Prediction of photoperiodic regulators from quantitative gene circuit models

Photoperiod sensors allow physiological adaptation to the changing seasons. The external coincidence hypothesis postulates that a light-responsive regulator is modulated by a circadian rhythm. Sufficient data are available to test this quantitatively in plants, though not yet in animals. In Arabidopsis, the clock-regulated genes CONSTANS (CO) and FLAVIN, KELCH, F-BOX (FKF1) and their lightsensitive proteins are thought to form an external coincidence sensor. We use 40 timeseries of molecular data to model the integration of light and timing information by CO, its target gene FLOWERING LOCUS T (FT), and the circadian clock. Among other predictions, the models show that FKF1 activates FT. We demonstrate experimentally that this effect is independent of the known activation of CO by FKF1, thus we locate a major, novel controller of photoperiodism. External coincidence is part of a complex photoperiod sensor: modelling makes this complexity explicit and may thus contribute to crop improvement

Prevalence of hyperuricemia and relation of serum uric acid with cardiovascular risk factors in a developing country

BACKGROUND: The prevalence of hyperuricemia has rarely been investigated in developing countries. The purpose of the present study was to investigate the prevalence of hyperuricemia and the association between uric acid levels and the various cardiovascular risk factors in a developing country with high average blood pressures (the Seychelles, Indian Ocean, population mainly of African origin). METHODS: This cross-sectional health examination survey was based on a population random sample from the Seychelles. It included 1011 subjects aged 25 to 64 years. Blood pressure (BP), body mass index (BMI), waist circumference, waist-to-hip ratio, total and HDL cholesterol, serum triglycerides and serum uric acid were measured. Data were analyzed using scatterplot smoothing techniques and gender-specific linear regression models. RESULTS: The prevalence of a serum uric acid level >420 μmol/L in men was 35.2% and the prevalence of a serum uric acid level >360 μmol/L was 8.7% in women. Serum uric acid was strongly related to serum triglycerides in men as well as in women (r = 0.73 in men and r = 0.59 in women, p < 0.001). Uric acid levels were also significantly associated but to a lesser degree with age, BMI, blood pressure, alcohol and the use of antihypertensive therapy. In a regression model, triglycerides, age, BMI, antihypertensive therapy and alcohol consumption accounted for about 50% (R2) of the serum uric acid variations in men as well as in women. CONCLUSIONS: This study shows that the prevalence of hyperuricemia can be high in a developing country such as the Seychelles. Besides alcohol consumption and the use of antihypertensive therapy, mainly diuretics, serum uric acid is markedly associated with parameters of the metabolic syndrome, in particular serum triglycerides. Considering the growing incidence of obesity and metabolic syndrome worldwide and the potential link between hyperuricemia and cardiovascular complications, more emphasis should be put on the evolving prevalence of hyperuricemia in developing countries

Impaction bone grafting of the acetabulum at hip revision using a mix of bone chips and a biphasic porous ceramic bone graft substitute: Good outcome in 43 patients followed for a mean of 2 years

Background and purpose One of the greatest problems of revision hip arthroplasty is dealing with lost bone stock. Good results have been obtained with impaction grafting of allograft bone. However, there have been problems of infection, reproducibility, antigenicity, stability, availability of bone, and cost. Thus, alternatives to allograft have been sought. BoneSave is a biphasic porous ceramic specifically designed for use in impaction grafting. BoneSave is 80% tricalcium phosphate and 20% hydroxyapatite. Previous in vitro and in vivo studies have yielded good results using mixtures of allograft and BoneSave, when compared with allograft alone. This study is the first reported human clinical trial of BoneSave in impaction grafting

Nothing a Hot Bath Won't Cure: Infection Rates of Amphibian Chytrid Fungus Correlate Negatively with Water Temperature under Natural Field Settings

Dramatic declines and extinctions of amphibian populations throughout the world have been associated with chytridiomycosis, an infectious disease caused by the pathogenic chytrid fungus Batrachochytrium dendrobatidis (Bd). Previous studies indicated that Bd prevalence correlates with cooler temperatures in the field, and laboratory experiments have demonstrated that Bd ceases growth at temperatures above 28°C. Here we investigate how small-scale variations in water temperature correlate with Bd prevalence in the wild. We sampled 221 amphibians, including 201 lowland leopard frogs (Rana [Lithobates] yavapaiensis), from 12 sites in Arizona, USA, and tested them for Bd. Amphibians were encountered in microhabitats that exhibited a wide range of water temperatures (10–50°C), including several geothermal water sources. There was a strong inverse correlation between the water temperature in which lowland leopard frogs were captured and Bd prevalence, even after taking into account the influence of year, season, and host size. In locations where Bd was known to be present, the prevalence of Bd infections dropped from 75–100% in water <15°C, to less than 10% in water >30°C. A strong inverse correlation between Bd infection status and water temperature was also observed within sites. Our findings suggest that microhabitats where water temperatures exceed 30°C provide lowland leopard frogs with significant protection from Bd, which could have important implications for disease dynamics, as well as management applications

Bovine liver slices combined with an androgen transcriptional activation assay: an in-vitro model to study the metabolism and bioactivity of steroids

Previously we described the properties of a rapid and robust yeast androgen bioassay for detection of androgenic anabolic compounds, validated it, and showed its added value for several practical applications. However, biotransformation of potent steroids into inactive metabolites, or vice versa, is not included in this screening assay. Within this context, animal-friendly in-vitro cellular systems resembling species-specific metabolism can be of value. We therefore investigated the metabolic capacity of precision-cut slices of bovine liver using 17β-testosterone (T) as a model compound, because this is an established standard compound for assessing the metabolic capacity of such cellular systems. However, this is the first time that slice metabolism has been combined with bioactivity measurements. Moreover, this study also involves bioactivation of inactive prohormones, for example dehydroepiandrosterone (DHEA) and esters of T, and although medium extracts are normally analyzed by HPLC, here the metabolites formed were identified with more certainty by ultra-performance liquid chromatography time-of-flight mass spectrometry (UPLC–TOFMS) with accurate mass measurement. Metabolism of T resulted mainly in the formation of the less potent phase I metabolites 4-androstene-3,17-dione (4-AD), the hydroxy-T metabolites 6α, 6β, 15β, and 16α-OH-T, and the phase II metabolite T-glucuronide. As a consequence the overall androgenic activity, as determined by the yeast androgen bioassay, decreased. In order to address the usefulness of bovine liver slices for activation of inactive steroids, liver slices were exposed to DHEA and two esters of T. This resulted in an increase of androgenic activity, because of the formation of 4-AD and T

High Levels of Sediment Contamination Have Little Influence on Estuarine Beach Fish Communities

While contaminants are predicted to have measurable impacts on fish assemblages, studies have rarely assessed this potential in the context of natural variability in physico-chemical conditions within and between estuaries. We investigated links between the distribution of sediment contamination (metals and PAHs), physico-chemical variables (pH, salinity, temperature, turbidity) and beach fish assemblages in estuarine environments. Fish communities were sampled using a beach seine within the inner and outer zones of six estuaries that were either heavily modified or relatively unmodified by urbanization and industrial activity. All sampling was replicated over two years with two periods sampled each year. Shannon diversity, biomass and abundance were all significantly higher in the inner zone of estuaries while fish were larger on average in the outer zone. Strong differences in community composition were also detected between the inner and outer zones. Few differences were detected between fish assemblages in heavily modified versus relatively unmodified estuaries despite high concentrations of sediment contaminants in the inner zones of modified estuaries that exceeded recognized sediment quality guidelines. Trends in species distributions, community composition, abundance, Shannon diversity, and average fish weight were strongly correlated to physico-chemical variables and showed a weaker relationship to sediment metal contamination. Sediment PAH concentrations were not significantly related to the fish assemblage. These findings suggest that variation in some physico-chemical factors (salinity, temperature, pH) or variables that co-vary with these factors (e.g., wave activity or grain size) have a much greater influence on this fish assemblage than anthropogenic stressors such as contamination

Effect of Fibrin Glue on the Biomechanical Properties of Human Descemet's Membrane

10.1371/journal.pone.0037456PLoS ONE75