Learning to live together: mutualism between self-splicing introns and their hosts

Group I and II introns can be considered as molecular parasites that interrupt protein-coding and structural RNA genes in all domains of life. They function as self-splicing ribozymes and thereby limit the phenotypic costs associated with disruption of a host gene while they act as mobile DNA elements to promote their spread within and between genomes. Once considered purely selfish DNA elements, they now seem, in the light of recent work on the molecular mechanisms regulating bacterial and phage group I and II intron dynamics, to show evidence of co-evolution with their hosts. These previously underappreciated relationships serve the co-evolving entities particularly well in times of environmental stress

Bioaccumulation and Toxicity of Organic Chemicals in Terrestrial Invertebrates

Terrestrial invertebrates are key components in ecosystems, with crucial roles in soil structure, functioning, and ecosystem services. The present chapter covers how terrestrial invertebrates are impacted by organic chemicals, focusing on up-to-date information regarding bioavailability, exposure routes and general concepts on bioaccumulation, toxicity, and existing models. Terrestrial invertebrates are exposed to organic chemicals through different routes, which are dependent on both the organismal traits and nature of exposure, including chemical properties and media characteristics. Bioaccumulation and toxicity data for several groups of organic chemicals are presented and discussed, attempting to cover plant protection products (herbicides, insecticides, fungicides, and molluscicides), veterinary and human pharmaceuticals, polycyclic aromatic compounds, polychlorinated biphenyls, flame retardants, and personal care products. Chemical mixtures are also discussed bearing in mind that chemicals appear simultaneously in the environment. The biomagnification of organic chemicals is considered in light of the consumption of terrestrial invertebrates as novel feed and food sources. This chapter highlights how science has contributed with data from the last 5 years, providing evidence on bioavailability, bioaccumulation, and toxicity derived from exposure to organic chemicals, including insights into the main challenges and shortcomings to extrapolate results to real exposure scenarios

A Novel Method to Verify Multilevel Computational Models of Biological Systems Using Multiscale Spatio-Temporal Meta Model Checking

Insights gained from multilevel computational models of biological systems can be translated into real-life applications only if the model correctness has been verified first. One of the most frequently employed in silico techniques for computational model verification is model checking. Traditional model checking approaches only consider the evolution of numeric values, such as concentrations, over time and are appropriate for computational models of small scale systems (e.g. intracellular networks). However for gaining a systems level understanding of how biological organisms function it is essential to consider more complex large scale biological systems (e.g. organs). Verifying computational models of such systems requires capturing both how numeric values and properties of (emergent) spatial structures (e.g. area of multicellular population) change over time and across multiple levels of organization, which are not considered by existing model checking approaches. To address this limitation we have developed a novel approximate probabilistic multiscale spatio-temporal meta model checking methodology for verifying multilevel computational models relative to specifications describing the desired/expected system behaviour. The methodology is generic and supports computational models encoded using various high-level modelling formalisms because it is defined relative to time series data and not the models used to generate it. In addition, the methodology can be automatically adapted to case study specific types of spatial structures and properties using the spatio-temporal meta model checking concept. To automate the computational model verification process we have implemented the model checking approach in the software tool Mule (http://mule.modelchecking.org). Its applicability is illustrated against four systems biology computational models previously published in the literature encoding the rat cardiovascular system dynamics, the uterine contractions of labour, the Xenopus laevis cell cycle and the acute inflammation of the gut and lung. Our methodology and software will enable computational biologists to efficiently develop reliable multilevel computational models of biological systems

Causes, consequences and biomarkers of stress in swine: an update

BACKGROUND: In recent decades there has been a growing concern about animal stress on intensive pig farms due to the undesirable consequences that stress produces in the normal physiology of pigs and its effects on their welfare and general productive performance. This review analyses the most important types of stress (social, environmental, metabolic, immunological and due to human handling), and their biological consequences for pigs. The physio-pathological changes associated with stress are described, as well as the negative effects of stress on pig production. In addition an update of the different biomarkers used for the evaluation of stress is provided. These biomarkers can be classified into four groups according to the physiological system or axis evaluated: sympathetic nervous system, hypothalamic-pituitary-adrenal axis, hypothalamic-pituitary-gonadal axis and immune system. CONCLUSIONS: Stress it is a process with multifactorial causes and produces an organic response that generates negative effects on animal health and production. Ideally, a panel of various biomarkers should be used to assess and evaluate the stress resulting from diverse causes and the different physiological systems involved in the stress response. We hope that this review will increase the understanding of the stress process, contribute to a better control and reduction of potential stressful stimuli in pigs and, finally, encourage future studies and developments to better monitor, detect and manage stress on pig farms

TEMPLATE-ASSEMBLED SYNTHETIC PROTEINS DESIGNED TO ADOPT A GLOBULAR, 4-HELIX BUNDLE CONFORMATION FORM IONIC CHANNELS IN LIPID BILAYERS

Template-assembled synthetic proteins (TASPs) designed to adopt globular, four-helix bundle structures form ion channels in lipid bilayers. The rationale behind this work is that a bundle of amphiphilic alpha-helices may constitute a functional pore-forming motif in a lipid environment. TASPs designated T4(4alpha11), T4(4alpha15), and T4(4alpha18) contain four identical, amphiphilic, helical modules of 11, 15, or 18 residues, respectively; secondary structure modules are attached to the lysine epsilon-amino groups of a cyclic template, Ac-CysLysAlaLysProGlyLysAlaLysCys-NH2, which directs the intramolecular folding. T4(4alpha15) and T4(4alpha18) form cation selective channels with single channel conductances in 500 mM NaCl of 10 and 50 pS for T4(4alpha15) and 9 and 25 pS for T4(4alpha18). In contrast, T4(4alpha11) does not produce discrete conductance events. Notably, channel activity is observed only for molecules that display well-defined alpha-helical structure in solution; K(alpha15), Which contains a single peptide module attached to the epsilon-amino group of Ac-Lys-NH2, does not elicit single channels and displays low alpha-helical content. By contrast, K(alpha18) displays spectral features associated with alpha-helical structure and forms channels with primary conductances of 3 and 9 pS. The occurrence of multiple conductances suggests that molecules aggregate and form heterogeneous conductive oligomers. The minimum length of helical modules required to span a lipid bilayer is established by investigating the channel activity of T4(4alpha15) in bilayers of increasing width. Taken together, results suggest that the relative orientation of amphiphilic segments depends on the hydrophobicity of surrounding media; accordingly, TASP molecules may form ionic channels through a reorientation of template-assembled helical modules to expose charged residues to a central hydrophilic pore

Receptor binding of gonadotropin-releasing hormone antagonists that inhibit release of gonadotropin-II and growth hormone in goldfish, Carassius auratus

In goldfish, GnRH stimulates gonadotropin-II (GTH-II) and growth hormone (GH) release. The two native forms of GnRH, salmon GnRH (sGnRH) and chicken GnRH-II (cGnRH-II), bind to two classes of GnRH binding sites: high- affinity/low-capacity sites and low-affinity/high-capacity sites. Our previous in vitro perifusion studies of goldfish pituitary fragments showed that [Ac-Δ3-Pro1, 4FD-Phe2, D-Trp3,6]-mGnRH (analog E), [Ac-Δ3- Pro1, 4FD-Phe2, D-Trp3,6]-sGnRH (analog C), and [Ac-D(2)Nal1, 4Cl-D- Phe2, D-(3)Pal3,6]-cGnRH-II (analog N) inhibited both sGnRH- and cGnRH- II-stimulated GTH-II and GH release. Interestingly, analog C stimulated GH release but not GTH-II release. The objectives of the present study were 1) to test the site of action of GnRH antagonists in goldfish, 2) to test the relationship between receptor binding affinity of antagonists and their in vitro inhibitory potencies and apparent duration of action, and 3) to compare the binding characteristics of analog C with its differential action on GTH- II and GH release. As in previous studies, analog E suppressed sGnRH- stimulated GTH-II and GH release from perifused pituitary fragments. Similarly, analog E suppressed both sGnRH- and cGnRH-II-stimulated GTH-II and GH release from perifused dispersed goldfish pituitary cells, indicating the direct action of GnRH antagonists at the pituitary cell level. In the receptor binding studies, analog E displaced 125I-[D-Arg6, Pro9NHEt]- sGnRH (sGnRH-A) from crude goldfish pituitary membrane preparations in a dose-dependent manner. The binding affinities to high-affinity GnRH binding sites of analog E, analog C, and analog N were significantly higher than those of native sGnRH and sGnRH-A. The rank order of high affinity was analog N ≥ C > E, and binding affinity had no positive relation with the inhibitory effects of these analogs on GTH-II or GH release in vitro. In conclusion, GnRH antagonists inhibit native GnRH-stimulated GTH-II and GH release by competitively binding to binding sites at the pituitary cells, although there was no positive relation between receptor binding affinity and in vitro GTH- II or GH release-inhibiting potency of the analogs tested.published_or_final_versio