Molecular basis of parathyroid hormone receptor signaling and trafficking: a family B GPCR paradigm

The parathyroid hormone (PTH) receptor type 1 (PTHR), a G protein-coupled receptor (GPCR), transmits signals to two hormone systems—PTH, endocrine and homeostatic, and PTH-related peptide (PTHrP), paracrine—to regulate different biological processes. PTHR responds to these hormonal stimuli by activating heterotrimeric G proteins, such as G_S that stimulates cAMP production. It was thought that the PTHR, as for all other GPCRs, is only active and signals through G proteins on the cell membrane, and internalizes into a cell to be desensitized and eventually degraded or recycled. Recent studies with cultured cell and animal models reveal a new pathway that involves sustained cAMP signaling from intracellular domains. Not only do these studies challenge the paradigm that cAMP production triggered by activated GPCRs originates exclusively at the cell membrane but they also advance a comprehensive model to account for the functional differences between PTH and PTHrP acting through the same receptor.     

Number and condition of seeds in ponderosa pine cones in central Arizona

Ponderosa pine cones from 10 areas in Arizona were collected prior to natural seed dispersal and dissected to determine the number of sound, hollow, and insect-damaged seeds in each cone. Total and sound seed yields per cone did not vary significantly among areas but did vary significantly among trees within each area. Numbers of hollow and Megastigmus -infested (Hymenoptera: Torymidae) seeds varied significantly among areas and trees within areas. Numbers of sound seed increased significantly with increasing cone length but did not change with increasing numbers of cones per cluster. The percentages of Megastigmus -infested seed did not change significantly with increasing cone length or number of cones per cluster.     

On Cowania and its intergeneric hybrids in Arizona

Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;} The putative intergeneric hybridization between Stansbury Cliffrose ( Cowania ) and Apache Plume ( Fallugia ) is found to be undocumented. Chromosome counts support reported base numbers for Cowania and Fallugia to be n = 9 and n = 14 respectively.     

Analysts’ Dynamic Decisions: Timeliness versus Accuracy

For analysts there is a tradeoff between the accuracy and the timeliness of their forecasts. Prior literature heavily investigates analyst forecast accuracy. Few papers investigate the importance of timeliness. To our best knowledge, there are no empirical papers to date to investigate the dynamic interplay between these key characteristics. We show that if analysts experience a period of high accuracy relative to their peers, they subsequently focus more on the timeliness of their forecasts in the subsequent period and thus issue their forecasts earlier than they did in the prior period. Copyright © 2016 John Wiley & Sons, Ltd.     

Horses damp the spring in their step.

The muscular work of galloping in horses is halved by storing and returning elastic strain energy in spring-like muscle-tendon units.These make the legs act like a child's pogo stick that is tuned to stretch and recoil at 2.5 strides per second. This mechanism is optimized by unique musculoskeletal adaptations: the digital flexor muscles have extremely short fibres and significant passive properties, whereas the tendons are very long and span several joints. Length change occurs by a stretching of the spring-like digital flexor tendons rather than through energetically expensive length changes in the muscle. Despite being apparently redundant for such a mechanism, the muscle fibres in the digital flexors are well developed. Here we show that the mechanical arrangement of the elastic leg permits it to vibrate at a higher frequency of 30-40 Hz that could cause fatigue damage to tendon and bone. Furthermore, we show that the digital flexor muscles have minimal ability to contribute to or regulate significantly the 2.5-Hz cycle of movement, but are ideally arranged to damp these high-frequency oscillations in the limb.     

Chemistry of ion coordination and hydration revealed by a K+ channel-Fab complex at 2.0 A resolution.

Ion transport proteins must remove an ion's hydration shell to coordinate the ion selectively on the basis of its size and charge. To discover how the K+ channel solves this fundamental aspect of ion conduction, we solved the structure of the KcsA K+ channel in complex with a monoclonal Fab antibody fragment at 2.0 A resolution. Here we show how the K+ channel displaces water molecules around an ion at its extracellular entryway, and how it holds a K+ ion in a square antiprism of water molecules in a cavity near its intracellular entryway. Carbonyl oxygen atoms within the selectivity filter form a very similar square antiprism around each K+ binding site, as if to mimic the waters of hydration. The selectivity filter changes its ion coordination structure in low K+ solutions. This structural change is crucial to the operation of the selectivity filter in the cellular context, where the K+ ion concentration near the selectivity filter varies in response to channel gating.     

On Joseph Fourier: the man,the mathematician and the physicist

In 1793 Lord Macartney arrived in China as ambassador of King George III. The aims of his embassy were largely directed towards the enlargement of British trade with the far east, and especially with China. The embassy also had a diplomatic and cultural mission, to impress the Chinese with British achievements. They were to do so largely by distributing presents of British manufactures, chief among them being scientific instruments. The Chinese refused the embassy's requests, and clearly regarded the gifts of instruments as merely ingenious toys. This paper describes the role of instruments in the embassy, and contrasts British expectations with Chinese attitudes to scientific instruments. The embassy's failure is shown to reveal fundamental differences in British and Chinese eighteenth-century responses to science, and has wide cultural implications.     

Richard Watson

The development of the circular dividing engine in England is traced from Henry Hindley and Jesse Ramsden through the improvements introduced by Ramsden's successors to the self-acting engine of William Simms. Particular emphasis is given to the invention, evolution and transmission of the methods used to achieve accuracy in: dividing the wheel; ratching the teeth and matching them to the endless screw; and mounting the cutter. The procedures adopted by Ramsden and Troughton for correcting initial dividing marks are also described.     

Range extension of Helianthus spp. (Asteraceae) in Arizona and Utah

Two populations of Helianthus niveus (Benth.) Brandegee ssp. canescens (A. Gray) Heiser were discovered in northern Arizona extending the range 300 miles north for this species. Helianthus deserticola Heiser range was extended 100 miles east in both Arizona and Utah.