Genome sequence and comparative analysis of the model rodent malaria parasite Plasmodium yoelii yoelii

Species of malaria parasite that infect rodents have long been used as models for malaria disease research. Here we report the whole-genome shotgun sequence of one species, Plasmodium yoelii yoelii, and comparative studies with the genome of the human malaria parasite Plasmodium falciparum clone 3D7. A synteny map of 2,212 P. y. yoelii contiguous DNA sequences (contigs) aligned to 14 P. falciparum chromosomes reveals marked conservation of gene synteny within the body of each chromosome. Of about 5,300 P. falciparum genes, more than 3,300 P. y. yoelii orthologues of predominantly metabolic function were identified. Over 800 copies of a variant antigen gene located in subtelomeric regions were found. This is the first genome sequence of a model eukaryotic parasite, and it provides insight into the use of such systems in the modelling of Plasmodium biology and disease.     

BRCA1 regulates the G2/M checkpoint by activating Chk1 kinase upon DNA damage

The breast cancer tumor-suppressor gene, BRCA1, encodes a protein with a BRCT domain-a motif that is found in many proteins that are implicated in DNA damage response and in genome stability. Phosphorylation of BRCA1 by the DNA damage-response proteins ATM, ATR and hCds1/Chk2 changes in response to DNA damage and at replication-block checkpoints. Although cells that lack BRCA1 have an abnormal response to DNA damage, the exact role of BRCA1 in this process has remained unclear. Here we show that BRCA1 is essential for activating the Chk1 kinase that regulates DNA damage-induced G2/M arrest. Thus, BRCA1 controls the expression, phosphorylation and cellular localization of Cdc25C and Cdc2/cyclin B kinase-proteins that are crucial for the G2/M transition. We show that BRCA1 regulates the expression of both Wee1 kinase, an inhibitor of Cdc2/cyclin B kinase, and the 14-3-3 family of proteins that sequesters phosphorylated Cdc25C and Cdc2/cyclin B kinase in the cytoplasm. We conclude that BRCA1 regulates key effectors that control the G2/M checkpoint and is therefore involved in regulating the onset of mitosis.     

Chondroitinase ABC promotes functional recovery after spinal cord injury

The inability of axons to regenerate after a spinal cord injury in the adult mammalian central nervous system (CNS) can lead to permanent paralysis. At sites of CNS injury, a glial scar develops, containing extracellular matrix molecules including chondroitin sulphate proteoglycans (CSPGs). CSPGs are inhibitory to axon growth in vitro, and regenerating axons stop at CSPG-rich regions in vivo. Removing CSPG glycosaminoglycan (GAG) chains attenuates CSPG inhibitory activity. To test the functional effects of degrading chondroitin sulphate (CS)-GAG after spinal cord injury, we delivered chondroitinase ABC (ChABC) to the lesioned dorsal columns of adult rats. We show that intrathecal treatment with ChABC degraded CS-GAG at the injury site, upregulated a regeneration-associated protein in injured neurons, and promoted regeneration of both ascending sensory projections and descending corticospinal tract axons. ChABC treatment also restored post-synaptic activity below the lesion after electrical stimulation of corticospinal neurons, and promoted functional recovery of locomotor and proprioceptive behaviours. Our results demonstrate that CSPGs are important inhibitory molecules in vivo and suggest that their manipulation will be useful for treatment of human spinal injuries.     

Experimental manipulations of fertile islands and nurse plant effects in the Mojave Desert, USA

In a mixed desert shrub community we removed and added shrub canopies to examine above- and belowground influences of 3 species of shrubs on islands of soil fertility and the survival of transplanted Ambrosia dumosa seedlings. Soils sampled under shrubs in the wet season had higher pH, water content, organic matter, and both total and mineralizable nitrogen than soils in adjacent open areas, confirming a widely established pattern in arid lands. However, we also found species differences in soil parameters. Soils under Coleogyne ramosissima had highest pH, soils under A. dumosa had highest water content and nitrogen mineralization rates, and soils under Larrea tridentata had lowest water content. Soils sampled under shrubs in the dry season, 7 months after experimental shrub removal, maintained higher organic matter and total and mineralizable nitrogen content than adjacent open soils, but pH and water were altered by shrub manipulations. Species differences persisted only in soil water levels ( A. dumosa soils were driest). Over a 1-year period, transplanted A. dumosa seedlings had highest survivorship in shrub removal and open treatments and died most rapidly under control shrubs of all 3 species, suggesting that shrubs had a strong negative effect on seedling survival, even in the presence of higher organic matter, nutrients, and (initially) higher water content of fertile islands. Our results suggest that nurse plants and islands of soil fertility have the potential to facilitate growth of other species by nutrient additions, but that the net effect of nurse plants can be negative due to shading and/or root competition.     

Kanab ambersnail and other terrestrial snails in south central Utah

Surveys for succineid snails were conducted to improve genetic and geographical information for the endangered Kanab ambersnail ( Oxyloma haydeni kanabensis Pilsbry) and related taxa within the Succineidae. Surveys were carried out in the Bureau of Land Management Kanab District, at the Grand Staircase Escalante National Monument, on 3 private holdings, and along Highways 89, 12, and 14, all in south central Utah. A population of Kanab ambersnails was known to exist in the region; other populations of Oxyloma were discovered in primarily seep-fed wetlands in Kanab Creek and in tributaries of and wetlands along the Virgin, Sevier, and Escalante rivers in Kane, Garfield, and Piute counties. None of the newly discovered populations was identified as Kanab ambersnail on the basis of anatomical evidence, although one was at the type locale for that species. We list other snail species encountered and discuss the status of the Kanab ambersnail in light of recent genetic research.     

X-ray illumination of the ejecta of supernova 1987A

When a massive star explodes as a supernova, substantial amounts of radioactive elements--primarily (56)Ni, (57)Ni and (44)Ti--are produced. After the initial flash of light from shock heating, the fading light emitted by the supernova is due to the decay of these elements. However, after decades, the energy powering a supernova remnant comes from the shock interaction between the ejecta and the surrounding medium. The transition to this phase has hitherto not been observed: supernovae occur too infrequently in the Milky Way to provide a young example, and extragalactic supernovae are generally too faint and too small. Here we report observations that show this transition in the supernova SN 1987A in the Large Magellanic Cloud. From 1994 to 2001, the ejecta faded owing to radioactive decay of (44)Ti as predicted. Then the flux started to increase, more than doubling by the end of 2009. We show that this increase is the result of heat deposited by X-rays produced as the ejecta interacts with the surrounding material. In time, the X-rays will penetrate farther into the ejecta, enabling us to analyse the structure and chemistry of the vanished star.     

Initial genome sequencing and analysis of multiple myeloma

Multiple myeloma is an incurable malignancy of plasma cells, and its pathogenesis is poorly understood. Here we report the massively parallel sequencing of 38 tumour genomes and their comparison to matched normal DNAs. Several new and unexpected oncogenic mechanisms were suggested by the pattern of somatic mutation across the data set. These include the mutation of genes involved in protein translation (seen in nearly half of the patients), genes involved in histone methylation, and genes involved in blood coagulation. In addition, a broader than anticipated role of NF-κB signalling was indicated by mutations in 11 members of the NF-κB pathway. Of potential immediate clinical relevance, activating mutations of the kinase BRAF were observed in 4% of patients, suggesting the evaluation of BRAF inhibitors in multiple myeloma clinical trials. These results indicate that cancer genome sequencing of large collections of samples will yield new insights into cancer not anticipated by existing knowledge.