The retinoblastoma susceptibility gene encodes a nuclear phosphoprotein associated with DNA binding activity

The human gene (RB) that determines susceptibility to hereditary retinoblastoma has been identified recently by molecular genetic techniques. Previous results indicate that complete inactivation of the RB gene is required for tumour formation. As a 'cancer suppressor' gene, RB thus functions in a manner opposite to that of most other oncogenes. Sequence analysis of RB complementary DNA clones demonstrated a long open reading frame encoding a hypothetical protein with features suggestive of a DNA-binding function. To further substantiate and identify the RB protein, we have prepared rabbit antisera against a trypE-RB fusion protein. The purified anti-RB IgG immunoprecipitates a protein doublet with apparent relative molecular mass (Mr) of 110,000-114,000. The specific protein(s) are present in all cell lines expressing normal RB mRNA, but are not detected in five retinoblastoma cell lines examined. The RB protein can be metabolically labelled with 32P-phosphoric acid, indicating that it is a phosphoprotein. Biochemical fractionation and immunofluorescence studies demonstrate that the majority of the protein is located within the nucleus. Furthermore, the protein can be retained by and eluted from DNA-cellulose columns, suggesting that it is associated with DNA binding activity. Taken together, these results imply that the RB gene product may function in regulating other genes within the cell.     

Chemical structure and biological activity of the Caenorhabditis elegans dauer-inducing pheromone

Pheromones are cell type-specific signals used for communication between individuals of the same species. When faced with overcrowding or starvation, Caenorhabditis elegans secrete the pheromone daumone, which facilitates communication between individuals for adaptation to adverse environmental stimuli. Daumone signals C. elegans to enter the dauer stage, an enduring and non-ageing stage of the nematode life cycle with distinctive adaptive features and extended life. Because daumone is a key regulator of chemosensory processes in development and ageing, the chemical identification of daumone is important for elucidating features of the daumone-mediated signalling pathway. Here we report the isolation of natural daumone from C. elegans by large-scale purification, as well as the total chemical synthesis of daumone. We present the stereospecific chemical structure of purified daumone, a fatty acid derivative. We demonstrate that both natural and chemically synthesized daumones equally induce dauer larva formation in C. elegans (N2 strain) and certain dauer mutants, and also result in competition between food and daumone. These results should help to elucidate the daumone-mediated signalling pathway, which might in turn influence ageing and obesity research and the development of antinematodal drugs.     

Extinction risk from climate change

Climate change over the past approximately 30 years has produced numerous shifts in the distributions and abundances of species and has been implicated in one species-level extinction. Using projections of species' distributions for future climate scenarios, we assess extinction risks for sample regions that cover some 20% of the Earth's terrestrial surface. Exploring three approaches in which the estimated probability of extinction shows a power-law relationship with geographical range size, we predict, on the basis of mid-range climate-warming scenarios for 2050, that 15-37% of species in our sample of regions and taxa will be 'committed to extinction'. When the average of the three methods and two dispersal scenarios is taken, minimal climate-warming scenarios produce lower projections of species committed to extinction ( approximately 18%) than mid-range ( approximately 24%) and maximum-change ( approximately 35%) scenarios. These estimates show the importance of rapid implementation of technologies to decrease greenhouse gas emissions and strategies for carbon sequestration.     

Structural basis for inhibition of the replication licensing factor Cdt1 by geminin

To maintain chromosome stability in eukaryotic cells, replication origins must be licensed by loading mini-chromosome maintenance (MCM2-7) complexes once and only once per cell cycle. This licensing control is achieved through the activities of geminin and cyclin-dependent kinases. Geminin binds tightly to Cdt1, an essential component of the replication licensing system, and prevents the inappropriate reinitiation of replication on an already fired origin. The inhibitory effect of geminin is thought to prevent the interaction between Cdt1 and the MCM helicase. Here we describe the crystal structure of the mouse geminin-Cdt1 complex using tGeminin (residues 79-157, truncated geminin) and tCdt1 (residues 172-368, truncated Cdt1). The amino-terminal region of a coiled-coil dimer of tGeminin interacts with both N-terminal and carboxy-terminal parts of tCdt1. The primary interface relies on the steric complementarity between the tGeminin dimer and the hydrophobic face of the two short N-terminal helices of tCdt1 and, in particular, Pro 181, Ala 182, Tyr 183, Phe 186 and Leu 189. The crystal structure, in conjunction with our biochemical data, indicates that the N-terminal region of tGeminin might be required to anchor tCdt1, and the C-terminal region of tGeminin prevents access of the MCM complex to tCdt1 through steric hindrance.     

Fisheries: mislabelling of a depleted reef fish

Any fish species that appears to be readily available in the marketplace will create an impression among the public that there is a plentiful supply of that fish in the sea, but this may belie the true state of the fisheries' stock. Here we use molecular genetic analysis to show that some three-quarters of the fish sold in the United States as 'red snapper'--the US Food and Drug Administration's legally designated common name for Lutjanus campechanus--belong to another species. Mislabelling to this extent not only defrauds consumers but could also adversely affect estimates of stock size if it influences the reporting of catch data that are used in fisheries management.     

An unusual isotope effect in a high-transition-temperature superconductor

In conventional superconductors, the electron pairing that allows superconductivity is caused by exchange of virtual phonons, which are quanta of lattice vibration. For high-transition-temperature (high-T(c)) superconductors, it is far from clear that phonons are involved in the pairing at all. For example, the negligible change in T(c) of optimally doped Bi2Sr2CaCu2O8+delta (Bi2212; ref. 1) upon oxygen isotope substitution (16O --> 18O leads to T(c) decreasing from 92 to 91 K) has often been taken to mean that phonons play an insignificant role in this material. Here we provide a detailed comparison of the electron dynamics of Bi2212 samples containing different oxygen isotopes, using angle-resolved photoemission spectroscopy. Our data show definite and strong isotope effects. Surprisingly, the effects mainly appear in broad high-energy humps, commonly referred to as 'incoherent peaks'. As a function of temperature and electron momentum, the magnitude of the isotope effect closely correlates with the superconducting gap--that is, the pair binding energy. We suggest that these results can be explained in a dynamic spin-Peierls picture, where the singlet pairing of electrons and the electron-lattice coupling mutually enhance each other.