Structure of a nanobody-stabilized active state of the β(2) adrenoceptor

G protein coupled receptors (GPCRs) exhibit a spectrum of functional behaviours in response to natural and synthetic ligands. Recent crystal structures provide insights into inactive states of several GPCRs. Efforts to obtain an agonist-bound active-state GPCR structure have proven difficult due to the inherent instability of this state in the absence of a G protein. We generated a camelid antibody fragment (nanobody) to the human β(2) adrenergic receptor (β(2)AR) that exhibits G protein-like behaviour, and obtained an agonist-bound, active-state crystal structure of the receptor-nanobody complex. Comparison with the inactive β(2)AR structure reveals subtle changes in the binding pocket; however, these small changes are associated with an 11?? outward movement of the cytoplasmic end of transmembrane segment 6, and rearrangements of transmembrane segments 5 and 7 that are remarkably similar to those observed in opsin, an active form of rhodopsin. This structure provides insights into the process of agonist binding and activation.     

Newtonianism and the enthusiasm of Enlightenment

The career of John Jackson (1686-1763), Arian theologian and controversialist, provides a key to unlocking the early reception and quick collapse of a Newtonian natural apologetic originally developed by Samuel Clarke. The importance of friendship and discipleship in eighteenth-century intellectual enquiry is emphasised, and the links between Newton and his followers are traced alongside those of a group of Cambridge Lockeans, led by Jackson’s direct contemporary Daniel Waterland, who proved instrumental in the initial dismantling of Clarke’s brand of Newtonian apologetic. The controversial context of this engagement is shown to have been largely provided by the religiously compromising rise of freethinking, and Tindal’s Christianity as old as the creation (1731) signalled the dangers to proponents of natural religion as an adjunct of Christian apologetic in such a heated atmosphere. Religious division of the sort that resulted paradoxically played into the hands of the freethinkers in the anticlerical atmosphere of the 1730s, and accusations were exchanged between Newtonians and Lockeans accordingly. The dynamic of England’s Enlightenment experience is, then, a complicated one, and, as the career and writings of Jackson and William Whiston demonstrate, it was one which absorbed as well as repudiated ‘enthusiasm’.     

The optical afterglow of the short gamma-ray burst GRB 050709

It has long been known that there are two classes of gamma-ray bursts (GRBs), mainly distinguished by their durations. The breakthrough in our understanding of long-duration GRBs (those lasting more than approximately 2 s), which ultimately linked them with energetic type Ic supernovae, came from the discovery of their long-lived X-ray and optical 'afterglows', when precise and rapid localizations of the sources could finally be obtained. X-ray localizations have recently become available for short (duration <2 s) GRBs, which have evaded optical detection for more than 30 years. Here we report the first discovery of transient optical emission (R-band magnitude approximately 23) associated with a short burst: GRB 050709. The optical afterglow was localized with subarcsecond accuracy, and lies in the outskirts of a blue dwarf galaxy. The optical and X-ray afterglow properties 34 h after the GRB are reminiscent of the afterglows of long GRBs, which are attributable to synchrotron emission from ultrarelativistic ejecta. We did not, however, detect a supernova, as found in most nearby long GRB afterglows, which suggests a different origin for the short GRBs.     

Corneal avascularity is due to soluble VEGF receptor-1

Corneal avascularity-the absence of blood vessels in the cornea-is required for optical clarity and optimal vision, and has led to the cornea being widely used for validating pro- and anti-angiogenic therapeutic strategies for many disorders. But the molecular underpinnings of the avascular phenotype have until now remained obscure and are all the more remarkable given the presence in the cornea of vascular endothelial growth factor (VEGF)-A, a potent stimulator of angiogenesis, and the proximity of the cornea to vascularized tissues. Here we show that the cornea expresses soluble VEGF receptor-1 (sVEGFR-1; also known as sflt-1) and that suppression of this endogenous VEGF-A trap by neutralizing antibodies, RNA interference or Cre-lox-mediated gene disruption abolishes corneal avascularity in mice. The spontaneously vascularized corneas of corn1 and Pax6+/- mice and Pax6+/- patients with aniridia are deficient in sflt-1, and recombinant sflt-1 administration restores corneal avascularity in corn1 and Pax6+/- mice. Manatees, the only known creatures uniformly to have vascularized corneas, do not express sflt-1, whereas the avascular corneas of dugongs, also members of the order Sirenia, elephants, the closest extant terrestrial phylogenetic relatives of manatees, and other marine mammals (dolphins and whales) contain sflt-1, indicating that it has a crucial, evolutionarily conserved role. The recognition that sflt-1 is essential for preserving the avascular ambit of the cornea can rationally guide its use as a platform for angiogenic modulators, supports its use in treating neovascular diseases, and might provide insight into the immunological privilege of the cornea.     

Density-dependent mortality and the latitudinal gradient in species diversity

Ecologists have long postulated that density-dependent mortality maintains high tree diversity in the tropics. If species experience greater mortality when abundant, then more rare species can persist. Agents of density-dependent mortality (such as host-specific predators, and pathogens) may be more prevalent or have stronger effects in tropical forests, because they are not limited by climatic factors. If so, decreasing density-dependent mortality with increasing latitude could partially explain the observed latitudinal gradient in tree diversity. This hypothesis has never been tested with latitudinal data. Here we show that several temperate tree species experience density-dependent mortality between seed dispersal and seedling establishment. The proportion of species affected is equivalent to that in tropical forests, failing to support the hypothesis that this mechanism is more prevalent at tropical latitudes. We further show that density-dependent mortality is misinterpreted in previous studies. Our results and evidence from other studies suggest that density-dependent mortality is important in many forests. Thus, unless the strength of density-dependent mortality varies with latitude, this mechanism is not likely to explain the high diversity of tropical forests.     

MATLAB入门：第二版适用于初高级用户

本书简明扼要地介绍了MATLAB7．0系统。主要内容包括MATLAB命令；MATLAB程序设计；图形、图表、图像模板；方程求解函数和丰富多彩的快捷界面。这些命令对低版本和高版本的MATLAB同样适用。数学计算与文本、图形相结合，形成新颖完整的交互式文件是MAT—LAB7．0的新特点。书中介绍的内容既兼顾了初学者，又顾及了熟悉MATLAB早期版本的用户。     

Lack of long-term cortical reorganization after macaque retinal lesions

Several aspects of cortical organization are thought to remain plastic into adulthood, allowing cortical sensorimotor maps to be modified continuously by experience. This dynamic nature of cortical circuitry is important for learning, as well as for repair after injury to the nervous system. Electrophysiology studies suggest that adult macaque primary visual cortex (V1) undergoes large-scale reorganization within a few months after retinal lesioning, but this issue has not been conclusively settled. Here we applied the technique of functional magnetic resonance imaging (fMRI) to detect changes in the cortical topography of macaque area V1 after binocular retinal lesions. fMRI allows non-invasive, in vivo, long-term monitoring of cortical activity with a wide field of view, sampling signals from multiple neurons per unit cortical area. We show that, in contrast with previous studies, adult macaque V1 does not approach normal responsivity during 7.5 months of follow-up after retinal lesions, and its topography does not change. Electrophysiology experiments corroborated the fMRI results. This indicates that adult macaque V1 has limited potential for reorganization in the months following retinal injury.