DNA sequence and analysis of human chromosome 8

The International Human Genome Sequencing Consortium (IHGSC) recently completed a sequence of the human genome. As part of this project, we have focused on chromosome 8. Although some chromosomes exhibit extreme characteristics in terms of length, gene content, repeat content and fraction segmentally duplicated, chromosome 8 is distinctly typical in character, being very close to the genome median in each of these aspects. This work describes a finished sequence and gene catalogue for the chromosome, which represents just over 5% of the euchromatic human genome. A unique feature of the chromosome is a vast region of approximately 15 megabases on distal 8p that appears to have a strikingly high mutation rate, which has accelerated in the hominids relative to other sequenced mammals. This fast-evolving region contains a number of genes related to innate immunity and the nervous system, including loci that appear to be under positive selection--these include the major defensin (DEF) gene cluster and MCPH1, a gene that may have contributed to the evolution of expanded brain size in the great apes. The data from chromosome 8 should allow a better understanding of both normal and disease biology and genome evolution.     

Reduced mixing generates oscillations and chaos in the oceanic deep chlorophyll maximum

Deep chlorophyll maxima (DCMs) are widespread in large parts of the world's oceans. These deep layers of high chlorophyll concentration reflect a compromise of phytoplankton growth exposed to two opposing resource gradients: light supplied from above and nutrients supplied from below. It is often argued that DCMs are stable features. Here we show, however, that reduced vertical mixing can generate oscillations and chaos in phytoplankton biomass and species composition of DCMs. These fluctuations are caused by a difference in the timescales of two processes: (1) rapid export of sinking plankton, withdrawing nutrients from the euphotic zone and (2) a slow upward flux of nutrients fuelling new phytoplankton production. Climate models predict that global warming will reduce vertical mixing in the oceans. Our model indicates that reduced mixing will generate more variability in DCMs, thereby enhancing variability in oceanic primary production and in carbon export into the ocean interior.     

Stratified prokaryote network in the oxic-anoxic transition of a deep-sea halocline

The chemical composition of the Bannock basin has been studied in some detail. We recently showed that unusual microbial populations, including a new division of Archaea (MSBL1), inhabit the NaCl-rich hypersaline brine. High salinities tend to reduce biodiversity, but when brines come into contact with fresher water the natural haloclines formed frequently contain gradients of other chemicals, including permutations of electron donors and acceptors, that may enhance microbial diversity, activity and biogeochemical cycling. Here we report a 2.5-m-thick chemocline with a steep NaCl gradient at 3.3 km within the water column betweeen Bannock anoxic hypersaline brine and overlying sea water. The chemocline supports some of the most biomass-rich and active microbial communities in the deep sea, dominated by Bacteria rather than Archaea, and including four major new divisions of Bacteria. Significantly higher metabolic activities were measured in the chemocline than in the overlying sea water and underlying brine; functional analyses indicate that a range of biological processes is likely to occur in the chemocline. Many prokaryotic taxa, including the phylogenetically new groups, were confined to defined salinities, and collectively formed a diverse, sharply stratified, deep-sea ecosystem with sufficient biomass to potentially contribute to organic geological deposits.     

Immunology: Toll-like receptors and antibody responses

Microbial components, such as lipopolysaccharides, augment immune responses by activating Toll-like receptors (TLRs). Some have interpreted this to mean that TLR signalling might not only help to initiate the adaptive immune response, but may also be required for it. The expanded view is shared by Pasare and Medzhitov, who conclude from an analysis of mice deficient in MyD88 (a TLR-signalling adaptor protein) that the generation of T-dependent antigen-specific antibody responses requires activation of TLRs in B cells. However, we show here that robust antibody responses can be elicited even in the absence of TLR signals. This appreciable TLR-independence of immune responses should be taken into account in the rational design of immunogenic and toleragenic vaccines.     

Insights into the dynamics of mantle plumes from uranium-series geochemistry

The long-standing paradigm that hotspot volcanoes such as Hawaii or Iceland represent the surface expression of mantle plumes--hot, buoyant upwelling regions beneath the Earth's lithosphere--has recently been the focus of controversy. Whether mantle plumes exist or not is pivotal for our understanding of the thermal, dynamic and compositional evolution of the Earth's mantle. Here we show that uranium-series disequilibria measured in hotspot lavas indicate that hotspots are indeed associated with hot and buoyant upwellings and that weaker (low buoyancy flux) hotspots such as Iceland and the Azores are characterized by lower excess temperatures than stronger hotspots such as Hawaii. This direct link between buoyancy flux and mantle temperature is evidence for the existence of mantle plumes.     

Towards molecular electronics with large-area molecular junctions

Electronic transport through single molecules has been studied extensively by academic and industrial research groups. Discrete tunnel junctions, or molecular diodes, have been reported using scanning probes, break junctions, metallic crossbars and nanopores. For technological applications, molecular tunnel junctions must be reliable, stable and reproducible. The conductance per molecule, however, typically varies by many orders of magnitude. Self-assembled monolayers (SAMs) may offer a promising route to the fabrication of reliable devices, and charge transport through SAMs of alkanethiols within nanopores is well understood, with non-resonant tunnelling dominating the transport mechanism. Unfortunately, electrical shorts in SAMs are often formed upon vapour deposition of the top electrode, which limits the diameter of the nanopore diodes to about 45 nm. Here we demonstrate a method to manufacture molecular junctions with diameters up to 100 microm with high yields (> 95 per cent). The junctions show excellent stability and reproducibility, and the conductance per unit area is similar to that obtained for benchmark nanopore diodes. Our technique involves processing the molecular junctions in the holes of a lithographically patterned photoresist, and then inserting a conducting polymer interlayer between the SAM and the metal top electrode. This simple approach is potentially low-cost and could pave the way for practical molecular electronics.     

From in vivo to in silico biology and back

The massive acquisition of data in molecular and cellular biology has led to the renaissance of an old topic: simulations of biological systems. Simulations, increasingly paired with experiments, are being successfully and routinely used by computational biologists to understand and predict the quantitative behaviour of complex systems, and to drive new experiments. Nevertheless, many experimentalists still consider simulations an esoteric discipline only for initiates. Suspicion towards simulations should dissipate as the limitations and advantages of their application are better appreciated, opening the door to their permanent adoption in everyday research.     

Prions and their partners in crime

Prions, the infectious agents of transmissible spongiform encephalopathies (TSEs), have defied full characterization for decades. The dogma has been that prions lack nucleic acids and are composed of a pathological, self-inducing form of the host's prion protein (PrP). Recent progress in propagating TSE infectivity in cell-free systems has effectively ruled out the involvement of foreign nucleic acids. However, host-derived nucleic acids or other non-PrP molecules seem to be crucial. Interactions between TSE-associated PrP and its normal counterpart are also pathologically important, so the physiological functions of normal PrP and how they might be corrupted by TSE infections have been the subject of recent research.