Physiological ecology of the ciliated protozoon Loxodes

Loxodes faces special problems in living close to the oxic-anoxic boundary. In tightly-stratified ponds like Priest Pot its optimum environment may be quite narrow and it can be displaced by the slightest turbulence. Loxodes cannot sense an O sub(2) gradient directly but its ability to perceive gravity allows it to make relatively long vertical migrations. It is also sensitive to light and oxygen and it uses these environmental cues to modulate the parameters of its random motility: in the dark, it aggregates at a low O sub(2) tension and in bright light it aggregates in anoxic water. The oxic-anoxic boundary is also a zone where O sub(2) may be a scarce and transient resource, but Loxodes) can switch to nitrate respiration and exploit the pool of nitrate that often exists close to the base of the oxycline

Targeting SHP-1,2 and SHIP pathways – a novel strategy for cancer treatment?

Well balanced levels of tyrosine phosphorylation, maintained by the reversible and coordinated actions of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs), are critical for a wide range of cellular processes including growth, differentiation, metabolism, migration, and survival. Aberrant tyrosine phosphorylation, as a result of a perturbed balance between the activities of PTKs and PTPs, however, is linked to the pathogenesis of numerous human diseases, including cancer, suggesting that PTPs may be innovative molecular targets for cancer treatment. Two PTPs that have an important inhibitory role in lymphocytes and other haematopoietic cells are SHP-1 and SHP-2 (SH2 domain-containing phosphatases 1 and 2), SHP-1,2 have been shown to promote cell growth and act by both upregulating positive signaling pathways and by downregulating negative signaling pathways. SHIP (SH2 domain-containing inositol phosphatase) is another inhibitory phosphatase that is rather specific for the inositol phospholipid phosphatidylinositol-3,4,5-trisphosphate (PIP3). SHIP acts as a negative regulator of immune response by hydrolysing PIP3, and, as a result, a SHIP defiency results in myeloproliferation and B cell lymphoma in mice. This strong validation of SHP-1,2 and SHIP as oncology targets has generated considerable interest in the development of small molecule inhibitors as potential therapeutic agents for haematologic malignancies and solid tumours, however, SHP-1,2 and SHIP have proven to be an extremely difficult target for drug discovery, due primarily to the highly conserved and positively charged nature of its PTP active site. The majority of reported PTP inhibitors lack either appropriate selectivity or membrane permeability, limiting their utility in modulating the activity of the intracellular PTPs. In order to overcome these caveats novel techniques have been employed to synthesise new inhibitors that specifically attentuate the PTP-dependent signaling inside the cell and amongst them some are already in clinical development (e.g., SHP-1 inhibitor sodium stibogluconate; SHP-2 inhibitor TNO155; SHIP-1 activator AQX-1125). In this review the mechanisms of action and the clinical development of newly available SHP-1,2 and SHIP inhibitors and activators are decribed and the major issues facing this rapidly evolving field are discussed

Caco<inf>3</inf> precipitation in multilayered cyanobacterial mats: Clues to explain the alternation of micrite and sparite layers in calcareous stromatolites

© 2015 by the authors; licensee MDPI, Basel, Switzerland. Marine cyanobacterial mats were cultured on coastal sediments (Nivå Bay, Øresund, Denmark) for over three years in a closed system. Carbonate particles formed in two different modes in the mat: (i) through precipitation of submicrometer-sized grains of Mg calcite within the mucilage near the base of living cyanobacterial layers, and (ii) through precipitation of a variety of mixed Mg calcite/aragonite morphs in layers of degraded cyanobacteria dominated by purple sulfur bacteria. The 13C values were about 2‰ heavier in carbonates from the living cyanobacterial zones as compared to those generated in the purple bacterial zones. Saturation indices calculated with respect to calcite, aragonite, and dolomite inside the mats showed extremely high values across the mat profile. Such high values were caused by high pH and high carbonate alkalinity generated within the mats in conjunction with increased concentrations of calcium and magnesium that were presumably stored in sheaths and extracellular polymer substances (EPS) of the living cyanobacteria and liberated during their post-mortem degradation. The generated CaCO3 morphs were highly similar to morphs reported from heterotrophic bacterial cultures, and from bacterially decomposed cyanobacterial biomass emplaced in Ca-rich media. They are also similar to CaCO3 morphs precipitated from purely inorganic solutions. No metabolically (enzymatically) controlled formation of particular CaCO3 morphs by heterotrophic bacteria was observed in the studied mats. The apparent alternation of in vivo and post-mortem generated calcareous layers in the studied cyanobacterial mats may explain the alternation of fine-grained (micritic) and coarse-grained (sparitic) laminae observed in modern and fossil calcareous cyanobacterial microbialites as the result of a probably similar multilayered mat organization

An explanatory model for food-web structure and evolution

Food webs are networks describing who is eating whom in an ecological community. By now it is clear that many aspects of food-web structure are reproducible across diverse habitats, yet little is known about the driving force behind this structure. Evolutionary and population dynamical mechanisms have been considered. We propose a model for the evolutionary dynamics of food-web topology and show that it accurately reproduces observed food-web characteristic in the steady state. It is based on the observation that most consumers are larger than their resource species and the hypothesis that speciation and extinction rates decrease with increasing body mass. Results give strong support to the evolutionary hypothesis.Comment: 16 pages, 3 figure

Notes about the Caratheodory number

In this paper we give sufficient conditions for a compactum in $\mathbb R^n$ to have Carath\'{e}odory number less than $n+1$, generalizing an old result of Fenchel. Then we prove the corresponding versions of the colorful Carath\'{e}odory theorem and give a Tverberg type theorem for families of convex compacta

On multiplicities in length spectra of arithmetic hyperbolic three-orbifolds

Asymptotic laws for mean multiplicities of lengths of closed geodesics in arithmetic hyperbolic three-orbifolds are derived. The sharpest results are obtained for non-compact orbifolds associated with the Bianchi groups SL(2,o) and some congruence subgroups. Similar results hold for cocompact arithmetic quaternion groups, if a conjecture on the number of gaps in their length spectra is true. The results related to the groups above give asymptotic lower bounds for the mean multiplicities in length spectra of arbitrary arithmetic hyperbolic three-orbifolds. The investigation of these multiplicities is motivated by their sensitive effect on the eigenvalue spectrum of the Laplace-Beltrami operator on a hyperbolic orbifold, which may be interpreted as the Hamiltonian of a three-dimensional quantum system being strongly chaotic in the classical limit.Comment: 29 pages, uuencoded ps. Revised version, to appear in NONLINEARIT

Common carotid intima media thickness and ankle-brachial pressure index correlate with local but not global atheroma burden:a cross sectional study using whole body magnetic resonance angiography

Common carotid intima media thickness (CIMT) and ankle brachial pressure index (ABPI) are used as surrogate marker of atherosclerosis, and have been shown to correlate with arterial stiffness, however their correlation with global atherosclerotic burden has not been previously assessed. We compare CIMT and ABPI with atheroma burden as measured by whole body magnetic resonance angiography (WB-MRA).50 patients with symptomatic peripheral arterial disease were recruited. CIMT was measured using ultrasound while rest and exercise ABPI were performed. WB-MRA was performed in a 1.5T MRI scanner using 4 volume acquisitions with a divided dose of intravenous gadolinium gadoterate meglumine (Dotarem, Guerbet, FR). The WB-MRA data was divided into 31 anatomical arterial segments with each scored according to degree of luminal narrowing: 0 = normal, 1 = <50%, 2 = 50-70%, 3 = 70-99%, 4 = vessel occlusion. The segment scores were summed and from this a standardized atheroma score was calculated.The atherosclerotic burden was high with a standardised atheroma score of 39.5±11. Common CIMT showed a positive correlation with the whole body atheroma score (β 0.32, p = 0.045), however this was due to its strong correlation with the neck and thoracic segments (β 0.42 p = 0.01) with no correlation with the rest of the body. ABPI correlated with the whole body atheroma score (β -0.39, p = 0.012), which was due to a strong correlation with the ilio-femoral vessels with no correlation with the thoracic or neck vessels. On multiple linear regression, no correlation between CIMT and global atheroma burden was present (β 0.13 p = 0.45), while the correlation between ABPI and atheroma burden persisted (β -0.45 p = 0.005).ABPI but not CIMT correlates with global atheroma burden as measured by whole body contrast enhanced magnetic resonance angiography in a population with symptomatic peripheral arterial disease. However this is primarily due to a strong correlation with ilio-femoral atheroma burden

Partial differential equations for self-organization in cellular and developmental biology

Understanding the mechanisms governing and regulating the emergence of structure and heterogeneity within cellular systems, such as the developing embryo, represents a multiscale challenge typifying current integrative biology research, namely, explaining the macroscale behaviour of a system from microscale dynamics. This review will focus upon modelling how cell-based dynamics orchestrate the emergence of higher level structure. After surveying representative biological examples and the models used to describe them, we will assess how developments at the scale of molecular biology have impacted on current theoretical frameworks, and the new modelling opportunities that are emerging as a result. We shall restrict our survey of mathematical approaches to partial differential equations and the tools required for their analysis. We will discuss the gap between the modelling abstraction and biological reality, the challenges this presents and highlight some open problems in the field