Transcriptional regulation of bacterial virulence gene expression by molecular oxygen and nitric oxide

© Jeffrey Green, Matthew D Rolfe, and Laura J Smith. Molecular oxygen (O2) and nitric oxide (NO) are diatomic gases that play major roles in infection. The host innate immune system generates reactive oxygen species and NO as bacteriocidal agents and both require O2 for their production. Furthermore, the ability to adapt to changes in O2 availability is crucial for many bacterial pathogens, as many niches within a host are hypoxic. Pathogenic bacteria have evolved transcriptional regulatory systems that perceive these gases and respond by reprogramming gene expression. Direct sensors possess iron-containing co-factors (iron-sulfur clusters, mononuclear iron, heme) or reactive cysteine thiols that react with O2 and/or NO. Indirect sensors perceive the physiological effects of O2 starvation. Thus, O2 and NO act as environmental cues that trigger the coordinated expression of virulence genes and metabolic adaptations necessary for survival within a host. Here, the mechanisms of signal perception by key O2and NO-responsive bacterial transcription factors and the effects on virulence gene expression are reviewed, followed by consideration of these aspects of gene regulation in two major pathogens, Staphylococcus aureus and Mycobacterium tuberculosis

On Hexagonal Structures in Higher Dimensional Theories

We analyze the geometrical background under which many Lie groups relevant to particle physics are endowed with a (possibly multiple) hexagonal structure. There are several groups appearing, either as special holonomy groups on the compactification process from higher dimensions, or as dynamical string gauge groups; this includes groups like SU(2),SU(3), G_2, Spin(7), SO(8) as well as E_8 and SO(32). We emphasize also the relation of these hexagonal structures with the octonion division algebra, as we expect as well eventually some role for octonions in the interpretation of symmetries in High Energy Physics.Comment: 9 pages, Latex, 3 figures. Accepted for publication in International Journal of Theoretical Physic

A within farm clinical trial to compare two treatments (parenteral antibacterials and hoof trimming) for sheep lame with footrot

From observational studies, farmers who use parenteral antibacterials to promptly treat all sheep with footrot (FR) or interdigital dermatitis (ID) have a prevalence of lameness of <2% compared with a prevalence of 9% lameness reported by farmers who treat lame sheep by trimming affected feet. We tested the hypothesis that prompt treatment of sheep lame with naturally developing FR or ID with parenteral and topical antibacterials reduces the prevalence and incidence of lameness with these conditions compared with less frequent treatment with trimming of hoof horn and applying topical antibacterials. A further hypothesis was that reduction of ID and FR would improve productivity. A lowland sheep flock with 700 ewes was used to test these hypotheses in an 18-month within farm clinical trial with four groups of ewes: two intervention and two control. The duration and severity of lameness was used to categorise sheep into three weighted scores of lameness (WLS): never lame (WLS0), mildly lame/lame for <6 days (WLS1) and severely or chronically lame (WLS2). The intervention reduced the prevalence of lameness due to FR and ID in ewes and lambs and the incidence of lameness in ewes. The WLS was also significantly lower in sheep in the intervention groups. Ewes with a higher WLS were subsequently significantly more likely to have a body condition score <2.5 and to have lame lambs. Significantly more ewes lambed and successfully reared more lambs that were ready for slaughter at a younger age in the intervention versus control groups. There was an increase in the gross margin of £630/100 ewes mated in the intervention group, including the cost of treatment of £150/100 ewes mated. We conclude that prompt parenteral and topical antibacterial treatment of sheep lame with ID and FR reduced the prevalence and incidence of these infectious conditions and led to improved health, welfare and productivity

The orbifold transform and its applications

We discuss the notion of the orbifold transform, and illustrate it on simple examples. The basic properties of the transform are presented, including transitivity and the exponential formula for symmetric products. The connection with the theory of permutation orbifolds is addressed, and the general results illustrated on the example of torus partition functions

Is N = 8 Supergravity Ultraviolet Finite?

Conventional wisdom holds that no four-dimensional gravity field theory can be ultraviolet finite. This understanding is based mainly on power counting. Recent studies confirm that one-loop N = 8 supergravity amplitudes satisfy the so-called `no-triangle hypothesis', which states that triangle and bubble integrals cancel from these amplitudes. A consequence of this hypothesis is that for any number of external legs, at one loop N = 8 supergravity and N = 4 super-Yang-Mills have identical superficial degrees of ultraviolet behavior in D dimensions. We describe how the unitarity method allows us to promote these one-loop cancellations to higher loops, suggesting that previous power counts were too conservative. We discuss higher-loop evidence suggesting that N = 8 supergravity has the same degree of divergence as N = 4 super-Yang-Mills theory and is ultraviolet finite in four dimensions. We comment on calculations needed to reinforce this proposal, which are feasible using the unitarity method.Comment: 7 pages, 5 figures, revte

Factors associated with changes of state of foot conformation and lameness in a flock of sheep

The aim of this research was to investigate transitions between foot conformation, lameness and footrot in sheep. Data came from one lowland flock of approximately 700 ewes studied for 18 months. Multilevel multistate analyses of transitions between good and poor foot conformation states in ewes, and lame and non-lame states in ewes and lambs were conducted. Key results were that the longer sheep had feet in good conformation, the more likely they were to stay in this state; similarly, the longer a ewe was not lame the more likely she was not to become lame. Ewes with poor foot conformation were more likely to become lame (OR: 1.83 (1.24-2.67)) and to be > 4 years (OR: 1.50(1.09-2.05)). Ewes with footrot were less likely to move to good foot conformation (OR: 0.48 (0.31-0.75)) and were more likely to become lame (OR: 3.81(2.60-5.59)). Ewes lame for > 4 days and not treated with parenteral antibacterials had a higher risk of developing (OR: 2.00 (1.08-3.61)), or remaining in (OR: 0.49 (0.29-0.95)) poor foot conformation compared with ewes never lame. Treatment of ewes lame with footrot with parenteral antibacterials increased the probability of transition from a lame to a non-lame state (OR: 1.46 (1.05-2.02)) and these ewes, even if lame for > 4 days, were not more likely to develop poor foot conformation. The risk of a ewe becoming lame increased when at least one of her offspring was lame (OR: 2.03 (1.42-2.92)) and when the prevalence of lameness in the group was ≥ 5% (OR: 1.42 (1.06-1.92)). Lambs were at increased risk of becoming lame when they were male (OR: 1.42 (1.01-2.01)), single (OR: 1.86 (1.34-2.59)) or had a lame dam or sibling (OR: 3.10 (1.81-5.32)). There were no explanatory variables associated with lambs recovering from lameness. We conclude that poor foot conformation in ewes increases the susceptibility of ewes to become lame and that this can arise from untreated footrot. Treatment of ewes lame with footrot with parenteral antibacterials leads to recovery from lameness and prevents or resolves poor foot conformation which then reduces the susceptibility to further lameness with footrot

Electrical Collection and Transmission Systems for Offshore Wind Power: Preprint

The electrical systems needed for offshore wind farms to collect power from wind turbines--and transmit it to shore--will be a significant cost element of these systems. This paper describes the development of a simplified model of the cost and performance of such systems

Corneal infection models : tools to investigate the role of biofilms in bacterial keratitis

Bacterial keratitis is a corneal infection which may cause visual impairment or even loss of the infected eye. It remains a major cause of blindness in the developing world. Staphylococcus aureus and Pseudomonas aeruginosa are common causative agents and these bacterial species are known to colonise the corneal surface as biofilm populations. Biofilms are complex bacterial communities encased in an extracellular polymeric matrix and are notoriously difficult to eradicate once established. Biofilm bacteria exhibit different phenotypic characteristics from their planktonic counterparts, including an increased resistance to antibiotics and the host immune response. Therefore, understanding the role of biofilms will be essential in the development of new ophthalmic antimicrobials. A brief overview of biofilm-specific resistance mechanisms is provided, but this is a highly multifactorial and rapidly expanding field that warrants further research. Progression in this field is dependent on the development of suitable biofilm models that acknowledge the complexity of the ocular environment. Abiotic models of biofilm formation (where biofilms are studied on non-living surfaces) currently dominate the literature, but co-culture infection models are beginning to emerge. In vitro, ex vivo and in vivo corneal infection models have now been reported which use a variety of different experimental techniques and animal models. In this review, we will discuss existing corneal infection models and their application in the study of biofilms and host-pathogen interactions at the corneal surface

On Signatures of Twisted Magnetic Flux Tube Emergence

Recent studies of NOAA active region 10953, by Okamoto {\it et al.} ({\it Astrophys. J. Lett.} {\bf 673}, 215, 2008; {\it Astrophys. J.} {\bf 697}, 913, 2009), have interpreted photospheric observations of changing widths of the polarities and reversal of the horizontal magnetic field component as signatures of the emergence of a twisted flux tube within the active region and along its internal polarity inversion line (PIL). A filament is observed along the PIL and the active region is assumed to have an arcade structure. To investigate this scenario, MacTaggart and Hood ({\it Astrophys. J. Lett.} {\bf 716}, 219, 2010) constructed a dynamic flux emergence model of a twisted cylinder emerging into an overlying arcade. The photospheric signatures observed by Okamoto {\it et al.} (2008, 2009) are present in the model although their underlying physical mechanisms differ. The model also produces two additional signatures that can be verified by the observations. The first is an increase in the unsigned magnetic flux in the photosphere at either side of the PIL. The second is the behaviour of characteristic photospheric flow profiles associated with twisted flux tube emergence. We look for these two signatures in AR 10953 and find negative results for the emergence of a twisted flux tube along the PIL. Instead, we interpret the photospheric behaviour along the PIL to be indicative of photospheric magnetic cancellation driven by flows from the dominant sunspot. Although we argue against flux emergence within this particular region, the work demonstrates the important relationship between theory and observations for the successful discovery and interpretation of signatures of flux emergence.Comment: 14 pages, 8 figures, accepted for publication in Solar Physic

Mask formulas for cograssmannian Kazhdan-Lusztig polynomials

We give two contructions of sets of masks on cograssmannian permutations that can be used in Deodhar's formula for Kazhdan-Lusztig basis elements of the Iwahori-Hecke algebra. The constructions are respectively based on a formula of Lascoux-Schutzenberger and its geometric interpretation by Zelevinsky. The first construction relies on a basis of the Hecke algebra constructed from principal lower order ideals in Bruhat order and a translation of this basis into sets of masks. The second construction relies on an interpretation of masks as cells of the Bott-Samelson resolution. These constructions give distinct answers to a question of Deodhar.Comment: 43 page