The celestial mechanics of Leibniz in the light of Newtonian criticism

By the middle of the nineteenth century science was developing into a profession demanding advanced training and devotion to research. American institutions, however, were still better suited to an earlier stage of popular science. Many of the difficulties and frustrations for would-be scientists created by the time lag in institutional change are illustrated in the career of Cleveland Abbe. In the fifteen years between 1856 and 1871 his attempts to become an astronomer touched upon many significant aspects of American science as a profession, including the American observatory movement, the creation of graduate education, government support for science, and the tension between the joint goals of the increase and the diffusion of knowledge.     

The adoption of self-induction by telephony, 1886–1889

Through 1886 to 1889 understanding of the mechanism of telephone transmission was transformed from an electrostatic and traditional view to an electrodynamic one conforming with Maxwell's scheme. Observed at the level of commercial application this painful adjustment occurred via a sequence of controversies connected with self-induction—on techniques of telephony, on electrical measurement, on lightning conductors and on matters of professional ethics—in which the parts played by evidence, by theory, and by authority were strangely mixed. The well-known confrontation of O. Heaviside and W. H. Preece was at the centre of the debate. An open division between traditionalists and progressives amongst electrical engineers was provoked, and the effectiveness of mathematical theory as against pure pragmatism at the practical level had in the end to be conceded.     

Ablation of cyclase-associated protein 2 (CAP2) leads to cardiomyopathy

Cyclase-associated proteins are highly conserved proteins that have a role in the regulation of actin dynamics. Higher eukaryotes have two isoforms, CAP1 and CAP2. To study the in vivo function of CAP2, we generated mice in which the CAP2 gene was inactivated by a gene-trap approach. Mutant mice showed a decrease in body weight and had a decreased survival rate. Further, they developed a severe cardiac defect marked by dilated cardiomyopathy (DCM) associated with drastic reduction in basal heart rate and prolongations in atrial and ventricular conduction times. Moreover, CAP2-deficient myofibrils exhibited reduced cooperativity of calcium-regulated force development. At the microscopic level, we observed disarrayed sarcomeres with development of fibrosis. We analyzed CAP2’s role in actin assembly and found that it sequesters G-actin and efficiently fragments filaments. This activity resides completely in its WASP homology domain. Thus CAP2 is an essential component of the myocardial sarcomere and is essential for physiological functioning of the cardiac system, and a deficiency leads to DCM and various cardiac defects.     

Structural basis of bacterial defense against g-type lysozyme-based innate immunity

Gram-negative bacteria can produce specific proteinaceous inhibitors to defend themselves against the lytic action of host lysozymes. So far, four different lysozyme inhibitor families have been identified. Here, we report the crystal structure of the Escherichia coli periplasmic lysozyme inhibitor of g-type lysozyme (PliG-Ec) in complex with Atlantic salmon g-type lysozyme (SalG) at a resolution of 0.95 Å, which is exceptionally high for a complex of two proteins. The structure reveals for the first time the mechanism of g-type lysozyme inhibition by the PliG family. The latter contains two specific conserved regions that are essential for its inhibitory activity. The inhibitory complex formation is based on a double ‘key-lock’ mechanism. The first key-lock element is formed by the insertion of two conserved PliG regions into the active site of the lysozyme. The second element is defined by a distinct pocket of PliG accommodating a lysozyme loop. Computational analysis indicates that this pocket represents a suitable site for small molecule binding, which opens an avenue for the development of novel antibacterial agents that suppress the inhibitory activity of PliG.     

Anti-apoptotic mechanisms of HIV: lessons and novel approaches to curing HIV

Past efforts at curing infection with the human immunodeficiency virus (HIV) have been blocked by the resistance of some infected cells to viral cytopathic effects and the associated development of a latent viral reservoir. Furthermore, current efforts to clear the viral reservoir by means of reactivating latent virus are hampered by the lack of cell death in the newly productively infected cells. The purpose of this review is to describe the many anti-apoptotic mechanisms of HIV, as well as the current limitations in the field. Only by understanding how infected cells avoid HIV-induced cell death can an effective strategy to kill infected cells be developed.     

第一条人类染色体序列正在完成拼接

当人类基因组计划向着在2000年3月前完成人类基因组30亿个碱基的一份草图的目标迈进时,三个测序小组正在到达一个不同的、也许更加有意义的里程碑：第一条人类染色体的完成图谱。在最近两周内,国际22号染色体测序协作组将宣布他们完成这项任务的好消息。与此同时,其他染色体的测序工作也将顺利地在2003年完成其测序的预定目标。参与协作的科学家分别来自：英国剑桥的桑格中心;美国诺曼州极克拉荷马大学;日本东京的庆应大学医学院。科学家们说他们的合作堪称国际学术合作的典范,“许多人为之抛洒了血汗和泪水。”尽管作为国际人类基因…