Retroelements and their impact on genome evolution and functioning

Retroelements comprise a considerable fraction of eukaryotic genomes. Since their initial discovery by Barbara McClintock in maize DNA, retroelements have been found in genomes of almost all organisms. First considered as a “junk DNA” or genomic parasites, they were shown to influence genome functioning and to promote genetic innovations. For this reason, they were suggested as an important creative force in the genome evolution and adaptation of an organism to altered environmental conditions. In this review, we summarize the up-to-date knowledge of different ways of retroelement involvement in structural and functional evolution of genes and genomes, as well as the mechanisms generated by cells to control their retrotransposition.     

Injection of adult neurospheres induces recovery in a chronic model of multiple sclerosis

Widespread demyelination and axonal loss are the pathological hallmarks of multiple sclerosis. The multifocal nature of this chronic inflammatory disease of the central nervous system complicates cellular therapy and puts emphasis on both the donor cell origin and the route of cell transplantation. We established syngenic adult neural stem cell cultures and injected them into an animal model of multiple sclerosis--experimental autoimmune encephalomyelitis (EAE) in the mouse--either intravenously or intracerebroventricularly. In both cases, significant numbers of donor cells entered into demyelinating areas of the central nervous system and differentiated into mature brain cells. Within these areas, oligodendrocyte progenitors markedly increased, with many of them being of donor origin and actively remyelinating axons. Furthermore, a significant reduction of astrogliosis and a marked decrease in the extent of demyelination and axonal loss were observed in transplanted animals. The functional impairment caused by EAE was almost abolished in transplanted mice, both clinically and neurophysiologically. Thus, adult neural precursor cells promote multifocal remyelination and functional recovery after intravenous or intrathecal injection in a chronic model of multiple sclerosis.     

Hermansky-Pudlak syndrome is caused by mutations in HPS4, the human homolog of the mouse light-ear gene

Hermansky-Pudlak syndrome (HPS) is a disorder of organelle biogenesis in which oculocutaneous albinism, bleeding and pulmonary fibrosis result from defects of melanosomes, platelet dense granules and lysosomes. HPS is common in Puerto Rico, where it is caused by mutations in the genes HPS1 and, less often, HPS3 (ref. 8). In contrast, only half of non-Puerto Rican individuals with HPS have mutations in HPS1 (ref. 9), and very few in HPS3 (ref. 10). In the mouse, more than 15 loci manifest mutant phenotypes similar to human HPS, including pale ear (ep), the mouse homolog of HPS1 (refs 13,14). Mouse ep has a phenotype identical to another mutant, light ear (le), which suggests that the human homolog of le is a possible human HPS locus. We have identified and found mutations of the human le homolog, HPS4, in a number of non-Puerto Rican individuals with HPS, establishing HPS4 as an important HPS locus in humans. In addition to their identical phenotypes, le and ep mutant mice have identical abnormalities of melanosomes, and in transfected melanoma cells the HPS4 and HPS1 proteins partially co-localize in vesicles of the cell body. In addition, the HPS1 protein is absent in tissues of le mutant mice. These results suggest that the HPS4 and HPS1 proteins may function in the same pathway of organelle biogenesis.     

Catalase activity among leptospires

Summary Catalase activity was measured by a quantitative method as an additional screening for discriminating between saprophytic and pathogenic leptospires. Results indicate that water-leptospires have little or no catalase activity.     

Human subtelomeres are hot spots of interchromosomal recombination and segmental duplication

Human subtelomeres are polymorphic patchworks of interchromosomal segmental duplications at the ends of chromosomes. Here we provide evidence that these patchworks arose recently through repeated translocations between chromosome ends. We assess the relative contribution of the principal mechanisms of ectopic DNA repair to the formation of subtelomeric duplications and find that non-homologous end-joining predominates. Once subtelomeric duplications arise, they are prone to homology-based sequence transfers as shown by the incongruent phylogenetic relationships of neighbouring sections. Interchromosomal recombination of subtelomeres is a potent force for recent change. Cytogenetic and sequence analyses reveal that pieces of the subtelomeric patchwork have changed location and copy number with unprecedented frequency during primate evolution. Half of the known subtelomeric sequence has formed recently, through human-specific sequence transfers and duplications. Subtelomeric dynamics result in a gene duplication rate significantly higher than the genome average and could have both advantageous and pathological consequences in human biology. More generally, our analyses suggest an evolutionary cycle between segmental polymorphisms and genome rearrangements.     

Methylated lysine 79 of histone H3 targets 53BP1 to DNA double-strand breaks

The mechanisms by which eukaryotic cells sense DNA double-strand breaks (DSBs) in order to initiate checkpoint responses are poorly understood. 53BP1 is a conserved checkpoint protein with properties of a DNA DSB sensor. Here, we solved the structure of the domain of 53BP1 that recruits it to sites of DSBs. This domain consists of two tandem tudor folds with a deep pocket at their interface formed by residues conserved in the budding yeast Rad9 and fission yeast Rhp9/Crb2 orthologues. In vitro, the 53BP1 tandem tudor domain bound histone H3 methylated on Lys 79 using residues that form the walls of the pocket; these residues were also required for recruitment of 53BP1 to DSBs. Suppression of DOT1L, the enzyme that methylates Lys 79 of histone H3, also inhibited recruitment of 53BP1 to DSBs. Because methylation of histone H3 Lys 79 was unaltered in response to DNA damage, we propose that 53BP1 senses DSBs indirectly through changes in higher-order chromatin structure that expose the 53BP1 binding site.     

Ultrathin compound semiconductor on insulator layers for high-performance nanoscale transistors

Over the past several years, the inherent scaling limitations of silicon (Si) electron devices have fuelled the exploration of alternative semiconductors, with high carrier mobility, to further enhance device performance. In particular, compound semiconductors heterogeneously integrated on Si substrates have been actively studied: such devices combine the high mobility of III-V semiconductors and the well established, low-cost processing of Si technology. This integration, however, presents significant challenges. Conventionally, heteroepitaxial growth of complex multilayers on Si has been explored-but besides complexity, high defect densities and junction leakage currents present limitations in this approach. Motivated by this challenge, here we use an epitaxial transfer method for the integration of ultrathin layers of single-crystal InAs on Si/SiO(2) substrates. As a parallel with silicon-on-insulator (SOI) technology, we use 'XOI' to represent our compound semiconductor-on-insulator platform. Through experiments and simulation, the electrical properties of InAs XOI transistors are explored, elucidating the critical role of quantum confinement in the transport properties of ultrathin XOI layers. Importantly, a high-quality InAs/dielectric interface is obtained by the use of a novel thermally grown interfacial InAsO(x) layer (~1?nm thick). The fabricated field-effect transistors exhibit a peak transconductance of ~1.6?mS?μm(-1) at a drain-source voltage of 0.5?V, with an on/off current ratio of greater than 10,000.