251 research outputs found
ÂčH, Âčâ”N, ÂčÂłC backbone resonance assignments of human phosphoglycerate kinase in a transition state analogue complex with ADP, 3-phosphoglycerate and magnesium trifluoride
Human phosphoglycerate kinase (PGK) is an energy generating glycolytic enzyme that catalyses the transfer of a phosphoryl group from 1,3-bisphosphoglycerate (BPG) to ADP producing 3-phosphoglycerate (3PG) and ATP. PGK is composed of two α/ÎČ Rossmann-fold domains linked by a central α-helix and the active site is located in the cleft formed between the N-domain which binds BPG or 3PG, and the C-domain which binds the nucleotides ADP or ATP. Domain closure is required to bring the two substrates into close proximity for phosphoryl transfer to occur, however previous structural studies involving a range of native substrates and substrate analogues only yielded open or partly closed PGK complexes. X-ray crystallography using magnesium trifluoride (MgF3(-)) as a isoelectronic and near-isosteric mimic of the transferring phosphoryl group (PO3(-)), together with 3PG and ADP has been successful in trapping human PGK in a fully closed transition state analogue (TSA) complex. In this work we report the (1)H, (15)N and (13)C backbone resonance assignments of human PGK in the solution conformation of the fully closed PGK:3PG:MgF3:ADP TSA complex. Assignments were obtained by heteronuclear multidimensional NMR spectroscopy. In total, 97% of all backbone resonances were assigned in the complex, with 385 out of a possible 399 residues assigned in the (1)H-(15)N TROSY spectrum. Prediction of solution secondary structure from a chemical shift analysis using the TALOS-N webserver is in good agreement with the published X-ray crystal structure of this complex
Topology by Design in Magnetic nano-Materials: Artificial Spin Ice
Artificial Spin Ices are two dimensional arrays of magnetic, interacting
nano-structures whose geometry can be chosen at will, and whose elementary
degrees of freedom can be characterized directly. They were introduced at first
to study frustration in a controllable setting, to mimic the behavior of spin
ice rare earth pyrochlores, but at more useful temperature and field ranges and
with direct characterization, and to provide practical implementation to
celebrated, exactly solvable models of statistical mechanics previously devised
to gain an understanding of degenerate ensembles with residual entropy. With
the evolution of nano--fabrication and of experimental protocols it is now
possible to characterize the material in real-time, real-space, and to realize
virtually any geometry, for direct control over the collective dynamics. This
has recently opened a path toward the deliberate design of novel, exotic
states, not found in natural materials, and often characterized by topological
properties. Without any pretense of exhaustiveness, we will provide an
introduction to the material, the early works, and then, by reporting on more
recent results, we will proceed to describe the new direction, which includes
the design of desired topological states and their implications to kinetics.Comment: 29 pages, 13 figures, 116 references, Book Chapte
Accelerated partial breast irradiation: the case for current use
The treatment of early stage breast cancer is evolving from traditional breast conservation techniques, employing conventionally fractionated whole breast irradiation, to techniques in which partial breast irradiation is used in an accelerated fractionation scheme. A growing body of evidence exists, including favorable findings. Additional studies are under way that may ultimately prove equivalence. The logic behind this approach is reviewed, and the currently available data are presented to support the current use of carefully applied partial breast irradiation techniques in appropriately selected and informed patients
Dynamical Mean-Field Theory
The dynamical mean-field theory (DMFT) is a widely applicable approximation
scheme for the investigation of correlated quantum many-particle systems on a
lattice, e.g., electrons in solids and cold atoms in optical lattices. In
particular, the combination of the DMFT with conventional methods for the
calculation of electronic band structures has led to a powerful numerical
approach which allows one to explore the properties of correlated materials. In
this introductory article we discuss the foundations of the DMFT, derive the
underlying self-consistency equations, and present several applications which
have provided important insights into the properties of correlated matter.Comment: Chapter in "Theoretical Methods for Strongly Correlated Systems",
edited by A. Avella and F. Mancini, Springer (2011), 31 pages, 5 figure
The Weaker Sex? The Propensity for Male-Biased Piglet Mortality
For the most part solutions to farm animal welfare issues, such as piglet mortality, are likely to lie within the scientific disciplines of environmental design and genetic selection, however understanding the ecological basis of some of the complex dynamics observed between parent and offspring could make a valuable contribution. One interesting, and often discussed, aspect of mortality is the propensity for it to be sex-biased. This study investigated whether known physiological and behavioural indicators of piglet survival differed between the sexes and whether life history strategies (often reported in wild or feral populations) relating to parental investment were being displayed in a domestic population of pigs. Sex ratio (proportion of males (males/males+females)) at birth was 0.54 and sex allocation (maternal investment measured as piglet birth weight/litter weight) was statistically significantly male-biased at 0.55 (t35â=â2.51 Pâ=â0.017), suggesting that sows invested more in sons than daughters during gestation. Despite this investment in birth weight, a known survival indicator, total pre-weaning male mortality was statistically significantly higher than female mortality (12% vs. 7% respectively zâ=â2.06 Pâ=â0.040). Males tended to suffer from crushing by the sow more than females and statistically significantly more males died from disease-related causes. Although males were born on average heavier, with higher body mass index and ponderal index, these differences were not sustained. In addition male piglets showed impaired thermoregulation compared to females. These results suggest male-biased mortality exists despite greater initial maternal investment, and therefore reflects the greater susceptibility of this sex to causal mortality factors. Life history strategies are being displayed by a domestic population of pigs with sows in this study displaying a form of parental optimism by allocating greater resources at birth to males and providing an over-supply of this more vulnerable sex in expectation of sex-biased mortality
Increased dynamics in the 40-57 Ω-loop of the G41S variant of human cytochrome c promote its pro-apoptotic conformation
Thrombocytopenia 4 is an inherited autosomal dominant thrombocytopenia, which occurs due to mutations in the human gene for cytochrome c that results in enhanced mitochondrial apoptotic activity. The Gly41Ser mutation was the first to be reported. Here we report stopped-flow kinetic studies of azide binding to human ferricytochrome c and its Gly41Ser variant, together with backbone amide H/D exchange and 15N-relaxation dynamics using NMR spectroscopy, to show that alternative conformations are kinetically and thermodynamically more readily accessible for the Gly41Ser variant than for the wild-type protein. Our work reveals a direct conformational link between the 40-57 Ω-loop in which residue 41 resides and the dynamical properties of the axial ligand to the heme iron, Met80, such that the replacement of glycine by serine promotes the dissociation of the Met80 ligand, thereby increasing the population of a peroxidase active state, which is a key non-native conformational state in apoptosis
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