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...

The northern East African Rift (EAR) is a unique location where we observe continental rifting in the Main Ethiopian Rift (MER) transitioning to incipient seafloor spreading in Afar. Here we present a 3‐D absolute shear wave velocity model of the crust and uppermost mantle of the northern EAR generated from ambient noise tomography. We generate 4,820 station pair correlation functions, from 170 stations (present over 12 years), which were inverted for phase velocity from 8–33 s period and finally for 3‐D absolute shear velocity structure to 60‐km depth. Everywhere in the uppermost mantle, shear velocity is slower than expected for a mantle peridotite composition (<4.1 km/s). This suggests the presence of pervasive partial melt, with focused upwelling and melt storage beneath the MER, where the slowest velocities (3.20 km/s ± 0.03) are observed. Average crustal shear velocity is faster beneath Afar (3.83 km/s ± 0.04) than the MER (3.60 km/s ± 0.04), albeit Afar has localized slow velocities beneath active volcanic centers. We interpret these slow‐velocity regions (including the MER) as magmatic intrusions and heating of the crust. Beneath the northwestern plateau, crustal velocities are laterally heterogeneous (3.3–3.65 ± 0.05 km/s at 10 km), suggesting a complex geological history and inhomogeneous magma distribution during rift development. Comparison between the MER and Afar allows us to draw conclusions between different stages of rifting. In particular, the MER has the slowest crustal velocities, consistent with longer magma residence times in the crust, early during the breakup process.

The Cameroon Volcanic Line (CVL) straddles the continent‐ocean boundary in West Africa but exhibits no clear age progression. This renders it difficult to explain by traditional plume/plate motion hypotheses; thus, there remains no consensus on the processes responsible for its development. To understand better the nature of asthenospheric flow beneath the CVL, and the effects of hotspot tectonism on the overlying lithosphere, we analyze mantle seismic anisotropy and seismicity. Cameroon is relatively aseismic compared to hotspots elsewhere, with little evidence for magmatism‐related crustal deformation away from Mount Cameroon, which last erupted in 2000. Low crustal Vp/Vs ratios (∼1.74) and a lack of evidence for seismically anisotropic aligned melt within the lithosphere both point toward a poorly developed magmatic plumbing system beneath the CVL. Null SKS splitting observations dominate the western continental portion of the CVL; elsewhere, anisotropic fast polarization directions parallel the strike of the Precambrian Central African Shear Zone (CASZ). The nulls may imply that the convecting upper mantle beneath the CVL is isotropic, or characterized by a vertically oriented olivine lattice preferred orientation fabric, perhaps due to a mantle plume or the upward limb of a small‐scale convection cell. Precambrian CASZ fossil lithospheric fabrics along the CVL may have been thermomechanically eroded during Gondwana breakup ∼130 Ma, with an isotropic lower lithosphere subsequently reforming due to cooling of the slow‐moving African plate. Small‐scale lithospheric delamination during the 30 Ma recent development of the line may also have contributed to the erosion of the CASZ lithospheric fossil anisotropy, at the same time as generating the low‐volume alkaline basaltic volcanism along the CVL.

We have identified five α-tubulin and six β-tubulin isotypes that are expressed in adult Fasciola hepatica. Amino acid sequence identities ranged between 72 and 95% for fluke α-tubulin and between 65 and 97% for β-tubulin isotypes. Nucleotide sequence identity ranged between 68–77% and 62–80%, respectively, for their coding sequences. Phylogenetic analysis indicated that two of the α-tubulins and two of the β-tubulins were distinctly divergent from the other trematode and nematode tubulin sequences described in this study, whereas the other isotypes segregated within the trematode clades. With regard to the proposed benzimidazole binding site on β-tubulin, three of the fluke isotypes had tyrosine at position 200 of β-tubulin, two had phenylalanine and one had leucine. All had phenylalanine at position 167 and glutamic acid at position 198. When isotype RT-PCR fragment sequences were compared between six individual flukes from the susceptible Cullompton isolate and from seven individual flukes from the two resistant isolates, Sligo and Oberon, these residues were conserved.

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