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Reversible Protonated Resting State of the Nitrogenase Active Site
Protonated states of the nitrogenase active site are mechanistically significant since substrate reduction is invariably accompanied by proton uptake. We report the low pH characterization by X-ray crystallography and EPR spectroscopy of the nitrogenase molybdenum iron (MoFe) proteins from two phylogenetically distinct nitrogenases (Azotobacter vinelandii, Av, and Clostridium pasteurianum, Cp) at pHs between 4.5 and 8. X-ray data at pHs of 4.5â6 reveal the repositioning of side chains along one side of the FeMo-cofactor, and the corresponding EPR data shows a new S = 3/2 spin system with spectral features similar to a state previously observed during catalytic turnover. The structural changes suggest that FeMo-cofactor belt sulfurs S3A or S5A are potential protonation sites. Notably, the observed structural and electronic low pH changes are correlated and reversible. The detailed structural rearrangements differ between the two MoFe proteins, which may reflect differences in potential protonation sites at the active site among nitrogenase species. These observations emphasize the benefits of investigating multiple nitrogenase species. Our experimental data suggest that reversible protonation of the resting state is likely occurring, and we term this state âE_0H+â, following the LoweâThorneley naming scheme
Numerical Ricci-flat metrics on K3
We develop numerical algorithms for solving the Einstein equation on
Calabi-Yau manifolds at arbitrary values of their complex structure and Kahler
parameters. We show that Kahler geometry can be exploited for significant gains
in computational efficiency. As a proof of principle, we apply our methods to a
one-parameter family of K3 surfaces constructed as blow-ups of the T^4/Z_2
orbifold with many discrete symmetries. High-resolution metrics may be obtained
on a time scale of days using a desktop computer. We compute various geometric
and spectral quantities from our numerical metrics. Using similar resources we
expect our methods to practically extend to Calabi-Yau three-folds with a high
degree of discrete symmetry, although we expect the general three-fold to
remain a challenge due to memory requirements.Comment: 38 pages, 10 figures; program code and animations of figures
downloadable from http://schwinger.harvard.edu/~wiseman/K3/ ; v2 minor
corrections, references adde
T. brucei cathepsin-L increases arrhythmogenic sarcoplasmic reticulum-mediated calcium release in rat cardiomyocytes
Aims: African trypanosomiasis, caused by Trypanosoma brucei species, leads to both neurological and cardiac dysfunction and can be fatal if untreated. While the neurological-related pathogenesis is well studied, the cardiac pathogenesis remains unknown. The current study exposed isolated ventricular cardiomyocytes and adult rat hearts to T. brucei to test whether trypanosomes can alter cardiac function independent of a systemic inflammatory/immune response.
Methods and results: Using confocal imaging, T. brucei and T. brucei culture media (supernatant) caused an increased frequency of arrhythmogenic spontaneous diastolic sarcoplasmic reticulum (SR)-mediated Ca2+ release (Ca2+ waves) in isolated adult rat ventricular cardiomyocytes. Studies utilising inhibitors, recombinant protein and RNAi all demonstrated that this altered SR function was due to T. brucei cathepsin-L (TbCatL). Separate experiments revealed that TbCatL induced a 10â15% increase of SERCA activity but reduced SR Ca2+ content, suggesting a concomitant increased SR-mediated Ca2+ leak. This conclusion was supported by data demonstrating that TbCatL increased Ca2+ wave frequency. These effects were abolished by autocamtide-2-related inhibitory peptide, highlighting a role for CaMKII in the TbCatL action on SR function. Isolated Langendorff perfused whole heart experiments confirmed that supernatant caused an increased number of arrhythmic events.
Conclusion: These data demonstrate for the first time that African trypanosomes alter cardiac function independent of a systemic immune response, via a mechanism involving extracellular cathepsin-L-mediated changes in SR function
A quantum McKay correspondence for fractional 2p-branes on LG orbifolds
We study fractional 2p-branes and their intersection numbers in non-compact
orbifolds as well the continuation of these objects in Kahler moduli space to
coherent sheaves in the corresponding smooth non-compact Calabi-Yau manifolds.
We show that the restriction of these objects to compact Calabi-Yau
hypersurfaces gives the new fractional branes in LG orbifolds constructed by
Ashok et. al. in hep-th/0401135. We thus demonstrate the equivalence of the
B-type branes corresponding to linear boundary conditions in LG orbifolds,
originally constructed in hep-th/9907131, to a subset of those constructed in
LG orbifolds using boundary fermions and matrix factorization of the
world-sheet superpotential. The relationship between the coherent sheaves
corresponding to the fractional two-branes leads to a generalization of the
McKay correspondence that we call the quantum McKay correspondence due to a
close parallel with the construction of branes on non-supersymmetric orbifolds.
We also provide evidence that the boundary states associated to these branes in
a conformal field theory description corresponds to a sub-class of the boundary
states associated to the permutation branes in the Gepner model associated with
the LG orbifold.Comment: LaTeX2e, 1+39 pages, 3 figures (v2) refs added, typos and report no.
correcte
Six-dimensional (1,0) effective action of F-theory via M-theory on Calabi-Yau threefolds
The six-dimensional effective action of F-theory compactified on a singular
elliptically fibred Calabi-Yau threefold is determined by using an M-theory
lift. The low-energy data are derived by comparing a circle reduction of a
general six-dimensional (1,0) gauged supergravity theory with the effective
action of M-theory on the resolved Calabi-Yau threefold. The derivation
includes six-dimensional tensor multiplets for which the (anti-) self-duality
constraints are imposed on the level of the five-dimensional action. The vector
sector of the reduced theory is encoded by a non-standard potential due to the
Green-Schwarz term in six dimensions. This Green-Schwarz term also contains
higher curvature couplings which are considered to establish the full map
between anomaly coefficients and geometry. F-/M-theory duality is exploited by
moving to the five-dimensional Coulomb branch after circle reduction and
integrating out massive vector multiplets and matter hypermultiplets. The
associated fermions then generate additional Chern-Simons couplings at
one-loop. Further couplings involving the graviphoton are induced by quantum
corrections due to excited Kaluza-Klein modes. On the M-theory side integrating
out massive fields corresponds to resolving the singularities of the Calabi-Yau
threefold, and yields intriguing relations between six-dimensional anomalies
and classical topology.Comment: 55 pages, v2: typos corrected, discussion of loop corrections
improve
A Geometric Unification of Dualities
We study the dynamics of a large class of N=1 quiver theories, geometrically
realized by type IIB D-brane probes wrapping cycles of local Calabi-Yau
threefolds. These include N=2 (affine) A-D-E quiver theories deformed by
superpotential terms, as well as chiral N=1 quiver theories obtained in the
presence of vanishing 4-cycles inside a Calabi-Yau. We consider the various
possible geometric transitions of the 3-fold and show that they correspond to
Seiberg-like dualities (represented by Weyl reflections in the A-D-E case or
`mutations' of bundles in the case of vanishing 4-cycles) or large N dualities
involving gaugino condensates (generalized conifold transitions). Also duality
cascades are naturally realized in these classes of theories, and are related
to the affine Weyl group symmetry in the A-D-E case.Comment: 94 pages, 18 figures. Added referenc
Dibaryons from Exceptional Collections
We discuss aspects of the dictionary between brane configurations in del
Pezzo geometries and dibaryons in the dual superconformal quiver gauge
theories. The basis of fractional branes defining the quiver theory at the
singularity has a K-theoretic dual exceptional collection of bundles which can
be used to read off the spectrum of dibaryons in the weakly curved dual
geometry. Our prescription identifies the R-charge R and all baryonic U(1)
charges Q_I with divisors in the del Pezzo surface without any Weyl group
ambiguity. As one application of the correspondence, we identify the cubic
anomaly tr R Q_I Q_J as an intersection product for dibaryon charges in large-N
superconformal gauge theories. Examples can be given for all del Pezzo surfaces
using three- and four-block exceptional collections. Markov-type equations
enforce consistency among anomaly equations for three-block collections.Comment: 47 pages, 11 figures, corrected ref
Quivers from Matrix Factorizations
We discuss how matrix factorizations offer a practical method of computing
the quiver and associated superpotential for a hypersurface singularity. This
method also yields explicit geometrical interpretations of D-branes (i.e.,
quiver representations) on a resolution given in terms of Grassmannians. As an
example we analyze some non-toric singularities which are resolved by a single
CP1 but have "length" greater than one. These examples have a much richer
structure than conifolds. A picture is proposed that relates matrix
factorizations in Landau-Ginzburg theories to the way that matrix
factorizations are used in this paper to perform noncommutative resolutions.Comment: 33 pages, (minor changes
Nitrogenase MoFe protein from Clostridium pasteurianum at 1.08 Ă resolution: comparison with the Azotobacter vinelandii MoFe protein
The X-ray crystal structure of the nitrogenase MoFe protein from Clostridium pasteurianum (Cp1) has been determined at 1.08 Ă
resolution by multiwavelength anomalous diffraction phasing. Cp1 and the ortholog from Azotobacter vinelandii (Av1) represent two distinct families of nitrogenases, differing primarily by a long insertion in the ι-subunit and a deletion in the β-subunit of Cp1 relative to Av1. Comparison of these two MoFe protein structures at atomic resolution reveals conserved structural arrangements that are significant to the function of nitrogenase. The FeMo cofactors defining the active sites of the MoFe protein are essentially identical between the two proteins. The surrounding environment is also highly conserved, suggesting that this structural arrangement is crucial for nitrogen reduction. The P clusters are likewise similar, although the surrounding protein and solvent environment is less conserved relative to that of the FeMo cofactor. The P cluster and FeMo cofactor in Av1 and Cp1 are connected through a conserved water tunnel surrounded by similar secondary-structure elements. The long -subunit insertion loop occludes the presumed Fe protein docking surface on Cp1 with few contacts to the remainder of the protein. This makes it plausible that this loop is repositioned to open up the Fe protein docking surface for complex formation
Instanton operators in five-dimensional gauge theories
This article is distributed under the terms of the Creative Commons
Attribution License (CC-BY 4.0), which permits any use, distribution and reproduction in
any medium, provided the original author(s) and source are creditedN.L. is supported in part by STFC grant ST/J002798/1. C.P. is a Royal Society Research Fellow.N.L. is supported in part by STFC grant ST/J002798/1. C.P. is a Royal Society Research Fellow.N.L. is supported in part by STFC grant ST/J002798/1. OPen Aceess funded by SCOAP
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