Transparency in organisms

Summary The occurrence in animal phyla of species having a relatively transparent body is noted and measurements of the transmittance of medusae made in a spectrophotometer are reported, but the approximate nature of the results obtained with a commercial instrument and the importance of the correct physical design of the measuring apparatus are emphasized. The application to invertebrates of the structural explanation of the predominant transmission of incident light by the vertebrate cornea is discussed and the role of other factors considered. Destructive interference of the scattered rays, sufficient to account for the transparency of the cornea, has been shown not to demand a completely regular arrangement of collagen fibres. The small diameter and regularity of the fibrillar components in the muscles ofSagitta may be adequate to account for their transparency.I am grateful to Dr.D. M. Maurice for the encouragement of this interest, to Dr.E. G. Jordan for electron micrographs ofSagitta and to Mr.G. Ross (Department of Physics, Queen Elizabeth College) for helpful and critical discussion.     

An origin in the local Universe for some short gamma-ray bursts

Gamma-ray bursts (GRBs) divide into two classes: 'long', which typically have initial durations of T90 > 2 s, and 'short', with durations of T90 < 2 s (where T90 is the time to detect 90% of the observed fluence). Long bursts, which on average have softer gamma-ray spectra, are known to be associated with stellar core-collapse events-in some cases simultaneously producing powerful type Ic supernovae. In contrast, the origin of short bursts has remained mysterious until recently. A subsecond intense 'spike' of gamma-rays during a giant flare from the Galactic soft gamma-ray repeater, SGR 1806-20, reopened an old debate over whether some short GRBs could be similar events seen in galaxies out to approximately 70 Mpc (refs 6-10; redshift z approximately 0.016). Shortly after that, localizations of a few short GRBs (with optical afterglows detected in two cases) have shown an apparent association with a variety of host galaxies at moderate redshifts. Here we report a correlation between the locations of previously observed short bursts and the positions of galaxies in the local Universe, indicating that between 10 and 25 per cent of short GRBs originate at low redshifts (z < 0.025).     

Entomology: Asian honeybees parasitize the future dead

The queen of a honeybee colony has a reproductive monopoly because her workers' ovaries are normally inactive and any eggs that they do lay are eaten by their fellow workers. But if a colony becomes queenless, the workers start to lay eggs, stop policing and rear a last batch of males before the colony finally dies out. Here we show that workers of the Asian dwarf red honeybee Apis florea from other colonies exploit this interval as an opportunity to move in and lay their own eggs while no policing is in force. Such parasitism of queenless colonies does not occur in the western honeybee A. mellifera and may be facilitated by the accessibility of A. florea nests, which are built out in the open.     

Early Pliocene sediments and fossils from the northern Kenya Rift Valley

Mammalian fossils, which include the tooth of an early hominid, have been recovered from the newly mapped Ngorora Formation in the Baringo District. Preliminary dating suggests that this formation is aged between 9 and 12 million years, and the new finds thus help to span a ten million year gap in the fossil mammal record in Africa south of the Sahara.     

The DNA sequence and biological annotation of human chromosome 1

The reference sequence for each human chromosome provides the framework for understanding genome function, variation and evolution. Here we report the finished sequence and biological annotation of human chromosome 1. Chromosome 1 is gene-dense, with 3,141 genes and 991 pseudogenes, and many coding sequences overlap. Rearrangements and mutations of chromosome 1 are prevalent in cancer and many other diseases. Patterns of sequence variation reveal signals of recent selection in specific genes that may contribute to human fitness, and also in regions where no function is evident. Fine-scale recombination occurs in hotspots of varying intensity along the sequence, and is enriched near genes. These and other studies of human biology and disease encoded within chromosome 1 are made possible with the highly accurate annotated sequence, as part of the completed set of chromosome sequences that comprise the reference human genome.     

Averting biodiversity collapse in tropical forest protected areas

The rapid disruption of tropical forests probably imperils global biodiversity more than any other contemporary phenomenon. With deforestation advancing quickly, protected areas are increasingly becoming final refuges for threatened species and natural ecosystem processes. However, many protected areas in the tropics are themselves vulnerable to human encroachment and other environmental stresses. As pressures mount, it is vital to know whether existing reserves can sustain their biodiversity. A critical constraint in addressing this question has been that data describing a broad array of biodiversity groups have been unavailable for a sufficiently large and representative sample of reserves. Here we present a uniquely comprehensive data set on changes over the past 20 to 30 years in 31 functional groups of species and 21 potential drivers of environmental change, for 60 protected areas stratified across the world’s major tropical regions. Our analysis reveals great variation in reserve ‘health’: about half of all reserves have been effective or performed passably, but the rest are experiencing an erosion of biodiversity that is often alarmingly widespread taxonomically and functionally. Habitat disruption, hunting and forest-product exploitation were the strongest predictors of declining reserve health. Crucially, environmental changes immediately outside reserves seemed nearly as important as those inside in determining their ecological fate, with changes inside reserves strongly mirroring those occurring around them. These findings suggest that tropical protected areas are often intimately linked ecologically to their surrounding habitats, and that a failure to stem broad-scale loss and degradation of such habitats could sharply increase the likelihood of serious biodiversity declines.     

RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E)

Activated RAS promotes dimerization of members of the RAF kinase family. ATP-competitive RAF inhibitors activate ERK signalling by transactivating RAF dimers. In melanomas with mutant BRAF(V600E), levels of RAS activation are low and these drugs bind to BRAF(V600E) monomers and inhibit their activity. This tumour-specific inhibition of ERK signalling results in a broad therapeutic index and RAF inhibitors have remarkable clinical activity in patients with melanomas that harbour mutant BRAF(V600E). However, resistance invariably develops. Here, we identify a new resistance mechanism. We find that a subset of cells resistant to vemurafenib (PLX4032, RG7204) express a 61-kDa variant form of BRAF(V600E), p61BRAF(V600E), which lacks exons 4-8, a region that encompasses the RAS-binding domain. p61BRAF(V600E) shows enhanced dimerization in cells with low levels of RAS activation, as compared to full-length BRAF(V600E). In cells in which p61BRAF(V600E) is expressed endogenously or ectopically, ERK signalling is resistant to the RAF inhibitor. Moreover, a mutation that abolishes the dimerization of p61BRAF(V600E) restores its sensitivity to vemurafenib. Finally, we identified BRAF(V600E) splicing variants lacking the RAS-binding domain in the tumours of six of nineteen patients with acquired resistance to vemurafenib. These data support the model that inhibition of ERK signalling by RAF inhibitors is dependent on levels of RAS-GTP too low to support RAF dimerization and identify a novel mechanism of acquired resistance in patients: expression of splicing isoforms of BRAF(V600E) that dimerize in a RAS-independent manner.     

Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease

We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ≤ 1 × 10(-5). We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10(-17); including ADGC data, meta P = 5.0 × 10(-21)) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10(-14); including ADGC data, meta P = 1.2 × 10(-16)) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10(-4); including ADGC data, meta P = 8.6 × 10(-9)), CD33 (GERAD+, P = 2.2 × 10(-4); including ADGC data, meta P = 1.6 × 10(-9)) and EPHA1 (GERAD+, P = 3.4 × 10(-4); including ADGC data, meta P = 6.0 × 10(-10)).