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Background: Protein phosphorylation is an important post-translational modification influencing many aspects of dynamic cellular behavior. Site-specific phosphorylation of amino acid residues serine, threonine, and tyrosine can have profound effects on protein structure, activity, stability, and interaction with other biomolecules. Phosphorylation sites can be affected in diverse ways in members of any species, one such way is through single nucleotide polymorphisms (SNPs). The availability of large numbers of experimentally identified phosphorylation sites, and of natural variation datasets in Arabidopsis thaliana prompted us to analyze the effect of non-synonymous SNPs (nsSNPs) onto phosphorylation sites.
Results: From the analyses of 7,178 experimentally identified phosphorylation sites we found that: (i) Proteins with multiple phosphorylation sites occur more often than expected by chance. (ii) Phosphorylation hotspots show a preference to be located outside conserved domains. (iii) nsSNPs affected experimental phosphorylation sites as much as the corresponding non-phosphorylated amino acid residues. (iv) Losses of experimental phosphorylation sites by nsSNPs were identified in 86 A. thaliana proteins, among them receptor proteins were overrepresented.
These results were confirmed by similar analyses of predicted phosphorylation sites in A. thaliana. In addition, predicted threonine phosphorylation sites showed a significant enrichment of nsSNPs towards asparagines and a significant depletion of the synonymous substitution. Proteins in which predicted phosphorylation sites were affected by nsSNPs (loss and gain), were determined to be mainly receptor proteins, stress response proteins and proteins involved in nucleotide and protein binding. Proteins involved in metabolism, catalytic activity and biosynthesis were less affected.
Conclusions: We analyzed more than 7,100 experimentally identified phosphorylation sites in almost 4,300 protein-coding loci in silico, thus constituting the largest phosphoproteomics dataset for A. thaliana available to date. Our findings suggest a relatively high variability in the presence or absence of phosphorylation sites between different natural accessions in receptor and other proteins involved in signal transduction. Elucidating the effect of phosphorylation sites affected by nsSNPs on adaptive responses represents an exciting research goal for the future.
We show that the residue density of the logarithm of a generalized Laplacian on a closed manifold definesan invariant polynomial-valued differential form. We express it in terms of a finite sum of residues ofclassical pseudodifferential symbols. In the case of the square of a Dirac operator, these formulas providea pedestrian proof of the Atiyah–Singer formula for a pure Dirac operator in four dimensions and for atwisted Dirac operator on a flat space of any dimension. These correspond to special cases of a moregeneral formula by Scott and Zagier. In our approach, which is of perturbative nature, we use either aCampbell–Hausdorff formula derived by Okikiolu or a noncommutative Taylor-type formula.
It has been suggested that coronal mass ejections (CMEs) remove the magnetic he-licity of their coronal source region from the Sun. Such removal is often regarded to be necessary due to the hemispheric sign preference of the helicity, which inhibits a simple annihilation by reconnection between volumes of opposite chirality. Here we monitor the relative magnetic he-licity contained in the coronal volume of a simulated flux rope CME, as well as the upward flux of relative helicity through horizontal planes in the simulation box. The unstable and erupting flux rope carries away only a minor part of the initial relative helicity; the major part remains in the volume. This is a consequence of the requirement that the current through an expanding loop must decrease if the magnetic energy of the configuration is to decrease as the loop rises, to provide the kinetic energy of the CME.
The Takab complex is composed of a variety of metamorphic rocks including amphibolites, metapelites, mafic granulites, migmatites and meta-ultramafics, which are intruded by the granitoid. The granitoid magmatic activity occurred in relation to the subduction of the Neo-Tethys oceanic crust beneath the Iranian crust during Tertiary times. The granitoids are mainly granodiorite, quartz monzodiorite, monzonite and quartz diorite. Chemically, the magmatic rocks are characterized by ASI < 1.04, AI < 0.87 and high contents of CaO (up to ∼ 14.5 wt %), which are consistent with the I-type magmatic series. Low FeO t /(FeO t +MgO) values (< 0.75) as well as low Nb, Y and K 2 O contents of the investigated rocks resemble the calc-alkaline series. Low SiO 2 , K 2 O/Na 2 O and Al 2 O 3 accompanied by high CaO and FeO contents indicate melting of metabasites as an appropriate source for the intrusions. Negative Ti and Nb anomalies verify a metaluminous crustal origin for the protoliths of the investigated igneous rocks. These are comparable with compositions of the associated mafic migmatites, in the Takab metamorphic complex, which originated from the partial melting of amphibolites. Therefore, crustal melting and a collision-related origin for the Takab calc-alkaline intrusions are proposed here on the basis of mineralogy and geochemical characteristics. The P–T evolution during magmatic crystallization and subsolidus cooling stages is determined by the study of mineral chemistry of the granodiorite and the quartz diorite. Magmatic crystallization pressure and temperature for the quartz-diorite and the granodiorite are estimated to be P ∼ 7.8 ± 2.5 kbar, T ∼ 760 ± 75 ◦C and P ∼ 5 ± 1 kbar, T ∼ 700 ◦C, respectively. Subsolidus conditions are consistent with temperatures of ∼ 620 ◦C and ∼ 600 ◦C, and pressures of ∼ 5 kbar and ∼ 3.5 kbar for the quartz-diorite and the granodiorite, respectively.
Background
Micrometer resolution placement and immobilization of probe molecules is an important step in the preparation of biochips and a wide range of lab-on-chip systems. Most known methods for such a deposition of several different substances are costly and only suitable for a limited number of probes. In this article we present a flexible procedure for simultaneous spatially controlled immobilization of functional biomolecules by molecular ink lithography.
Results
For the bottom-up fabrication of surface bound nanostructures a universal method is presented that allows the immobilization of different types of biomolecules with micrometer resolution. A supporting surface is biotinylated and streptavidin molecules are deposited with an AFM (atomic force microscope) tip at distinct positions. Subsequent incubation with a biotinylated molecule species leads to binding only at these positions. After washing streptavidin is deposited a second time with the same AFM tip and then a second biotinylated molecule species is coupled by incubation. This procedure can be repeated several times. Here we show how to immobilize different types of biomolecules in an arbitrary arrangement whereas most common methods can deposit only one type of molecules. The presented method works on transparent as well as on opaque substrates. The spatial resolution is better than 400 nm and is limited only by the AFM's positional accuracy after repeated z-cycles since all steps are performed in situ without moving the supporting surface. The principle is demonstrated by hybridization to different immobilized DNA oligomers and was validated by fluorescence microscopy.
Conclusions
The immobilization of different types of biomolecules in high-density microarrays is a challenging task for biotechnology. The method presented here not only allows for the deposition of DNA at submicrometer resolution but also for proteins and other molecules of biological relevance that can be coupled to biotin.
Two recent magnetic field models, GRIMM and xCHAOS, describe core field accelerations with similar behavior up to Spherical Harmonic (SH) degree 5, but which differ significantly for higher degrees. These discrepancies, due to different approaches in smoothing rapid time variations of the core field, have strong implications for the interpretation of the secular variation. Furthermore, the amount of smoothing applied to the highest SH degrees is essentially the modeler’s choice. We therefore investigate new ways of regularizing core magnetic field models. Here we propose to constrain field models to be consistent with the frozen flux induction equation by co-estimating a core magnetic field model and a flow model at the top of the outer core. The flow model is required to have smooth spatial and temporal behavior. The implementation of such constraints and their effects on a magnetic field model built from one year of CHAMP satellite and observatory data, are presented. In particular, it is shown that the chosen constraints are efficient and can be used to build reliable core magnetic field secular variation and acceleration model components.
Quantifying uncertainty, variability and likelihood for ordinary differential equation models
(2010)
Background
In many applications, ordinary differential equation (ODE) models are subject to uncertainty or variability in initial conditions and parameters. Both, uncertainty and variability can be quantified in terms of a probability density function on the state and parameter space.
Results
The partial differential equation that describes the evolution of this probability density function has a form that is particularly amenable to application of the well-known method of characteristics. The value of the density at some point in time is directly accessible by the solution of the original ODE extended by a single extra dimension (for the value of the density). This leads to simple methods for studying uncertainty, variability and likelihood, with significant advantages over more traditional Monte Carlo and related approaches especially when studying regions with low probability.
Conclusions
While such approaches based on the method of characteristics are common practice in other disciplines, their advantages for the study of biological systems have so far remained unrecognized. Several examples illustrate performance and accuracy of the approach and its limitations.
An efficient electrocatalytic biosensor for sulfite detection was developed by co-immobilizing sulfite oxidase and cytochrome c with polyaniline sulfonic acid in a layer-by-layer assembly. QCM, UV-Vis spectroscopy and cyclic voltammetry revealed increasing loading of electrochemically active protein with the formation of multilayers. The sensor operates reagentless at low working potential. A catalytic oxidation current was detected in the presence of sulfite at the modified gold electrode, polarized at +0.1 V ( vs. Ag/AgCl 1 M KCl). The stability of the biosensor performance was characterized and optimized. A 17-bilayer electrode has a linear range between 1 and 60 mu M sulfite with a sensitivity of 2.19 mA M-1 sulfite and a response time of 2 min. The electrode retained a stable response for 3 days with a serial reproducibility of 3.8% and lost 20% of sensitivity after 5 days of operation. It is possible to store the sensor in a dry state for more than 2 months. The multilayer electrode was used for determination of sulfite in unspiked and spiked samples of red and white wine. The recovery and the specificity of the signals were evaluated for each sample.
We present varve chronologies for sediments from two maar lakes in the Valle de Santiago region (Central Mexico): Hoya La Alberca (AD 1852-1973) and Hoya Rincn de Parangueo (AD 1839-1943). These are the first varve chronologies for Mexican lakes. The varved sections were anchored with tephras from Colima (1913) and Paricutin (1943/1944) and (210)Pb ages. We compare the sequences using the thickness of seasonal laminae and element counts (Al, Si, S, Cl, K, Ti, Mn, Fe, and Sr) determined by micro X-ray fluorescence spectrometry. The formation of the varve sublaminae is attributed to the strongly seasonal climate regime. Limited rainfall and high evaporation rates in winter and spring induce precipitation of carbonates (high Ca, Sr) enriched in (13)C and (18)O, whereas rainfall in summer increases organic and clastic input (plagioclase, quartz) with high counts of lithogenic elements (K, Al, Ti, and Si). Eolian input of Ti occurs also in the dry season. Moving correlations (5-yr windows) of the Ca and Ti counts show similar development in both sequences until the 1930s. Positive correlations indicate mixing of allochthonous Ti and autochthonous Ca, while negative correlations indicate their separation in sublaminae. Negative excursions in the correlations correspond with historic and reconstructed droughts, El Nio events, and positive SST anomalies. Based on our data, droughts (3-7 year duration) were severe and centred around the following years: the early 1850s, 1865, 1880, 1895, 1905, 1915 and the late 1920s with continuation into the 1930s. The latter dry period brought both lake systems into a critical state making them susceptible to further drying. Groundwater overexploitation due to the expansion of irrigation agriculture in the region after 1940 induced the transition from calcite to aragonite precipitation in Alberca and halite infiltration in Rincn. The proxy data indicate a faster response to increased evaporation for Rincn, the lake with the larger maar dimensions, solar radiation receipt and higher conductivity, whereas the smaller, steeper Alberca maar responded rapidly to increased precipitation.
Special p-forms are forms which have components fµ1…µp equal to +1, -1 or 0 in some orthonormal basis. A p-form ϕ ∈ pRd is called democratic if the set of nonzero components {ϕμ1...μp} is symmetric under the transitive action of a subgroup of O(d,Z) on the indices {1, . . . , d}. Knowledge of these symmetry groups allows us to define mappings of special democratic p-forms in d dimensions to special democratic P-forms in D dimensions for successively higher P = p and D = d. In particular, we display a remarkable nested structure of special forms including a U(3)-invariant 2-form in six dimensions, a G2-invariant 3-form in seven dimensions, a Spin(7)-invariant 4-form in eight dimensions and a special democratic 6-form O in ten dimensions. The latter has the remarkable property that its contraction with one of five distinct bivectors, yields, in the orthogonal eight dimensions, the Spin(7)-invariant 4-form. We discuss various properties of this ten dimensional form.