A hierarchy of timescales in protein dynamics is linked to enzyme catalysis

The synergy between structure and dynamics is essential to the function of biological macromolecules. Thermally driven dynamics on different timescales have been experimentally observed or simulated, and a direct link between micro- to milli-second domain motions and enzymatic function has been established. However, very little is understood about the connection of these functionally relevant, collective movements with local atomic fluctuations, which are much faster. Here we show that pico- to nano-second timescale atomic fluctuations in hinge regions of adenylate kinase facilitate the large-scale, slower lid motions that produce a catalytically competent state. The fast, local mobilities differ between a mesophilic and hyperthermophilic adenylate kinase, but are strikingly similar at temperatures at which enzymatic activity and free energy of folding are matched. The connection between different timescales and the corresponding amplitudes of motions in adenylate kinase and their linkage to catalytic function is likely to be a general characteristic of protein energy landscapes.     

Prevalence of Elaeophora schneideri and Onchocerca cervipedis in mule deer from central Utah

Thirteen of 265 deer (4.9 percent) from central Utah were positive for Elaeophora schneideri, and 180 (67.9 percent) were infected with Onchocerca cervipedis. The rate of infection for E. schneideri and O. cervipedis increased significantly with age of the host (chi - square of 17.5 and 15.5, respectively, p     

Responses of Utah deer hunters to a checking station questionnaire

During the 1987 deer hunt 4,250 card questionnaires were distributed to Utah hunters at nine checking stations. Return rates varied from a mean 23% when cards were simply handed to hunters, to 50% when hunters' names and telephone numbers were taken. Results concerning methodology suggest that questionnaire surveys conducted from checking stations are efficient and accurate in obtaining hunter opinions. Questionnaire results indicated that most hunters rated the Utah deer hunt as moderately satisfactory, but may prefer alternative options that would result in a higher quality hunt. The majority of hunters indicated that hunter numbers should be limited to current levels or decreased. Unretrieved kill was reported as 21 deer per 100 hunters.     

Sensing the fuels: glucose and lipid signaling in the CNS controlling energy homeostasis

The central nervous system (CNS) is capable of gathering information on the body’s nutritional state and it implements appropriate behavioral and metabolic responses to changes in fuel availability. This feedback signaling of peripheral tissues ensures the maintenance of energy homeostasis. The hypothalamus is a primary site of convergence and integration for these nutrient-related feedback signals, which include central and peripheral neuronal inputs as well as hormonal signals. Increasing evidence indicates that glucose and lipids are detected by specialized fuel-sensing neurons that are integrated in these hypothalamic neuronal circuits. The purpose of this review is to outline the current understanding of fuel-sensing mechanisms in the hypothalamus, to integrate the recent findings in this field, and to address the potential role of dysregulation in these pathways in the development of obesity and type 2 diabetes mellitus.     

G-protein-coupled receptor heterodimerization modulates receptor function.

The opioid system modulates several physiological processes, including analgesia, the stress response, the immune response and neuroendocrine function. Pharmacological and molecular cloning studies have identified three opioid-receptor types, delta, kappa and mu, that mediate these diverse effects. Little is known about the ability of the receptors to interact to form new functional structures, the simplest of which would be a dimer. Structural and biochemical studies show that other G-protein-coupled receptors (GPCRs) interact to form homodimers. Moreover, two non-functional receptors heterodimerize to form a functional receptor, suggesting that dimerization is crucial for receptor function. However, heterodimerization between two fully functional receptors has not been documented. Here we provide biochemical and pharmacological evidence for the heterodimerization of two fully functional opioid receptors, kappa and delta. This results in a new receptor that exhibits ligand binding and functional properties that are distinct from those of either receptor. Furthermore, the kappa-delta heterodimer synergistically binds highly selective agonists and potentiates signal transduction. Thus, heterodimerization of these GPCRs represents a novel mechanism that modulates their function.     

A universal trend of amino acid gain and loss in protein evolution

Amino acid composition of proteins varies substantially between taxa and, thus, can evolve. For example, proteins from organisms with (G + C)-rich (or (A + T)-rich) genomes contain more (or fewer) amino acids encoded by (G + C)-rich codons. However, no universal trends in ongoing changes of amino acid frequencies have been reported. We compared sets of orthologous proteins encoded by triplets of closely related genomes from 15 taxa representing all three domains of life (Bacteria, Archaea and Eukaryota), and used phylogenies to polarize amino acid substitutions. Cys, Met, His, Ser and Phe accrue in at least 14 taxa, whereas Pro, Ala, Glu and Gly are consistently lost. The same nine amino acids are currently accrued or lost in human proteins, as shown by analysis of non-synonymous single-nucleotide polymorphisms. All amino acids with declining frequencies are thought to be among the first incorporated into the genetic code; conversely, all amino acids with increasing frequencies, except Ser, were probably recruited late. Thus, expansion of initially under-represented amino acids, which began over 3,400 million years ago, apparently continues to this day.     

High-power terahertz radiation from relativistic electrons

Terahertz (THz) radiation, which lies in the far-infrared region, is at the interface of electronics and photonics. Narrow-band THz radiation can be produced by free-electron lasers and fast diodes. Broadband THz radiation can be produced by thermal sources and, more recently, by table-top laser-driven sources and by short electron bunches in accelerators, but so far only with low power. Here we report calculations and measurements that confirm the production of high-power broadband THz radiation from subpicosecond electron bunches in an accelerator. The average power is nearly 20 watts, several orders of magnitude higher than any existing source, which could enable various new applications. In particular, many materials have distinct absorptive and dispersive properties in this spectral range, so that THz imaging could reveal interesting features. For example, it would be possible to image the distribution of specific proteins or water in tissue, or buried metal layers in semiconductors; the present source would allow full-field, real-time capture of such images. High peak and average power THz sources are also critical in driving new nonlinear phenomena and for pump-probe studies of dynamical properties of materials.     

Principles of the eradication or control of tsetse flies

The success of attempts to control African trypanosomiasis afflicting both men and animals through the destruction of the tsetse vector depends on a realistic assessment of human and ecological factors in infested regions. The complete eradication of tsetse is at present possible only in limited areas, and elsewhere the advantages of periodic control campaigns have to be weighed carefully against their cost.     

Colorectal cancer: mutations in a signalling pathway

Protein kinases are enzymes that are important for controlling cellular growth and invasion, and their malfunction is implicated in the development of some tumours. We analysed human colorectal cancers for genetic mutations in 340 serine/threonine kinases and found mutations in eight genes, including in three members of the phosphatidylinositol-3-OH kinase (PI(3)K) pathway. The discovery of this mutational activation of a key cell-signalling pathway may provide new targets for therapeutic intervention.