Cyclic AMP Regulation of Protein Lysine Acetylation in Mycobacterium Tuberculosis

Protein lysine acetylation networks can regulate central processes such as carbon metabolism and gene expression in bacteria. In Escherichia coli, cyclic-AMP (cAMP) regulates protein lysine acetyltransferase (PAT) activity at the transcriptional level, but in Mycobacterium tuberculosis, fusion of a cyclic-nucleotide binding domain to a Gcn5-like PAT domain enables direct cAMP control of protein acetylation. Here we describe the allosteric activation mechanism of M. tuberculosis PAT. The crystal structures of the auto-inhibited and cAMP-activated PAT reveal that cAMP binds to a cryptic site in the regulatory domain over 32 Å from the catalytic site. An extensive conformational rearrangement relieves auto-inhibition by a substrate-mimicking lid that covers the protein-substrate binding surface. A steric double latch couples the domains by harnessing a classic, cAMP-mediated, conformational switch. The structures suggest general features that enable the evolution of long-range communication between linked domains

Maximum Edge-Disjoint Paths in kk-sums of Graphs

We consider the approximability of the maximum edge-disjoint paths problem (MEDP) in undirected graphs, and in particular, the integrality gap of the natural multicommodity flow based relaxation for it. The integrality gap is known to be $\Omega(\sqrt{n})$ even for planar graphs due to a simple topological obstruction and a major focus, following earlier work, has been understanding the gap if some constant congestion is allowed. In this context, it is natural to ask for which classes of graphs does a constant-factor constant-congestion property hold. It is easy to deduce that for given constant bounds on the approximation and congestion, the class of "nice" graphs is nor-closed. Is the converse true? Does every proper minor-closed family of graphs exhibit a constant factor, constant congestion bound relative to the LP relaxation? We conjecture that the answer is yes. One stumbling block has been that such bounds were not known for bounded treewidth graphs (or even treewidth 3). In this paper we give a polytime algorithm which takes a fractional routing solution in a graph of bounded treewidth and is able to integrally route a constant fraction of the LP solution's value. Note that we do not incur any edge congestion. Previously this was not known even for series parallel graphs which have treewidth 2. The algorithm is based on a more general argument that applies to $k$-sums of graphs in some graph family, as long as the graph family has a constant factor, constant congestion bound. We then use this to show that such bounds hold for the class of $k$-sums of bounded genus graphs

Theory of Thermodynamic Magnetic Oscillations in Quasi-One-Dimensional Conductors

The second order correction to free energy due to the interaction between electrons is calculated for a quasi-one-dimensional conductor exposed to a magnetic field perpendicular to the chains. It is found that specific heat, magnetization and torque oscillate when the magnetic field is rotated in the plane perpendicular to the chains or when the magnitude of magnetic filed is changed. This new mechanism of thermodynamic magnetic oscillations in metals, which is not related to the presence of any closed electron orbits, is applied to explain behavior of the organic conductor (TMTSF)$_2$ClO$_4$.Comment: 11 pages + 5 figures (included

Via Hexagons to Squares in Ferrofluids: Experiments on Hysteretic Surface Transformations under Variation of the Normal Magnetic Field

We report on different surface patterns on magnetic liquids following the Rosensweig instability. We compare the bifurcation from the flat surface to a hexagonal array of spikes with the transition to squares at higher fields. From a radioscopic mapping of the surface topography we extract amplitudes and wavelengths. For the hexagon--square transition, which is complex because of coexisting domains, we tailor a set of order parameters like peak--to--peak distance, circularity, angular correlation function and pattern specific amplitudes from Fourier space. These measures enable us to quantify the smooth hysteretic transition. Voronoi diagrams indicate a pinning of the domains. Thus the smoothness of the transition is roughness on a small scale.Comment: 17 pages, 14 figure

Spectroscopy of 18^{18}Na: Bridging the two-proton radioactivity of 19^{19}Mg

The unbound nucleus $^{18}$Na, the intermediate nucleus in the two-proton radioactivity of $^{19}$Mg, was studied by the measurement of the resonant elastic scattering reaction $^{17}$Ne(p,$^{17}$Ne)p performed at 4 A.MeV. Spectroscopic properties of the low-lying states were obtained in a R-matrix analysis of the excitation function. Using these new results, we show that the lifetime of the $^{19}$Mg radioactivity can be understood assuming a sequential emission of two protons via low energy tails of $^{18}$Na resonances

Destruction of density-wave states by a pseudo-gap in high magnetic fields: application to (TMTSF)2_2ClO4_4

A model is presented for the destruction of density-wave states in quasi-one-dimensional crystals by high magnetic fields. The model is consistent with previously unexplained properties of the organic conductors (TMTSF)$_2$ClO$_4$ and (BEDT-TTF)$_2$MHg(SCN)$_4$ (M=K,Rb,Tl). As the magnetic field increases quasi-one-dimensional density-wave fluctuations increase, producing a pseudo-gap in the electronic density of states near the transition temperature. When the pseudo-gap becomes larger than the mean-field transition temperature formation of a density-wave state is not possible.Comment: 4 pages, RevTeX, 2 figures in uuencoded compressed tar file. Small changes to text and Figure 1. Final version to appear in Physical Review Letter

Diagnostic tool or screening programme? Asymptomatic testing for SARS-CoV-2 needs clear goals and protocols.

Background: Drug-resistant enteric fever is increasingly common in the Indian subcontinent. Correctly determining azithromycin resistance matters where drug-resistant enteric fever is common and oral therapy necessary. Case report: In two patients returning from Pakistan to the UK with cephalosporin-resistant Salmonella enterica serovar Typhi, gradient strip testing erroneously indicated azithromycin resistance; the errors were detected by repeat testing and confirmed by whole genome sequencing. Results: Both patients were treated with meropenem and, when revised susceptibility results were known, with azithromycin, allowing a switch to oral therapy. Conclusion: As cephalosporin resistance becomes more common, azithromycin will be key for treating enteric fever and optimizing practice in susceptibility testing will be crucial. Practitioners should be aware of key steps to minimize error in azithromycin susceptibility testing, and should be alert for possible errors when reported azithromycin resistance is discordant with known prevalence of resistance.Mason Medical Research Foundatio

Factors Influencing Optical Coherence Tomography Peripapillary Choroidal Thickness: A Multicenter Study.

Purpose:To quantify peripapillary choroidal thickness (PCT) and the factors that influence it in healthy participants who represent the racial and ethnic composition of the U.S. population. Methods:A total of 362 healthy participants underwent optical coherence tomography (OCT) enhanced depth imaging of the optic nerve head with a 24 radial B-scan pattern aligned to the fovea to Bruch's membrane opening axis. Bruch's membrane, anterior scleral canal opening (ASCO), and the anterior scleral surface were manually segmented. PCT was measured at 100, 300, 500, 700, 900, and 1100 μm from the ASCO globally and within 12 clock-hour sectors. The effects of age, axial length, intraocular pressure, ethnicity, sex, sector, and ASCO area on PCT were assessed by ANOVA and univariable and multivariable regressions. Results:Globally, PCT was thicker further from the ASCO border and thinner with older age, longer axial length, larger ASCO area, European descent, and female sex. Among these effectors, age and axial length explained the greatest proportion of variance. The rate of age-related decline increased further from the ASCO border. Sectorally, the inferior-temporal sectors were thinnest (10.7%-20.0% thinner than the thickest sector) and demonstrated a higher rate of age-related loss (from 15.6% to 20.7% faster) at each ASCO distance. Conclusions:In healthy eyes, PCT was thinnest in the inferior temporal sectors and thinner PCT was associated with older age, European descent, longer axial length, larger ASCO area, and female sex. Among these associations, age had the strongest influence, and its effect was greatest within the inferior temporal sectors

Theoretical study of the two-proton halo candidate 17^{17}Ne including contributions from resonant continuum and pairing correlations

With the relativistic Coulomb wave function boundary condition, the energies, widths and wave functions of the single proton resonant orbitals for $^{17}$Ne are studied by the analytical continuation of the coupling constant (ACCC) approach within the framework of the relativistic mean field (RMF) theory. Pairing correlations and contributions from the single-particle resonant orbitals in the continuum are taken into consideration by the resonant Bardeen-Cooper-Schrieffer (BCS) approach, in which constant pairing strength is used. It can be seen that the fully self-consistent calculations with NL3 and NLSH effective interactions mostly agree with the latest experimental measurements, such as binding energies, matter radii, charge radii and densities. The energy of $\pi$2s$_{1/2}$ orbital is slightly higher than that of $\pi1d_{5/2}$ orbital, and the occupation probability of the $(\pi$2s$_{1/2})^2$ orbital is about 20%, which are in accordance with the shell model calculation and three-body model estimation

Developing effective practice learning for tomorrow's social workers

This paper considers some of the changes in social work education in the UK, particularly focusing on practice learning in England. The changes and developments are briefly identified and examined in the context of what we know about practice learning. The paper presents some findings from a small scale qualitative study of key stakeholders involved in practice learning and education in social work and their perceptions of these anticipated changes, which are revisited at implementation. The implications for practice learning are discussed