Quantitative variability of 342 plasma proteins in a human twin population

The degree and the origins of quantitative variability of most human plasma proteins are largely unknown. Because the twin study design provides a natural opportunity to estimate the relative contribution of heritability and environment to different traits in human population, we applied here the highly accurate and reproducible SWATH mass spectrometry technique to quantify 1,904 peptides defining 342 unique plasma proteins in 232 plasma samples collected longitudinally from pairs of monozygotic and dizygotic twins at intervals of 2–7 years, and proportioned the observed total quantitative variability to its root causes, genes, and environmental and longitudinal factors. The data indicate that different proteins show vastly different patterns of abundance variability among humans and that genetic control and longitudinal variation affect protein levels and biological processes to different degrees. The data further strongly suggest that the plasma concentrations of clinical biomarkers need to be calibrated against genetic and temporal factors. Moreover, we identified 13 cis‐SNPs significantly influencing the level of specific plasma proteins. These results therefore have immediate implications for the effective design of blood‐based biomarker studies.     

Scanning X-Ray Nanodiffraction on Dictyostelium discoideum

We have performed scanning x-ray nanobeam diffraction experiments on single cells of the amoeba Dictyostelium discoideum. Cells have been investigated in 1), freeze-dried, 2), frozen-hydrated (vitrified), and 3), initially alive states. The spatially resolved small-angle x-ray scattering signal shows characteristic streaklike patterns in reciprocal space, which we attribute to fiber bundles of the actomyosin network. From the intensity distributions, an anisotropy parameter can be derived that indicates pronounced local variations within the cell. In addition to nanobeam small-angle x-ray scattering, we have evaluated the x-ray differential phase contrast in view of the projected electron density. Different experimental aspects of the x-ray experiment, sample preparation, and data analysis are discussed. Finally, the x-ray results are correlated with optical microscopy (differential phase contrast and confocal microscopy of mutant strains with fluorescently labeled actin and myosin II), which have been carried out in live and fixed states, including optical microscopy under cryogenic conditions.     

Symmetry breakage in the vertebrate embryo: When does it happen and how does it work?

Asymmetric development of the vertebrate embryo has fascinated embryologists for over a century. Much has been learned since the asymmetric Nodal signaling cascade in the left lateral plate mesoderm was detected, and began to be unraveled over the past decade or two. When and how symmetry is initially broken, however, has remained a matter of debate. Two essentially mutually exclusive models prevail. Cilia-driven leftward flow of extracellular fluids occurs in mammalian, fish and amphibian embryos. A great deal of experimental evidence indicates that this flow is indeed required for symmetry breaking. An alternative model has argued, however, that flow simply acts as an amplification step for early asymmetric cues generated by ion flux during the first cleavage divisions. In this review we critically evaluate the experimental basis of both models. Although a number of open questions persist, the available evidence is best compatible with flow-based symmetry breakage as the archetypical mode of symmetry breakage.     

Stable adducts of nerve agents sarin,soman and cyclosarin with TRIS,TES and related buffer compounds—Characterization by LC-ESI-MS/MS and NMR and implications for analytical chemistry

Buffering compounds like TRIS are frequently used in chemical, biochemical and biomedical applications to control pH in solution. One of the prerequisites of a buffer compound, in addition to sufficient buffering capacity and pH stability over time, is its non-reactivity with other constituents of the solution. This is especially important in the field of analytical chemistry where analytes are to be determined quantitatively. Investigating the enzymatic hydrolysis of G-type nerve agents sarin, soman and cyclosarin in buffered solution we have identified stable buffer adducts of TRIS, TES and other buffer compounds with the nerve agents. We identified the molecular structure of these adducts as phosphonic diesters using 1D ¹H-³¹P HSQC NMR and LC-ESI-MS/MS techniques. Reaction rates with TRIS and TES are fast enough to compete with spontaneous hydrolysis in aqueous solution and to yield substantial amounts (up to 20–40%) of buffer adduct over the course of several hours. A reaction mechanism is proposed in which the amino function of the buffer serves as an intramolecular proton acceptor rendering the buffer hydroxyl groups nucleophilic enough for attack on the phosphorus atom of the agents. Results show that similar buffer adducts are formed with a range of hydroxyl and amino function containing buffers including TES, BES, TRIS, BIS-TRIS, BIS-TRIS propane, Tricine, Bicine, HEPES and triethanol amine. It is recommended to use alternative buffers like MOPS, MES and CHES when working with G-type nerve agents especially at higher concentrations and over prolonged times.     

Individualized medicine 2010

Molecular and cell biology have revolutionized not only diagnosis, therapy and prevention of human diseases but also greatly contributed to the understanding of their pathogenesis. Based on modern molecular and biochemical methods it is possible to identify on the one hand point mutations and single nucleotide polymorphisms. On the other hand, using high throughput array technologies, it is possible to analyse thousands of genes or gene products simultaneously, resulting in an individual gene or gene expression profile (signature). These data increasingly allow to define the individual risk for a given disease and to predict the individual prognosis of a disease as well as the efficacy of therapeutic strategies (individualized medicine). In the following sections some of the recent advances of predictive medicine and their clinical relevance will be addressed.     

Robust and efficient walking with spring-like legs

The development of bipedal walking robots is inspired by human walking. A way of implementing walking could be performed by mimicking human leg dynamics. A fundamental model, representing human leg dynamics during walking and running, is the bipedal spring-mass model which is the basis for this paper. The aim of this study is the identification of leg parameters leading to a compromise between robustness and energy efficiency in walking. It is found that, compared to asymmetric walking, symmetric walking with flatter angles of attack reveals such a compromise. With increasing leg stiffness, energy efficiency increases continuously. However, robustness is the maximum at moderate leg stiffness and decreases slightly with increasing stiffness. Hence, an adjustable leg compliance would be preferred, which is adaptable to the environment. If the ground is even, a high leg stiffness leads to energy efficient walking. However, if external perturbations are expected, e.g. when the robot walks on uneven terrain, the leg should be softer and the angle of attack flatter. In the case of underactuated robots with constant physical springs, the leg stiffness should be larger than k = 14 in order to use the most robust gait. Soft legs, however, lack in both robustness and efficiency.     

Flagellar motility and structure in the hyperthermoacidophilic archaeon Sulfolobus solfataricus

Flagellation in archaea is widespread and is involved in swimming motility. Here, we demonstrate that the structural flagellin gene from the crenarchaeaon Sulfolobus solfataricus is highly expressed in stationary-phase-grown cells and under unfavorable nutritional conditions. A mutant in a flagellar auxiliary gene, flaJ, was found to be nonmotile. Electron microscopic imaging of the flagellum indicates that the filaments are composed of right-handed helices.     

Low Si combined with drought causes reduced transpiration in sorghum Lsi1 mutant

Plant and Soil - High and stable plant productivity is a major aim in agricultural research. Silicon fertilization improves yields of various crops under stress. Nonetheless, broad application of...     

Spatial and temporal comparisons of salt marsh soil fungal communities following the deepwater horizon spill

Wetlands Ecology and Management - The unprecedented size of the deepwater horizon oil spill and scope of the subsequent response elicited intense and sustained interest in microbial responses to...