Cloned pigs produced by nuclear transfer from adult somatic cells

Since the first report of live mammals produced by nuclear transfer from a cultured differentiated cell population in 1995 (ref. 1), successful development has been obtained in sheep, cattle, mice and goats using a variety of somatic cell types as nuclear donors. The methodology used for embryo reconstruction in each of these species is essentially similar: diploid donor nuclei have been transplanted into enucleated MII oocytes that are activated on, or after transfer. In sheep and goat pre-activated oocytes have also proved successful as cytoplast recipients. The reconstructed embryos are then cultured and selected embryos transferred to surrogate recipients for development to term. In pigs, nuclear transfer has been significantly less successful; a single piglet was reported after transfer of a blastomere nucleus from a four-cell embryo to an enucleated oocyte; however, no live offspring were obtained in studies using somatic cells such as diploid or mitotic fetal fibroblasts as nuclear donors. The development of embryos reconstructed by nuclear transfer is dependent upon a range of factors. Here we investigate some of these factors and report the successful production of cloned piglets from a cultured adult somatic cell population using a new nuclear transfer procedure.     

Simulating dynamical features of escape panic

One of the most disastrous forms of collective human behaviour is the kind of crowd stampede induced by panic, often leading to fatalities as people are crushed or trampled. Sometimes this behaviour is triggered in life-threatening situations such as fires in crowded buildings; at other times, stampedes can arise during the rush for seats or seemingly without cause. Although engineers are finding ways to alleviate the scale of such disasters, their frequency seems to be increasing with the number and size of mass events. But systematic studies of panic behaviour and quantitative theories capable of predicting such crowd dynamics are rare. Here we use a model of pedestrian behaviour to investigate the mechanisms of (and preconditions for) panic and jamming by uncoordinated motion in crowds. Our simulations suggest practical ways to prevent dangerous crowd pressures. Moreover, we find an optimal strategy for escape from a smoke-filled room, involving a mixture of individualistic behaviour and collective 'herding' instinct.     

The crystal structure of DNA mismatch repair protein MutS binding to a G x T mismatch

DNA mismatch repair ensures genomic integrity on DNA replication. Recognition of a DNA mismatch by a dimeric MutS protein initiates a cascade of reactions and results in repair of the newly synthesized strand; however, details of the molecular mechanism remain controversial. Here we present the crystal structure at 2.2 A of MutS from Escherichia coli bound to a G x T mismatch. The two MutS monomers have different conformations and form a heterodimer at the structural level. Only one monomer recognizes the mismatch specifically and has ADP bound. Mismatch recognition occurs by extensive minor groove interactions causing unusual base pairing and kinking of the DNA. Nonspecific major groove DNA-binding domains from both monomers embrace the DNA in a clamp-like structure. The interleaved nucleotide-binding sites are located far from the DNA. Mutations in human MutS alpha (MSH2/MSH6) that lead to hereditary predisposition for cancer, such as hereditary non-polyposis colorectal cancer, can be mapped to this crystal structure.     

Importance of stirring in the development of an iron-fertilized phytoplankton bloom

The growth of populations is known to be influenced by dispersal, which has often been described as purely diffusive. In the open ocean, however, the tendrils and filaments of phytoplankton populations provide evidence for dispersal by stirring. Despite the apparent importance of horizontal stirring for plankton ecology, this process remains poorly characterized. Here we investigate the development of a discrete phytoplankton bloom, which was initiated by the iron fertilization of a patch of water (7 km in diameter) in the Southern Ocean. Satellite images show a striking, 150-km-long bloom near the experimental site, six weeks after the initial fertilization. We argue that the ribbon-like bloom was produced from the fertilized patch through stirring, growth and diffusion, and we derive an estimate of the stirring rate. In this case, stirring acts as an important control on bloom development, mixing phytoplankton and iron out of the patch, but also entraining silicate. This may have prevented the onset of silicate limitation, and so allowed the bloom to continue for as long as there was sufficient iron. Stirring in the ocean is likely to be variable, so blooms that are initially similar may develop very differently.     

arrow encodes an LDL-receptor-related protein essential for Wingless signalling

The Wnt family of secreted molecules functions in cell-fate determination and morphogenesis during development in both vertebrates and invertebrates (reviewed in ref. 1). Drosophila Wingless is a founding member of this family, and many components of its signal transduction cascade have been identified, including the Frizzled class of receptor. But the mechanism by which the Wingless signal is received and transduced across the membrane is not completely understood. Here we describe a gene that is necessary for all Wingless signalling events in Drosophila. We show that arrow gene function is essential in cells receiving Wingless input and that it acts upstream of Dishevelled. arrow encodes a single-pass transmembrane protein, indicating that it may be part of a receptor complex with Frizzled class proteins. Arrow is a low-density lipoprotein (LDL)-receptor-related protein (LRP), strikingly homologous to murine and human LRP5 and LRP6. Thus, our data suggests a new and conserved function for this LRP subfamily in Wingless/Wnt signal reception.     

The role of microbes in accretion, lamination and early lithification of modern marine stromatolites

For three billion years, before the Cambrian diversification of life, laminated carbonate build-ups called stromatolites were widespread in shallow marine seas. These ancient structures are generally thought to be microbial in origin and potentially preserve evidence of the Earth's earliest biosphere. Despite their evolutionary significance, little is known about stromatolite formation, especially the relative roles of microbial and environmental factors in stromatolite accretion. Here we show that growth of modern marine stromatolites represents a dynamic balance between sedimentation and intermittent lithification of cyanobacterial mats. Periods of rapid sediment accretion, during which stromatolite surfaces are dominated by pioneer communities of gliding filamentous cyanobacteria, alternate with hiatal intervals. These discontinuities in sedimentation are characterized by development of surface films of exopolymer and subsequent heterotrophic bacterial decomposition, forming thin crusts of microcrystalline carbonate. During prolonged hiatal periods, climax communities develop, which include endolithic coccoid cyanobacteria. These coccoids modify the sediment, forming thicker lithified laminae. Preservation of lithified layers at depth creates millimetre-scale lamination. This simple model of modern marine stromatolite growth may be applicable to ancient stromatolites.     

Tat-specific cytotoxic T lymphocytes select for SIV escape variants during resolution of primary viraemia

Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections are characterized by early peaks of viraemia that decline as strong cellular immune responses develop. Although it has been shown that virus-specific CD8-positive cytotoxic T lymphocytes (CTLs) exert selective pressure during HIV and SIV infection, the data have been controversial. Here we show that Tat-specific CD8-positive T-lymphocyte responses select for new viral escape variants during the acute phase of infection. We sequenced the entire virus immediately after the acute phase, and found that amino-acid replacements accumulated primarily in Tat CTL epitopes. This implies that Tat-specific CTLs may be significantly involved in controlling wild-type virus replication, and suggests that responses against viral proteins that are expressed early during the viral life cycle might be attractive targets for HIV vaccine development.