The medaka draft genome and insights into vertebrate genome evolution

Teleosts comprise more than half of all vertebrate species and have adapted to a variety of marine and freshwater habitats. Their genome evolution and diversification are important subjects for the understanding of vertebrate evolution. Although draft genome sequences of two pufferfishes have been published, analysis of more fish genomes is desirable. Here we report a high-quality draft genome sequence of a small egg-laying freshwater teleost, medaka (Oryzias latipes). Medaka is native to East Asia and an excellent model system for a wide range of biology, including ecotoxicology, carcinogenesis, sex determination and developmental genetics. In the assembled medaka genome (700 megabases), which is less than half of the zebrafish genome, we predicted 20,141 genes, including approximately 2,900 new genes, using 5'-end serial analysis of gene expression tag information. We found single nucleotide polymorphisms (SNPs) at an average rate of 3.42% between the two inbred strains derived from two regional populations; this is the highest SNP rate seen in any vertebrate species. Analyses based on the dense SNP information show a strict genetic separation of 4 million years (Myr) between the two populations, and suggest that differential selective pressures acted on specific gene categories. Four-way comparisons with the human, pufferfish (Tetraodon), zebrafish and medaka genomes revealed that eight major interchromosomal rearrangements took place in a remarkably short period of approximately 50 Myr after the whole-genome duplication event in the teleost ancestor and afterwards, intriguingly, the medaka genome preserved its ancestral karyotype for more than 300 Myr.     

Autoradiographic studies on the experimental pulmonary fibrosis of rats after H3-proline injection

Zusammenfassung Mit einer 2-, 4-, 8- und 16-Wochenbehandlung wurde bei Ratten experimentell eine Lungenfibrose durch SiO₂ verursacht. Später wurde i.p. H³-Prolin injiziert und durch Autoradiographie die pulmonale Fibrose bewertet. In den Pneumokoniose-Herden wurde die Radioaktivität mit der Zeit am intensivsten, wobei die höchste Aktivität in den Kollagenfasern gemessen wurde.     

Electronic nematicity above the structural and superconducting transition in BaFe2(As(1-x)P(x))2

Electronic nematicity, a unidirectional self-organized state that breaks the rotational symmetry of the underlying lattice, has been observed in the iron pnictide and copper oxide high-temperature superconductors. Whether nematicity plays an equally important role in these two systems is highly controversial. In iron pnictides, the nematicity has usually been associated with the tetragonal-to-orthorhombic structural transition at temperature T(s). Although recent experiments have provided hints of nematicity, they were performed either in the low-temperature orthorhombic phase or in the tetragonal phase under uniaxial strain, both of which break the 90° rotational C(4) symmetry. Therefore, the question remains open whether the nematicity can exist above T(s) without an external driving force. Here we report magnetic torque measurements of the isovalent-doping system BaFe(2)(As(1-x)P(x))(2), showing that the nematicity develops well above T(s) and, moreover, persists to the non-magnetic superconducting regime, resulting in a phase diagram similar to the pseudogap phase diagram of the copper oxides. By combining these results with synchrotron X-ray measurements, we identify two distinct temperatures-one at T*, signifying a true nematic transition, and the other at T(s) (相似文献   

Genetic dissection of the circuit for hand dexterity in primates

It is generally accepted that the direct connection from the motor cortex to spinal motor neurons is responsible for dexterous hand movements in primates. However, the role of the 'phylogenetically older' indirect pathways from the motor cortex to motor neurons, mediated by spinal interneurons, remains elusive. Here we used a novel double-infection technique to interrupt the transmission through the propriospinal neurons (PNs), which act as a relay of the indirect pathway in macaque monkeys (Macaca fuscata and Macaca mulatta). The PNs were double infected by injection of a highly efficient retrograde gene-transfer vector into their target area and subsequent injection of adeno-associated viral vector at the location of cell somata. This method enabled reversible expression of green fluorescent protein (GFP)-tagged tetanus neurotoxin, thereby permitting the selective and temporal blockade of the motor cortex–PN–motor neuron pathway. This treatment impaired reach and grasp movements, revealing a critical role for the PN-mediated pathway in the control of hand dexterity. Anti-GFP immunohistochemistry visualized the cell bodies and axonal trajectories of the blocked PNs, which confirmed their anatomical connection to motor neurons. This pathway-selective and reversible technique for blocking neural transmission does not depend on cell-specific promoters or transgenic techniques, and is a new and powerful tool for functional dissection in system-level neuroscience studies.     

Human large granular lymphocytes are potent producers of interleukin-1

Natural killer (NK) activity against tumour and virus-infected target cells is shown by a subpopulation of peripheral blood mononuclear leukocytes with the morphological features of large granular lymphocytes (LGL). The lineage of human LGL is still controversial, as they display surface markers of both T lymphocytes and myelomonocytic cells. LGL have recently been reported to produce lymphokines such as interleukin-2 (IL-2) and alpha- as well as gamma-interferons, functions associated mainly with T cells. To determine whether cytokines associated with other cell lineages are also produced by LGL, we examined whether they might produce a myelomonocyte -associated cytokine such as interleukin-1 (IL-1). IL-1 is a 12-18,000 molecular weight (MW) lymphokine produced by a variety of cell types such as monocytes, keratinocytes and a human dendritic cell line, which plays a crucial role in immunoregulation and inflammation. Moreover, IL-1 has recently been reported to act synergistically with IL-2 and interferons in boosting LGL-mediated NK activity. We now show that a subset of highly purified human LGL with NK activity can be stimulated to secrete a soluble factor with the biochemical and biological characteristics of human IL-1.     

Restoration of type VII collagen expression and function in dystrophic epidermolysis bullosa

Dystrophic epidermolysis bullosa (DEB) is a family of inherited mechano-bullous disorders caused by mutations in the human type VII collagen gene (COL7A1). Individuals with DEB lack type VII collagen and anchoring fibrils, structures that attach epidermis and dermis. The current lack of treatment for DEB is an impetus to develop gene therapy strategies that efficiently transfer and stably express genes delivered to skin cells in vivo. In this study, we delivered and expressed full-length type VII collagen using a self-inactivating minimal lentivirus-based vector. Transduction of lentiviral vectors containing the COL7A1 transgene into recessive DEB (RDEB) keratinocytes and fibroblasts (in which type VII collagen was absent) resulted in persistent synthesis and secretion of type VII collagen. Unlike RDEB parent cells, the gene-corrected cells had normal morphology, proliferative potential, matrix attachment and motility. We used these gene-corrected cells to regenerate human skin on immune-deficient mice. Human skin regenerated by gene-corrected RDEB cells had restored expression of type VII collagen and formation of anchoring fibrils at the dermal-epidermal junction in vivo. These studies demonstrate that it is possible to restore type VII collagen gene expression in RDEB skin in vivo.