Structure of a mutant of tyrosyl-tRNA synthetase with enhanced catalytic properties

One surprising outcome of applying the techniques of protein engineering to the enzyme tyrosyl-transfer RNA synthetase was that the enzyme's activity could actually be increased by a specific sequence change. In particular, altering residue threonine 51 to a proline (mutant TP51) increased the enzyme's affinity for tyrosyl adenylate complexes. The non-additive effect of combining the TP51 mutation with a second sequence alteration (histidine 48 to a glycine) suggested that the effect of the TP51 change might be mediated by a structural change involving the peptide backbone. To address the question of the mechanism by which the TP51 change increases the activity of tyrosyl-tRNA synthetase we have determined the structure of the mutant enzyme. We find the change has a purely local effect on the structure of the enzyme, and conclude that the increased activity of the TP51 mutant probably results from the replacement of the polar threonine residue by a non-polar group: in the wild-type enzyme substrate binding is disfavoured by the displacement of solvent from the vicinity of threonine 51. This unfavourable effect is absent in the TP51 mutant.     

'Magic' nucleus 42Si

Nuclear shell structures--the distribution of the quantum states of individual protons and neutrons--provide one of our most important guides for understanding the stability of atomic nuclei. Nuclei with 'magic numbers' of protons and/or neutrons (corresponding to closed shells of strongly bound nucleons) are particularly stable. Whether the major shell closures and magic numbers change in very neutron-rich nuclei (potentially causing shape deformations) is a fundamental, and at present open, question. A unique opportunity to study these shell effects is offered by the 42Si nucleus, which has 28 neutrons--a magic number in stable nuclei--and 14 protons. This nucleus has a 12-neutron excess over the heaviest stable silicon nuclide, and has only one neutron fewer than the heaviest silicon nuclide observed so far. Here we report measurements of 42Si and two neighbouring nuclei using a technique involving one- and two-nucleon knockout from beams of exotic nuclei. We present strong evidence for a well-developed proton subshell closure at Z = 14 (14 protons), the near degeneracy of two different (s(1/2) and d(3/2)) proton orbits in the vicinity of 42Si, and a nearly spherical shape for 42Si.     

用Bochner－Riesz平均逼近及Hardy求和

设ｆ∈（Ｑ＿ｎ），ｎ∈Ｎ且Ｓ＿Ｒ￣（ｎ－１）／２（ｆ）是ｆ的临界阶Ｂｏｃｈｎｅｒ─Ｒｉｅｓｚ平均．求得了（Ｈ，ｑ）逼近的阶的估计：其中ω＿２表示二阶连续模，ｑ＞０且ｃ是常数．同时研究了这类逼近的饱和问题．     

High-energy particle acceleration in the shell of a supernova remnant

A significant fraction of the energy density of the interstellar medium is in the form of high-energy charged particles (cosmic rays). The origin of these particles remains uncertain. Although it is generally accepted that the only sources capable of supplying the energy required to accelerate the bulk of Galactic cosmic rays are supernova explosions, and even though the mechanism of particle acceleration in expanding supernova remnant (SNR) shocks is thought to be well understood theoretically, unequivocal evidence for the production of high-energy particles in supernova shells has proven remarkably hard to find. Here we report on observations of the SNR RX J1713.7 - 3946 (G347.3 - 0.5), which was discovered by ROSAT in the X-ray spectrum and later claimed as a source of high-energy gamma-rays of TeV energies (1 TeV = 10(12) eV). We present a TeV gamma-ray image of the SNR: the spatially resolved remnant has a shell morphology similar to that seen in X-rays, which demonstrates that very-high-energy particles are accelerated there. The energy spectrum indicates efficient acceleration of charged particles to energies beyond 100 TeV, consistent with current ideas of particle acceleration in young SNR shocks.     

Approaching a state shift in Earth's biosphere

Localized ecological systems are known to shift abruptly and irreversibly from one state to another when they are forced across critical thresholds. Here we review evidence that the global ecosystem as a whole can react in the same way and is approaching a planetary-scale critical transition as a result of human influence. The plausibility of a planetary-scale 'tipping point' highlights the need to improve biological forecasting by detecting early warning signs of critical transitions on global as well as local scales, and by detecting feedbacks that promote such transitions. It is also necessary to address root causes of how humans are forcing biological changes.     

Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation

How tissues generate and maintain the correct number of cells is a fundamental problem in biology. In principle, tissue turnover can occur by the differentiation of stem cells, as is well documented for blood, skin and intestine, or by the duplication of existing differentiated cells. Recent work on adult stem cells has highlighted their potential contribution to organ maintenance and repair. However, the extent to which stem cells actually participate in these processes in vivo is not clear. Here we introduce a method for genetic lineage tracing to determine the contribution of stem cells to a tissue of interest. We focus on pancreatic beta-cells, whose postnatal origins remain controversial. Our analysis shows that pre-existing beta-cells, rather than pluripotent stem cells, are the major source of new beta-cells during adult life and after pancreatectomy in mice. These results suggest that terminally differentiated beta-cells retain a significant proliferative capacity in vivo and cast doubt on the idea that adult stem cells have a significant role in beta-cell replenishment.     

A soluble CD4 protein selectively inhibits HIV replication and syncytium formation

The CD4 (T4) molecule is expressed on a subset of T lymphocytes involved in class II MHC recognition, and is probably the physiological receptor for one or more monomorphic regions of class II MHC (refs 1-3). CD4 also functions as a receptor for the human immunodeficiency virus (HIV) exterior envelope glycoprotein (gp120) (refs 4-9), being essential for virus entry into the host cell and for membrane fusion, which contributes to cell-to-cell transmission of the virus and to its cytopathic effects. We have used a baculovirus expression system to generate mg quantities of a hydrophilic extracellular segment of CD4. Concentrations of soluble CD4 in the nanomolar range, like certain anti-CD4 monoclonal antibodies, inhibit syncytium formation and HIV infection by binding gp120-expressing cells. Perhaps more importantly, class II specific T-cell interactions are uninhibited by soluble CD4 protein, whereas they are virtually abrogated by equivalent amounts of anti-T4 antibody. This may reflect substantial differences in CD4 affinity for gp120 and class II MHC.