A two-galectin network establishes mesenchymal condensation phenotype in limb development.

Previous work showed that Gal-1A and Gal-8, two proteins belonging to the galactoside-binding galectin family, are the earliest determinants of the patterning of the skeletal elements of embryonic chicken limbs, and further, that their experimentally determined interactions in the embryonic limb bud can be interpreted via a reaction-diffusion-adhesion (2GL: two galectin plus ligands) model. Here, we use an ordinary differential equation-based approach to analyze the intrinsic switching modality of the 2GL network and characterize the network behavior independent of the diffusive and adhesive arms of the patterning mechanism. We identify two states: where the concentrations of both the galectins are respectively, negligible, and very high. This bistable switch-like system arises via a saddle-node bifurcation from a monostable state. For the case of mass-action production terms, we provide an explicit Lyapunov function for the system, which shows that it has no periodic solutions. Our model therefore predicts that the galectin network may exist in low expression and high expression states separated in space or time, without any intermediate states. We test these predictions in experiments performed with high density cultures of chick limb mesenchymal cells and observe that cells inside precartilage protocondensations express Gal-1A at a much higher rate than those outside, for which it was negligible. The Gal-1A and -8-based patterning network is therefore sufficient to partition the mesenchymal cell population into two discrete cell states with different developmental (chondrogenic vs. non-chondrogenic) fates. When incorporated into an adhesion and diffusion-enabled framework this system can generate a spatially patterned limb skeleton.

Potential of in-plant intramuscular fat predictions to enable sheep breeders to incorporate consumer preferences in breeding programmes.

The inclusion of eating quality traits in sheep genetic improvement programmes is desirable. Intramuscular fat (IMF) plays a key role in ensuring consumer satisfaction when eating lamb, but genetic progress for IMF is constrained by a lack of routine data collection. This study investigated the potential for IMF predictor traits to substitute for measured IMF in genetic improvement programmes. Carcass and predicted IMF (near-infrared estimated IMF and marbling score) data were available on 10,113 New Zealand lambs, 1678 of which also had measured chemical IMF on a slice of M. longissimus lumborum on which the predictions of IMF had been made. Genetic antagonisms were observed between carcass lean traits and IMF. The genetic correlation between the predictors and measured IMF approached one, indicating that predictors of IMF can be used in genetic improvement programmes. Through using selection indexes, simultaneous increases in IMF and the existing terminal selection index are possible, provided all traits are measured. This study highlights the importance and potential of predicted IMF to achieve genetic improvement in traits of importance to consumers.

A Field Guide to Finding Fossils on Mars.

The Martian surface is cold, dry, exposed to biologically harmful radiation and apparently barren today. Nevertheless, there is clear geological evidence for warmer, wetter intervals in the past that could have supported life at or near the surface. This evidence has motivated National Aeronautics and Space Administration and European Space Agency to prioritize the search for any remains or traces of organisms from early Mars in forthcoming missions. Informed by (1) stratigraphic, mineralogical and geochemical data collected by previous and current missions, (2) Earth's fossil record, and (3) experimental studies of organic decay and preservation, we here consider whether, how, and where fossils and isotopic biosignatures could have been preserved in the depositional environments and mineralizing media thought to have been present in habitable settings on early Mars. We conclude that Noachian-Hesperian Fe-bearing clay-rich fluvio-lacustrine siliciclastic deposits, especially where enriched in silica, currently represent the most promising and best understood astropaleontological targets. Siliceous sinters would also be an excellent target, but their presence on Mars awaits confirmation. More work is needed to improve our understanding of fossil preservation in the context of other environments specific to Mars, particularly within evaporative salts and pore/fracture-filling subsurface minerals.

Experimental fossilization of mat-forming cyanobacteria in coarse-grained siliciclastic sediments.

Microbial fossils and textures are commonly preserved in Ediacaran and early Cambrian coarse-grained siliciclastic sediments that were deposited in tidal and intertidal marine settings. In contrast, the fossilization of micro-organisms in similar marine environments of post-Cambrian age is less frequently reported. Thus, temporal discrepancies in microbial preservation may have resulted from the opening and closing of a unique taphonomic window during the terminal Proterozoic and early Phanerozoic, respectively. Here, we expand upon previous work to identify environmental factors which may have facilitated the preservation of cyanobacteria growing on siliciclastic sand, by experimentally determining the ability of microbial mats to trap small, suspended mineral grains, and precipitate minerals from ions in solution. We show that (i) fine grains coat the sheaths of filamentous cyanobacteria (e.g., Nodosilinea sp.) residing within the mat, after less than 1 week of cell growth under aerobic conditions, (ii) clay minerals do not coat sterile cellulose fibers and rarely coat unsheathed cyanobacterial cells (e.g., Nostoc sp.), (iii) stronger disturbances (where culture jars were agitated at 170 rpm; 3 mm orbital diameter) produce the smoothest and most extensive mineral veneers around cells, compared with those agitated at slower rotational speeds (150 and 0 rpm), and (iv) mineral veneers coating cyanobacterial cells are ~1 µm in width. These new findings suggest that sheathed filamentous cyanobacteria may be preferentially preserved under conditions of high fluid energy. We integrate these results into a mechanistic model that explains the preservation of microbial fossils and textures in Ediacaran sandstones and siltstones, and in fine-grained siliciclastic deposits that contain exceptionally preserved microbial mats.

Molecular biosignatures reveal common benthic microbial sources of organic matter in ooids and grapestones from Pigeon Cay, The Bahamas.

Ooids are sedimentary grains that are distributed widely in the geologic record. Their formation is still actively debated, which limits our understanding of the significance and meaning of these grains in Earth's history. Central questions include the role played by microbes in the formation of ooids and the sources of ubiquitous organic matter within ooid cortices. To address these issues, we investigated the microbial community composition and associated lipids in modern oolitic sands at Pigeon Cay on Cat Island, The Bahamas. Surface samples were taken along a transect from the shallow, turbulent surf zone to calmer, deeper water. Grains transitioned from shiny and abraded ooids in the surf zone, to biofilm-coated ooids at about 3 m water depth. Further offshore, grapestones (cemented aggregates of ooids) dominated. Benthic diatoms and Proteobacteria dominated biofilms. Taxa that may promote carbonate precipitation were abundant, particularly those associated with sulfur cycling. Compared to the lipids associated with surface biofilms, relict lipids bound within carbonate exhibited remarkably similar profiles in all grain types. The enhanced abundance of methyl-branched fatty acids and ß-hydroxy fatty acids, 1-O-monoalkyl glycerol ethers and hopanoids bound within ooid and grapestone carbonate confirms a clear association of benthic sedimentary bacteria with these grains. Lipids bound within ooid cortices also contain molecular indicators of microbial heterotrophic degradation of organic matter, possibly in locally reducing conditions. These included the loss of labile unsaturated fatty acids, enhanced long-chain fatty acids/short-chain fatty acids, enriched stable carbon isotopes ratios of fatty acids, and very high stanol/stenol ratios. To what extent some of these molecular signals are derived from later heterotrophic endolithic activity remains to be fully resolved. We speculate that some ooid carbonate forms in microbial biofilms and that early diagenetic degradation of biofilms may also play a role in early stage carbonate precipitation around ooids.

Genetic analysis and genomic selection of stayability and productive life in New Zealand ewes.

Genetic parameters for ewes were estimated for stayability (STAY) and productive life (Prodlife). Records from 658,871 animals from 241 seed stock or ram breeder flocks and one research flock were used to estimate parameters for ram breeder flock STAY and Prodlife. These flocks would have a culling policy based on criteria typical of a commercial enterprise, but including culls based on knowledge such as estimated breeding values. A subset of 35,688 of these animals from 4 ram breeder and one research flock was used to infer the animals that might be culled based on the perspective of a commercial flock as these flocks recorded reasons for culling. These data were used to estimate parameters for commercial flock STAY and Prodlife. Heritability for ram breeder flock STAY until age 3 to 6 yr ranged from 0.07 to 0.09. The heritability of commercial flock STAY was similar in yr 5 and 6, but lower at 0.05 (age 3) and 0.07 (age 4). Heritability of Prodlife for ram breeder flock and commercial flock was respectively 0.10 and 0.13. The genetic correlations between ram breeder flock STAY and commercial flock STAY ranged from 0.20 to 0.99. Both STAY and Prodlife were most correlated genetically with the trait number of lambs born, at about 0.4, and to a lesser degree, live weight up to the age of 12 mo for the traits analyzed with lower genetic correlations estimated for the commercial flocks. Live weight at 18 mo and fleece weight had little or no correlation with STAY and Prodlife. From the data set used to estimate genetic parameters from a ram breeder flock, 4,330 animals were genotyped with the Illumina OvineSNP50 BeadChip and the genotypes used to develop genomic predictions via genomic best linear unbiased prediction. The animals used in the training data set were multibreed, but were heavily Romney breed based. The genomic prediction accuracy for ram breeder flock STAY, according to breed, was dependent on sample size and ranged from 0.4 to 0.44 for Romney and 0.26 to 0.4 for Coopworth. Accuracies for Perendale and Composites, for which sample sizes were less, were more variable. This study has derived genetic parameters for STAY and Prodlife and investigated genomic predictions for these traits. As these traits are of low heritability, sex limited and expressed late in life genomic selection will be useful.

Derivation of a new lamb survival trait for the New Zealand sheep industry.

Previous research identified that a review of the current industry New Zealand lamb survival trait was necessary as its recording accuracy was reliant on farmers notifying their Sheep Improvement Limited bureau of lamb deaths. This paper reports the decision rules and genetic parameters for a new lamb survival trait for the New Zealand sheep industry. These rules define the new lamb survival trait (NEWSUR) using lamb birth fate (BFATE) codes and the presence/absence of lamb weight measurements. Six univariate animal models were tested and used to estimate variance or covariance components and the resulting direct and maternal heritabilities for NEWSUR. The models differed in the way they adjust for the effect of day of birth, the exclusion or inclusion of a litter (dam/year of birth) random effect, and the application or not of a logit transformation of the phenotypes. For both the linear and logistic methods, models including the random effect of litter provided the best fit for NEWSUR according to log-likelihood values. Log-likelihoods for the linear and logistic models cannot be compared; therefore, a cross-validation method was used to assess whether the logit transformation was appropriate by analyzing the predictive ability of the models. The mean square errors were slightly lower for the linear compared with the logistic model, and therefore, the linear model was recommended for industry use. The heritability attributed to direct effects ranged from 2 to 5.5%. A direct heritability of 5.5% resulted from a linear model without litter effect and omitting the effect of day of birth on survival, whereas a direct heritability of 2% resulted from the logistic model fitting a random litter effect. The heritability attributed to maternal genetic effects ranged from 1.9 to 7.7%. A maternal genetic heritability of 7.7% resulted from the logistic model omitting the litter effect, whereas a maternal genetic heritability of 1.9% resulted from the linear model fitting a random litter effect. The addition of the litter random effect substantially decreased the maternal heritabilities in all cases and was recommended for industry use to avoid overestimation of the maternal genetic variance. Sheep Improvement Limited has implemented NEWSUR and the associated genetic evaluation model based on information described in this paper. Industry-wide implementation will enable sheep breeders to produce more accurate genetic evaluations to their commercial clients.

Review of evidence for dietary influences on atopic dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease affecting children and adolescents worldwide. The relationship of AD to diet has been a matter of curiosity for many years. Here we look at the evidence in the literature of the association between AD and diet, and the effectiveness of elimination diets and diet supplementation in the management of AD. Several studies have found an association between clinical food allergy and AD, and more recent investigations have also suggested that dietary elements may promote late AD exacerbations. Diet elimination trials in select patients who are clinically allergic to eggs have shown promise in reducing symptoms. Additionally, elimination of food additives in a subgroup of patients was found to be beneficial. Finally, diet supplementations with evening primrose oil and an omega-3 fatty acid (docosahexaenoic acid) may be appropriate in certain AD candidates.

Genomic prediction of breeding values in the New Zealand sheep industry using a 50K SNP chip.

The aim of genomic prediction is to predict breeding value from genomic data. We describe the development of genomic prediction equations and accuracies for molecular breeding values (MBV) for industry use, focusing on the methodology used to deal with predictions for the New Zealand sheep population structure. This is made up of a mixture of pure and crossbred animals, but principally Romney based. In particular, we used pedigree-based EBV for 8 traits (weaning weight as a direct effect, weaning weight as a maternal effect, live weight at 8 mo, live weight at 12 mo, greasy fleece weight at 12 mo, lamb fleece weight, adult fleece weight, and number of lambs born) and Illumina OvineSNP50 BeadChip genotypes from 13,420 animals to investigate BLUP with different genomic relationship matrices (GRM) based on SNP markers and to investigate varying sets of older animals (training sets) to predict the MBV of younger animals (validation sets). The GRM tested included modifications to account for allele frequency differences between breeds, rescaling so that the mean GRM is equal to the mean of the traditional pedigree numerator relationship matrix A: , and combining of the GRM with A: using a convex combination with a weight estimated by maximizing a conditional restricted likelihood. We found that these modifications were beneficial and recommend using a breed-adjusted GRM combined with A: . Training data sets with Romney, Coopworth, and Perendale animals all together usually predicted better than using just a pure breed training data set for all traits. But predictions for the breed Perendale were more accurate with a Perendale training set for 3 of the 8 traits. We concluded that using a mixed-breed training set for all combinations of traits and breeds was best but advise that increasing the number of Perendale animals genotyped should be a priority to increase the MBV accuracies obtained for that breed.

Modeling the morphodynamic galectin patterning network of the developing avian limb skeleton.

We present a mathematical model for the morphogenesis and patterning of the mesenchymal condensations that serve as primordia of the avian limb skeleton. The model is based on the experimentally established dynamics of a multiscale regulatory network consisting of two glycan-binding proteins expressed early in limb development: CG (chicken galectin)-1A, CG-8 and their counterreceptors that determine the formation, size, number and spacing of the "protocondensations" that give rise to the condensations and subsequently the cartilaginous elements that serve as the templates of the bones. The model, a system of partial differential and integro-differential equations containing a flux term to represent local adhesion gradients, is simulated in a "full" and a "reduced" form to confirm that the system has pattern-forming capabilities and to explore the nature of the patterning instability. The full model recapitulates qualitatively and quantitatively the experimental results of network perturbation and leads to new predictions, which are verified by further experimentation. The reduced model is used to demonstrate that the patterning process is inherently morphodynamic, with cell motility being intrinsic to it. Furthermore, subtle relationships between cell movement and the positive and negative interactions between the morphogens produce regular patterns without the requirement for activators and inhibitors with widely separated diffusion coefficients. The described mechanism thus represents an extension of the category of activator-inhibitor processes capable of generating biological patterns with repetitive elements beyond the morphostatic mechanisms of the Turing/Gierer-Meinhardt type.

On multiscale approaches to three-dimensional modelling of morphogenesis.

In this paper we present the foundation of a unified, object-oriented, three-dimensional biomodelling environment, which allows us to integrate multiple submodels at scales from subcellular to those of tissues and organs. Our current implementation combines a modified discrete model from statistical mechanics, the Cellular Potts Model, with a continuum reaction-diffusion model and a state automaton with well-defined conditions for cell differentiation transitions to model genetic regulation. This environment allows us to rapidly and compactly create computational models of a class of complex-developmental phenomena. To illustrate model development, we simulate a simplified version of the formation of the skeletal pattern in a growing embryonic vertebrate limb.

CompuCell, a multi-model framework for simulation of morphogenesis.

MOTIVATION: CompuCell is a multi-model software framework for simulation of the development of multicellular organisms known as morphogenesis. It models the interaction of the gene regulatory network with generic cellular mechanisms, such as cell adhesion, division, haptotaxis and chemotaxis. A combination of a state automaton with stochastic local rules and a set of differential equations, including subcellular ordinary differential equations and extracellular reaction-diffusion partial differential equations, model gene regulation. This automaton in turn controls the differentiation of the cells, and cell-cell and cell-extracellular matrix interactions that give rise to cell rearrangements and pattern formation, e.g. mesenchymal condensation. The cellular Potts model, a stochastic model that accurately reproduces cell movement and rearrangement, models cell dynamics. All these models couple in a controllable way, resulting in a powerful and flexible computational environment for morphogenesis, which allows for simultaneous incorporation of growth and spatial patterning. RESULTS: We use CompuCell to simulate the formation of the skeletal architecture in the avian limb bud. AVAILABILITY: Binaries and source code for Microsoft Windows, Linux and Solaris are available for download from http://sourceforge.net/projects/compucell/

Quadriceps voluntary activation at different joint angles measured by two stimulation techniques.

People are able to fully activate their quadriceps at mid-length during a brief isometric contraction but it is uncertain whether this is the case at other muscle lengths. With the twitch superimposition technique for determining levels of voluntary activation (VA), the muscle may be stimulated through the intramuscular branches of the nerve or via the nerve trunk itself. The former technique is easier to use, but different populations of motor units may be stimulated if the joint position is changed to alter muscle length. The purpose of this study was to investigate quadriceps VA at a range of knee joint angles using both magnetic stimulation of the motor nerve and percutaneous electrical stimulation over the muscle belly. Eight healthy subjects (six females, mean age 29 years) performed maximal voluntary contractions of the quadriceps at knee joint angles at 10-110 degrees of flexion. Surface electromyography (EMG) of quadriceps and hamstrings was recorded as an indication of the amount of muscle activity. Nearly all subjects showed >95% VA at all joint angles. VA did not vary with joint angle nor were there significant differences between the two stimulation techniques. Similarly, there was no significant effect of knee joint angle on the EMG activity of either muscle group. These findings indicate that VA of the quadriceps during a brief isometric contraction is not affected by muscle length and can be measured by either stimulation technique.

Rates of change in measures of body size vary by ethnicity and gender.

Obesity, a major risk factor for a variety of diseases, is more common in Blacks than in Whites. In the current study, a cohort of young Blacks and Whites was followed longitudinally to determine rates of change in body mass index (BMI) and subscapular and triceps skinfold thickness from the ages of 5 to 25 years. A significant difference in the rate of change of BMI (P<.0001) between Blacks and Whites was observed with Blacks gaining at a faster rate. The rate of increase of subscapular (P<.0001) and triceps fat (P<.0001) was significantly higher in the girls than in the boys. We also examined for differences by household income and maternal education level. Children from poorer families had more fat (P<.01 for all three outcomes), whereas education level was not related to the amount of body fat. Differences in the prevalence of obesity between Blacks and Whites and between males and females that manifest during adulthood appear to begin in childhood. The results re-emphasize the important need for early intervention in weight control measures.

Abdominal muscle activity during the abdominal hollowing manoeuvre in the four point kneeling and prone positions.

This study investigated the pattern of recruitment of the abdominal muscles during the abdominal hollowing manoeuvre (AHM), in four point kneeling and prone. Muscle activity was detected and recorded by surface electromyography (EMG), in 20 healthy subjects, 8 male and 12 female, aged between 19 and 30 during both maximal activity, and the AHM. The degree of activation during hollowing was expressed as a percentage of maximal. There was activity in the internal abdominal oblique (IO) during all hollowing manoeuvres, in both starting positions, whilst only two subjects showed any activity in rectus abdominis (RA). Simultaneous activity in IO and EO occurred both in four point kneeling (45% of the subjects) and especially in prone (75% of the subjects). Across both positions IO activity was significantly greater than EO. There was no significant difference in EO or IO activity comparing across positions. These results suggest that the AHM when performed in four point kneeling and prone always activates IO and rarely activates RA, whilst elimination of activity in EO is more difficult to achieve, particularly in prone. Isolated activity in the deep abdominal muscles may not always be achievable in these starting positions.

Phenotypic and dynamical transitions in model genetic networks. II. Application to the evolution of segmentation mechanisms.

Knowledge of the genetic control of segmentation in Drosophila has made insect segmentation a paradigmatic case in the study of the evolution of developmental mechanisms. In Drosophila, the patterns of expression of segmentation genes are established simultaneously in all segments by a complex set of interactions between transcriptional factors that diffuse in a syncytium occupying the whole embryo. Such mechanisms cannot act in short germ-band insects where segments appear sequentially from a cellularized posterior proliferative zone. Here, we compare mechanisms of segmentation in different organisms and discuss how the transition between the different types of segmentation can be explained by small and progressive changes in the underlying gene networks. The recent discovery of a temporal oscillation in expression during somitogenesis of vertebrate homologs of the pair-rule gene hairy enhances the plausibility of an earlier proposal that the evolutionary origin of both the short- and long germ-band modes of segmentation was an oscillatory genetic network (Newman 1993). An implication of this scenario is that the self-organizing, pattern-forming system embodied in an oscillatory network operating in the context of a syncytium (i.e., a reaction-diffusion system)-which is hypothesized to have originated the simultaneous mode of segmentation-must have been replaced by the genetic hierarchy seen in modern-day Drosophila over the course of evolution. As demonstrated by the simulations in the accompanying article, the tendency for "emergent" genetic networks, associated with self-organizing processes, to be replaced through natural selection with hierarchical networks is discussed in relation to the evolution of segmentation.

Phenotypic and dynamical transitions in model genetic networks. I. Emergence of patterns and genotype-phenotype relationships.

Genotype-phenotype interactions during the evolution of form in multicellular organisms is a complex problem but one that can be aided by computational approaches. We present here a framework within which developmental patterns and their underlying genetic networks can be simulated. Gene networks were chosen to reflect realistic regulatory circuits, including positive and negative feedback control, and the exchange of a subset of gene products between cells, or within a syncytium. Some of these networks generate stable spatial patterns of a subset of their molecular constituents, and can be assigned to categories (e.g., "emergent" or "hierarchic") based on the topology of molecular circuitry. These categories roughly correspond to what has been discussed in the literature as "self-organizing" and "programmed" processes of development. The capability of such networks to form patterns of repeating stripes was studied in network ensembles in which parameters of gene-gene interaction were caused to vary in a manner analogous to genetic mutation. The evolution under mutational change of individual representative networks of each category was also simulated. We have found that patterns with few stripes (< or =3) are most likely to originate in the form of a hierarchic network, whereas those with greater numbers of stripes (> or =4) originate most readily as emergent networks. However, regardless of how many stripes it contains, once a pattern is established, there appears to be an evolutionary tendency for emergent mechanisms to be replaced by hierarchic mechanisms. These results have potential significance for the understanding of genotype-phenotype relationships in the evolution of metazoan form.