Listeriolysin S, a Novel Peptide Haemolysin Associated with a Subset of Lineage I Listeria monocytogenes

peer-reviewedStreptolysin S (SLS) is a bacteriocin-like haemolytic and cytotoxic virulence factor that plays a key role in the virulence of Group A Streptococcus (GAS), the causative agent of pharyngitis, impetigo, necrotizing fasciitis and streptococcal toxic shock syndrome. Although it has long been thought that SLS and related peptides are produced by GAS and related streptococci only, there is evidence to suggest that a number of the most notorious Gram-positive pathogenic bacteria, including Listeria monocytogenes, Clostridium botulinum and Staphylococcus aureus, produce related peptides. The distribution of the L. monocytogenes cluster is particularly noteworthy in that it is found exclusively among a subset of lineage I strains; i.e., those responsible for the majority of outbreaks of listeriosis. Expression of these genes results in the production of a haemolytic and cytotoxic factor, designated Listeriolysin S, which contributes to virulence of the pathogen as assessed by murine- and human polymorphonuclear neutrophil–based studies. Thus, in the process of establishing the existence of an extended family of SLS-like modified virulence peptides (MVPs), the genetic basis for the enhanced virulence of a proportion of lineage I L. monocytogenes may have been revealed.Work is funded by the Irish Government under the National Development Plan, through a Science Foundation Ireland Investigator award to CH, PR and PC (06/IN.1/B98)

Holomorphic Supercurves and Supersymmetric Sigma Models

We introduce a natural generalisation of holomorphic curves to morphisms of supermanifolds, referred to as holomorphic supercurves. More precisely, supercurves are morphisms from a Riemann surface, endowed with the structure of a supermanifold which is induced by a holomorphic line bundle, to an ordinary almost complex manifold. They are called holomorphic if a generalised Cauchy-Riemann condition is satisfied. We show, by means of an action identity, that holomorphic supercurves are special extrema of a supersymmetric action functional.Comment: 30 page

Compactness for Holomorphic Supercurves

We study the compactness problem for moduli spaces of holomorphic supercurves which, being motivated by supergeometry, are perturbed such as to allow for transversality. We give an explicit construction of limiting objects for sequences of holomorphic supercurves and prove that, in important cases, every such sequence has a convergent subsequence provided that a suitable extension of the classical energy is uniformly bounded. This is a version of Gromov compactness. Finally, we introduce a topology on the moduli spaces enlarged by the limiting objects which makes these spaces compact and metrisable.Comment: 38 page

A large sample study of spin relaxation and magnetometric sensitivity of paraffin-coated Cs vapor cells

We have manufactured more than 250 nominally identical paraffin-coated Cs vapor cells (30 mm diameter bulbs) for multi-channel atomic magnetometer applications. We describe our dedicated cell characterization apparatus. For each cell we have determined the intrinsic longitudinal, \sGamma{01}, and transverse, \sGamma{02}, relaxation rates. Our best cell shows \sGamma{01}/2\pi\approx 0.5 Hz, and \sGamma{02}/2\pi\approx 2 Hz. We find a strong correlation of both relaxation rates which we explain in terms of reservoir and spin exchange relaxation. For each cell we have determined the optimal combination of rf and laser powers which yield the highest sensitivity to magnetic field changes. Out of all produced cells, 90% are found to have magnetometric sensitivities in the range of 9 to 30 fTHz. Noise analysis shows that the magnetometers operated with such cells have a sensitivity close to the fundamental photon shot noise limit

The specificity and patterns of staining in human cells and tissues of p16INK4a antibodies demonstrate variant antigen binding

The validity of the identification and classification of human cancer using antibodies to detect biomarker proteins depends upon antibody specificity. Antibodies that bind to the tumour-suppressor protein p16INK4a are widely used for cancer diagnosis and research. In this study we examined the specificity of four commercially available anti-p16INK4a antibodies in four immunological applications. The antibodies H-156 and JC8 detected the same 16 kDa protein in western blot and immunoprecipitation tests, whereas the antibody F-12 did not detect any protein in western blot analysis or capture a protein that could be recognised by the H-156 antibody. In immunocytochemistry tests, the antibodies JC8 and H-156 detected a predominately cytoplasmic localised antigen, whose signal was depleted in p16INK4a siRNA experiments. F-12, in contrast, detected a predominately nuclear located antigen and there was no noticeable reduction in this signal after siRNA knockdown. Furthermore in immunohistochemistry tests, F-12 generated a different pattern of staining compared to the JC8 and E6H4 antibodies. These results demonstrate that three out of four commercially available p16INK4a antibodies are specific to, and indicate a mainly cytoplasmic localisation for, the p16INK4a protein. The F-12 antibody, which has been widely used in previous studies, gave different results to the other antibodies and did not demonstrate specificity to human p16INK4a. This work emphasizes the importance of the validation of commercial antibodies, aside to the previously reported use, for the full verification of immunoreaction specificity

The actin-myosin regulatory MRCK kinases: regulation, biological functions and associations with human cancer

The contractile actin-myosin cytoskeleton provides much of the force required for numerous cellular activities such as motility, adhesion, cytokinesis and changes in morphology. Key elements that respond to various signal pathways are the myosin II regulatory light chains (MLC), which participate in actin-myosin contraction by modulating the ATPase activity and consequent contractile force generation mediated by myosin heavy chain heads. Considerable effort has focussed on the role of MLC kinases, and yet the contributions of the myotonic dystrophy-related Cdc42-binding kinases (MRCK) proteins in MLC phosphorylation and cytoskeleton regulation have not been well characterized. In contrast to the closely related ROCK1 and ROCK2 kinases that are regulated by the RhoA and RhoC GTPases, there is relatively little information about the CDC42-regulated MRCKα, MRCKβ and MRCKγ members of the AGC (PKA, PKG and PKC) kinase family. As well as differences in upstream activation pathways, MRCK and ROCK kinases apparently differ in the way that they spatially regulate MLC phosphorylation, which ultimately affects their influence on the organization and dynamics of the actin-myosin cytoskeleton. In this review, we will summarize the MRCK protein structures, expression patterns, small molecule inhibitors, biological functions and associations with human diseases such as cancer

Testing isotropy of the universe using the Ramsey resonance technique on ultracold neutron spins

Physics at the Planck scale could be revealed by looking for tiny violations of fundamental symmetries in low energy experiments. In 2008, a sensitive test of the isotropy of the Universe using has been performed with stored ultracold neutrons (UCN), this is the first clock-comparison experiment performed with free neutrons. During several days we monitored the Larmor frequency of neutron spins in a weak magnetic field using the Ramsey resonance technique. An non-zero cosmic axial field, violating rotational symmetry, would induce a daily variation of the precession frequency. Our null result constitutes one of the most stringent tests of Lorentz invariance to date.Comment: proceedings of the PNCMI2010 conferenc

Prenatal Exposure to Lead, δ-Aminolevulinic Acid, and Schizophrenia: Further Evidence

Background: A previously conducted study of prenatal lead exposure and schizophrenia using δ-aminolevulinic acid, a biologic marker of Pb exposure, in archived maternal serum samples collected from subjects enrolled in the Childhood Health and Development Study (1959–1966) based in Oakland, California, suggested a possible association between prenatal Pb exposure and the development of schizophrenia in later life. Objectives: In the present study we extend these findings using samples collected from the New England cohort of the National Collaborative Perinatal Project (1959–1966). Using similar methods, in this study we found results that suggest a comparable association in this cohort. Methods: We pooled matched sets of cases and controls from both the California and New England sites using a multilevel random-intercept logistic regression model, accounting for matching and site structure as well as adjusting for maternal age at delivery and maternal education. Results: The estimated odds ratio for schizophrenia associated with exposure corresponding to 15 μg/dL of blood Pb was 1.92 (95% confidence interval, 1.05–3.87; p = 0.03). Conclusion: Although several limitations constrain generalizability, these results are consistent with previous findings and provide further evidence for the role of early environmental exposures in the development of adult-onset psychiatric disorders

Optical Magnetometry

Some of the most sensitive methods of measuring magnetic fields utilize interactions of resonant light with atomic vapor. Recent developments in this vibrant field are improving magnetometers in many traditional areas such as measurement of geomagnetic anomalies and magnetic fields in space, and are opening the door to new ones, including, dynamical measurements of bio-magnetic fields, detection of nuclear magnetic resonance (NMR), magnetic-resonance imaging (MRI), inertial-rotation sensing, magnetic microscopy with cold atoms, and tests of fundamental symmetries of Nature.Comment: 11 pages; 4 figures; submitted to Nature Physic