The roles and regulation of the Drosophila Lgl tumour suppressor in cell division

Cell polarity is a fundamental feature of most cells, and is required for a diverse range of cell functions. A conserved set of proteins is involved in the establishment and maintenance of cell polarity. Several of these polarity proteins in Drosophila are recognized as neoplastic tumour suppressors, and loss of cell polarity in general has been linked to cancer malignancy. Although much is known about the general role of the polarity proteins, many questions still remain about the details and extent of their functions. I have focused on the Lgl protein in Drosophila epithelia: a basolaterally-localized tumour suppressor. In mitosis, Lgl undergoes a dramatic relocalisation away from the plasma membrane into the cytoplasm. I have found that this is regulated by direct phosphorylation by the Aurora cell cycle kinases: this is in contrast to the regulation of Lgl in interphase polarity, which is mediated by aPKC. The mitotic relocalisation event appears to play an important role in the correct orientation of the mitotic spindle and cell division in epithelia, which may be necessary for maintaining tissue integrity. Thus in addition to the established role for Lgl in cell polarity, my work suggests a novel function for Lgl during mitosis

Renormalisation of heavy-light light ray operators

We calculate the renormalisation of different light ray operators with one light degree of freedom and a static heavy quark. Both $2\to2$- and $2\to3$-kernels are considered. A comparison with the light-light case suggests that the mixing with three-particle operators is solely governed by the light degrees of freedom. Additionally we show that conformal symmetry is already broken at the level of the one loop counterterms due to the additional UV-renormalisation of a cusp in the two contributing Wilson-lines. This general feature can be used to fix the $2\to2$-renormalisation kernels up to a constant. Some examples for applications of our results are given.Comment: 23 pages, 5 figures; v2: changed some wording, added a few references and one appendix concerning some subtleties related to gauge fixing and ghost terms; v3: clarified calculation in section 3.2., added an explicit calculation in section 5.2, corrected a few typos and one figure, added a few comments, results unchanged, except for typesetting matches version to appear in JHE

Audition in vampire bats, Desmodus rotundus

1. Within the tonotopic organization of the inferior colliculus two frequency ranges are well represented: a frequency range within that of the echolocation signals from 50 to 100 kHz, and a frequency band below that of the echolocation sounds, from 10 to 35 kHz. The frequency range between these two bands, from about 40 to 50 kHz is distinctly underrepresented (Fig. 3B). 2. Units with BFs in the lower frequency range (10–25 kHz) were most sensitive with thresholds of -5 to -11 dB SPL, and units with BFs within the frequency range of the echolocation signals had minimal thresholds around 0 dB SPL (Fig. 1). 3. In the medial part of the rostral inferior colliculus units were encountered which preferentially or exclusively responded to noise stimuli. — Seven neurons were found which were only excited by human breathing noises and not by pure tones, frequency modulated signals or various noise bands. These neurons were considered as a subspeciality of the larger sample of noise-sensitive neurons. — The maximal auditory sensitivity in the frequency range below that of echolocation, and the conspicuous existence of noise and breathing-noise sensitive units in the inferior colliculus are discussed in context with the foraging behavior of vampire bats

Gaps in detailed knowledge of human papillomavirus (HPV) and the HPV vaccine among medical students in Scotland

<p>Background: A vaccination programme targeted against human papillomavirus (HPV) types16 and 18 was introduced in the UK in 2008, with the aim of decreasing incidence of cervical disease. Vaccine roll out to 12–13 year old girls with a catch-up programme for girls aged up to 17 years and 364 days was accompanied by a very comprehensive public health information (PHI) campaign which described the role of HPV in the development of cervical cancer.</p> <p>Methods: A brief questionnaire, designed to assess acquisition of knowledge of HPV infection and its association to cervical cancer, was administered to two different cohorts of male and female 1st year medical students (school leavers: 83% in age range 17–20) at a UK university. The study was timed so that the first survey in 2008 immediately followed a summer's intensive PHI campaign and very shortly after vaccine roll-out (150 students). The second survey was exactly one year later over which time there was a sustained PHI campaign (213 students).</p> <p>Results: We addressed three research questions: knowledge about three specific details of HPV infection that could be acquired from PHI, whether length of the PHI campaign and/or vaccination of females had any bearing on HPV knowledge, and knowledge differences between men and women regarding HPV. No female student in the 2008 cohort had completed the three-dose vaccine schedule compared to 58.4% of female students in 2009. Overall, participants’ knowledge regarding the sexually transmitted nature of HPV and its association with cervical cancer was high in both year groups. However, in both years, less than 50% of students correctly identified that HPV causes over 90% of cases of cervical cancer. Males gave fewer correct answers for these two details in 2009. In 2008 only around 50% of students recognised that the current vaccine protects against a limited subset of cervical cancer-causing HPV sub-types, although there was a significant increase in correct response among female students in the 2009 cohort compared to the 2008 cohort.</p> <p>onclusions: This study highlights a lack of understanding regarding the extent of protection against cervical cancer conferred by the HPV vaccine, even among an educated population in the UK who could have a vested interest in acquiring such knowledge. The intensive PHI campaign accompanying the first year of HPV vaccination seemed to have little effect on knowledge over time. This is one of the first studies to assess detailed knowledge of HPV in both males and females. There is scope for continued improvements to PHI regarding the link between HPV infection and cervical cancer.</p&gt

Pulmonary talc granulomatosis mimicking malignant disease 30 years after last exposure: a case report

<p>Abstract</p> <p>Introduction</p> <p>Pulmonary talc granulomatosis is a rare disorder characterized by the development of foreign body granuloma secondary to talc exposure. Previous case reports have documented the illness in current intravenous drug users who inject medications intended for oral use. We present a rare case of the disease in a patient with a distant history of heroin abuse who presented initially with history and imaging findings highly suggestive of malignancy.</p> <p>Case presentation</p> <p>A 53-year-old man reported a 4-month history of increasing dyspnea and weight loss. He had a long history of smoking and admission chest X-ray revealed a density in the right hemithorax. Computed tomography confirmed a probable mass with further speculated opacities in both lung fields suspicious for malignant spread. Biopsies obtained using endobronchial ultrasound-guided aspiration returned negative for malignancy and showed bronchial epithelial cells with foreign body giant cell reaction and polarizable birefringent talc crystals.</p> <p>Conclusion</p> <p>This case demonstrates a rare presentation of talc granulomatosis three decades after the last likely exposure. The history and imaging findings in a chronic smoker were initially strongly suggestive of malignant disease, and we recommend that talc-induced lung disease is considered in any patient with multiple scattered pulmonary lesions and a history of intravenous drug use. Confirmation of the disease by biopsy is essential, but unfortunately there are few successful proven management options for patients with worsening disease.</p

Distances from Surface Brightness Fluctuations

The practice of measuring galaxy distances from their spatial fluctuations in surface brightness is now a decade old. While several past articles have included some review material, this is the first intended as a comprehensive review of the surface brightness fluctuation (SBF) method. The method is conceptually quite simple, the basic idea being that nearby (but unresolved) star clusters and galaxies appear "bumpy", while more distant ones appear smooth. This is quantified via a measurement of the amplitude of the Poisson fluctuations in the number of unresolved stars encompassed by a CCD pixel (usually in an image of an elliptical galaxy). Here, we describe the technical details and difficulties involved in making SBF measurements, discuss theoretical and empirical calibrations of the method, and review the numerous applications of the method from the ground and space, in the optical and near-infrared. We include discussions of stellar population effects and the "universality" of the SBF standard candle. A final section considers the future of the method.Comment: Invited review article to appear in: `Post-Hipparcos Cosmic Candles', A. Heck & F. Caputo (Eds), Kluwer Academic Publ., Dordrecht, in press. 22 pages, including 3 postscript figures; uses Kluwer's crckapb.sty LaTex macro file, enclose

A Pilot Randomized Controlled Trial of Omega-3 Fatty Acids for Autism Spectrum Disorder

We conducted a pilot randomized controlled trial to determine the feasibility and initial safety and efficacy of omega-3 fatty acids (1.3 g/day) for the treatment of hyperactivity in 27 children ages 3–8 with autism spectrum disorder (ASD). After 12 weeks, hyperactivity, as measured by the Aberrant Behavior Checklist, improved 2.7 (±4.8) points in the omega-3 group compared to 0.3 (±7.2) points in the placebo group (p = 0.40; effect size = 0.38). Correlations were found between decreases in five fatty acid levels and decreases in hyperactivity, and the treatment was well tolerated. Although this pilot study did not find a statistically significant benefit from omega-3 fatty acids, the small sample size does not rule out small to moderate beneficial effects

The 10th Biennial Hatter Cardiovascular Institute workshop: cellular protection—evaluating new directions in the setting of myocardial infarction, ischaemic stroke, and cardio-oncology

Due to its poor capacity for regeneration, the heart is particularly sensitive to the loss of contractile cardiomyocytes. The onslaught of damage caused by ischaemia and reperfusion, occurring during an acute myocardial infarction and the subsequent reperfusion therapy, can wipe out upwards of a billion cardiomyocytes. A similar program of cell death can cause the irreversible loss of neurons in ischaemic stroke. Similar pathways of lethal cell injury can contribute to other pathologies such as left ventricular dysfunction and heart failure caused by cancer therapy. Consequently, strategies designed to protect the heart from lethal cell injury have the potential to be applicable across all three pathologies. The investigators meeting at the 10th Hatter Cardiovascular Institute workshop examined the parallels between ST-segment elevation myocardial infarction (STEMI), ischaemic stroke, and other pathologies that cause the loss of cardiomyocytes including cancer therapeutic cardiotoxicity. They examined the prospects for protection by remote ischaemic conditioning (RIC) in each scenario, and evaluated impasses and novel opportunities for cellular protection, with the future landscape for RIC in the clinical setting to be determined by the outcome of the large ERIC-PPCI/CONDI2 study. It was agreed that the way forward must include measures to improve experimental methodologies, such that they better reflect the clinical scenario and to judiciously select combinations of therapies targeting specific pathways of cellular death and injury

Lepton Acceleration in Pulsar Wind Nebulae

Pulsar Wind Nebulae (PWNe) act as calorimeters for the relativistic pair winds emanating from within the pulsar light cylinder. Their radiative dissipation in various wavebands is significantly different from that of their pulsar central engines: the broadband spectra of PWNe possess characteristics distinct from those of pulsars, thereby demanding a site of lepton acceleration remote from the pulsar magnetosphere. A principal candidate for this locale is the pulsar wind termination shock, a putatively highly-oblique, ultra-relativistic MHD discontinuity. This paper summarizes key characteristics of relativistic shock acceleration germane to PWNe, using predominantly Monte Carlo simulation techniques that compare well with semi-analytic solutions of the diffusion-convection equation. The array of potential spectral indices for the pair distribution function is explored, defining how these depend critically on the parameters of the turbulent plasma in the shock environs. Injection efficiencies into the acceleration process are also addressed. Informative constraints on the frequency of particle scattering and the level of field turbulence are identified using the multiwavelength observations of selected PWNe. These suggest that the termination shock can be comfortably invoked as a principal injector of energetic leptons into PWNe without resorting to unrealistic properties for the shock layer turbulence or MHD structure.Comment: 19 pages, 5 figures, invited review to appear in Proc. of the inaugural ICREA Workshop on "The High-Energy Emission from Pulsars and their Systems" (2010), eds. N. Rea and D. Torres, (Springer Astrophysics and Space Science series

Roles for Treg expansion and HMGB1 signaling through the TLR1-2-6 axis in determining the magnitude of the antigen-specific immune response to MVA85A

© 2013 Matsumiya et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedA better understanding of the relationships between vaccine, immunogenicity and protection from disease would greatly facilitate vaccine development. Modified vaccinia virus Ankara expressing antigen 85A (MVA85A) is a novel tuberculosis vaccine candidate designed to enhance responses induced by BCG. Antigen-specific interferon-γ (IFN-γ) production is greatly enhanced by MVA85A, however the variability between healthy individuals is extensive. In this study we have sought to characterize the early changes in gene expression in humans following vaccination with MVA85A and relate these to long-term immunogenicity. Two days post-vaccination, MVA85A induces a strong interferon and inflammatory response. Separating volunteers into high and low responders on the basis of T cell responses to 85A peptides measured during the trial, an expansion of circulating CD4+ CD25+ Foxp3+ cells is seen in low but not high responders. Additionally, high levels of Toll-like Receptor (TLR) 1 on day of vaccination are associated with an increased response to antigen 85A. In a classification model, combined expression levels of TLR1, TICAM2 and CD14 on day of vaccination and CTLA4 and IL2Rα two days post-vaccination can classify high and low responders with over 80% accuracy. Furthermore, administering MVA85A in mice with anti-TLR2 antibodies may abrogate high responses, and neutralising antibodies to TLRs 1, 2 or 6 or HMGB1 decrease CXCL2 production during in vitro stimulation with MVA85A. HMGB1 is released into the supernatant following atimulation with MVA85A and we propose this signal may be the trigger activating the TLR pathway. This study suggests an important role for an endogenous ligand in innate sensing of MVA and demonstrates the importance of pattern recognition receptors and regulatory T cell responses in determining the magnitude of the antigen specific immune response to vaccination with MVA85A in humans.This work was funded by the Wellcome Trust. MM has a Wellcome Trust PhD studentship and HM is a Wellcome Trust Senior Fello