1,092 research outputs found
Kinetic and Structural Analysis of the Mg2+ -binding Site of the Guanine Nucleotide-binding Protein p21 H-ras.
The coordination and binding of the Mg2+ ion in the nucleotideâbinding site of p21 have been investigated using siteâdirected mutagenesis, kinetic methods, and phosphorous NMR. Mg2+ in the p21.nucleotide.Mg2+ complex appears to be in fast equilibrium with the solvent. The dissociation constant between Mg2+ and the p21.GDP complex was determined to be 2.8 microM. It decreases 30â or 16âfold on substituting Serâ17 or Aspâ57 with alanine, respectively, whereas the T35A mutation has no effect. All three mutations influence the dissociation constants and the association and dissociation rate constants of the interaction between guanine nucleotides and p21, but to a different degree. We conclude that Thrâ35 is only complexed to Mg2+ in the GTP conformation and both Aspâ57 and Serâ17 appear to be critical for both GDP and GTP binding. 31P NMR spectra of the GDP and Gpp(NH)p (guanosineâ5'â(beta,gammaâimido)triphosphate) complexes of mutated p21 show a remarkable perturbation of the guanine nucleotideâ binding site compared to wildâtype protein. The mutant proteins show reduced GTPase rates, which are not stimulated by the GTPaseâactivating protein GAP. p21(S17A) has been reported to function just as p21(S17N) as a dominant negative inhibitor of normal p21. We find that it inhibits oncogenic p21âinduced survival of primary neuron
Crystal structure of the GAP domain of Gyp1p: first insights into interaction with Ypt/Rab proteins.
Light as a trigger for time-resolved structural experiments on muscle, lipids, p21 and bacteriorhodopsin
Understanding Anthropological Understanding: for a merological anthropology
In this paper I argue for a merological anthropology in which ideas of âpartialityâ and âpractical adequacyâ provide a way out of the impasse of relativism which is implied by post-modernism and the related abandonment of a concern with âtruthâ. Ideas such as âaptnessâ and âfaithfulnessâ enable us to re-establish empirical foundations without having to espouse a simple realism which has been rightly criticised. Ideas taken from ethnomethodology, particularly the way we bootstrap from âpractical adequacyâ to âwarrants for confidenceâ point to a merological anthropology in which we recognize that we do not and cannot know everything, but that we can have reasons for being confident in the little we know
Turing instabilities in a mathematical model for signaling networks
GTPase molecules are important regulators in cells that continuously run
through an activation/deactivation and membrane-attachment/membrane-detachment
cycle. Activated GTPase is able to localize in parts of the membranes and to
induce cell polarity. As feedback loops contribute to the GTPase cycle and as
the coupling between membrane-bound and cytoplasmic processes introduces
different diffusion coefficients a Turing mechanism is a natural candidate for
this symmetry breaking. We formulate a mathematical model that couples a
reaction-diffusion system in the inner volume to a reaction-diffusion system on
the membrane via a flux condition and an attachment/detachment law at the
membrane. We present a reduction to a simpler non-local reaction-diffusion
model and perform a stability analysis and numerical simulations for this
reduction. Our model in principle does support Turing instabilities but only if
the lateral diffusion of inactivated GTPase is much faster than the diffusion
of activated GTPase.Comment: 23 pages, 5 figures; The final publication is available at
http://www.springerlink.com http://dx.doi.org/10.1007/s00285-011-0495-
Predictive use of the Maximum Entropy Production principle for Past and Present Climates
In this paper, we show how the MEP hypothesis may be used to build simple
climate models without representing explicitly the energy transport by the
atmosphere. The purpose is twofold. First, we assess the performance of the MEP
hypothesis by comparing a simple model with minimal input data to a complex,
state-of-the-art General Circulation Model. Next, we show how to improve the
realism of MEP climate models by including climate feedbacks, focusing on the
case of the water-vapour feedback. We also discuss the dependence of the
entropy production rate and predicted surface temperature on the resolution of
the model
Methane in the atmosphere of the transiting hot Neptune GJ436b?
We present an analysis of seven primary transit observations of the hot
Neptune GJ436b at 3.6, 4.5 and m obtained with the Infrared Array Camera
(IRAC) on the Spitzer Space Telescope. After correcting for systematic effects,
we fitted the light curves using the Markov Chain Monte Carlo technique.
Combining these new data with the EPOXI, HST and ground-based and
published observations, the range m can be covered. Due to
the low level of activity of GJ436, the effect of starspots on the combination
of transits at different epochs is negligible at the accuracy of the dataset.
Representative climate models were calculated by using a three-dimensional,
pseudo-spectral general circulation model with idealised thermal forcing.
Simulated transit spectra of GJ436b were generated using line-by-line radiative
transfer models including the opacities of the molecular species expected to be
present in such a planetary atmosphere. A new, ab-initio calculated, linelist
for hot ammonia has been used for the first time. The photometric data observed
at multiple wavelengths can be interpreted with methane being the dominant
absorption after molecular hydrogen, possibly with minor contributions from
ammonia, water and other molecules. No clear evidence of carbon monoxide and
dioxide is found from transit photometry. We discuss this result in the light
of a recent paper where photochemical disequilibrium is hypothesised to
interpret secondary transit photometric data. We show that the emission
photometric data are not incompatible with the presence of abundant methane,
but further spectroscopic data are desirable to confirm this scenario.Comment: 19 pages, 10 figures, 1 table, Astrophysical Journal in pres
âSons of athelings given to the earthâ: Infant Mortality within Anglo-Saxon Mortuary Geography
FOR 20 OR MORE YEARS early Anglo-Saxon archaeologists have believed children are underrepresented in the cemetery evidence. They conclude that excavation misses small bones, that previous attitudes to reporting overlook the very young, or that infants and children were buried elsewhere. This is all well and good, but we must be careful of oversimplifying compound social and cultural responses to childhood and infant mortality. Previous approaches have offered methodological quandaries in the face of this under-representation. However, proportionally more infants were placed in large cemeteries and sometimes in specific zones. This trend is statistically significant and is therefore unlikely to result entirely from preservation or excavation problems. Early medieval cemeteries were part of regional mortuary geographies and provided places to stage events that promoted social cohesion across kinship systems extending over tribal territories. This paper argues that patterns in early Anglo-Saxon infant burial were the result of female mobility. Many women probably travelled locally to marry in a union which reinforced existing social networks. For an expectant mother, however, the safest place to give birth was with experience women in her maternal home. Infant identities were affected by personal and legal association with their motherâs parental kindred, so when an infant died in childbirth or months and years later, it was their motherâs identity which dictated burial location. As a result, cemeteries central to tribal identities became places to bury the sons and daughters of a regional tribal aristocracy
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