Nicolas Béguelin and his search for a crucial experiment on the nature of light (1772)

In the second half of the eighteenth century a lively debate was going on in Germany about the nature of light. One important contribution to this discussion, namely a paper by Nicolas Béguelin, is studied in this article. In his essay, Béguelin compared the Newtonian emission theory of light and the wave theory of Leonhard Euler. Whereas others opted for one of the two theories by invoking arguments or authorities, Béguelin made a systematic search for experiments which he hoped would settle the dispute. Two of these experiments were most original. The first, which Béguelin himself performed, concerned light rays grazing a glass surface. For several reasons it did not have the impact it deserved. The second one was a thought experiment which was meant to illustrate a major tenet of the wave theory, that is, the analogy between light and sound. An analysis is given of these two experiments, and it is shown that neither of them brought the debate to an end.     

Sir William Hamilton (1730–1803): His work and influence in geology

In the formative period of London's scientific instrument industry membership of a guild was a necessary step towards owning a business in the City. Through the guilds' formal system of apprenticeship, boys received first-class training in a skilled trade, and learned essential marketing and managerial techniques. By analysing the guilds' records of apprenticeship and subsequent guild life it is possible to determine chains of masters and apprentices by which the knowledge passed from generation to generation. At the same time, dates can be established for the training and subsequent working life of many known makers. The chains of knowledge reveal new and often important masters who were previously unknown because, by chance, their instruments or advertisements have not survived to the present day. Two guilds have been used to illustrate the chains: Broderers' Company and Joiners' Company.     

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.     

The role of estrogen receptor α in the regulation of bone and growth plate cartilage

Estrogens are important endocrine regulators of skeletal growth and maintenance in both females and males. Studies have demonstrated that the estrogen receptor (ER)-α is the main mediator of these estrogenic effects in bone. Therefore, estrogen signaling via ERα is a target both for affecting longitudinal bone growth and bone remodeling. However, treatment with estradiol (E2) leads to an increased risk of side effects such as venous thromboembolism and breast cancer. Thus, an improved understanding of the signaling pathways of ERα will be essential in order to find better bone specific treatments with minimal adverse effects for different estrogen-related bone disorders. This review summarizes the recent data regarding the intracellular signaling mechanisms, in vivo, mediated by the ERα activation functions (AFs), AF-1 and AF-2, and the effect on bone, growth plate and other estrogen responsive tissues. In addition, we review the recent cell-specific ERα-deleted mouse models lacking ERα specifically in neuronal cells or growth plate cartilage. The newly characterized signaling pathways of estrogen, described in this review, provide a better understanding of the ERα signaling pathways, which may facilitate the design of new, bone-specific treatment strategies with minimal adverse effects.