How to change the oligomeric state of a circular protein assembly: switch from 11-subunit to 12-subunit TRAP suggests a general mechanism

Many critical cellular functions are performed by multisubunit circular protein oligomers whose internal geometry has evolved to meet functional requirements. The subunit number is arguably the most critical parameter of a circular protein assembly, affecting the internal and external diameters of the assembly and often impacting on the protein's function. Although accurate structural information has been obtained for several circular proteins, a lack of accurate information on alternative oligomeric states has prevented engineering such transitions. In this study we used the bacterial transcription regulator TRAP as a model system to investigate the features that define the oligomeric state of a circular protein and to question how the subunit number could be manipulated.We find that while Bacillus subtilis and Bacillus stearothermophilus TRAP form 11-subunit oligomers, the Bacillus halodurans TRAP exclusively forms 12-subunit assemblies. Significantly, the two states of TRAP are related by a simple rigid body rotation of individual subunits around inter-subunit axes. We tested if such a rotation could be induced by insertion or deletion mutations at the subunit interface. Using wild type 11-subunit TRAP, we demonstrate that removal of five C-terminal residues at the outer side of the inter-subunit axis or extension of an amino acid side chain at the opposite, inner side, increased the subunit number from 11 to 12. Our findings are supported by crystal structures of TRAP oligomers and by native mass spectrometry data.The subunit number of the TRAP oligomer can be manipulated by introducing deletion or addition mutations at the subunit interface. An analysis of available and emerging structural data on alternative oligomeric states indicates that the same principles may also apply to the subunit number of other circular assemblies suggesting that the deletion/addition approach could be used generally to engineer transitions between different oligomeric states

Debunking Rumors in Networks

We study the diffusion of a true and a false message (the rumor) in a social network. Upon hearing a message, individuals may believe it, disbelieve it, or debunk it through costly verification. Whenever the truth survives in steady state, so does the rumor. Online social communication exacerbates relative rumor prevalence as long as it increases homophily or verification costs. Our model highlights that successful policies in the fight against rumors increase individuals' incentives to verify

Crystal structure of afghanite, the eight-layer member of the cancrinite-group: Evidence for long-range Si,Al ordering

Afghanite, ideally [(Na,K)(22)Ca-10][Si24Al24O96](SO4)(6)Cl-6, is the eight-layer member of the cancrinite-group (ABABACAC stacking sequence). Its structure was refined in the P31c space group to R = 4.5% by means of single-crystal X-ray diffraction data. The cell parameters are a = 12.8013(7) Angstrom, c = 21.4119(18) Angstrom. The P6(3)mc space group proposed in a previous structure refinement is not consistent with the ordered Si,AI pattern suggested by an Si/Al ratio equal to 1 shown by afghanite and other members of the cancrinite-group. The Si-O and Al-O bond distances, 1.61(2) Angstrom and 1.72(2) Angstrom respectively, found in the structure refinement, are in accordance with an ordered Si,AI distribution which is allowed by the P31c space group, a maximal non isomorphic subgroup of P6(3)mc. Afghanite contains six 11-hedra (cancrinite) cages and two 23-hedra (liottite) cages. Four cancrinite cages are stacked along [0 0 z]. They contain a regular....Ca-Cl-Ca-Cl.... chain similar to that observed in davyne and related phases: in particular Ca is located near the center of the bases whereas Cl is near the center of the cage. A liottite cage with a base-sharing cancrinite cage is stacked along [2/3 1/3 z] and [1/3 2/3 z]. The liottite cage hosts a maximum of three sulphate groups which alternate regularly with cation-containing planes. The cancrinite cage, that shares the bases with the liottite cages, presents a disordered distribution of Cl and F reading to two possible configurations similar to those observed in liottite

Anomalous dust temperature in dusty plasma experiments

Dust heating in dusty plasmas due to thermal electric field fluctuations and dust acoustic waves is examined. It is shown that dust particles acquire large random motion in fluctuating electric fields (within dust cloud) of background plasma causing dust electrostatic pressure PE [K. Avinash, Phys. Plasmas 13 (2006) 012109] and corresponding large temperature TE. Due to quadratic dependence on qd and high dust charge (∼ 103–104e), TE is much bigger than the dust kinetic temperature Td and is in the range of 10–300 eV for typical experimental numbers. Using global energy constraints dust heating due to dust acoustic waves is examined. It is shown that dust acoustic waves are potentially capable of heating dust to high temperatures in the range of a few hundreds of eV

Screening of a Moving Parton in the Quark-Gluon Plasma

The screening potential of a parton moving through a quark-gluon plasma is calculated using the semi-classical transport theory. An anisotropic potential showing a minimum in the direction of the parton velocity is found. As consequences possible new bound states and J/psi dissociation are discussed.Comment: 4 pages, 2 figures, final, extended version, to be published in Phys.Rev.

An FPGA-based flexible demo-board for endoscopic capsule design optimization

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An FPGA-based versatile development system for endoscopic capsule design optimization

This work presents a development system, based on Field Programmable Gate Array (FPGA), that was specifically designed for testing the entire electronics to be integrated in an endoscopic capsule, such as a camera, an image compression engine, a high-speed telemetric system, illumination and inertial sensors. Thanks to its high flexibility, several features were tested and evaluated, thus allowing to find the optimal configuration, in terms of power consumption, performances and size, to be fit in a capsule. As final result, an average frame rate of 19 frame per second (fps) over a transmission channel of 1.5 Mbit/s was chosen as the best choice for the development of a miniaturized endoscopic capsule prototype

Diverse mobilized class 1 integrons are common in the chromosomes of pathogenic Pseudomonas aeruginosa clinical isolates

Eleven clinical class 1 integron-containing Pseudomonas aeruginosa isolates from Australia and Uruguay were investigated for the genomic locations of these elements. Several novel class 1 integrons/transposons were found in at least four distinct locations in the chromosome, including genomic islands. These elements seem to be undergoing successful dispersal by lateral gene transfer since integrons were identified across several lineages and more than one clonal line. Copyright © 2012, American Society for Microbiology. All Rights Reserved

Novel anti-inflammatory and chondroprotective effects of the human melanocortin MC1 receptor agonist BMS-470539 dihydrochloride and human melanocortin MC3 receptor agonist PG-990 on lipopolysaccharide activated chondrocytes

Human melanocortin MC1 and MC3 receptors expressed on C-20/A4 chondrocytes exhibit chondroprotective and anti-inflammatory effects when activated by melanocortin peptides. Nearly 9 million people in the UK suffer from osteoarthritis, and bacterial infections play a role in its development. Here, we evaluate the effect of a panel of melanocortin peptides with different selectivity for human melanocortin MC1 (alpha-MSH, BMS-470539 dihydrochloride) and MC3 receptors ([DTrp8]-g-MSH, PG-990) and C-terminal peptide alpha-MSH11-13(KPV), on inhibiting LPS-induced chondrocyte death, pro-inflammatory mediators and induction of anti-inflammatory proteins. C-20/A4 chondrocytes were treated with a panel of melanocortin peptides prophylactically and therapeutically in presence of LPS (0.1 ug/ml). The chondroprotective properties of these peptides determined by cell viability assay, RT-PCR, ELISA for detection of changes in inflammatory markers (IL-6, IL-8 and MMP-1, -3 and -13) and western blotting for expression of the anti-inflammatory protein heme-oxygenase-1. C-20/A4 expressed human melanocortin MC1 and MC3 receptors and melanocortin peptides elevated cAMP. LPS stimulation caused a reduction in C-20/A4 viability, attenuated by the human melanocortin MC1 receptor agonist BMS-470539 dihydrochloride, and MC3 receptor agonists PG-990 and [DTrp8]-g-MSH. Prophylactic and therapeutic regimes of [DTrp8]-g-MSH significantly inhibited LPS-induced modulation of cartilage-damaging IL-6, IL-8, MMPs -1,-3 and -13 mediators both prophylactically and therapeutically, whilst human melanocortin MC1 and MC3 receptor agonists promoted an increase in HO-1 production. In the presence of LPS, activation of human melanocortin MC1 and MC3 receptors provided potent chondroprotection, upregulation of anti-inflammatory proteins and downregulation of inflammatory and proteolytic mediators involved in cartilage degradation, suggesting a new avenue for osteoarthritis treatment

The Quark-Gluon-Plasma Liquid

The quark-gluon plasma close to the critical temperature is a strongly interacting system. Using strongly coupled, classical, non-relativistic plasmas as an analogy, we argue that the quark-gluon plasma is in the liquid phase. This allows to understand experimental observations in ultrarelativistic heavy-ion collisions and to interpret lattice QCD results. It also supports the indications of the presence of a strongly coupled QGP in ultrarelativistic heavy-ion collisions.Comment: 8 pages, 2 figures, final version, to bepublished in J. Phys.