Co-evolution of quaternary organization and novel RNA tertiary interactions revealed in the crystal structure of a bacterial protein–RNA toxin–antitoxin system

Genes encoding toxin–antitoxin (TA) systems are near ubiquitous in bacterial genomes and they play key roles in important aspects of bacterial physiology, including genomic stability, formation of persister cells under antibiotic stress, and resistance to phage infection. The CptIN locus from Eubacterium rectale is a member of the recently-discovered Type III class of TA systems, defined by a protein toxin suppressed by direct interaction with a structured RNA antitoxin. Here, we present the crystal structure of the CptIN protein–RNA complex to 2.2 Å resolution. The structure reveals a new heterotetrameric quaternary organization for the Type III TA class, and the RNA antitoxin bears a novel structural feature of an extended A-twist motif within the pseudoknot fold. The retention of a conserved ribonuclease active site as well as traits normally associated with TA systems, such as plasmid maintenance, implicates a wider functional role for Type III TA systems. We present evidence for the co-variation of the Type III component pair, highlighting a distinctive evolutionary process in which an enzyme and its substrate co-evolve

Anti-GQ1b ganglioside positive Miller Fisher syndrome - evidence of paranodal pathology on nerve biopsy

BACKGROUND: Miller Fisher syndrome is a regional variant of Guillain-Barre syndrome with a characteristic clinical triad of ophthalmoplegia, areflexia and ataxia and occasionally distal limb sensory loss. 90% of patients have associated antibodies to the GQ1b ganglioside. The pathophysiology of antibody-mediated peripheral nerve impairment remains uncertain. This report includes the first description of a peripheral sensory nerve biopsy in Miller Fisher syndrome. RESULTS: A single case report is described of a 46 year old woman who presented with 2 weeks of distal glove and stocking sensory loss to both deep and superficial sensory modalities, areflexia and weight loss. This was followed by rapid onset of ataxia, ophthalmoplegia, and bulbar impairment. Peripheral neurophysiology showed reduced sensory nerve amplitudes with preserved conduction velocities in keeping with an axonal pattern of impairment. Clinical concerns of a systemic inflammatory disorder led to a diagnostic peripheral nerve biopsy from the sensory branch of the radial nerve. However she subsequently made a complete recovery over 5 weeks. Combinatorial glycoarrays confirmed restricted serum binding for GQ1b in acute serum which later resolved in a convalescent sample. The nerve biopsy showed lengthening of nodes of Ranvier, myelin splitting and macrophage internodal axonal invasion without any features of demyelination. CONCLUSIONS: The pathological features were strikingly similar to those found in acute motor axonal neuropathy and indicate the region of the node of Ranvier to be a primary focus of GQ1b induced damage in Miller Fisher syndrome, at least in this particular overlap syndrome with prominent sensory nerve involvement

Bianchi type II,III and V diagonal Einstein metrics re-visited

We present, for both minkowskian and euclidean signatures, short derivations of the diagonal Einstein metrics for Bianchi type II, III and V. For the first two cases we show the integrability of the geodesic flow while for the third case a somewhat unusual bifurcation phenomenon takes place: for minkowskian signature elliptic functions are essential in the metric while for euclidean signature only elementary functions appear

Lagrangian Description of the Variational Equations

A variant of the usual Lagrangian scheme is developed which describes both the equations of motion and the variational equations of a system. The required (prolonged) Lagrangian is defined in an extended configuration space comprising both the original configurations of the system and all the virtual displacements joining any two integral curves. Our main result establishes that both the Euler-Lagrange equations and the corresponding variational equations of the original system can be viewed as the Lagrangian vector field associated with the first prolongation of the original LagrangianAfter discussing certain features of the formulation, we introduce the so-called inherited constants of the motion and relate them to the Noether constants of the extended system

The power of effective study design in animal Experimentation: Exploring the statistical and ethical implications of asking multiple questions of a data set

One of the chief advantages of using highly standardised biological models including model organisms is that multiple variables can be precisely controlled so that the variable of interest is more easily studied. However, such an approach often obscures effects in sub-populations resulting from natural population heterogeneity. Efforts to expand our fundamental understanding of multiple sub-populations are in progress. However, such stratified or personalised approaches require fundamental modifications of our usual study designs that should be implemented in Brain, Behavior and Immunity (BBI) research going forward. Here we explore the statistical feasibility of asking multiple questions (including incorporating sex) within the same experimental cohort using statistical simulations of real data. We illustrate and discuss the large explosion in sample numbers necessary to detect effects with appropriate power for every additional question posed using the same data set. This exploration highlights the strong likelihood of type II errors (false negatives) for standard data and type I errors when dealing with complex genomic data, where studies are too under-powered to appropriately test these interactions. We show this power may differ for males and females in high throughput data sets such as RNA sequencing. We offer a rationale for the use of alternative experimental and statistical strategies based on interdisciplinary insights and discuss the realworld implications of increasing the complexities of our experimental designs, and the implications of not attempting to alter our experimental designs going forward.R.A. Ankeny, A.L. Whittaker, M. Ryan, J. Boer, M. Plebanski, J. Tuke, S.J. Spence

Order Parameters of the Dilute A Models

The free energy and local height probabilities of the dilute A models with broken \Integer_2 symmetry are calculated analytically using inversion and corner transfer matrix methods. These models possess four critical branches. The first two branches provide new realisations of the unitary minimal series and the other two branches give a direct product of this series with an Ising model. We identify the integrable perturbations which move the dilute A models away from the critical limit. Generalised order parameters are defined and their critical exponents extracted. The associated conformal weights are found to occur on the diagonal of the relevant Kac table. In an appropriate regime the dilute A$_3$ model lies in the universality class of the Ising model in a magnetic field. In this case we obtain the magnetic exponent $\delta=15$ directly, without the use of scaling relations.Comment: 53 pages, LaTex, ITFA 93-1

Control of the porous structure of polystyrene particles obtained by nonsolvent induced phase separation

Porous polystyrene microspheres were produced by a process of nonsolvent induced phase separation (NIPS) from ternary polymer-solvent-nonsolvent (polystyrene-toluene-ethanol) systems and characterized by scanning electron microscopy (SEM) and small-angle X-ray scattering (SAXS) techniques. This study provides evidence for a link between the structural morphology of the porous polystyrene particles and the polystyrene concentration in the initial solutions. A reciprocal relationship between pore diameter and polymer concentration was observed for the systems with the polymer amount below the critical chain overlap concentration, C*. Above C*, this relationship breaks down. The reciprocal relationship between porosity and polymer concentration can be used to facilitate the fine control of the void size. We demonstrate that the observed reciprocal relationship between pore diameter and polymer concentration correlates well with the relative amount of nonsolvent present in the system at the onset of the phase separation process. The pore size can be reduced and, consequently, the pore surface area can be increased either by reducing the polymer concentration in the initial solution or by decreasing the polymer molecular weight in the sample composition

Assessment of Pain and Inflammation in Domestic Animals Using Infrared Thermography: A Narrative Review

Pain assessment in domestic animals has gained importance in recent years due to the recognition of the physiological, behavioral, and endocrine consequences of acute pain on animal production, welfare, and animal model validity. Current approaches to identifying acute pain mainly rely on behavioral-based scales, quantifying pain-related biomarkers, and the use of devices monitoring sympathetic activity. Infrared thermography is an alternative that could be used to correlate the changes in the superficial temperature with other tools and thus be an additional or alternate acute pain assessment marker. Moreover, its non-invasiveness and the objective nature of its readout make it potentially very valuable. However, at the current time, it is not in widespread use as an assessment strategy. The present review discusses scientific evidence for infrared thermography as a tool to evaluate pain, limiting its use to monitor acute pain in pathological processes and invasive procedures, as well as its use for perioperative monitoring in domestic animals.Alexandra L. Whittaker, Ramon Muns, Dehua Wang, Julio Martínez-Burnes, Ismael Hernández-Ávalos, Alejandro Casas-Alvarado, Adriana Domínguez-Oliva, and Daniel Mota-Roja

A combined first and second order variational approach for image reconstruction

In this paper we study a variational problem in the space of functions of bounded Hessian. Our model constitutes a straightforward higher-order extension of the well known ROF functional (total variation minimisation) to which we add a non-smooth second order regulariser. It combines convex functions of the total variation and the total variation of the first derivatives. In what follows, we prove existence and uniqueness of minimisers of the combined model and present the numerical solution of the corresponding discretised problem by employing the split Bregman method. The paper is furnished with applications of our model to image denoising, deblurring as well as image inpainting. The obtained numerical results are compared with results obtained from total generalised variation (TGV), infimal convolution and Euler's elastica, three other state of the art higher-order models. The numerical discussion confirms that the proposed higher-order model competes with models of its kind in avoiding the creation of undesirable artifacts and blocky-like structures in the reconstructed images -- a known disadvantage of the ROF model -- while being simple and efficiently numerically solvable.Comment: 34 pages, 89 figure