1075), 8 Chinese (n =10 801), 1 Filipino (n = 3841), 7 Japanese (n = 7934), 1 Mongolian (n = 1991), and 14 European (n = 20 979) studies. The prevalence of diabetes, hypertension and central obesity was estimated, using descriptive statistics, and the differences were determined with the χ2 test. The odds ratios (ORs) or  coefficients (from the logistic model) and hazard ratios (HRs, from the Cox model to interval censored data) for BMI, WC, waist-to-hip ratio (WHR), and waist-to-stature ratio (WSR) were estimated for diabetes and hypertension. The differences between BMI and WC, WHR or WSR were compared, applying paired homogeneity tests (Wald statistics with 1 df). Hierarchical three-level Bayesian change point analysis, adjusting for age, was applied to identify the most likely cut-off/change point values for BMI and WC in association with previously undiagnosed diabetes. The ORs for diabetes in men (women) with BMI, WC, WHR and WSR were 1.52 (1.59), 1.54 (1.70), 1.53 (1.50) and 1.62 (1.70), respectively and the corresponding ORs for hypertension were 1.68 (1.55), 1.66 (1.51), 1.45 (1.28) and 1.63 (1.50). For diabetes the OR for BMI did not differ from that for WC or WHR, but was lower than that for WSR (p = 0.001) in men while in women the ORs were higher for WC and WSR than for BMI (both p < 0.05). Hypertension was more strongly associated with BMI than with WHR in men (p < 0.001) and most strongly with BMI than with WHR (p < 0.001), WSR (p < 0.01) and WC (p < 0.05) in women. The HRs for incidence of diabetes and hypertension did not differ between BMI and the other three central obesity measures in Mauritian Indians and Mauritian Creoles during follow-ups of 5, 6 and 11 years. The prevalence of diabetes was highest in Asian Indians, lowest in Europeans and intermediate in others, given the same BMI or WC category. The  coefficients for diabetes in BMI (kg/m2) were (men/women): 0.34/0.28, 0.41/0.43, 0.42/0.61, 0.36/0.59 and 0.33/0.49 for Asian Indian, Chinese, Japanese, Mauritian Indian and European (overall homogeneity test: p > 0.05 in men and p < 0.001 in women). Similar results were obtained in WC (cm). Asian Indian women had lower  coefficients than women of other ethnicities. The change points for BMI were 29.5, 25.6, 24.0, 24.0 and 21.5 in men and 29.4, 25.2, 24.9, 25.3 and 22.5 (kg/m2) in women of European, Chinese, Mauritian Indian, Japanese, and Asian Indian descent. The change points for WC were 100, 85, 79 and 82 cm in men and 91, 82, 82 and 76 cm in women of European, Chinese, Mauritian Indian, and Asian Indian. The prevalence of central obesity using the 2005 IDF definition was higher in Japanese men but lower in Japanese women than in their Asian counterparts. The prevalence of central obesity was 52 times higher in Japanese men but 0.8 times lower in Japanese women compared to the National Cholesterol Education Programme definition. The findings suggest that both BMI and WC predicted diabetes and hypertension equally well in all ethnic groups. At the same BMI or WC level, the prevalence of diabetes was highest in Asian Indians, lowest in Europeans and intermediate in others. Ethnic- and sex-specific change points of BMI and WC should be considered in setting diagnostic criteria for obesity to detect undiagnosed or newly diagnosed diabetes.

Konsumerismi, potilaiden ja kuluttajien aktiivinen toiminta sekä erityisesti lääkäreiden kokemukset ja näkemykset potilaista kuluttajina

Consumerism emphasises the patient s position and freedom of choice. Consumerism is being promoted by a range of phenomena occurring in society and health care. Different actors hold different views on the patient as a consumer and on his or her participation. Consumer demand is created outside the patient physician relationship and the commercialisation of services generates new expectations with respect to physician s work. More and more patients may be interested in adopting a more equal position in the care relationship, and trying to negotiate with the physician or to even dictate how he or she should be cared for. In Finland, very little research has been conducted on patients and consumers organising themselves at national system level, patients as choosers, and physicians attitudes to various consumerist phenomena or the choice made by the patient. In the empirical data for this study, the term consumer-patient refers to active consumers and patients making choices related to their clinical care prior to a physician s diagnosis. Consumer-patients are also represented by consumer and patient organisations and movements. The main research question is: How do physicians regard the care choice made by the patient? This question is addressed from a perspective encompassing patients and consumers organised activities and individuals active behaviour in health care as well as physicians experiences and their views on patients as consumers making choices related to their care. The first part (Study I), examines the patient organisation field, information sources used including the websites of such organisations, files from Finland s Slot Machine Association, RAY, a survey conducted by a Finnish television news department and interviews of patient organisations. Based on observation and a physician survey, Study II examines physicians attitudes to the idea that patients could obtain information through consumer movements about physicians care practices before seeking medical care. Studies III−IV use a physician survey to examine physicians attitudes to direct-to-consumer-advertising of prescription drugs (DTCA) and their experiences and views of patient requests related to treatments and examinations. Study V uses comparative surveys to examine the attitudes of health care professionals and the population to the introduction of new technologies in health care, using genetic screenings and tests as an example. The number of patient organisations increased, with a particular escalation as of the 1990s. The characteristics and operating methods of the organisations varied greatly. Physicians organisations adopted a negative or neutral attitude towards the consumer movements idea of distributing information on care practices, whereas individual physicians attitudes were slightly more positive. Physicians regarded direct-to-consumer-advertising of prescription drugs as negative, but took a more permissive attitude towards indirect advertising. More than every third physician considered drug advertisements in general to be harmful or useless in the distribution of drug information to patients or consumers. More than half of physicians conducting patient work reported that they (very) often encountered patients who stated upon arrival for a consultation that they wanted specific treatments or examinations, and that the number of such situations had increased. Such situations were viewed as positive with regard to the care relationship by every fifth physician and as negative by two fifths. Physicians justified a reserved attitude to the patients consumer role by referring to their medical expertise and position as care decision-makers, the patient physician relationship and the public health care system. Reasons for a positive attitude included the patient s participation and co-operation, the patient physician relationship and the patient s knowledge. Professionals were more reserved than lay people about the introduction and extension of genetic technologies in health care. A significant minority of the physicians did not take a clear pro or con attitude to the patients consumer role or to the use of new technologies in health care. The physicians age, gender, place of work and specialisation influenced their attitudes to the patient s consumer role, and private physicians viewed it in a more positive light than those working in public health care. Active consumer-patients challenge the society to hold a discussion of the patient s choice, participation in care decision-making and participation in health care policy in general. Their transformation into customers and consumers implies not only a new division of individuals roles and powers, but also contributes to changing relationships between system level roles: between citizens and the state and between public and private health care. This phenomenon raises various issues related to health care policy. In conclusion, topics are presented for discussion, practical measures and further research. Keywords: health care, consumerism, distribution of technologies, commercialisation, physicians, patients, consumers, patient s choice, patient s role.

Stroke and coronary heart disease in relation to hyperglycemia gender and age

This study was carried out to compare the fasting plasma glucose (FPG) and 2-h plasma glucose (2-h PG) criteria for diabetes with regard to their relation to stroke mortality and the incidence of ischemic and hemorrhagic stroke. In addition, the age-and gender difference in the incidence of coronary heart disease (CHD) and stroke and their relation with known cardiovascular disease risk factors and diabetes mellitus was examined. The study was a sub-data analysis of the Diabetes Epidemiology: Collaborative analysis Of Diagnostic criteria in Europe (DECODE) study including 25 181 individuals, 11 844 (47%) men and 13 345 (53%) women aged 25 to 90 years, from 14 European cohorts. In individuals without a history of diabetes elevated 2-h post-challenge glucose was a better predictor of stroke mortality than elevated fasting glucose in men, whereas the latter was better than the former in women. Elevated FPG and 2-h PG levels were associated with an increased risk of ischemic stroke incidence. 2-h PG contributed to the risk more strongly than FPG. No relationship between hyperglycemia and the risk of hemorrhagic stroke was found. The risk of CHD and ischemic stroke incidence increased with age in both genders, but was higher in all age groups in men than in women. The gender difference was, however, more marked for CHD than for ischemic stroke. Age, smoking and diabetes contributed to the development of both CHD and ischemic stroke. Elevated cholesterol levels predicted CHD only, whereas elevated blood pressure was a risk predictor for the incidence of ischemic stroke. The CHD and ischemic stroke risk was higher in men than in women with and without diabetes, however, the gender difference diminished for CHD but enlarged for ischemic stroke in diabetic individuals. The known risk factors including diabetes contributed differently to the risk of CHD and ischemic stroke in women and in men. Hyperglycemia defined by FPG or 2-h PG increases the risk of ischemic stroke in individuals without diabetes. FPG better predicts stroke mortality in women and 2-h PG in men. The risk of acute CHD and ischemic stroke is higher in men than in women in all ages, but such gender difference is more marked for CHD than for ischemic stroke. CHD risk is higher in men than in women, but the difference is reduced in diabetic population. Diabetes, however, increases stroke risk more in men than in women in all ages.

Oncolytic Adenoviruses for Gynecologic Cancer

Gene therapy is a promising novel approach for treating cancers resistant to or escaping currently available modalities. Treatment approaches are based on taking advantage of molecular differences between normal and tumor cells. Various strategies are currently in clinical development with adenoviruses as the most popular vehicle. Recent developments include improving targeting strategies for gene delivery to tumor cells with tumor specific promoters or infectivity enhancement. A rapidly developing field is as well replication competent agents, which allow improved tumor penetration and local amplification of the anti-tumor effect. Adenoviral cancer gene therapy approaches lack cross-resistance with other treatment options and therefore synergistic effects are possible. This study focused on development of adenoviral vectors suitable for treatment of various gynecologic cancer types, describing the development of the field from non-replicating adenoviral vectors to multiple-modified conditional replicating viruses. Transcriptional targeting of gynecologic cancer cells by the use of the promoter of vascular endothelial growth factor receptor type 1 (flt-1) was evaluated. Flt-1 is not expressed in the liver and thus an ideal promoter for transcriptional targeting of adenoviruses. Our studies implied that the flt-1 promoter is active in teratocarcinomas.and therefore a good candidate for development of oncolytic adenoviruses for treatment of this often problematic disease with then poor outcome. A tropism modified conditionally replicating adenovirus (CRAd), Ad5-Δ24RGD, was studied in gynecologic cancers. Ad5-Δ24RGD is an adenovirus selectively replication competent in cells defective in the p16/Rb pathway, including many or most tumor cells. The fiber of Ad5-Δ24RGD contains an integrin binding arginine-glycine-aspartic acid motif (RGD-4C), allowing coxackie-adenovirus receptor independent infection of cancer cells. This approach is attractive because expression levels of CAR are highly variable and often low on primary gynecological cancer cells. Oncolysis could be shown for a wide variety of ovarian and cervical cancer cell lines as well as primary ovarian cancer cell spheroids, a novel system developed for in vitro analysis of CRAds on primary tumor substrates. Biodistribution was evaluated and preclinical safety data was obtained by demonstrating lack of replication in human peripheral blood mononuclear cells. The efficicacy of Ad5-Δ24RGD was shown in different orthotopic murine models including a highly aggressive intraperitoneal model of disseminated ovarian cancer cells, where Ad5-Δ24RGD resulted in complete eradication of intraperitoneal disease in half of the mice. To further improve the selectivity and specificity of CRAds, triple-targeted oncolytic adenoviruses were cloned, featuring the cyclo-oxygenase-2 (cox-2) promoter, E1A transcomplementation and serotype chimerism. Those viruses were evaluated on ovarian cancer cells for specificity and oncolytic potency with regard to two different cox2 versions and three different variants of E1A (wild type, delta24 and delta2delta24). Ad5/3cox2Ld24 emerged as the best combination due to enhanced selectivity without potency lost in vitro or in an aggressive intraperitoneal orthotopic ovarian tumor model. In summary, the preclinical therapeutic efficacy of the CRAds tested in this study, taken together with promising biodistribution and safety data, suggest that these CRAds are interesting candidates for translation into clinical trials for gynecologic cancer.

A hidden Markov model approach for determining vessel activity from vessel monitoring system data.

Many fisheries worldwide have adopted vessel monitoring systems (VMS) for compliance purposes. An added benefit of these systems is that they collect a large amount of data on vessel locations at very fine spatial and temporal scales. This data can provide a wealth of information for stock assessment, research, and management. However, since most VMS implementations record vessel location at set time intervals with no regard to vessel activity, some methodology is required to determine which data records correspond to fishing activity. This paper describes a probabilistic approach, based on hidden Markov models (HMMs), to determine vessel activity. A HMM provides a natural framework for the problem and, by definition, models the intrinsic temporal correlation of the data. The paper describes the general approach that was developed and presents an example of this approach applied to the Queensland trawl fishery off the coast of eastern Australia. Finally, a simulation experiment is presented that compares the misallocation rates of the HMM approach with other approaches.

Organic inputs, tillage and rotation practices influence soil health and suppressiveness to soilborne pests and pathogens of ginger.

A field experiment was established in which an amendment of poultry manure and sawdust (200 t/ha) was incorporated into some plots but not others and then a permanent pasture or a sequence of biomass-producing crops was grown with and without tillage, with all biomass being returned to the soil. After 4 years, soil C levels were highest in amended plots, particularly those that had been cropped using minimum tillage, and lowest in non-amended and fallowed plots, regardless of how they had been tilled. When ginger was planted, symphylans caused severe damage to all treatments, indicating that cropping, tillage and organic matter management practices commonly used to improve soil health are not necessarily effective for all crops or soils. During the rotational phase of the experiment, the development of suppressiveness to three key pathogens of ginger was monitored using bioassays. Results for root-knot nematode (Meloidogyne javanica) indicated that for the first 2 years, amended soil was more suppressive than non-amended soil from the same cropping and tillage treatment, whereas under pasture, the amendment only enhanced suppressiveness in the first year. Suppressiveness was generally associated with higher C levels and enhanced biological activity (as measured by the rate of fluorescein diacetate (FDA) hydrolysis and numbers of free-living nematodes). Reduced tillage also enhanced suppressiveness, as gall ratings and egg counts in the second and third years were usually significantly lower in cropped soils under minimum rather than conventional tillage. Additionally, soil that was not disturbed during the process of setting up bioassays was more suppressive than soil which had been gently mixed by hand. Results of bioassays with Fusarium oxysporum f. sp. zingiberi were too inconsistent to draw firm conclusions, but the severity of fusarium yellows was generally higher in fumigated fallow soil than in other treatments, with soil management practices having little impact on disease severity. With regard to Pythium myriotylum, biological factors capable of reducing rhizome rot were present, but were not effective enough to suppress the disease under environmental conditions that were ideal for disease development.

Degenerate rhombohedral and orthorhombic states in Ca-substituted Na0.5Bi0.5TiO3

Neutron powder diffraction and temperature dependent dielectric studies were carried out on Ca-substituted Na0.5Bi0.5TiO3, i.e., (Na0.5Bi0.5)(1-x)CaxTiO3. Stabilization of an orthorhombic phase even at a low Ca concentration (0.05 < x < 0.10) suggests that Na0.5Bi0.5TiO3 (NBT) is susceptible to orthorhombic distortion. The orthorhombic and rhombohedral phases coexist for x=0.10, suggesting these phases to be nearly degenerate. The orthorhombic distortion favoring tendency of Ca assists in promoting the inherent instability with regard to this structure in pure NBT, which was reported recently.