Chaos in the Takens-Bogdanov bifurcation with O(2) symmetry

The Takens–Bogdanov bifurcation is a codimension two bifurcation that provides a key to the presence of complex dynamics in many systems of physical interest. When the system is translation invariant in one spatial dimension with no left-right preference the imposition of periodic boundary conditions leads to the Takens–Bogdanov bifurcation with O(2) symmetry. This bifurcation, analyzed by G. Dangelmayr and E. Knobloch, Phil. Trans. R. Soc. London A 322, 243 (1987), describes the interaction between steady states and traveling and standing waves in the nonlinear regime and predicts the presence of modulated traveling waves as well. The analysis reveals the presence of several global bifurcations near which the averaging method (used in the original analysis) fails. We show here, using a combination of numerical continuation and the construction of appropriate return maps, that near the global bifurcation that terminates the branch of modulated traveling waves, the normal form for the Takens–Bogdanov bifurcation admits cascades of period-doubling bifurcations as well as chaotic dynamics of Shil’nikov type. Thus chaos is present arbitrarily close to the codimension two point

The fate of steroid estrogens: Partitioning during wastewater treatment and onto river sediments

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2010 Springer Science+Business Media B.V.The partitioning of steroid estrogens in wastewater treatment and receiving waters is likely to influence their discharge to, and persistence in, the environment. This study investigated the partitioning behaviour of steroid estrogens in both laboratory and field studies. Partitioning onto activated sludge from laboratory-scale Husmann units was rapid with equilibrium achieved after 1 h. Sorption isotherms and Kd values decreased in the order 17α-ethinyl estradiol > 17α-estradiol > estrone > estriol without a sorption limit being achieved (1/n >1). Samples from a wastewater treatment works indicated no accumulation of steroid estrogens in solids from primary or secondary biological treatment, however, a range of steroid estrogens were identified in sediment samples from the River Thames. This would indicate that partitioning in the environment may play a role in the long-term fate of estrogens, with an indication that they will be recalcitrant in anaerobic conditions.EPSR

Applying refinement to the use of mice and rats in rheumatoid arthritis research

Rheumatoid arthritis (RA) is a painful, chronic disorder and there is currently an unmet need for effective therapies that will benefit a wide range of patients. The research and development process for therapies and treatments currently involves in vivo studies, which have the potential to cause discomfort, pain or distress. This Working Group report focuses on identifying causes of suffering within commonly used mouse and rat ‘models’ of RA, describing practical refinements to help reduce suffering and improve welfare without compromising the scientific objectives. The report also discusses other, relevant topics including identifying and minimising sources of variation within in vivo RA studies, the potential to provide pain relief including analgesia, welfare assessment, humane endpoints, reporting standards and the potential to replace animals in RA research

Experimental non-classicality of an indivisible quantum system

Quantum theory demands that, in contrast to classical physics, not all properties can be simultaneously well defined. The Heisenberg Uncertainty Principle is a manifestation of this fact. Another important corollary arises that there can be no joint probability distribution describing the outcomes of all possible measurements, allowing a quantum system to be classically understood. We provide the first experimental evidence that even for a single three-state system, a qutrit, no such classical model can exist that correctly describes the results of a simple set of pairwise compatible measurements. Not only is a single qutrit the simplest system in which such a contradiction is possible, but, even more importantly, the contradiction cannot result from entanglement, because such a system is indivisible, and it does not even allow the concept of entanglement between subsystems.Comment: 11 pages, 4 figures, 2 table

On the Evolution of Hexose Transporters in Kinetoplastid Potozoans

Glucose, an almost universally used energy and carbon source, is processed through several well-known metabolic pathways, primarily glycolysis. Glucose uptake is considered to be the first step in glycolysis. In kinetoplastids, a protozoan group that includes relevant human pathogens, the importance of glucose uptake in different phases of the life cycles is well established, and hexose transporters have been proposed as targets for therapeutic drugs. However, little is known about the evolutionary history of these hexose transporters. Hexose transporters contain an intracellular N- and C- termini, and 12 transmembrane spans connected by alternate intracellular and extracellular loops. In the present work we tested the hypothesis that the evolutionary rate of the transmembrane span is different from that of the whole sequence and that it is possible to define evolutionary units inside the sequence. The phylogeny of whole molecules was compared to that of their transmembrane spans and the loops connecting the transmembrane spans. We show that the evolutionary units in these proteins primarily consist of clustered rather than individual transmembrane spans. These analyses demonstrate that there are evolutionary constraints on the organization of these proteins; more specifically, the order of the transmembrane spans along the protein is highly conserved. Finally, we defined a signature sequence for the identification of kinetoplastid hexose transporters

Ethical and Scientific Considerations Regarding Animal Testing and Research

In 1959, William Russell and Rex Burch published the seminal book, The Principles of Humane Experimental Technique, which emphasized reduction, refinement, and replacement of animal use, principles which have since been referred to as the ‘‘3 Rs’’. These principles encouraged researchers to work to reduce the number of animals used in experiments to the minimum considered necessary, refine or limit the pain and distress to which animals are exposed, and replace the use of animals with non-animal alternatives when possible. Despite the attention brought to this issue by Russell and Burch and since, the number of animals used in research and testing has continued to increase, raising serious ethical and scientific issues. Further, while the ‘‘3 Rs’’ capture crucially important concepts, they do not adequately reflect the substantial developments in our new knowledge about the cognitive and emotional capabilities of animals, the individual interests of animals, or an updated understanding of potential harms associated with animal research. This Overview provides a brief summary of the ethical and scientific considerations regarding the use of animals in research and testing, and accompanies a Collection entitled Animals, Research, and Alternatives: Measuring Progress 50 Years Later, which aims to spur ethical and scientific advancement

Prolonged Depression-Like Behavior Caused by Immune Challenge: Influence of Mouse Strain and Social Environment

Immune challenge by bacterial lipopolysaccharide (LPS) causes short-term behavioral changes indicative of depression. The present study sought to explore whether LPS is able to induce long-term changes in depression-related behavior and whether such an effect depends on mouse strain and social context. LPS (0.83 mg/kg) or vehicle was administered intraperitoneally to female CD1 and C57BL/6 mice that were housed singly or in groups of 4. Depression-like behavior was assessed with the forced swim test (FST) 1 and 28 days post-treatment. Group-housed CD1 mice exhibited depression-like behavior 1 day post-LPS, an effect that leveled off during the subsequent 28 days, while the behavior of singly housed CD1 mice was little affected. In contrast, singly housed C57BL/6 mice responded to LPS with an increase in depression-like behavior that was maintained for 4 weeks post-treatment and confirmed by the sucrose preference test. Group-housed C57BL/6 mice likewise displayed an increased depression-like behavior 4 weeks post-treatment. The behavioral changes induced by LPS in C57BL/6 mice were associated with a particularly pronounced rise of interleukin-6 in blood plasma within 1 day post-treatment and with changes in the dynamics of the corticosterone response to the FST. The current data demonstrate that immune challenge with LPS is able to induce prolonged depression-like behavior, an effect that depends on genetic background (strain). The discovery of an experimental model of long-term depression-like behavior after acute immune challenge is of relevance to the analysis of the epigenetic and pathophysiologic mechanisms of immune system-related affective disorders

Assignment of chromosomal locations for unassigned SNPs/scaffolds based on pair-wise linkage disequilibrium estimates

<p>Abstract</p> <p>Background</p> <p>Recent developments of high-density SNP chips across a number of species require accurate genetic maps. Despite rapid advances in genome sequence assembly and availability of a number of tools for creating genetic maps, the exact genome location for a number of SNPs from these SNP chips still remains unknown. We have developed a locus ordering procedure based on linkage disequilibrium (LODE) which provides estimation of the chromosomal positions of unaligned SNPs and scaffolds. It also provides an alternative means for verification of genetic maps. We exemplified LODE in cattle.</p> <p>Results</p> <p>The utility of the LODE procedure was demonstrated using data from 1,943 bulls genotyped for 73,569 SNPs across three different SNP chips. First, the utility of the procedure was tested by analysing the masked positions of 1,500 randomly-chosen SNPs with known locations (50 from each chromosome), representing three classes of minor allele frequencies (MAF), namely >0.05, 0.01<MAF ≤ 0.05 and 0.001<MAF ≤ 0.01. The efficiency (percentage of masked SNPs that could be assigned a location) was 96.7%, 30.6% and 2.0%; with an accuracy (the percentage of SNPs assigned correctly) of 99.9%, 98.9% and 33.3% in the three classes of MAF, respectively. The average precision for placement of the SNPs was 914, 3,137 and 6,853 kb, respectively. Secondly, 4,688 of 5,314 SNPs unpositioned in the Btau4.0 assembly were positioned using the LODE procedure. Based on these results, the positions of 485 unordered scaffolds were determined. The procedure was also used to validate the genome positions of 53,068 SNPs placed on Btau4.0 bovine assembly, resulting in identification of problem areas in the assembly. Finally, the accuracy of the LODE procedure was independently validated by comparative mapping on the hg18 human assembly.</p> <p>Conclusion</p> <p>The LODE procedure described in this study is an efficient and accurate method for positioning SNPs (MAF>0.05), for validating and checking the quality of a genome assembly, and offers a means for positioning of unordered scaffolds containing SNPs. The LODE procedure will be helpful in refining genome sequence assemblies, especially those being created from next-generation sequencing where high-throughput SNP discovery and genotyping platforms are integrated components of genome analysis.</p

Anticancer potential of Thevetia peruviana fruit methanolic extract

Abstract Background: Thevetia peruviana (Pers.) K. Schum or Cascabela peruviana (L.) Lippold (commonly known as ayoyote, codo de fraile, lucky nut, or yellow oleander), native to Mexico and Central America, is a medicinal plant used traditionally to cure diseases like ulcers, scabies, hemorrhoids and dissolve tumors. The purpose of this study was to evaluate the cytotoxic, antiproliferative and apoptotic activity of methanolic extract of T. peruviana fruits on human cancer cell lines. Methods: The cytotoxic activity of T. peruviana methanolic extract was carried out on human breast, colorectal, prostate and lung cancer cell lines and non-tumorigenic control cells (fibroblast and Vero), using the MTT assay. For proliferation and motility, clonogenic and wound-healing assays were performed. Morphological alterations were monitored by trypan blue exclusion, as well as DNA fragmentation and AO/EB double staining was performed to evaluate apoptosis. The extract was separated using flash chromatography, and the resulting fractions were evaluated on colorectal cancer cells for their cytotoxic activity. The active fractions were further analyzed through mass spectrometry. Results: The T. peruviana methanolic extract exhibited cytotoxic activity on four human cancer cell lines: prostate, breast, colorectal and lung, with values of IC50 1.91 ± 0.76, 5.78 ± 2.12, 6.30 ± 4.45 and 12.04 ± 3.43 μg/mL, respectively. The extract caused a significant reduction of cell motility and colony formation on all evaluated cancer cell lines. In addition, morphological examination displayed cell size reduction, membrane blebbing and detachment of cells, compared to non-treated cancer cell lines. The T. peruviana extract induced apoptotic cell death, which was confirmed by DNA fragmentation and AO/EB double staining. Fractions 4 and 5 showed the most effective cytotoxic activity and their MS analysis revealed the presence of the secondary metabolites: thevetiaflavone and cardiac glycosides. Conclusion: T. peruviana extract has potential as natural anti-cancer product with critical effects in the proliferation, motility, and adhesion of human breast and colorectal cancer cells, and apoptosis induction in human prostate and lung cancer cell lines, with minimal effects on non-tumorigenic cell lines. Keywords: Cytotoxic activity, Anti-proliferative activity, Motility, Apoptosis, Human cancer cells, Flavonoid, Cardiac glycoside