Gene duplication: a drive for phenotypic diversity and cause of human disease

Gene duplication is one of the key factors driving genetic innovation, i.e., producing novel genetic variants. Although the contribution of whole-genome and segmental duplications to phenotypic diversity across species is widely appreciated, the phenotypic spectrum and potential pathogenicity of small-scale duplications in individual genomes are less well explored. This review discusses the nature of small-scale duplications and the phenotypes produced by such duplications. Phenotypic variation and disease phenotypes induced by duplications are more diverse and widespread than previously anticipated, and duplications are a major class of disease-related genomic variation. Pathogenic duplications particularly involve dosage-sensitive genes with both similar and dissimilar over- and underexpression phenotypes, and genes encoding proteins with a propensity to aggregate. Phenotypes related to human-specific copy number variation in genes regulating environmental responses and immunity are increasingly recognized. Small genomic duplications containing defense-related genes also contribute to complex common phenotypes.

Drug-induced respiratory depression: an integrated model of drug effects on the hypercapnic and hypoxic drive

Drug-induced respiratory depression is a common side effect of the agents used in anesthesia practice to provide analgesia and sedation. Depression of the ventilatory drive in the spontaneously breathing patient can lead to severe cardiorespiratory events and it is considered a primary cause of morbidity. Reliable predictions of respiratory inhibition in the clinical setting would therefore provide a valuable means to improve the safety of drug delivery. Although multiple studies investigated the regulation of breathing in man both in the presence and absence of ventilatory depressant drugs, a unified description of respiratory pharmacodynamics is not available. This study proposes a mathematical model of human metabolism and cardiorespiratory regulation integrating several isolated physiological and pharmacological aspects of acute drug-induced ventilatory depression into a single theoretical framework. The description of respiratory regulation has a parsimonious yet comprehensive structure with substantial predictive capability. Simulations relative to the synergistic interaction of the hypercarbic and hypoxic respiratory drive and the global effect of drugs on the control of breathing are in good agreement with published experimental data. Besides providing clinically relevant predictions of respiratory depression, the model can also serve as a test bed to investigate issues of drug tolerability and dose finding/control under non-steady-state conditions.

A genetically explicit model of speciation by sensory drive within a continuous population in aquatic environments

BACKGROUND: The sensory drive hypothesis predicts that divergent sensory adaptation in different habitats may lead to premating isolation upon secondary contact of populations. Speciation by sensory drive has traditionally been treated as a special case of speciation as a byproduct of adaptation to divergent environments in geographically isolated populations. However, if habitats are heterogeneous, local adaptation in the sensory systems may cause the emergence of reproductively isolated species from a single unstructured population. In polychromatic fishes, visual sensitivity might become adapted to local ambient light regimes and the sensitivity might influence female preferences for male nuptial color. In this paper, we investigate the possibility of speciation by sensory drive as a byproduct of divergent visual adaptation within a single initially unstructured population. We use models based on explicit genetic mechanisms for color vision and nuptial coloration. RESULTS: We show that in simulations in which the adaptive evolution of visual pigments and color perception are explicitly modeled, sensory drive can promote speciation along a short selection gradient within a continuous habitat and population. We assumed that color perception evolves to adapt to the modal light environment that individuals experience and that females prefer to mate with males whose nuptial color they are most sensitive to. In our simulations color perception depends on the absorption spectra of an individual's visual pigments. Speciation occurred most frequently when the steepness of the environmental light gradient was intermediate and dispersal distance of offspring was relatively small. In addition, our results predict that mutations that cause large shifts in the wavelength of peak absorption promote speciation, whereas we did not observe speciation when peak absorption evolved by stepwise mutations with small effect. CONCLUSION: The results suggest that speciation can occur where environmental gradients create divergent selection on sensory modalities that are used in mate choice. Evidence for such gradients exists from several animal groups, and from freshwater and marine fishes in particular. The probability of speciation in a continuous population under such conditions may then critically depend on the genetic architecture of perceptual adaptation and female mate choice.

The Aplitic Body Bordering Roosevelt Drive South of Butte, Montana

The area studied consists of a large body of aplite situated 12 miles south of Butte. It extends eastward almost to the Butte-Pipestone road, southward to Lime Kiln Hill and westward a distance of 3000 feet. The petrographic work was supplemented by a map of the area. Special attention was given to those frequent "Limonite Specks" found in the aplite.

Learning for sustainability - LforS: Simulation games - a creative tool for interactive learning

Description of simulation and training games as tool for awareness and capacity development in multi steakeholder processes

Creative Commons International The International License Porting Project

When Creative Commons (CC) was founded in 2001, the core Creative Commons licenses were drafted according to United States Copyright Law. Since their first introduction in December 2002, Creative Commons licenses have been enthusiastically adopted by many creators, authors, and other content producers – not only in the United States, but in many other jurisdictions as well. Global interest in the CC licenses prompted a discussion about the need for national versions of the CC licenses. To best address this need, the international license porting project (“Creative Commons International” – formerly known as “International Commons”) was launched in 2003. Creative Commons International works to port the core Creative Commons licenses to different copyright legislations around the world. The porting process includes both linguistically translating the licenses and legally adapting the licenses to a particular jurisdiction such that they are comprehensible in the local jurisdiction and legally enforceable but concurrently retain the same key elements. Since its inception, Creative Commons International has found many supporters all over the world. With Finland, Brazil, and Japan as the first completed jurisdiction projects, experts around the globe have followed their lead and joined the international collaboration with Creative Commons to adapt the licenses to their local copyright. This article aims to present an overview of the international porting process, explain and clarify the international license architecture, its legal and promotional aspects, as well as its most recent challenges.

Creative Commons Olympics. How Big Media is Learning to License From Amateur Authors

NBC Universal’s decision to use Creative Commons-licensed photographs in an Olympic broadcast is an example of how media conglomerates are experimenting with collaboration with amateurs, but it also reveals potential problems of letting non-lawyers negotiate copyright licensing agreements. In the process, NBC’s producers nearly opened the door for a multimillion-dollar infringement law suit. To avoid such pitfalls, media companies need to adopt policies and best practices for using amateur licensed works. These guidelines should instruct how a production can attribute collaborating authors and how the Open Content licensing terms affect the licensing of the productions. The guidelines should also instruct how producers can seek alternative licensing arrangements with amateurs and contribute back to the Open Content community.

Creative Commons licences and design Are the two compatible?

This article analyses whether Creative Commons licences are applicable to and compatible with design. The first part focuses on the peculiar and complex nature of a design, which can benefit from a copyright and a design protection. This shows how it can affect the use of Creative Commons licences. The second and third parts deal with a specific case study. Some Internet platforms have recently emerged that offer users the possibility to download blueprints of design products in order to build them. Designers and creative users are invited to share their blueprints and creations under Creative Commons licences. The second part of the article assesses whether digital blueprints can be copyrightable and serve as the subject matter of Creative Commons licences, while the last part assesses whether the right to reproduce the digital blueprint, as provided by Creative Commons licences, extends to the right to build the product.

Transnational Law for Transnational Communities The Emergence of a Lex Mercatoria (or Lex Informatica) for International Creative Communities

Open Source Communities and content-oriented projects (Creative Commons etc.) have reached a new level of economic and cultural significance in some areas of the Internet ecosystem. These communities have developed their own set of legal rules covering licensing issues, intellectual property management, project governance rules etc. Typical Open Source licenses and project rules are written without any reference to national law. This paper considers the question whether these license contracts and other legal rules are to be qualified as a lex mercatoria (or lex informatica) of these communities.