The 67LR (67 kDa laminin receptor) is a cell-surface receptor with high affinity for its primary ligand. Its role as a laminin receptor makes it an important molecule both in cell adhesion to the basement membrane and in signalling transduction following this binding event. The protein also plays critical roles in the metastasis of tumour cells. Isolation of the protein from either normal or cancerous cells results in a product with an approx. molecular mass of 67 kDa. This protein is believed to be derived from a smaller precursor, the 37LRP (37 kDa laminin receptor precursor). However, the precise mechanism by which cytoplasmic 37LRP becomes cell-membrane-embedded 67LR is unclear. The process may involve post-translational fatty acylation of the protein combined with either homo- or hetero-dimerization, possibly with a galectin-3-epitope-containing partner. Furthermore, it has become clear that acting as a receptor for laminin is not the only function of this protein. 67LR also acts as a receptor for viruses, such as Sindbis virus and dengue virus, and is involved with internalization of the prion protein. Interestingly, unmodified 37LRP is a ribosomal component and homologues of this protein are found in all five kingdoms. In addition, it appears to be strongly associated with histones in the eukaryotic cell nucleus, although the precise role of these interactions is not clear. Here we review the current understanding of the structure and function of this molecule, as well as highlighting areas requiring further research.

The flagella connector (FC) of procyclic trypanosomes is a mobile, transmembrane junction important in providing cytotactic morphogenetic information to the daughter cell. Quantitative analyses of FC positioning along the old flagellum, involving direct observations and use of the MPM2 anti-phosphoprotein monoclonal reveals a `stop point' is reached on the old flagellum which correlates well with the initiation of basal body migration and kinetoplast segregation. This demonstrates further complexities of the FC and its movement in morphogenetic events in trypanosomes than have hitherto been described. We used intraflagellar transport RNAi mutants to ablate the formation of a new flagellum. Intriguingly the FC could still move, indicating that a motor function beyond the new flagellum is sufficient to move it. When such a FC moves, it drags a sleeve of new flagellar membrane out of the flagellar pocket. This axoneme-less flagellar membrane maintains appropriate developmental relationships to the cell body including following the correct helical path and being connected to the internal cytoskeleton by macula adherens junctions. Movement of the FC in the apparent absence of intraflagellar transport raises the possibility of a new form of motility within a eukaryotic flagellum.

Despite the importance of continental breakup in plate tectonics, precisely how extensional processes such as brittle faulting, ductile plate stretching, and magma intrusion evolve in space and time during the development of new ocean basins remains poorly understood. The rifting of Arabia from Africa in the Afar depression is an ideal natural laboratory to address this problem since the region exposes subaerially the tectonically active transition from continental rifting to incipient seafloor spreading. We review recent constraints on along-axis variations in rift morphology, crustal and mantle structure, the distribution and style of ongoing faulting, subsurface magmatism and surface volcanism in the Red Sea rift of Afar to understand processes ultimately responsible for the formation of magmatic rifted continental margins. Our synthesis shows that there is a fundamental change in rift morphology from central Afar northward into the Danakil depression, spatially coincident with marked thinning of the crust, an increase in the volume of young basalt flows, and subsidence of the land towards and below sea-level. The variations can be attributed to a northward increase in proportion of extension by ductile plate stretching at the expense of magma intrusion. This is likely in response to a longer history of localised heating and weakening in a narrower rift. Thus, although magma intrusion accommodates strain for a protracted period during rift development, the final stages of breakup are dominated by a phase of plate stretching with a shift from intrusive to extrusive magmatism. This late-stage pulse of decompression melting due to plate thinning may be responsible for the formation of seaward dipping reflector sequences of basalts and sediments, which are ubiquitous at magmatic rifted margins worldwide.

Trypanosomatids of the order Kinetoplastida are major contributors to global disease and morbidity, and understanding their basic biology coupled with the development of new drug targets represents a critical need. Additionally, trypanosomes are among the more accessible divergent eukaryote experimental systems. The genome of Trypanosoma brucei contains 8,131 predicted open reading frames (ORFs), of which over half have no known homologues beyond the Kinetoplastida and a substantial number of others are poorly defined by in silico analysis. Thus, a major challenge following completion of the T. brucei genome sequence is to obtain functional data for all trypanosome ORFs. As T. brucei is more experimentally tractable than the related Trypanosoma cruzi and Leishmania spp. and shares >75% of their genes, functional analysis of T. brucei has the potential to inform a range of parasite biology. Here, we report methods for systematic mRNA ablation by RNA interference (RNAi) and for phenotypic analysis, together with online data dissemination. This represents the first systematic analysis of gene function in a parasitic organism. In total, 210 genes have been targeted in the bloodstream form parasite, representing an essentially complete phenotypic catalogue of chromosome I together with a validation set. Over 30% of the chromosome I genes generated a phenotype when targeted by RNAi; most commonly, this affected cell growth, viability, and/or cell cycle progression. RNAi against approximately 12% of ORFs was lethal, and an additional 11% had growth defects but retained short-term viability in culture. Although we found no evidence for clustering or a bias towards widely evolutionarily conserved genes within the essential ORF cohort, the putative chromosome I centromere is adjacent to a domain containing genes with no associated phenotype. Involvement of such a large proportion of genes in robust growth in vitro indicates that a high proportion of the expressed trypanosome genome is required for efficient propagation; many of these gene products represent potential drug targets.Protozoan parasites are responsible for a significant proportion of global morbidity, mortality, and economic hardship, and in most countries current control and treatment regimes are either failing or under serious threat (6). African trypanosomiasis, caused by Trypanosoma brucei spp., is responsible for tens to hundreds of thousands of human infections annually in areas of sub-Saharan Africa where the infection is endemic and is compounded by the impact of the disease on animal welfare and productivity. Without treatment trypanosomiasis is invariably fatal, and the need for new treatments is urgent. Mechanisms for combating pathogenic protozoa rely on development and exploitation of new drug targets and/or vaccine candidates as well as efforts at vector control, all of which require detailed understanding of the biology of the pathogen and its relationship with the host and vector. The presence of efficient antigenic variation in T. brucei make...