Definition of a consensus binding site for p53.

Recent experiments have suggested that p53 action may be mediated through its interaction with DNA. We have now identified 18 human genomic clones that bind to p53 in vitro. Precise mapping of the binding sequences within these clones revealed a consensus binding site with a striking internal symmetry, consisting of two copies of the 10 base pair motif 5'-PuPuPuC(A/T)(T/A)GPyPyPy-3' separated by 0-13 base pairs. One copy of the motif was insufficient for binding, and subtle alterations of the motif, even when present in multiple copies, resulted in loss of affinity for p53. Mutants of p53, representing each of the four "hot spots" frequently altered in human cancers, failed to bind to the consensus dimer. These results define the DNA sequence elements with which p53 interacts in vitro and which may be important for p53 action in vivo.     

Dynamic personalities of proteins

Because proteins are central to cellular function, researchers have sought to uncover the secrets of how these complex macromolecules execute such a fascinating variety of functions. Although static structures are known for many proteins, the functions of proteins are governed ultimately by their dynamic character (or 'personality'). The dream is to 'watch' proteins in action in real time at atomic resolution. This requires addition of a fourth dimension, time, to structural biology so that the positions in space and time of all atoms in a protein can be described in detail.     

Exploitation of structural and regulatory diversity in glutamate racemases

Glutamate racemase is an enzyme essential to the bacterial cell wall biosynthesis pathway, and has therefore been considered as a target for antibacterial drug discovery. We characterized the glutamate racemases of several pathogenic bacteria using structural and biochemical approaches. Here we describe three distinct mechanisms of regulation for the family of glutamate racemases: allosteric activation by metabolic precursors, kinetic regulation through substrate inhibition, and D-glutamate recycling using a d-amino acid transaminase. In a search for selective inhibitors, we identified a series of uncompetitive inhibitors specifically targeting Helicobacter pylori glutamate racemase that bind to a cryptic allosteric site, and used these inhibitors to probe the mechanistic and dynamic features of the enzyme. These structural, kinetic and mutational studies provide insight into the physiological regulation of these essential enzymes and provide a basis for designing narrow-spectrum antimicrobial agents.     

Prediction from the One‐Way Error Components Model with AR(1) Disturbances

In this paper we extend the works of Baillie and Baltagi (1999, in Analysis of Panels and Limited Dependent Variables Models, Hsiao C et al. (eds). Cambridge University Press: Cambridge, UK; 255–267) and generalize certain results from the Baltagi and Li (1992, Journal of Forecasting 11 : 561–567) paper accounting for AR(1) errors in the disturbance term. In particular, we derive six predictors for the one‐way error components model, as well as their associated asymptotic mean squared error of multi‐step prediction in the presence of AR(1) errors in the disturbance term. In addition, we also provide both theoretical and simulation evidence as to the relative efficiency of our alternative predictors. The adequacy of the prediction AMSE formula is also investigated by the use of Monte Carlo methods and indicates that the ordinary optimal predictor performs well for various accuracy criteria. Copyright © 2011 John Wiley & Sons, Ltd.     

Mechanisms and convergence of compensatory evolution in mammalian mitochondrial tRNAs

The function of protein and RNA molecules depends on complex epistatic interactions between sites. Therefore, the deleterious effect of a mutation can be suppressed by a compensatory second-site substitution. In relating a list of 86 pathogenic mutations in human tRNAs encoded by mitochondrial genes to the sequences of their mammalian orthologs, we noted that 52 pathogenic mutations were present in normal tRNAs of one or several nonhuman mammals. We found at least five mechanisms of compensation for 32 pathogenic mutations that destroyed a Watson-Crick pair in one of the four tRNA stems: restoration of the affected Watson-Crick interaction (25 cases), strengthening of another pair (4 cases), creation of a new pair (8 cases), changes of multiple interactions in the affected stem (11 cases) and changes involving the interaction between the loop and stem structures (3 cases). A pathogenic mutation and its compensating substitution are fixed in a lineage in rapid succession, and often a compensatory interaction evolves convergently in different clades. At least 10%, and perhaps as many as 50%, of all nucleotide substitutions in evolving mammalian tRNAs participate in such interactions, indicating that the evolution of tRNAs proceeds along highly epistatic fitness ridges.     

Ferromagnetism in one-dimensional monatomic metal chains

Two-dimensional systems, such as ultrathin epitaxial films and superlattices, display magnetic properties distinct from bulk materials. A challenging aim of current research in magnetism is to explore structures of still lower dimensionality. As the dimensionality of a physical system is reduced, magnetic ordering tends to decrease as fluctuations become relatively more important. Spin lattice models predict that an infinite one-dimensional linear chain with short-range magnetic interactions spontaneously breaks up into segments with different orientation of the magnetization, thereby prohibiting long-range ferromagnetic order at a finite temperature. These models, however, do not take into account kinetic barriers to reaching equilibrium or interactions with the substrates that support the one-dimensional nanostructures. Here we demonstrate the existence of both short- and long-range ferromagnetic order for one-dimensional monatomic chains of Co constructed on a Pt substrate. We find evidence that the monatomic chains consist of thermally fluctuating segments of ferromagnetically coupled atoms which, below a threshold temperature, evolve into a ferromagnetic long-range-ordered state owing to the presence of anisotropy barriers. The Co chains are characterized by large localized orbital moments and correspondingly large magnetic anisotropy energies compared to two-dimensional films and bulk Co.     

Optical pulsations from the anomalous X-ray pulsar 4U0142+61

Anomalous X-ray pulsars (AXPs) differ from ordinary radio pulsars in that their X-ray luminosity is orders of magnitude greater than their rate of rotational energy loss, and so they require an additional energy source. One possibility is that AXPs are highly magnetized neuron stars or 'magnetars' having surface magnetic fields greater than 10(14) G. This would make them similar to the soft gamma-ray repeaters (SGRs), but alternative models that do not require extreme magnetic fields also exist. An optical counterpart to the AXP 4U0142+61 was recently discovered, consistent with emission from a magnetar, but also from a magnetized hot white dwarf, or an accreting isolated neutron star. Here we report the detection of optical pulsations from 4U0142+61. The pulsed fraction of optical light (27 per cent) is five to ten times greater than that of soft X-rays, from which we conclude that 4U0142+61 is a magnetar. Although this establishes a direct relationship between AXPs and the soft gamma-ray repeaters, the evolutionary connection between AXPs, SGRs and radio pulsars remains controversial.     

The recent expansion of Pluto's atmosphere

Stellar occultations--the passing of a relatively nearby body in front of a background star--can be used to probe the atmosphere of the closer body with a spatial resolution of a few kilometres (ref. 1). Such observations can yield the scale height, temperature profile, and other information about the structure of the occulting atmosphere. Occultation data acquired for Pluto's atmosphere in 1988 revealed a nearly isothermal atmosphere above a radius of approximately 1,215 km. Below this level, the data could be interpreted as indicating either an extinction layer or the onset of a large thermal gradient, calling into question the fundamental structure of this atmosphere. Another question is to what extent Pluto's atmosphere might be collapsing as it recedes from the Sun (passing perihelion in 1989 in its 248-year orbital period), owing to the extreme sensitivity of the equilibrium surface pressure to the surface temperature. Here we report observations at a variety of visible and infrared wavelengths of an occultation of a star by Pluto in August 2002. These data reveal evidence for extinction in Pluto's atmosphere and show that it has indeed changed, having expanded rather than collapsed, since 1988.     

Prediction in the two‐way random‐effect model with heteroskedasticity

In this paper we extend Taub (1979) approach for prediction in the context of the variance components model. The extension obtained is based on the two‐way random‐effect model with heteroskedasticity. Prediction functions are then obtained in three heteroskedasticity cases (heteroskedasticity on the individual term , heteroskedasticity on the composite term ?_it, and heteroskedasticity on the temporal term ). Copyright © 2008 John Wiley & Sons, Ltd.     

地球内核的地震波速各向异性与其自转有关

地球内核相对于外部地球存在差异的转动，固体内核表面相对于液态外核运动的线速度在赤道上最大，在两极为零，因此内核生长速度在赤道附近比两极处快，引力作用将驱动某内部的物质内赤道向两极流动使其保持近似球形，与这一流动相应的轴对称应力场使得六方紧密堆积（ｈｃＰ）铁晶体的ｃ轴沿内核自转轴方向排列，导致地震波速度各向异性。