Estimating the reproduction number, R0, from individual-based models of tree disease spread

Tree populations worldwide are facing an unprecedented threat from a variety of tree diseases and invasive pests. Their spread, exacerbated by increasing globalisation and climate change, has an enormous environmental, economic and social impact. Computational individual-based models are a popular tool for describing and forecasting the spread of tree diseases due to their flexibility and ability to reveal collective behaviours. In this paper we present a versatile individual-based model with a Gaussian infectivity kernel to describe the spread of a generic tree disease through a synthetic treescape. We then explore several methods of calculating the basic reproduction number R0, a characteristic measurement of disease infectivity, defining the expected number of new infections resulting from one newly infected individual throughout their infectious period. It is a useful comparative summary parameter of a disease and can be used to explore the threshold dynamics of epidemics through mathematical models. We demonstrate several methods of estimating R0 through the individual-based model, including contact tracing, inferring the Kermack–McKendrick SIR model parameters using the linear noise approximation, and an analytical approximation. As an illustrative example, we then use the model and each of the methods to calculate estimates of R0 for the ash dieback epidemic in the UK

Probabilistic Model to Optimize Formulation and Baiting Strategies for the Pesticide CPTH (3-chloro-4-methylaniline hydrochloride)

ABSTRACT: A probabilistic model was validated for estimating avian mortality associated with the application of the avicide CPTH (3-chloro-4-methylaniline hydrochloride) to minimize sprouting rice damage in the southern United States. CPTH exposures for individual birds were predicted by random sampling from species-specific non-parametric distributions of bait seed consumption and CPTH residues detected on individual bait seeds. Mortality was predicted from the species-specific exposure versus mortality relationship. Individual variations in this response were captured in the model by Monte Carlo sampling from species-specific distributions of slopes and median toxicity values (LD 50 ) for each bird. The model was used to evaluate the effects of formulation, bait preparation and application procedures on target and non-target mortalities. The results of these analyses indicate that: 1) decreasing the concentration of CPTH on the treated bait seeds from 400 to 300 µg CPTH/seed will improve bait performance by decreasing non-target mortalities, 2) the current dilution ratio of 1 treated seed to 25 diluent seeds is optimal and 3) preparing a bait seed product in which CPTH is homogeneously distributed throughout the bait seed mixture will significantly increase bait performance by increasing red-winged blackbird (target) mortality and decreasing mortality for savannah sparrows and meadowlarks (non-targets)

Effect of thermal treatment and storage on bioactive compounds, organic acids and antioxidant activity of baobab fruit (Adansonia digitata) pulp from Malawi

Bioactive compounds of baobab (Adansonia digitata) pulp from Malawi were investigated. The effect of thermal treatment and storage on selected quality attributes of the juice was also evaluated. Organic compounds were analysed by HPLC; total phenol content (TPC) and total antioxidant activity (FRAP, ABTS and DPPH) were measured by spectrophotometry. Malawi baobab pulp contains high levels of procyanidin B2 (533 ± 22.6 mg/100 g FW), vitamin C (AA + DHA) (466 ± 2.5 mg/100 g FW), gallic acid (68.5 ± 12.4 mg/100 g FW) and (−)-epicatechin (43.0 ± 3.0 mg/100 g FW) and showed a maximum TPC of 1.89 × 103 ± 1.61 mg GAE/100 g FW. The maximum antioxidant activity was 2.81 × 103 ± 92.8 mg TEAC/100 g FW for FRAP, 1.52 × 103 ± 17.1 mg TEAC/100 g FW for ABTS and 50.9 ± 0.43% DPPH for DPPH. Thermal pasteurisation (72 °C, 15 s) retained vitamin C which further showed extended half-life under refrigeration temperature (6 °C). Procyanidin B2, (−)-epicatechin, TPC and antioxidant activity fluctuated during storage. Antioxidant activity was significantly correlated (p ≤ 0.05) with bioactive compounds and TPC

Macrocyclic colibactin induces DNA double-strand breaks via copper-mediated oxidative cleavage.

Colibactin is an assumed human gut bacterial genotoxin, whose biosynthesis is linked to the clb genomic island that has a widespread distribution in pathogenic and commensal human enterobacteria. Colibactin-producing gut microbes promote colon tumour formation and enhance the progression of colorectal cancer via cellular senescence and death induced by DNA double-strand breaks (DSBs); however, the chemical basis that contributes to the pathogenesis at the molecular level has not been fully characterized. Here, we report the discovery of colibactin-645, a macrocyclic colibactin metabolite that recapitulates the previously assumed genotoxicity and cytotoxicity. Colibactin-645 shows strong DNA DSB activity in vitro and in human cell cultures via a unique copper-mediated oxidative mechanism. We also delineate a complete biosynthetic model for colibactin-645, which highlights a unique fate of the aminomalonate-building monomer in forming the C-terminal 5-hydroxy-4-oxazolecarboxylic acid moiety through the activities of both the polyketide synthase ClbO and the amidase ClbL. This work thus provides a molecular basis for colibactin's DNA DSB activity and facilitates further mechanistic study of colibactin-related colorectal cancer incidence and prevention

Acoustic attenuation spectroscopy and helium ion microscopy study of rehydration of dairy powder

Complete hydration is essential for the production of structured dairy products from powders. It is essential that the ingredients used hydrate completely. Determination of an end point of rehydration is non-trivial, but ultrasound-based methodologies have demonstrated potential in this area and are well suited to measuring bulk samples in situ. Here, acoustic attenuation spectroscopy (AAS) is used to monitor rehydration of skim milk powder, and recombined systems of micellar casein isolate with lactose and whey protein isolate. Dynamic light scattering, zeta-potential measurements and AAS as a function of pH characterise each component around its isoelectric point to assess its functionality. Scanning helium ion microscopy was used to image the dry powders, without any conductive coating, producing resolution equivalent to scanning electron microscopy, but with much larger focal lengths and fewer imaging artefacts. Imaging the powders provides information on particle size and morphology which can affect dissolution behaviour. Reconstituted skim milk powder and recombined samples were monitored showing there are changes occurring over several hours. Attenuation coefficients are shown to predict the end point of hydration. Model fitting is used to extract volume fractions and average particle sizes of large and small particle populations in recombined samples over time. AAS is demonstrated to be capable of tracking the dynamics in rehydrating dispersions over time. Physical parameters such as the volume fraction and particle size of the dispersed phase can be determined

Capillary electrophoresis mass spectrometry-based saliva metabolomics identified oral, breast and pancreatic cancer-specific profiles

Saliva is a readily accessible and informative biofluid, making it ideal for the early detection of a wide range of diseases including cardiovascular, renal, and autoimmune diseases, viral and bacterial infections and, importantly, cancers. Saliva-based diagnostics, particularly those based on metabolomics technology, are emerging and offer a promising clinical strategy, characterizing the association between salivary analytes and a particular disease. Here, we conducted a comprehensive metabolite analysis of saliva samples obtained from 215 individuals (69 oral, 18 pancreatic and 30 breast cancer patients, 11 periodontal disease patients and 87 healthy controls) using capillary electrophoresis time-of-flight mass spectrometry (CE-TOF-MS). We identified 57 principal metabolites that can be used to accurately predict the probability of being affected by each individual disease. Although small but significant correlations were found between the known patient characteristics and the quantified metabolites, the profiles manifested relatively higher concentrations of most of the metabolites detected in all three cancers in comparison with those in people with periodontal disease and control subjects. This suggests that cancer-specific signatures are embedded in saliva metabolites. Multiple logistic regression models yielded high area under the receiver-operating characteristic curves (AUCs) to discriminate healthy controls from each disease. The AUCs were 0.865 for oral cancer, 0.973 for breast cancer, 0.993 for pancreatic cancer, and 0.969 for periodontal diseases. The accuracy of the models was also high, with cross-validation AUCs of 0.810, 0.881, 0.994, and 0.954, respectively. Quantitative information for these 57 metabolites and their combinations enable us to predict disease susceptibility. These metabolites are promising biomarkers for medical screening

Nat Genet

The function of the majority of genes in the mouse and human genomes remains unknown. The mouse embryonic stem cell knockout resource provides a basis for the characterization of relationships between genes and phenotypes. The EUMODIC consortium developed and validated robust methodologies for the broad-based phenotyping of knockouts through a pipeline comprising 20 disease-oriented platforms. We developed new statistical methods for pipeline design and data analysis aimed at detecting reproducible phenotypes with high power. We acquired phenotype data from 449 mutant alleles, representing 320 unique genes, of which half had no previous functional annotation. We captured data from over 27,000 mice, finding that 83% of the mutant lines are phenodeviant, with 65% demonstrating pleiotropy. Surprisingly, we found significant differences in phenotype annotation according to zygosity. New phenotypes were uncovered for many genes with previously unknown function, providing a powerful basis for hypothesis generation and further investigation in diverse systems.Comment in : Genetic differential calculus. [Nat Genet. 2015] Comment in : Scaling up phenotyping studies. [Nat Biotechnol. 2015