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.     

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.     

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.     

Vascular growth factors in neuropsychiatry

Recent advances in understanding the cellular and molecular basis of psychiatric illnesses have shed light on the important role played by trophic factors in modulating functional parameters associated with disease causality and drug action. Disease mechanisms are now thought to involve multiple cell types, including neurons and endothelial cells. These functionally distinct but interactively coupled cell types engage in cellular cross talk via shared and common signaling molecules. Dysregulation in their cellular signaling pathways influences brain function and alters behavioral performance. Multifunctional trophic factors such as VEGF and EPO that possess both neurotrophic and angiogenic actions are of particular interest due to their ability to rescue structural and plasticity deficits in neurons and vasculature. Obtaining insight into the behavioral, cellular and molecular actions of multi-functional trophic factors has the potential to open new and transformative therapeutic approaches.     

Diversity of IL-17-producing T lymphocytes

Interleukin (IL)-17 is a pro-inflammatory cytokine that plays critical roles in host defense against extracellular bacteria and fungi and also in the pathogenesis of autoimmune diseases. While CD4+ TCRαβ+ T helper (Th) 17 cells are the best-described cellular source of IL-17, many innate-like T cells are in fact potent producers of IL-17. Given the increasing interest in therapeutic modulation of the IL-17 axis, it is crucial to better understand the cellular origins of IL-17 in various infection and diseases settings. While the diverse population of IL-17-producing T cells share many common characteristics, notable differences also exist. In this review, we discuss the heterogeneity of IL-17-producing T cell types focusing on their development, regulation, and function.     

Nesting phenology and productivity of birds in the White and Inyo Mountains, California, as assessed with nest-boxes

Nest-boxes were monitored from 1988 to 1992 on 5 grids in the pinyon-juniper ( Pinus-Juniperus ) woodlands of the White and Inyo Mountains, California, to determine breeding phenology and productivity of cavity-nesting birds, and characteristics of used and non-used nest-boxes. We found a total of 112 nests of 6 species. Bewicks Wrens ( Thryomanes bewicki i; 64 nests), Mountain Chickadees ( Poecile gambeli ; 18), Ash-throated Flycatchers ( Myiarchus cinerascens ; 12), and Juniper Titmice ( Baeolophus ridgwayi ; 11) were the most common species utilizing the boxes. Nest phenology and numbers of young were similar to values reported elsewhere in the literature for the species, although nesting success for Mountain Chickadees appeared lower in our study. Chickadees were associated with relatively dense, mature vegetation on southern slopes. Juniper Titmice used areas with tall juniper shrubs and generally sparse vegetation. Bewicks Wrens used areas with short trees, sparse vegetation, and many stumps. Nest-boxes were underutilized (< 15% use) by most species relative to their availability and relative to detected abundances of the species. We suggest that nest-boxes can provide valuable breeding biology information and can potentially increase the productivity of rare and cavity-limited species.     

Summer habitat use and selection by female Sage Grouse ( Centrocercus urophasianus ) in Oregon

Cover types and vegetative characteristics (e.g., grasses, forbs, shrubs) used by female Sage Grouse ( Centrocercus urophasianus ) during summer were compared with available habitat on two study areas in southeastern Oregon. Broodless hens, which constituted 114 of the 125 (91%) radio-marked hens studied, selected big ( Artemisia tridentata ) subspp.) and low sagebrush ( A. arbuscular ) cover types at both study areas. At Hart Mountain, broodless hens did not select specific vegetative characteristics within cover types. However, at Jackass Creek, forb cover was greater ( P = .004) at broodless hen sites than at random locations. Differences in habitat use by broodless hens between study areas were associated with differences in forb availability. Broodless hens used a greater diversity of cover types than hens with broods. Broodless hens gathered in flocks and remained separate from but near hens with broods during early summer. By early July broodless hens moved to meadows while hens with broods remained in upland habitats.     

Differential responses to nitrogen form and concentration for Oryzopsis hymenoides and Elymus lanceolatus

In a greenhouse experiment, effects of nitrogen form and concentration on productivity and dry matter allocation differed between two species native to semiarid ecosystems of the Great Basin. Aboveground production of green surface area and of dry matter were consistently enhanced by increased nitrogen for the rhizomatous grass Elymus lanceolatus , but not for the bunchgrass Oryzopsis hymenoides . These differences were likely due to inherently low growth rates of O. hymenoides . Aboveground dry matter allocation also differed between the two species. O. hymenoides had more leaves per tiller with increased nitrogen, whereas leaf size but not number increased for E. lanceolatus . Furthermore, increases in tiller density with increased nitrogen for E. lanceolatus were almost three times greater than those for O. hymenoides . E. lanceolatus , but not O. hymenoides , was sensitive to the form of nitrogen supplied to the plants. When NH 4 -N was the only form of nitrogen supplied, high concentrations of NH 4 -N inhibited aboveground production of E. lanceolatus .