Glycosidase activity in the excretory-secretory products of the liver fluke, Fasciola hepatica

Fasciola hepatica secretes proteolytic enzymes and other molecules that are essential for host penetration and migration. This mixture may include enzymes required for the degradation of supramucosal gels, which defend epithelial surfaces against pathogen entry. These contain hydrated mucins that are heavily glycosylated. Excretory-secretory products (ES) from F. hepatica were examined for a range of glycosidase activities, using synthetic 4-methylumbelliferyl glycosides as substrates. The ES product contained at least 8 different glycosidase activities, the most abundant of which were β-N- acetylhexosaminidase, β-galactosidase and β-glucosidase. Alpha-fucosidase, β-glucuronidase, α-galactosidase, α-mannosidase and neuraminidase were also present. β-N- acetylhexosaminidase and β-galactosidase were present in multiple isoforms (at least 4), whereas β-glucosidase appeared to exist as one isoenzyme with a pI <3.8. All three enzymes had acidic pH optima (4.5-5.0). Ovine small intestinal mucin was degraded by ES at pH 4.5 or 7.0, with or without active cathepsin L, the major protease found in F. hepatica ES. The ability of F. hepatica ES to degrade mucin in the presence or absence of active cathepsin L suggests that cathepsin L is not essential for mucin degradation. The abundance of β-galactosidase and β-hexosaminidase in ES supports a role for these enzymes in mucin degradation

Coping with Commitment: Projected Thermal Stress on Coral Reefs under Different Future Scenarios

BACKGROUND: Periods of anomalously warm ocean temperatures can lead to mass coral bleaching. Past studies have concluded that anthropogenic climate change may rapidly increase the frequency of these thermal stress events, leading to declines in coral cover, shifts in the composition of corals and other reef-dwelling organisms, and stress on the human populations who depend on coral reef ecosystems for food, income and shoreline protection. The ability of greenhouse gas mitigation to alter the near-term forecast for coral reefs is limited by the time lag between greenhouse gas emissions and the physical climate response. METHODOLOGY/PRINCIPAL FINDINGS: This study uses observed sea surface temperatures and the results of global climate model forced with five different future emissions scenarios to evaluate the "committed warming" for coral reefs worldwide. The results show that the physical warming commitment from current accumulation of greenhouse gases in the atmosphere could cause over half of the world's coral reefs to experience harmfully frequent (p> or =0.2 year(-1)) thermal stress by 2080. An additional "societal" warming commitment, caused by the time required to shift from a business-as-usual emissions trajectory to a 550 ppm CO(2) stabilization trajectory, may cause over 80% of the world's coral reefs to experience harmfully frequent events by 2030. Thermal adaptation of 1.5 degrees C would delay the thermal stress forecast by 50-80 years. CONCLUSIONS/SIGNIFICANCE: The results suggest that adaptation -- via biological mechanisms, coral community shifts and/or management interventions -- could provide time to change the trajectory of greenhouse gas emissions and possibly avoid the recurrence of harmfully frequent events at the majority (97%) of the world's coral reefs this century. Without any thermal adaptation, atmospheric CO(2) concentrations may need to be stabilized below current levels to avoid the degradation of coral reef ecosystems from frequent thermal stress events

Dietary Supplementation with Soluble Plantain Non-Starch Polysaccharides Inhibits Intestinal Invasion of Salmonella Typhimurium in the Chicken

Soluble fibres (non-starch polysaccharides, NSP) from edible plants but particularly plantain banana (Musa spp.), have been shown in vitro and ex vivo to prevent various enteric pathogens from adhering to, or translocating across, the human intestinal epithelium, a property that we have termed contrabiotic. Here we report that dietary plantain fibre prevents invasion of the chicken intestinal mucosa by Salmonella. In vivo experiments were performed with chicks fed from hatch on a pellet diet containing soluble plantain NSP (0 to 200 mg/d) and orally infected with S.Typhimurium 4/74 at 8 d of age. Birds were sacrificed 3, 6 and 10 d post-infection. Bacteria were enumerated from liver, spleen and caecal contents. In vitro studies were performed using chicken caecal crypts and porcine intestinal epithelial cells infected with Salmonella enterica serovars following pre-treatment separately with soluble plantain NSP and acidic or neutral polysaccharide fractions of plantain NSP, each compared with saline vehicle. Bacterial adherence and invasion were assessed by gentamicin protection assay. In vivo dietary supplementation with plantain NSP 50 mg/d reduced invasion by S.Typhimurium, as reflected by viable bacterial counts from splenic tissue, by 98.9% (95% CI, 98.1–99.7; P<0.0001). In vitro studies confirmed that plantain NSP (5–10 mg/ml) inhibited adhesion of S.Typhimurium 4/74 to a porcine epithelial cell-line (73% mean inhibition (95% CI, 64–81); P<0.001) and to primary chick caecal crypts (82% mean inhibition (95% CI, 75–90); P<0.001). Adherence inhibition was shown to be mediated via an effect on the epithelial cells and Ussing chamber experiments with ex-vivo human ileal mucosa showed that this effect was associated with increased short circuit current but no change in electrical resistance. The inhibitory activity of plantain NSP lay mainly within the acidic/pectic (homogalacturonan-rich) component. Supplementation of chick feed with plantain NSP was well tolerated and shows promise as a simple approach for reducing invasive salmonellosis

Modifiers of short-term effects of ozone on mortality in eastern Massachusetts - A case-crossover analysis at individual level

<p>Abstract</p> <p>Background</p> <p>Substantial epidemiological studies demonstrate associations between exposure to ambient ozone and mortality. A few studies simply examine the modification of this ozone effect by individual characteristics and socioeconomic status, but socioeconomic status was usually coded at the city level.</p> <p>Methods</p> <p>This study used a case-crossover design to examine whether impacts of ozone on mortality were modified by socioeconomic status coded at the tract or characteristics at an individual level in eastern Massachusetts, US for a period May-September, 1995-2002, with a total of 157,197 non-accident deaths aging 35 years or older. We used moving averages of maximal 8-hour concentrations of ozone monitored at 8 stationary stations as personal exposure.</p> <p>Results</p> <p>A 10 ppb increase in the four-day moving average of maximal 8-hour ozone was associated with 1.68% (95% confidence interval (CI): 0.51%, 2.87%), 1.96% (95% CI: -1.83%, 5.90%), 8.28% (95% CI: 0.66%, 16.48%), 0.44% (95% CI: -1.45%, 2.37%), -0.83% (95% CI: -2.94%, 1.32%), -1.09% (95% CI: -4.27%, 2.19%) and 6.5% (95% CI: 1.74%, 11.49%) changes in all natural deaths, respiratory disorders, diabetes, cardiovascular diseases, heart diseases, acute myocardial infarction and stroke, respectively. We did not find any evidence that the associations were significantly modified by socioeconomic status or individual characteristics although small differences of estimates across subpopulations were demonstrated.</p> <p>Conclusions</p> <p>Exposure to ozone was associated with specific cause mortality in Eastern Massachusetts during May-September, 1995-2002. There was no evidence that effects of ozone on mortality were significantly modified by socioeconomic status and individual characteristics.</p

Incidence and characteristics of distal radius fractures in a southern Swedish region

<p>Abstract</p> <p>Background</p> <p>The incidence of distal radius fracture has increased substantially during the last 50 years according to several studies that estimated the overall incidence in various general populations. The incidence of fracture classified according to severity has not been well documented. The aim of this population-based study was to estimate the overall and type-specific incidence rates of distal radius fracture in a representative population in southern Sweden.</p> <p>Methods</p> <p>During 2001, all persons older than 18 years with acute distal radius fracture in the southern Swedish region of Northeastern Scania were prospectively recorded. A radiologist classified the fractures according to the AO system and measured volar tilt and ulnar variance. A fracture with volar tilt outside a range of -5° to 20° and/or ulnar variance of 2 mm or greater was defined as displaced.</p> <p>Results</p> <p>335 persons with acute distal radius fracture were recorded during the 1-year period. The overall incidence rate was 26 (95% confidence interval 23–29) per 10,000 person-years. Among women the incidence rate increased rapidly from the age of 50 and reached a peak of 119 per 10,000 person-years in women 80 years and older. The incidence rate among women 50 to 79 years old (56 per 10,000 person-years) was lower than that reported in previous studies of similar populations. Among men the incidence rate was low until the age of 80 years and older when it increased to 28 per 10,000 person-years. Fractures classified as AO type A comprised about 80% of the fractures in women and 64% in men. Almost two-thirds of all fractures were displaced and among men and women 80 years and older more than 80% of the fractures were displaced.</p> <p>Conclusion</p> <p>The incidence rate of distal radius fracture in women 50 to 79 years old was lower than previously reported, which may indicate declining incidence in this group. In both sexes, the incidence was highest in the age group of 80 years and older. With a growing number of elderly in the general population, the impact of distal radius fracture in the future may be considerable.</p

Oral cancer treatment: developments in chemotherapy and beyond

Oncology is one of the few areas of medicine where most patients are treated intravenously rather than receiving oral drugs. Recently, several oral anti-cancer drugs have been approved and there are many more in development. Oral chemotherapy is attractive because of its convenience and ease of administration, particularly in the palliative setting. With an increasing number of oral agents emerging, we can expect to see a rapid rise in the use of oral chemotherapy in years to come. This article reviews recent developments in oral chemotherapy, both of traditional cytotoxics and novel, targeted agents, from the viewpoint of patients, physicians, drug developers and health-care providers

Major-Effect Alleles at Relatively Few Loci Underlie Distinct Vernalization and Flowering Variation in Arabidopsis Accessions

We have explored the genetic basis of variation in vernalization requirement and response in Arabidopsis accessions, selected on the basis of their phenotypic distinctiveness. Phenotyping of F2 populations in different environments, plus fine mapping, indicated possible causative genes. Our data support the identification of FRI and FLC as candidates for the major-effect QTL underlying variation in vernalization response, and identify a weak FLC allele, caused by a Mutator-like transposon, contributing to flowering time variation in two N. American accessions. They also reveal a number of additional QTL that contribute to flowering time variation after saturating vernalization. One of these was the result of expression variation at the FT locus. Overall, our data suggest that distinct phenotypic variation in the vernalization and flowering response of Arabidopsis accessions is accounted for by variation that has arisen independently at relatively few major-effect loci

Potential for early warning of viral influenza activity in the community by monitoring clinical diagnoses of influenza in hospital emergency departments

<p>Abstract</p> <p>Background</p> <p>Although syndromic surveillance systems are gaining acceptance as useful tools in public health, doubts remain about whether the anticipated early warning benefits exist. Many assessments of this question do not adequately account for the confounding effects of autocorrelation and trend when comparing surveillance time series and few compare the syndromic data stream against a continuous laboratory-based standard. We used time series methods to assess whether monitoring of daily counts of Emergency Department (ED) visits assigned a clinical diagnosis of influenza could offer earlier warning of increased incidence of viral influenza in the population compared with surveillance of daily counts of positive influenza test results from laboratories.</p> <p>Methods</p> <p>For the five-year period 2001 to 2005, time series were assembled of ED visits assigned a provisional ED diagnosis of influenza and of laboratory-confirmed influenza cases in New South Wales (NSW), Australia. Poisson regression models were fitted to both time series to minimise the confounding effects of trend and autocorrelation and to control for other calendar influences. To assess the relative timeliness of the two series, cross-correlation analysis was performed on the model residuals. Modelling and cross-correlation analysis were repeated for each individual year.</p> <p>Results</p> <p>Using the full five-year time series, short-term changes in the ED time series were estimated to precede changes in the laboratory series by three days. For individual years, the estimate was between three and 18 days. The time advantage estimated for the individual years 2003–2005 was consistently between three and four days.</p> <p>Conclusion</p> <p>Monitoring time series of ED visits clinically diagnosed with influenza could potentially provide three days early warning compared with surveillance of laboratory-confirmed influenza. When current laboratory processing and reporting delays are taken into account this time advantage is even greater.</p