Quantifying airborne dispersal routes of pathogens over continents to safeguard global wheat supply.

Infectious crop diseases spreading over large agricultural areas pose a threat to food security. Aggressive strains of the obligate pathogenic fungus Puccinia graminis f.sp. tritici (Pgt), causing the crop disease wheat stem rust, have been detected in East Africa and the Middle East, where they lead to substantial economic losses and threaten livelihoods of farmers. The majority of commercially grown wheat cultivars worldwide are susceptible to these emerging strains, which pose a risk to global wheat production, because the fungal spores transmitting the disease can be wind-dispersed over regions and even continents 1-11 . Targeted surveillance and control requires knowledge about airborne dispersal of pathogens, but the complex nature of long-distance dispersal poses significant challenges for quantitative research 12-14 . We combine international field surveys, global meteorological data, a Lagrangian dispersion model and high-performance computational resources to simulate a set of disease outbreak scenarios, tracing billions of stochastic trajectories of fungal spores over dynamically changing host and environmental landscapes for more than a decade. This provides the first quantitative assessment of spore transmission frequencies and amounts amongst all wheat producing countries in Southern/East Africa, the Middle East and Central/South Asia. We identify zones of high air-borne connectivity that geographically correspond with previously postulated wheat rust epidemiological zones (characterized by endemic disease and free movement of inoculum) 10,15 , and regions with genetic similarities in related pathogen populations 16,17 . We quantify the circumstances (routes, timing, outbreak sizes) under which virulent pathogen strains such as 'Ug99' 5,6 pose a threat from long-distance dispersal out of East Africa to the large wheat producing areas in Pakistan and India. Long-term mean spore dispersal trends (predominant direction, frequencies, amounts) are summarized for all countries in the domain (Supplementary Data). Our mechanistic modelling framework can be applied to other geographic areas, adapted for other pathogens and used to provide risk assessments in real-time 3 .

Streptomyces coelicolor Dps-like proteins: differential dual roles in response to stress during vegetative growth and in nucleoid condensation during reproductive cell division.

The Dps protein, a member of the ferritin family, contributes to DNA protection during oxidative stress and plays a central role in nucleoid condensation during stationary phase in unicellular eubacteria. Genome searches revealed the presence of three Dps-like orthologues within the genome of the Gram-positive bacterium Streptomyces coelicolor. Disruption of the S. coelicolor dpsA, dpsB and dpsC genes resulted in irregular condensation of spore nucleoids in a gene-specific manner. These irregularities are correlated with changes to the spacing between sporulation septa. This is the first example of these proteins playing a role in bacterial cell division. Translational fusions provided evidence for both developmental control of DpsA and DpsC expression and their localization to sporogenic compartments of aerial hyphae. In addition, various stress conditions induced expression of the Dps proteins in a stimulus-dependent manner in vegetative hyphae, suggesting stress-induced, protein-specific protective functions in addition to their role during reproductive cell division. Unlike in other bacteria, the S. coelicolor Dps proteins are not induced in response to oxidative stress.

Effective control of hypercholesterolemia in children with dietary interventions based in pediatric practice.

BACKGROUND: Based on recent recommendations, the number of hypercholesterolemic children who would require dietary therapy could overwhelm current preventive pediatric cardiology resources. No previous studies have established the efficacy of such therapy in the pediatrician's office. The purpose of this study was to evaluate two programs of office-based therapy. METHODS: We randomly assigned 295 children with hypercholesterolemia (> 185 mg/dl) two interventions: one single or four multiple 90-min sessions of family-oriented nutritional education, based in pediatric practices. We examined total cholesterol, 3-day food records, height and weight, and in the multisession group high-density lipoprotein cholesterol and triglycerides at the beginning and at intervals of 8.5-9 and 21 to 33 weeks (single-session and multisession groups, respectively). RESULTS: Total cholesterol was lowered equally in both treatment groups over the course of the study. This was accompanied by dietary changes: a decrease in calories derived from total and saturated fats, and increased intake of fiber, protein, and carbohydrate. However, more single-session patients withdrew from the program during the study. CONCLUSIONS: The two interventions were equally effective in lowering total and low-density lipoprotein cholesterol and in reducing intake of total and saturated fat. However, the higher completion rate of the multisession group suggests that this approach may be the more effective.

Comparison of complement fixation and fluorescent immunoassay (FIAX) for measuring antibodies to cytomegalovirus and herpes simplex virus.

An automated fluorescent immunoassay system (FIAX) was compared with complement fixation (CF) for measuring antibodies to cytomegalovirus (CMV) and herpes simplex virus (HSV) in clinical specimens. Compared with CF the specificity of FIAX (ability to detect a negative titer) was 95% for CMV and 92% for HSV. The sensitivity of FIAX (ability to detect a positive titer) was 98% for CMV and 95% for HSV. When paired samples were tested for significant titer rises, the concordance of the two assays for CMV was 96% and for HSV 80%. The FIAX assay was found to be reproducible when sera were tested within the same laboratory and in two different laboratories. The assay is fast, simple to perform, and not affected by anticomplementary activity. It is seen as a useful alternative to CF testing in a clinical virology laboratory.

Detection of antibodies to Legionella pneumophila in immune guinea pig serum by solid-phase immunofluorescence.

A semiautomated solid-phase immunofluorescence apparatus (FIAX; International Diagnostic Technology, Santa Clara, Calif.) was utilized to develop a rapid method for detection of antibody to Legionella pneumophila. The sera from guinea pigs immunized with a mixture of killed L. pneumophila and Freund complete adjuvant displayed markedly enhanced antibody activity as measured by FIAX when compared with that obtained from adjuvant-injected or unimmunized animals. A correlation was observed between FIAX net fluorescence units and microagglutination titers of serum samples obtained from immunized animals. Within-run and between-run coefficients of variation performed on selected immune serum samples were low. These results demonstrated that the FIAX method could readily and reproducibly detect Legionella-specific antibodies in the sera of actively immunized animals and suggest the possibility of a broader application of FIAX in the serological detection of exposure to L. pneumophila antigen.

Quantitative fluorescent immunoassay for measurement of antibody to Dirofilaria immitis in dogs.

An automated fluorescent immunoassay technique (FIAX; International Diagnostic Technology, Santa Clara, Calif.) has been developed for the quantitation of circulating antibodies in dogs infected with Dirofilaria immitis. Two groups of sera, group I consisting of 77 samples and group II consisting of 126 samples, were obtained from experimentally infected microfilaremic dogs, known negative controls, and clinically diagnosed cases of occult dirofilariasis. Antibody against a partially purified trichloroacetic acid-soluble extract of a soluble somatic extract of D. immitis was measured by FIAX and by an enzyme-linked immunosorbent assay (ELISA). A standard curve was drawn from four samples with known FIAX titers and fluorescent signal unit values. The standard curve was used to determine titers of unknown samples. The correlation coefficients determined in the analysis of log10 ELISA and log10 FIAX values were r = 0.9057 and r = 0.8976 in groups I and II, respectively. Eighty-three percent of the titer values calculated by FIAX in group I were within one dilution, and 95% were within two dilutions, of those titers obtained by ELISA. In group II, 79 and 96% of the values obtained by FIAX were within one and two dilutions, respectively, of those obtained by ELISA. FIAX proved to be a reproducible and convenient assay for the measurement of serum antibody in dogs experimentally infected with Dirofilaria.

Standardization of FIAXtm for schistosomiasis using crude cercarial and adult worm antigens.

A fluoroimmunoassay (FIAXTM) has been developed for quantitating the antibody response to schistosomiasis by using cercarial and adult worm antigens of Schistosoma mansoni. The FIAXTM assay was calibrated by using an enzyme-linked immunosorbent assay (ELISA) performed with the same antigens. Studies of reproducibility and preliminary data on a battery of sera from proven cases of schistosomiasis an uninfected control sera are presented.

Evaluation of solid-phase immunofluorescence for quantitation of antibodies to herpes simplex virus and cytomegalovirus.

A recently developed semiautomated technique based on solid-phase immunofluorescence (FIAX) was compared with complement fixation for the determination of antibody levels to herpes simplex virus and cytomegalovorus in human serum samples. The results demonstrated that the FIAX method was in aggreement with the complement fixation technique for 97% of the serum samples tested. Reproducible titers were obtained from multiple FIAX determinations of representative sera within the same experimental run and between separate experimental runs. However, variability was rather high for patient sera with low (less than or equal to 1:5) antibody levels to cytomegalovirus. Hence, the results obtained by the FIAX technique were reproducible, and the FIAX system was as sensitive as complement fixation for the determination of antibody levels to herpes simplex virus and cytomegalovirus.

Calcium stimulation of gastrin and gastric acid secretion: effect of small doses of calcium carbonate.

Oral calcium carbonate (0-5 g, pH 9-4) increased serum gastrin and gastric acid output with slight but insignificant change in serum calcium. A similar rise in serum calcium during an intravenous infusion of calcium gluconate failed to increase serum gastrin and gastric acid output. Both intragastric calcium actions were abolished by acidification of the calcium carbonate solution (pH 1-0). The increase in serum gastrin and gastric acid output after intragastric calcium carbonate was not affected, however, by a simultaneous intraduodenal acid load. Equivalent neutralising doses of magnesium hydroxide (pH 9-4) did not increase serum gastrin and gastric acid output above basal levels, whereas antral acidification with 20 ml 0-1 N HCl resulted in a slight decrease in serum gastrin. Intraduodenal calcium carbonate (pH 3-0) also increased serum gastrin and gastric acid output, whereas an equivalent volume of intraduodenal saline (pH 3-0) had no effect. These findings indicate that calcium increases serum gastrin by local stimulation of antral and duodenal mucosa. They also suggest that the action of calcium on gastric secretion is partly mediated by gastrin.

The antiphlogistic, antinociceptive and antipyretic properties of fenclorac.

Fenclorac (a,m-dichloro-p-cyclohexlphenylacetic acid, diethylammonium salt) is a potent nonsteroidal anti-inflammatory agent with significant analgesic and antipyretic activity. Fenclorac had an ED50 of 7.9 mg/kg in the carrageenan paw edema assay and had a duration of action of 18-22 hours. Comparative tests in the carrageenan paw edema assay in the rat indicated that the potency of fenclorac was 13 times that of aspirin, 3.4 times phenylbutazone, 3 times ibuprofen and 0.3 times indomethacin. Fenclorac was less potent than indomethacin, but more potent than phenylbutazone or aspirin in treatment of developing or established adjuvant arthritis. The anti-inflammatory effectiveness of fenclorac did not depend upon the integrity of the adrenopituitary axis and was not affected by the route of administration or sex of the test animal. Fenclorac was 77 times more potent than aspirin and more than twice as potent as indomethacin in reducing fever in rats rendered hyperthermic with brewer's yeast. Fenclorac did not affect normal body temperatures. Fenclorac did not interfere with cellular immune mechanisms as measured by its lack of effectiveness in experimental allergic encephalomyelitis. Antinociceptive testing indicated that fenclorac had peripheral but not central analgesic activity. Fenclorac had an acute oral LD50 in rats and mice of 285 and 430 mg/kg, respectively. The acute gastric lesion UD50 for fenclorac was 7 mg/kg in the fasted rat. Studies using 51Cr-tagged erythrocytes indicated that fenclorac did not produce significant fecal blood loss in the rat at twice the therapeutic ED50 dose for up to 12 days after dosing. Extensive and prolonged fecal blood loss was observed with a corresponding dose of indomethacin for up to nine days after administration. Comparison of the anti-inflammatory pharmacology, Therapeutic Ratio and the data obtained from the 51Cr-fecal blood loss studies indicated that fenclorac was well tolerated after acute or subacute administration to the rat.