The structure of α-haemoglobin in complex with a haemoglobin-binding domain from Staphylococcus aureus reveals the elusive α-haemoglobin dimerization interface

Adult haemoglobin (Hb) is made up of two α and two β subunits. Mutations that reduce expression of the α- or β-globin genes lead to the conditions α- or β-thalassaemia, respectively. Whilst both conditions are characterized by anaemia of variable severity, other details of their pathophysiology are different, in part owing to the greater stability of the β chains that is conferred through β self-association. In contrast, α subunits interact weakly, and in the absence of stabilizing quaternary interactions the α chain (α) is prone to haem loss and denaturation. The molecular contacts that confer weak self-association of α have not been determined previously. Here, the first structure of an α2 homodimer is reported in complex with one domain of the Hb receptor from Staphylococcus aureus. The α2 dimer interface has a highly unusual, approximately linear, arrangement of four His side chains within hydrogen-bonding distance of each other. Some interactions present in the α1β1 dimer interface of native Hb are preserved in the α2 dimer. However, a marked asymmetry is observed in the α2 interface, suggesting that steric factors limit the number of stabilizing interactions that can form simultaneously across the interface. © 2014 CrossMark

The structure of haemoglobin bound to the haemoglobin receptor IsdH from Staphylococcus aureus shows disruption of the native α-globin haem pocket

© 2015 International Union of Crystallography. Staphylococcus aureus is a common and serious cause of infection in humans. The bacterium expresses a cell-surface receptor that binds to, and strips haem from, human haemoglobin (Hb). The binding interface has previously been identified; however, the structural changes that promote haem release from haemoglobin were unknown. Here, the structure of the receptor-Hb complex is reported at 2.6 Å resolution, which reveals a conformational change in the α-globin F helix that disrupts the haem-pocket structure and alters the Hb quaternary interactions. These features suggest potential mechanisms by which the S. aureus Hb receptor induces haem release from Hb

Combining type I and type II seesaw mechanisms in the minimal 3-3-1 model

The minimal 3-3-1 model is perturbative until energies around 4-5TeV, posing a challenge to generate neutrino masses at eV scale, mainly if one aims to take advantage of the seesaw mechanism. As a means to circumvent this problem we propose a modification of the model such that it accommodates the type I and type II seesaw mechanisms altogether. We show that the conjunction of both mechanisms yield a neutrino mass expression suppressed by a high power of the cutoff scale, $M^5$, in its denominator. With such a suppression term we naturally obtain neutrino masses at eV scale when $M$ is around few TeV. We also investigate the size of lepton flavor violation through the process $\mu \rightarrow e\gamma$.Comment: about 15 pages, no figure

A Simple Realization of the Inverse Seesaw Mechanism

Differently from the canonical seesaw mechanism, which is grounded in grand unified theories, the inverse seesaw mechanism lacks a special framework that realizes it naturally. In this work we advocate that the 3-3-1 model with right-handed neutrinos has such an appropriate framework to accommodate the inverse seesaw mechanism. We also provide an explanation for the smallness of the $\mu$ parameter and estimate the branching ratio for the rare lepton flavor violation process $\mu \rightarrow e\gamma$.Comment: About 14pages, no figures, basis corrected, to appear at the PR

Structural basis for hemoglobin capture by Staphylococcus aureus cell-surface protein, IsdH

Pathogens must steal iron from their hosts to establish infection. In mammals, hemoglobin (Hb) represents the largest reservoir of iron, and pathogens express Hb-binding proteins to access this source. Here, we show how one of the commonest and most significant human pathogens, Staphylococcus aureus, captures Hb as the first step of an iron-scavenging pathway. The x-ray crystal structure of Hb bound to a domain from the Isd (iron-regulated surface determinant) protein, IsdH, is the first structure of a Hb capture complex to be determined. Surface mutations in Hb that reduce binding to the Hb-receptor limit the capacity of S. aureus to utilize Hb as an iron source, suggesting that Hb sequence is a factor in host susceptibility to infection. The demonstration that pathogens make highly specific recognition complexes with Hb raises the possibility of developing inhibitors of Hb binding as antibacterial agents. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc

Obtaining the equation of motion for a fermionic particle in a generalized Lorentz-violating system framework

Using a generalized procedure for obtaining the dispersion relation and the equation of motion for a propagating fermionic particle, we examine previous claims for a preferred axis at $n_{\mu}$($\equiv(1,0,0,1)$), $n^{2}=0$ embedded in the framework of very special relativity (VSR). We show that, in a relatively high energy scale, the corresponding equation of motion is reduced to a conserving lepton number chiral equation previously predicted in the literature. Otherwise, in a relatively low energy scale, the equation is reduced to the usual Dirac equation for a free propagating fermionic particle. It is accomplished by the suggestive analysis of some special cases where a nonlinear modification of the action of the Lorentz group is generated by the addition of a modified conformal transformation which, meanwhile, preserves the structure of the ordinary Lorentz algebra in a very peculiar way. Some feasible experiments, for which Lorentz violating effects here pointed out may be detectable, are suggested.Comment: 10 page

The experience of enchantment in human-computer interaction

Improving user experience is becoming something of a rallying call in human–computer interaction but experience is not a unitary thing. There are varieties of experiences, good and bad, and we need to characterise these varieties if we are to improve user experience. In this paper we argue that enchantment is a useful concept to facilitate closer relationships between people and technology. But enchantment is a complex concept in need of some clarification. So we explore how enchantment has been used in the discussions of technology and examine experiences of film and cell phones to see how enchantment with technology is possible. Based on these cases, we identify the sensibilities that help designers design for enchantment, including the specific sensuousness of a thing, senses of play, paradox and openness, and the potential for transformation. We use these to analyse digital jewellery in order to suggest how it can be made more enchanting. We conclude by relating enchantment to varieties of experience.</p

Physical limits of inference

I show that physical devices that perform observation, prediction, or recollection share an underlying mathematical structure. I call devices with that structure "inference devices". I present a set of existence and impossibility results concerning inference devices. These results hold independent of the precise physical laws governing our universe. In a limited sense, the impossibility results establish that Laplace was wrong to claim that even in a classical, non-chaotic universe the future can be unerringly predicted, given sufficient knowledge of the present. Alternatively, these impossibility results can be viewed as a non-quantum mechanical "uncertainty principle". Next I explore the close connections between the mathematics of inference devices and of Turing Machines. In particular, the impossibility results for inference devices are similar to the Halting theorem for TM's. Furthermore, one can define an analog of Universal TM's (UTM's) for inference devices. I call those analogs "strong inference devices". I use strong inference devices to define the "inference complexity" of an inference task, which is the analog of the Kolmogorov complexity of computing a string. However no universe can contain more than one strong inference device. So whereas the Kolmogorov complexity of a string is arbitrary up to specification of the UTM, there is no such arbitrariness in the inference complexity of an inference task. I end by discussing the philosophical implications of these results, e.g., for whether the universe "is" a computer.Comment: 43 pages, updated version of Physica D version, which originally appeared in 2007 CNLS conference on unconventional computatio

Analyticity, Unitarity and One-loop Graviton Corrections to Compton Scattering

We compute spin-flip cross section for graviton photoproduction on a spin-1/2 target of finite mass. Using this tree-level result, we find one-loop graviton correction to the spin-flip low-energy forward Compton scattering amplitude by using Gerasimov-Drell-Hearn sum rule. We show that this result agrees with the corresponding perturbative computations, implying the validity of the sum rule at one-loop level, contrary to the previous claims. We discuss possible effects from the black hole production and string Regge trajectory exchange at very high energies. These effects seem to soften the UV divergence present at one-loop graviton level. Finally, we discuss the relation of these observations with the models that involve extra dimensions.Comment: 15 pages, 3 figure