141 research outputs found
Linear fuzzy gene network models obtained from microarray data by exhaustive search
BACKGROUND: Recent technological advances in high-throughput data collection allow for experimental study of increasingly complex systems on the scale of the whole cellular genome and proteome. Gene network models are needed to interpret the resulting large and complex data sets. Rationally designed perturbations (e.g., gene knock-outs) can be used to iteratively refine hypothetical models, suggesting an approach for high-throughput biological system analysis. We introduce an approach to gene network modeling based on a scalable linear variant of fuzzy logic: a framework with greater resolution than Boolean logic models, but which, while still semi-quantitative, does not require the precise parameter measurement needed for chemical kinetics-based modeling. RESULTS: We demonstrated our approach with exhaustive search for fuzzy gene interaction models that best fit transcription measurements by microarray of twelve selected genes regulating the yeast cell cycle. Applying an efficient, universally applicable data normalization and fuzzification scheme, the search converged to a small number of models that individually predict experimental data within an error tolerance. Because only gene transcription levels are used to develop the models, they include both direct and indirect regulation of genes. CONCLUSION: Biological relationships in the best-fitting fuzzy gene network models successfully recover direct and indirect interactions predicted from previous knowledge to result in transcriptional correlation. Fuzzy models fit on one yeast cell cycle data set robustly predict another experimental data set for the same system. Linear fuzzy gene networks and exhaustive rule search are the first steps towards a framework for an integrated modeling and experiment approach to high-throughput "reverse engineering" of complex biological systems
Optimized unconventional superconductivity in a molecular Jahn-Teller metal
Understanding the relationship between the superconducting, the neighboring insulating, and the normal metallic state above Tc is a major challenge for all unconventional superconductors. The molecular A3C60 fulleride superconductors have a parent antiferromagnetic insulator in common with the atom-based cuprates, but here, the C603– electronic structure controls the geometry and spin state of the structural building unit via the on-molecule Jahn-Teller effect. We identify the Jahn-Teller metal as a fluctuating microscopically heterogeneous coexistence of both localized Jahn-Teller–active and itinerant electrons that connects the insulating and superconducting states of fullerides. The balance between these molecular and extended lattice features of the electrons at the Fermi level gives a dome-shaped variation of Tc with interfulleride separation, demonstrating molecular electronic structure control of superconductivity
Structural and electronic response upon hole-doping of rare-earth iron oxyarsenides Nd1-xSrxFeAsO (0 < x < 0.2)
Hole-doping of NdFeAsO via partial replacement of Nd3+ by Sr2+ is a
successful route to obtain superconducting phases (Tc = 13.5 K for a Sr2+
content of 20%); however, the structural and electronic response with doping is
different from and non-symmetric to that in the electron-doped side of the
phase diagram.Comment: 4 pages, 4 figure
Crystal structure of the new FeSe1-x superconductor
The newly discovered superconductor FeSe1-x (x=0.08, Tconset=13.5 K at
ambient pressure rising to 27 K at 1.48 GPa) exhibits a structural phase
transition from tetragonal to orthorhombic below 70 K at ambient pressure - the
crystal structure in the superconducting state shows remarkable similarities to
that of the REFeAsO1-xFx (RE = rare earth) superconductorsComment: Chem. Commun. (2008
Metal-Insulator Transition and Orbital Order in PbRuO3
Anomalous low temperature electronic and structural behaviour has been
discovered in PbRuO3. The structure (space group Pnma, a = 5.56314(1), b =
7.86468(1), c = 5.61430(1) A) and metallic conductivity at 290 K are similar to
those of SrRuO3 and other ruthenate perovskites, but a sharp metal-insulator
transition at which the resistivity increases by four orders of magnitude is
discovered at 90 K. This is accompanied by a first order structural transition
to an Imma phase (a = 5.56962(1), b = 7.74550(1), c = 5.66208(1) A at 25 K)
that shows a coupling of Ru4+ 4d orbital order to distortions from Pb2+ 6s6p
orbital hybridization. The Pnma to Imma transition is an unconventional
reversal of the group-subgroup symmetry relationship. No long range magnetic
order is evident down to 1.5 K. Electronic structure calculations show that
hybridization of Pb 6s6p and Ru 4d orbitals and strong spin-orbit coupling
stabilise this previously hidden ground state for ruthenate perovskite
Molecular envelopes derived from protein powder diffraction Molecular envelopes derived from protein powder diffraction data
The preparation of single crystals suitable for X-ray analysis is frequently the most difficult step in structural studies of proteins.With the aid of two examples, it is shown that de novo solution of the crystallographic phase problem can be achieved at low resolution using microcrystalline powder samples via the single isomorphous replacement method. With synchrotron radiation and optimized instrumentation, high-quality powder patterns have been recorded, from which it was possible to generate phase information for structure factors up to 6 A resolution. pH- and radiation-induced anisotropic lattice changes were exploited to reduce the problem of overlapping reflections, which is a major challenge in protein powder diffraction. The resulting data were of sufficient quality to compute molecular envelopes of the protein molecule and to map out the solvent channels in the crystals. The results show that protein powder diffraction can yield low-resolution data that are potentially useful for the characterization of microcrystalline proteins as novel micro- and mesoporous materials as well as for structural studies of biologically important macromolecules
Observation of Binding and Rotation of Methane and Hydrogen within a Functional Metal-Organic Framework
The key requirement for a portable
store of natural gas is to maximize
the amount of gas within the smallest possible space. The packing
of methane (CH<sub>4</sub>) in a given storage medium at the highest
possible density is, therefore, a highly desirable but challenging
target. We report a microporous hydroxyl-decorated material, MFM-300(In)
(MFM = Manchester Framework Material, replacing the NOTT designation),
which displays a high volumetric uptake of 202 v/v at 298 K and 35
bar for CH<sub>4</sub> and 488 v/v at 77 K and 20 bar for H<sub>2</sub>. Direct observation and quantification of the location, binding,
and rotational modes of adsorbed CH<sub>4</sub> and H<sub>2</sub> molecules
within this host have been achieved, using neutron diffraction and
inelastic neutron scattering experiments, coupled with density functional
theory (DFT) modeling. These complementary techniques reveal a very
efficient packing of H<sub>2</sub> and CH<sub>4</sub> molecules within
MFM-300(In), reminiscent of the condensed gas in pure component crystalline
solids. We also report here, for the first time, the experimental
observation of a direct binding interaction between adsorbed CH<sub>4</sub> molecules and the hydroxyl groups within the pore of a material.
This is different from the arrangement found in CH<sub>4</sub>/water
clathrates, the CH<sub>4</sub> store of nature
Selective adsorption of sulfur dioxide in a robust metal-organic framework material
Selective adsorption of SO2 is realized in a porous metal–organic framework material, and in-depth structural and spectroscopic investigations using X-rays, infrared, and neutrons define the underlying interactions that cause SO2 to bind more strongly than CO2 and N2
Astrocytic αVβ3 Integrin Inhibits Neurite Outgrowth and Promotes Retraction of Neuronal Processes by Clustering Thy-1
Thy-1 is a membrane glycoprotein suggested to stabilize or inhibit growth of neuronal processes. However, its precise function has remained obscure, because its endogenous ligand is unknown. We previously showed that Thy-1 binds directly to αVβ3 integrin in trans eliciting responses in astrocytes. Nonetheless, whether αVβ3 integrin might also serve as a Thy-1-ligand triggering a neuronal response has not been explored. Thus, utilizing primary neurons and a neuron-derived cell line CAD, Thy-1-mediated effects of αVβ3 integrin on growth and retraction of neuronal processes were tested. In astrocyte-neuron co-cultures, endogenous αVβ3 integrin restricted neurite outgrowth. Likewise, αVβ3-Fc was sufficient to suppress neurite extension in Thy-1(+), but not in Thy-1(−) CAD cells. In differentiating primary neurons exposed to αVβ3-Fc, fewer and shorter dendrites were detected. This effect was abolished by cleavage of Thy-1 from the neuronal surface using phosphoinositide-specific phospholipase C (PI-PLC). Moreover, αVβ3-Fc also induced retraction of already extended Thy-1(+)-axon-like neurites in differentiated CAD cells as well as of axonal terminals in differentiated primary neurons. Axonal retraction occurred when redistribution and clustering of Thy-1 molecules in the plasma membrane was induced by αVβ3 integrin. Binding of αVβ3-Fc was detected in Thy-1 clusters during axon retraction of primary neurons. Moreover, αVβ3-Fc-induced Thy-1 clustering correlated in time and space with redistribution and inactivation of Src kinase. Thus, our data indicates that αVβ3 integrin is a ligand for Thy-1 that upon binding not only restricts the growth of neurites, but also induces retraction of already existing processes by inducing Thy-1 clustering. We propose that these events participate in bi-directional astrocyte-neuron communication relevant to axonal repair after neuronal damage
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