Germline rates of de novo meiotic deletions and duplications causing several genomic disorders

Meiotic recombination between highly similar duplicated sequences (nonallelic homologous recombination, NAHR) generates deletions, duplications, inversions and translocations, and it is responsible for genetic diseases known as 'genomic disorders', most of which are caused by altered copy number of dosage-sensitive genes. NAHR hot spots have been identified within some duplicated sequences. We have developed sperm-based assays to measure the de novo rate of reciprocal deletions and duplications at four NAHR hot spots. We used these assays to dissect the relative rates of NAHR between different pairs of duplicated sequences. We show that (i) these NAHR hot spots are specific to meiosis, (ii) deletions are generated at a higher rate than their reciprocal duplications in the male germline and (iii) some of these genomic disorders are likely to have been underascertained clinically, most notably that resulting from the duplication of 7q11, the reciprocal of the deletion causing Williams-Beuren syndrome.     

Comparative genomic analysis of three Leishmania species that cause diverse human disease

Leishmania parasites cause a broad spectrum of clinical disease. Here we report the sequencing of the genomes of two species of Leishmania: Leishmania infantum and Leishmania braziliensis. The comparison of these sequences with the published genome of Leishmania major reveals marked conservation of synteny and identifies only approximately 200 genes with a differential distribution between the three species. L. braziliensis, contrary to Leishmania species examined so far, possesses components of a putative RNA-mediated interference pathway, telomere-associated transposable elements and spliced leader-associated SLACS retrotransposons. We show that pseudogene formation and gene loss are the principal forces shaping the different genomes. Genes that are differentially distributed between the species encode proteins implicated in host-pathogen interactions and parasite survival in the macrophage.     

ADVANCES IN SUSTAINABLE SECURITY SYSTEMS ENGINEERING WITH DRAMA THEORY （DT） II

We put forth Drama Theory II (DT II) as a formal multiple participant decision making framework that can be used to systematically model complex security challenges, and advance the field of Sustainable Security Systems Engineering. DT II is defined as a theory of “large world” pre-game communication and equilibrium selection. While game theoretic tools have been widely applied to resolve environmental conflicts and promote global security, traditional game theory assumes that decision makers, options, and preferences are fixed. A mathematical treatment of key drama theoretic concepts (i.e. positions, intentions, doubts and dilemmas) is provided. The dynamics of the drama theoretic process are discussed and the expected equilibrium set is derived. The fundamental theorem of drama theory is proven and all theoretical results are applied to promote sustainable security solutions. It is emphasized that DT II represents a flexible systems engineering technique to address time-sensitive, multi-faceted, and complex multiple participant negotiations.     

Scattering by chorus waves as the dominant cause of diffuse auroral precipitation

Earth's diffuse aurora occurs over a broad latitude range and is primarily caused by the precipitation of low-energy (0.1-30-keV) electrons originating in the central plasma sheet, which is the source region for hot electrons in the nightside outer magnetosphere. Although generally not visible, the diffuse auroral precipitation provides the main source of energy for the high-latitude nightside upper atmosphere, leading to enhanced ionization and chemical changes. Previous theoretical studies have indicated that two distinct classes of magnetospheric plasma wave, electrostatic electron cyclotron harmonic waves and whistler-mode chorus waves, could be responsible for the electron scattering that leads to diffuse auroral precipitation, but it has hitherto not been possible to determine which is the more important. Here we report an analysis of satellite wave data and Fokker-Planck diffusion calculations which reveals that scattering by chorus is the dominant cause of the most intense diffuse auroral precipitation. This resolves a long-standing controversy. Furthermore, scattering by chorus can remove most electrons as they drift around Earth's magnetosphere, leading to the development of observed pancake distributions, and can account for the global morphology of the diffuse aurora.