Statistical evaluation of alternative models of human evolution

An appropriate model of recent human evolution is not only important to understand our own history, but it is necessary to disentangle the effects of demography and selection on genome diversity. Although most genetic data support the view that our species originated recently in Africa, it is still unclear if it completely replaced former members of the Homo genus, or if some interbreeding occurred during its range expansion. Several scenarios of modern human evolution have been proposed on the basis of molecular and paleontological data, but their likelihood has never been statistically assessed. Using DNA data from 50 nuclear loci sequenced in African, Asian and Native American samples, we show here by extensive simulations that a simple African replacement model with exponential growth has a higher probability (78%) as compared with alternative multiregional evolution or assimilation scenarios. A Bayesian analysis of the data under this best supported model points to an origin of our species approximate to 141 thousand years ago (Kya), an exit out-of-Africa approximate to 51 Kya, and a recent colonization of the Americas approximate to 10.5 Kya. We also find that the African replacement model explains not only the shallow ancestry of mtDNA or Y-chromosomes but also the occurrence of deep lineages at some autosomal loci, which has been formerly interpreted as a sign of interbreeding with Homo erectus.

Thioquinolobactin, a pseudomonas siderophore with antifungal and anti-pythium activity

Under conditions of iron limitation Pseudomonas fluorescens ATCC 17400 produces two siderophores, pyoverdine, and a second siderophore quinolobactin, which itself results from the hydrolysis of the unstable molecule 8-hydroxy-4-methoxy-2-quinoline thiocarboxylic acid (thioquinolobactin). Pseudomonas fluorescens ATCC 17400 also displays a strong in vitro antagonism against the Oomycete Pythium, which is repressed by iron, suggesting the involvement of a siderophore(s). While a pyoverdine-negative mutant retains most of its antagonism, a thioquinolobactin-negative mutant only slowed-down Pythium growth, and a double pyoverdine-, thioquinolobactin-negative mutant, which does not produce any siderophore, totally lost its antagonism against Pythium. The siderophore thioquinolobactin could be purified and identified from spent medium and showed anti-Pythium activity, but it was quickly hydrolysed to quinolobactin, which we showed has no antimicrobial activity. Analysis of antagonism-affected transposon mutants revealed that genes involved in haem biosynthesis and sulfur assimilation are important for the production of thioquinolobactin and the expression of antagonism.

Amino-acid cycling drives nitrogen fixation in the legume - Rhizobium symbiosis

The biological reduction of atmospheric N-2 to ammonium (nitrogen fixation) provides about 65% of the biosphere's available nitrogen. Most of this ammonium is contributed by legume rhizobia symbioses(1), which are initiated by the infection of legume hosts by bacteria (rhizobia), resulting in formation of root nodules. Within the nodules, rhizobia are found as bacteroids, which perform the nitrogen fixation: to do this, they obtain sources of carbon and energy from the plant, in the form of dicarboxylic acids(2,3). It has been thought that, in return, bacteroids simply provide the plant with ammonium. But here we show that a more complex amino-acid cycle is essential for symbiotic nitrogen fixation by Rhizobium in pea nodules. The plant provides amino acids to the bacteroids, enabling them to shut down their ammonium assimilation. In return, bacteroids act like plant organelles to cycle amino acids back to the plant for asparagine synthesis. The mutual dependence of this exchange prevents the symbiosis being dominated by the plant, and provides a selective pressure for the evolution of mutualism.

Developing a quantitative approach for determining the in vitro prebiotic potential of dietary oligosaccharides

Prebiotics are nondigestible carbohydrates that beneficially affect the host by selectively stimulating the growth and/or activity of one, or a limited number of, bacteria present in the colon. The selected genera should have the capacity to improve host health (e.g. Bifidobacterium, Lactobacillus). To help identify preferred types, for inclusion into the diet, a quantitative equation [measure of the prebiotic effect (MPE)] is suggested. This will help evaluate, in vitro, the fermentation of dietary carbohydrates and compare their prebiotic effect. Although the approach is not meant to define health values, it is formulated to better inform the choice of prebiotic. It therefore, compares measurements of bacterial changes through the determination of maximum growth rates of predominant groups present in faeces, rate of substrate assimilation and the production of lactic, acetic, propionic and butyric acids. The equation will allow further in vitro comparisons of MPE, leading towards further studies (e.g. in humans) to determine the success of dietary intervention. (C) 2004 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved.

Expression of four beta-galactosidases from Bifidobacterium bifidum NCIMB41171 and their contribution on the hydrolysis and synthesis of galactooligosaccharides

This paper deals with two aspects tightly related to the enzymatic characteristics and expression of four beta-galactosidases (BbgI, BbgII, BbgIII and BbgIV) from Bifidobacterium bifidum NCIMB41171. The growth patterns of this strain indicated a preference towards complex (i.e. lactose, galactooligosaccharides (GOSs)) rather than simple carbohydrates (i.e. glucose and galactose) and a collaborative action and synergistic relation of more than one beta-galactosidase isoenzyme for either lactose or GOS hydrolysis and subsequent assimilation. Native polyacrylamide gel electrophoresis analysis of protein extracts from cells growing on different carbohydrates (i.e. glucose, lactose or GOS) indicated that two lactose hydrolysing enzymes (BbgI and BbgIII) and one GOS hydrolysing enzyme (BbgII) were constitutively expressed, whereas a fourth lactose hydrolysing enzyme (BbgIV) was induced in the presence of lactose or different GOS fractions. Furthermore, the beta-galactosidase expression profiles of B. bifidum cells and the transgalactosylating properties of each individual isoenzyme, with lactose as substrate, clearly indicated that mainly three isoenzymes (BbgI, BbgIII and BbgIV) are implicated in GOS synthesis when whole B. bifidum cells are utilised. Two of the isoenzymes (BbgI and BbgIV) proved to have better transgalactosylating properties giving yields ranging from 42% to 47% whereas the rest (BbgI and BbgIII) showed lower yields (15% and 29%, respectively).

Functional petit-suisse cheese: measure of the prebiotic effect

Prebiotics and probiotics are increasingly being used to produce potentially synbiotic foods, particularly through dairy products as vehicles. It is well known that both ingredients may offer benefits to improve the host health. This research aimed to evaluate the prebiotic potential of novel petit-suisse cheeses using an in vitro fermentation model. Five petit-suisse cheese formulations combining candidate prebiotics (inulin. oligofructose. hone) and probiotics (Lactobacillus acidophilus, Bifidobacterium lactis) were tested in vitro using, sterile. stirred, batch culture fermentations with human faecal slurry. Measurement of prebiotic effect (MPE) values were generated comparing bacterial changes through determination of maximum growth rates of groups, rate of substrate assimilation and production of lactate and short chain fatty acids. Fastest fermentation and high lactic acid production, promoting increased growth rates of bifidobacteria and lactobacilli. were achieved with addition of prebiotics to a probiotic cheese (made using starter + probiotics). Addition of probiotic strains to control cheese (made using just a starter culture) also resulted in high lactic acid production. Highest MPE values were obtained with addition of prebiotics to a probiotic cheese, followed by addition of prebiotics and/or probiotics to a control cheese. Under the in vitro conditions used, cheese made with the combination of different prebiotics and probiotics resulted in the most promising functional petit-suisse cheese. The study allowed comparison of potentially functional petit-suisse cheeses and screening of preferred synbiotic potential for future market use. (c) 2007 Elsevier Ltd. All rights reserved.

Incorporation of cis-9, trans-11 or trans-10, cis-12 conjugated linoleic acid into human erythrocytes in vivo

The purpose of this study was to determine the incorporation into erythrocytes of cis (c)-9,trans (t)-11 conjugated linoleic acid (CLA) and t10,c12 CLA consumed as supplements highly enriched in these isomers. Healthy men (31 8 years) consumed 1, 2, and 4 capsules containing approximately 80 g/100 g of either c9,t11 CLA or t10,c12 CLA for sequential 8-week periods. Fatty acid concentrations in erythrocyte total lipids were determined at baseline and after consumption of the highest dose. The increase in c9,t11 CLA concentration (0.31 g/100 g) was significantly greater than that in t10,c12 CLA (0.19 g/100 g). This was associated with minor changes in concentrations of some fatty acids of chain length greater than 20 carbons. These data suggest selective assimilation of individual CLA isomers into erythrocyte lipids and partial substitution for specific saturated and polyunsaturated fatty acids. (C) 2005 Elsevier Inc. All rights reserved.

Can drug-bearing liposomes penetrate intact skin?

Using liposomes to deliver drugs to and through human skin is controversial, as their function varies with type and composition. Thus they may act as drug carriers controlling release of the medicinal agent. Alternatively, they may provide a localized depot in the skin so minimizing systemic effects or can be used for targeting delivery to skin appendages (hair follicles and sweat glands). Liposomes may also enhance transdermal drug delivery, increasing systemic drug concentrations. With such a multiplicity of functions, it is not surprising that mechanisms of liposomal delivery of therapeutic agents to and through the skin are unclear. Accordingly, this article provides an overview of the modes and mechanisms of action of different vesicles as drug delivery vectors in human skin. Our conclusion is that vesicles, depending on the composition and method of preparation, can vary with respect to size, lamellarity, charge, membrane fluidity or elasticity and drug entrapment. This variability allows for multiple functions ranging from local to transdermal effects. Application to dissimilar skins (animal or human) via diverse protocols may reveal different mechanisms of action with possible vesicle skin penetration reaching different depths, from surface assimilation to (rarely) the viable tissue and subsequent systemic absorption.

A nutrient increment method for reducing bias in global biogeochemical models

Assimilation of physical variables into coupled physical/biogeochemical models poses considerable difficulties. One problem is that data assimilation can break relationships between physical and biological variables. As a consequence, biological tracers, especially nutrients, are incorrectly displaced in the vertical, resulting in unrealistic biogeochemical fields. To prevent this, we present the idea of applying an increment to the nutrient field within a data assimilating model to ensure that nutrient-potential density relationships are maintained within a water column during assimilation. After correcting the nutrients, it is assumed that other biological variables rapidly adjust to the corrected nutrient fields. We applied this method to a 17 year run of the 2° NEMO ocean-ice model coupled to the PlankTOM5 ecosystem model. Results were compared with a control with no assimilation, and with a model with physical assimilation but no nutrient increment. In the nutrient incrementing experiment, phosphate distributions were improved both at high latitudes and at the equator. At midlatitudes, assimilation generated unrealistic advective upwelling of nutrients within the boundary currents, which spread into the subtropical gyres resulting in more biased nutrient fields. This result was largely unaffected by the nutrient increment and is probably due to boundary currents being poorly resolved in a 2° model. Changes to nutrient distributions fed through into other biological parameters altering primary production, air-sea CO2 flux, and chlorophyll distributions. These secondary changes were most pronounced in the subtropical gyres and at the equator, which are more nutrient limited than high latitudes.

A note on the analysis error associated with 3D-FGAT

The analysis-error variance of a 3D-FGAT assimilation is examined analytically using a simple scalar equation. It is shown that the analysis-error variance may be greater than the error variances of the inputs. The results are illustrated numerically with a scalar example and a shallow-water model.

The transformation of earth-system observations into information of socio-economic value in GEOSS

The Group on Earth Observations System of Systems, GEOSS, is a co-ordinated initiative by many nations to address the needs for earth-system information expressed by the 2002 World Summit on Sustainable Development. We discuss the role of earth-system modelling and data assimilation in transforming earth-system observations into the predictive and status-assessment products required by GEOSS, across many areas of socio-economic interest. First we review recent gains in the predictive skill of operational global earth-system models, on time-scales of days to several seasons. We then discuss recent work to develop from the global predictions a diverse set of end-user applications which can meet GEOSS requirements for information of socio-economic benefit; examples include forecasts of coastal storm surges, floods in large river basins, seasonal crop yield forecasts and seasonal lead-time alerts for malaria epidemics. We note ongoing efforts to extend operational earth-system modelling and assimilation capabilities to atmospheric composition, in support of improved services for air-quality forecasts and for treaty assessment. We next sketch likely GEOSS observational requirements in the coming decades. In concluding, we reflect on the cost of earth observations relative to the modest cost of transforming the observations into information of socio-economic value.

Forecast impact of targeted observations: sensitivity to observation error and proximity to steep orography

For a targeted observations case, the dependence of the size of the forecast impact on the targeted dropsonde observation error in the data assimilation is assessed. The targeted observations were made in the lee of Greenland; the dependence of the impact on the proximity of the observations to the Greenland coast is also investigated. Experiments were conducted using the Met Office Unified Model (MetUM), over a limited-area domain at 24-km grid spacing, with a four-dimensional variational data assimilation (4D-Var) scheme. Reducing the operational dropsonde observation errors by one-half increases the maximum forecast improvement from 5% to 7%–10%, measured in terms of total energy. However, the largest impact is seen by replacing two dropsondes on the Greenland coast with two farther from the steep orography; this increases the maximum forecast improvement from 5% to 18% for an 18-h forecast (using operational observation errors). Forecast degradation caused by two dropsonde observations on the Greenland coast is shown to arise from spreading of data by the background errors up the steep slope of Greenland. Removing boundary layer data from these dropsondes reduces the forecast degradation, but it is only a partial solution to this problem. Although only from one case study, these results suggest that observations positioned within a correlation length scale of steep orography may degrade the forecast through the anomalous upslope spreading of analysis increments along terrain-following model levels.

Physics-based modelling for remote sensing of snow

Remote sensing is the only practicable means to observe snow at large scales. Measurements from passive microwave instruments have been used to derive snow climatology since the late 1970’s, but the algorithms used were limited by the computational power of the era. Simplifications such as the assumption of constant snow properties enabled snow mass to be retrieved from the microwave measurements, but large errors arise from those assumptions, which are still used today. A better approach is to perform retrievals within a data assimilation framework, where a physically-based model of the snow properties can be used to produce the best estimate of the snow cover, in conjunction with multi-sensor observations such as the grain size, surface temperature, and microwave radiation. We have developed an existing snow model, SNOBAL, to incorporate mass and energy transfer of the soil, and to simulate the growth of the snow grains. An evaluation of this model is presented and techniques for the development of new retrieval systems are discussed.

Ensemble prediction for nowcasting with a convection-permitting model - II: forecast error statistics

A 24-member ensemble of 1-h high-resolution forecasts over the Southern United Kingdom is used to study short-range forecast error statistics. The initial conditions are found from perturbations from an ensemble transform Kalman filter. Forecasts from this system are assumed to lie within the bounds of forecast error of an operational forecast system. Although noisy, this system is capable of producing physically reasonable statistics which are analysed and compared to statistics implied from a variational assimilation system. The variances for temperature errors for instance show structures that reflect convective activity. Some variables, notably potential temperature and specific humidity perturbations, have autocorrelation functions that deviate from 3-D isotropy at the convective-scale (horizontal scales less than 10 km). Other variables, notably the velocity potential for horizontal divergence perturbations, maintain 3-D isotropy at all scales. Geostrophic and hydrostatic balances are studied by examining correlations between terms in the divergence and vertical momentum equations respectively. Both balances are found to decay as the horizontal scale decreases. It is estimated that geostrophic balance becomes less important at scales smaller than 75 km, and hydrostatic balance becomes less important at scales smaller than 35 km, although more work is required to validate these findings. The implications of these results for high-resolution data assimilation are discussed.

An ECOOP web portal for visualising and comparing distributed coastal oceanography model and in situ data

As part of a large European coastal operational oceanography project (ECOOP), we have developed a web portal for the display and comparison of model and in situ marine data. The distributed model and in situ datasets are accessed via an Open Geospatial Consortium Web Map Service (WMS) and Web Feature Service (WFS) respectively. These services were developed independently and readily integrated for the purposes of the ECOOP project, illustrating the ease of interoperability resulting from adherence to international standards. The key feature of the portal is the ability to display co-plotted timeseries of the in situ and model data and the quantification of misfits between the two. By using standards-based web technology we allow the user to quickly and easily explore over twenty model data feeds and compare these with dozens of in situ data feeds without being concerned with the low level details of differing file formats or the physical location of the data. Scientific and operational benefits to this work include model validation, quality control of observations, data assimilation and decision support in near real time. In these areas it is essential to be able to bring different data streams together from often disparate locations.