Lifespan, growth rate, and body size across latitude in marine Bivalvia, with implications for Phanerozoic evolution.

Mean body size in marine animals has increased more than 100-fold since the Cambrian, a discovery that brings to attention the key life-history parameters of lifespan and growth rate that ultimately determine size. Variation in these parameters is not well understood on the planet today, much less in deep time. Here, we present a new global database of maximum reported lifespan and shell growth coupled with body size data for 1 148 populations of marine bivalves and show that (i) lifespan increases, and growth rate decreases, with latitude, both across the group as a whole and within well-sampled species, (ii) growth rate, and hence metabolic rate, correlates inversely with lifespan, and (iii) opposing trends in lifespan and growth combined with high variance obviate any demonstrable pattern in body size with latitude.

Plasmodium falciparum Rab5B is an N-terminally myristoylated Rab GTPase that is targeted to the parasite's plasma and food vacuole membranes.

Plasmodium falciparum (Pf) has a family of 11 Rab GTPases to regulate its vesicular transport. However, PfRab5B is unique in lacking a C-terminal geranyl-geranylation motif, while having N-terminal palmitoylation and myristoylation motifs. We show that the N-terminal glycine is required for PfRab5B myristoylation in vitro and when an N-terminal PfRab5B fragment possessing both acylation motifs is fused to GFP and expressed in transgenic P.

Discovery of novel and ligand-efficient inhibitors of Plasmodium falciparum and Plasmodium vivax N-myristoyltransferase.

N-Myristoyltransferase (NMT) is an attractive antiprotozoan drug target. A lead-hopping approach was utilized in the design and synthesis of novel benzo[b]thiophene-containing inhibitors of Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) NMT. These inhibitors are selective against Homo sapiens NMT1 (HsNMT), have excellent ligand efficiency (LE), and display antiparasitic activity in vitro.

Design and synthesis of inhibitors of Plasmodium falciparum N-myristoyltransferase, a promising target for antimalarial drug discovery.

Design of inhibitors for N-myristoyltransferase (NMT), an enzyme responsible for protein trafficking in Plasmodium falciparum , the most lethal species of parasites that cause malaria, is described. Chemistry-driven optimization of compound 1 from a focused NMT inhibitor library led to the identification of two early lead compounds 4 and 25, which showed good enzyme and cellular potency and excellent selectivity over human NMT. These molecules provide a valuable starting point for further development.

Plasmodium falciparum 19-kilodalton merozoite surface protein 1 (MSP1)-specific antibodies that interfere with parasite growth in vitro can inhibit MSP1 processing, merozoite invasion, and intracellular parasite development.

Merozoite surface protein 1 (MSP1) is a target for malaria vaccine development. Antibodies to the 19-kDa carboxy-terminal region referred to as MSP1(19) inhibit erythrocyte invasion and parasite growth, with some MSP1-specific antibodies shown to inhibit the proteolytic processing of MSP1 that occurs at invasion. We investigated a series of antibodies purified from rabbits immunized with MSP1(19) and AMA1 recombinant proteins for their ability to inhibit parasite growth, initially looking at MSP1 processing.

Interaction and dynamics of the Plasmodium falciparum MTIP-MyoA complex, a key component of the invasion motor in the malaria parasite.

The myosin tail domain interacting protein-myosin A (MTIP-MyoA) protein complex is an essential element of the motor driving invasion of red blood cells by the Plasmodium species that cause malaria. Here we report the key determinants of binding at the MTIP/MyoA interface, and the first structural study on the complex in solution using protein NMR.

Microtubule plus-end and minus-end capture at adherens junctions is involved in the assembly of apico-basal arrays in polarised epithelial cells.

Apico-basal polarisation of epithelial cells involves a dramatic reorganisation of the microtubule cytoskeleton. The classic radial array of microtubules focused on a centrally located centrosome typical of many animal cells is lost or greatly reduced and a non-centrosomal apico-basal array develops. The molecules and mechanisms responsible for the assembly and positioning of these non-centrosomal microtubules have not been fully elucidated.

Dynamic release of nuclear RanGTP triggers TPX2-dependent microtubule assembly during the apoptotic execution phase.

During apoptosis, the interphase microtubule network is dismantled then later replaced by a novel, non-centrosomal microtubule array. These microtubules assist in the peripheral redistribution of nuclear fragments in the apoptotic cell; however, the regulation of apoptotic microtubule assembly is not understood. Here, we demonstrate that microtubule assembly depends upon the release of nuclear RanGTP into the apoptotic cytoplasm because this process is blocked in apoptotic cells overexpressing dominant-negative GDP-locked Ran (T24N).

Ninein is released from the centrosome and moves bi-directionally along microtubules.

Cell-to-cell contact and polarisation of epithelial cells involve a major reorganisation of the microtubules and centrosomal components. The radial microtubule organisation is lost and an apico-basal array develops that is no longer anchored at the centrosome. This involves not only the relocation of microtubules but also of centrosomal anchoring proteins to apical non-centrosomal sites.

Microtubules: forgotten players in the apoptotic execution phase.

A cell entering the execution phase of apoptosis (regulated cell death) undergoes characteristic rearrangements, in which the cytoskeleton has major roles. Historically, this reorganisation has been attributed entirely to actomyosin contractility, with microtubule and intermediate filament systems both reported to be lost at an early stage. However, recent results indicate that microtubule networks re-form during the later stages of apoptosis and assist in the dispersal of nuclear and cellular fragments--steps that are thought to be important for preventing inflammation.

A novel role for microtubules in apoptotic chromatin dynamics and cellular fragmentation.

Dramatic changes in cellular dynamics characterise the apoptotic execution phase, culminating in fragmentation into membrane-bound apoptotic bodies. Previous evidence suggests that actin-myosin plays a dominant role in apoptotic cellular remodelling, whereas all other cytoskeletal elements dismantle. We have used fixed cells and live-cell imaging to confirm that interphase microtubules rapidly depolymerise at the start of the execution phase.

Actuating Cycloaromatization of a Bicyclo[7.3.1]enediyne by Annelation: An Example of Inverse Dependence on Bridge Atom Hybridization.

Although the acetylenic carbon atoms in 2 are closer together than those in 1, only the latter undergoes Bergman cyclization. In contrast, in analogous enediynes without an annelated cyclohexane ring a change in the hybridization of the bridging carbon atom from sp to sp leads to a dramatic increase in the cyclization rate.

Stereogenic Propargylic Centers via Base-Mediated Terminal Allene Isomerization.

A study of alkali metal amide-mediated isomerizations of terminal allenes is described. The isomerizations of substituted ethenylidenecyclohexanes to form diastereomeric mixtures of terminal alkynes have been conducted to determine factors which may influence the stereochemistry at the newly formed propargylic centers. An initial base screen revealed that potassium N-methylbutylamide (KMBA) exhibits the highest level of equatorial to axial alkyne diastereoselectivity.