Unique near isometric ontogeny in the pterosaur Rhamphorhynchus suggests hatchlings could fly

Rhamphorhynchus muensteri is one of the best‐known flying reptiles, represented by >130 well‐preserved fossil specimens, from hatchlings to full adults. The life history of this pterosaur remains controversial as to when in ontogeny they took flight. Here, we assess the growth of these animals based on the lengths of numerous key elements. We show that changes in the skeletal anatomy of this reptile across its post‐hatch size range reveal that R.muensteri exhibited overall near isometric growth in the wings, with slightly negative allometry in the humerus, radius and stronger negative allometry in the fourth metacarpal compared to body length, and slightly positive allometry in the second and third phalanges compared to body length. This pattern is near unique among flying vertebrates and suggests R.muensteri flew soon after hatching. In bats and birds, offspring do not typically fly until nearly adult sized. Conversely, near isometric growth in Rhamphorhynchus suggests it was a precocial flier and that individuals may have inhabited several sequential foraging niches over their lifespan, as some terrestrial and aquatic vertebrates do today.     

Optimal parameter settings for information processing in gene regulatory networks

Gene networks can often be interpreted as computational circuits. This article investigates the computational properties of gene regulatory networks defined in terms of the speed and the accuracy of the output of a gene network. It will be shown that there is no single optimal set of parameters, but instead, there is a trade-off between speed and accuracy. Using the trade-off it will also be shown how systems with various parameters can be ranked with respect to their computational efficiency. Numerical analysis suggests that the trade-off can be improved when the output gene is repressing itself, even though the accuracy or the speed of the auto-regulated system may be worse than the unregulated system.     

Marine metagenomics: strategies for the discovery of novel enzymes with biotechnological applications from marine environments

Metagenomic based strategies have previously been successfully employed as powerful tools to isolate and identify enzymes with novel biocatalytic activities from the unculturable component of microbial communities from various terrestrial environmental niches. Both sequence based and function based screening approaches have been employed to identify genes encoding novel biocatalytic activities and metabolic pathways from metagenomic libraries. While much of the focus to date has centred on terrestrial based microbial ecosystems, it is clear that the marine environment has enormous microbial biodiversity that remains largely unstudied. Marine microbes are both extremely abundant and diverse; the environments they occupy likewise consist of very diverse niches. As culture-dependent methods have thus far resulted in the isolation of only a tiny percentage of the marine microbiota the application of metagenomic strategies holds great potential to study and exploit the enormous microbial biodiversity which is present within these marine environments.     

Strain persistence of invasive Candida albicans in chronic hyperplastic candidosis that underwent malignant change

Objectives: The aim of this study was to assess persistence and tissue invasion of Candida albicans strains isolated from a 65 year‐old patient with chronic hyperplastic candidosis (CHC), that subsequently developed into squamous cell carcinoma (SCC). Materials and Methods: C. albicans (n=7) were recovered from the oral cavity of the patient over seven years. Confirmation of CHC and SCC in this patient was achieved by histopathological examination of incisional biopsy tissue. DNA fingerprinting was performed on the seven isolates from the CHC patient together with a further eight isolates from patients with normal oral mucosa (n=2), chronic atrophic candidosis (n=1), SCC (n=1) and CHC (n=4). Genotyping involved the use of inter‐repeat PCR using the eukaryotic repeat primer 1251. Characterisation of the tissue invasive abilities of the isolates was achieved by infecting a commercially available reconstituted human oral epithelium (RHE; SkinEthic, Nice, France). After 24 h. C. albicans tissue invasion was assessed by histopathological examination. Results: DNA fingerprinting demonstrated strain persistence of C. albicans in the CHC patient over a seven year period despite provision of systemic antifungal therapy. The strain of C. albicans isolated from this patient was categorised as a high invader within the RHE compared to other isolates. Conclusions: Candidal strain persistence was evident in a patient with CHC over seven years. This persistence may be due to incomplete eradication from the oral cavity following antifungal therapy or subsequent recolonisation from other body sites or separate exogenous sources. The demonstration of enhanced in vitro tissue invasion by this particular strain may, in part, explain the progression to carcinoma.     

An InCytes from MBC Selection: Plasma Membrane Area Increases with Spread Area by Exocytosis of a GPI-anchored Protein Compartment

The role of plasma membrane (PM) area as a critical factor during cell motility is poorly understood, mainly due to an inability to precisely follow PM area dynamics. To address this fundamental question, we developed static and dynamic assays to follow exocytosis, endocytosis, and PM area changes during fibroblast spreading. Because the PM area cannot increase by stretch, spreading proceeds by the flattening of membrane folds and/or by the addition of new membrane. Using laser tweezers, we found that PM tension progressively decreases during spreading, suggesting the addition of new membrane. Next, we found that exocytosis increases the PM area by 40–60% during spreading. Reducing PM area reduced spread area, and, in a reciprocal manner, reducing spreadable area reduced PM area, indicating the interconnection between these two parameters. We observed that Golgi, lysosomes, and glycosylphosphatidylinositol-anchored protein vesicles are exocytosed during spreading, but endoplasmic reticulum and transferrin receptor-containing vesicles are not. Microtubule depolymerization blocks lysosome and Golgi exocytosis but not the exocytosis of glycosylphosphatidylinositol-anchored protein vesicles or PM area increase. Therefore, we suggest that fibroblasts are able to regulate about half of their original PM area by the addition of membrane via a glycosylphosphatidylinositol-anchored protein compartment.     

Relative roles of LDLr and LRP in the metabolism of chylomicron remnants in genetically manipulated mice

Remnant-like emulsions labeled with cholesteryl [(13)C]-oleate were prepared with lipid compositions similar to remnants derived from triacylglycerol-rich lipoproteins. When injected into the bloodstream of conscious mice, the remnant-like emulsions were metabolized in the liver leading to the appearance of (13)CO(2) in the breath. Previously, using this technique, we found that remnant metabolism was significantly impaired but not completely inhibited in mice lacking low density lipoprotein receptors (LDLr). We have now found in mice with non-functional low density lipoprotein receptor-related protein (LRP) that breath enrichment of (13)CO(2) was significantly decreased, indicating that the LRP also plays an important role in the metabolism of chylomicron remnants (CR). The enrichment of (13)CO(2) in the expired breath was negligible in mice lacking both LDLr and receptor-associated protein (-/-), essential for normal function of LRP. In mice pre-injected with gluthatione S-transferase-receptor-associated protein to block LRP binding, there was a marked inhibition of the appearance of (13)CO(2) in the expired breath of homozygous LDLr-deficient mice, supporting the role of LRP in vivo. Whether or not LDLr were present, in mouse and human fibroblast cells human apoE3 or E4 but not apoE2 were essential for binding of remnant-like emulsions, while lactoferrin and suramin completely inhibited binding. We conclude that in normal mice LDLr are important for the physiological metabolism of CR. When LDLr are absent the evidence supports a role for the LRP in the uptake of CR in liver cells and in fibroblasts, with binding characteristics for CR-associated apoE similar to LDLr.     

Force generated by actomyosin contraction builds bridges between adhesive contacts

Extracellular matrices in vivo are heterogeneous structures containing gaps that cells bridge with an actomyosin network. To understand the basis of bridging, we plated cells on surfaces patterned with fibronectin (FN)‐coated stripes separated by non‐adhesive regions. Bridges developed large tensions where concave cell edges were anchored to FN by adhesion sites. Actomyosin complexes assembled near those sites (both actin and myosin filaments) and moved towards the centre of the non‐adhesive regions in a treadmilling network. Inhibition of myosin‐II (MII) or Rho‐kinase collapsed bridges, whereas extension continued over adhesive areas. Inhibition of actin polymerization (latrunculin‐A, jasplakinolide) also collapsed the actomyosin network. We suggest that MII has distinct functions at different bridge regions: (1) at the concave edges of bridges, MIIA force stimulates actin filament assembly at adhesions and (2) in the body of bridges, myosin cross‐links actin filaments and stimulates actomyosin network healing when breaks occur. Both activities ensure turnover of actin networks needed to maintain stable bridges from one adhesive region to another.     

Body Size Distribution of the Dinosaurs

The distribution of species body size is critically important for determining resource use within a group or clade. It is widely known that non-avian dinosaurs were the largest creatures to roam the Earth. There is, however, little understanding of how maximum species body size was distributed among the dinosaurs. Do they share a similar distribution to modern day vertebrate groups in spite of their large size, or did they exhibit fundamentally different distributions due to unique evolutionary pressures and adaptations? Here, we address this question by comparing the distribution of maximum species body size for dinosaurs to an extensive set of extant and extinct vertebrate groups. We also examine the body size distribution of dinosaurs by various sub-groups, time periods and formations. We find that dinosaurs exhibit a strong skew towards larger species, in direct contrast to modern day vertebrates. This pattern is not solely an artefact of bias in the fossil record, as demonstrated by contrasting distributions in two major extinct groups and supports the hypothesis that dinosaurs exhibited a fundamentally different life history strategy to other terrestrial vertebrates. A disparity in the size distribution of the herbivorous Ornithischia and Sauropodomorpha and the largely carnivorous Theropoda suggests that this pattern may have been a product of a divergence in evolutionary strategies: herbivorous dinosaurs rapidly evolved large size to escape predation by carnivores and maximise digestive efficiency; carnivores had sufficient resources among juvenile dinosaurs and non-dinosaurian prey to achieve optimal success at smaller body size.