Comparative and demographic analysis of orang-utan genomes

'Orang-utan' is derived from a Malay term meaning 'man of the forest' and aptly describes the southeast Asian great apes native to Sumatra and Borneo. The orang-utan species, Pongo abelii (Sumatran) and Pongo pygmaeus (Bornean), are the most phylogenetically distant great apes from humans, thereby providing an informative perspective on hominid evolution. Here we present a Sumatran orang-utan draft genome assembly and short read sequence data from five Sumatran and five Bornean orang-utan genomes. Our analyses reveal that, compared to other primates, the orang-utan genome has many unique features. Structural evolution of the orang-utan genome has proceeded much more slowly than other great apes, evidenced by fewer rearrangements, less segmental duplication, a lower rate of gene family turnover and surprisingly quiescent Alu repeats, which have played a major role in restructuring other primate genomes. We also describe a primate polymorphic neocentromere, found in both Pongo species, emphasizing the gradual evolution of orang-utan genome structure. Orang-utans have extremely low energy usage for a eutherian mammal, far lower than their hominid relatives. Adding their genome to the repertoire of sequenced primates illuminates new signals of positive selection in several pathways including glycolipid metabolism. From the population perspective, both Pongo species are deeply diverse; however, Sumatran individuals possess greater diversity than their Bornean counterparts, and more species-specific variation. Our estimate of Bornean/Sumatran speciation time, 400,000?years ago, is more recent than most previous studies and underscores the complexity of the orang-utan speciation process. Despite a smaller modern census population size, the Sumatran effective population size (N(e)) expanded exponentially relative to the ancestral N(e) after the split, while Bornean N(e) declined over the same period. Overall, the resources and analyses presented here offer new opportunities in evolutionary genomics, insights into hominid biology, and an extensive database of variation for conservation efforts.     

Changes in riparian vegetation along the Colorado River and Rio Grande, Colorado

Changes in vegetation including area occupied, canopy cover, and maturity class of cottonwoods ( Populus spp.) within lower-elevation zones of the Colorado River and Rio Grande in Colorado were monitored over 25- and 27-year intervals, respectively, using photo-interpretative methods. Estimated loss of cottonwoods along the Colorado River was 2ha/km (-17.5%), and remaining stands had become more open and older. Cottonwoods along the Rio Grande increased 1.6 ha/km (9.3%) with minor canopy cover and maturity class changes. Area occupied by shrubs and river channel changed little along the Colorado River, but declined along the Rio Grande. Loss of hay meadow occurred along both rivers, whereas developed land increased along the Colorado River and farmland increased along the Rio Grande. Wildlife habitats along the Colorado deteriorated much more rapidly than those along the Rio Grande during monitored intervals.     

Covert skill learning in a cortical-basal ganglia circuit

We learn complex skills such as speech and dance through a gradual process of trial and error. Cortical-basal ganglia circuits have an important yet unresolved function in this trial-and-error skill learning; influential 'actor-critic' models propose that basal ganglia circuits generate a variety of behaviours during training and learn to implement the successful behaviours in their repertoire. Here we show that the anterior forebrain pathway (AFP), a cortical-basal ganglia circuit, contributes to skill learning even when it does not contribute to such 'exploratory' variation in behavioural performance during training. Blocking the output of the AFP while training Bengalese finches to modify their songs prevented the gradual improvement that normally occurs in this complex skill during training. However, unblocking the output of the AFP after training caused an immediate transition from naive performance to excellent performance, indicating that the AFP covertly gained the ability to implement learned skill performance without contributing to skill practice. In contrast, inactivating the output nucleus of the AFP during training completely prevented learning, indicating that learning requires activity within the AFP during training. Our results suggest a revised model of skill learning: basal ganglia circuits can monitor the consequences of behavioural variation produced by other brain regions and then direct those brain regions to implement more successful behaviours. The ability of the AFP to identify successful performances generated by other brain regions indicates that basal ganglia circuits receive a detailed efference copy of premotor activity in those regions. The capacity of the AFP to implement successful performances that were initially produced by other brain regions indicates precise functional connections between basal ganglia circuits and the motor regions that directly control performance.     

A simple method for the collection of leucocytes from rat blood

Zusammenfassung Blutleukozyten von Ratten wurden mit menschlichem (normalem) Serum behandelt. Die Viabilität dieser Präparationen konnte dadurch demonstriert werden, dass die Zellen durch Phytohemagglutinin in «blast» Formen umgewandelt wurden.     

Die katalytische Wirkung von Metallionen auf die Stabilität von Phosphagenen

Summary Phosphoroguanidates, a class of compounds which includes the enzymatically-active phosphagens, exhibit exceptionalin vitro stability. This lack of reactivity implies anin vivo mode of activation, as yet undiscerned. A variety of metal ions catalyse the cleavage of the phosphorus-nitrogen bond with consequent phosphoryl-group transfer, but the enhancement of rate seems insufficient to account for the known activities of phosphoro-creatine and phosphoro-arginine. It is suggested that yet another mode of activation, chemical or biochemical, awaits discovery.     

The pathology, pathobiology and pathogenesis of schistosomiasis.

Although the general pathology of schistosomiasis has been well understood for more than 70 years, it is only recently that it has been possible to analyse the disease at the molecular level and to understand the relationship between the number of parasites in an infected individual and the appearance of overt disease.     

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.