In Vitro HPV-11 Infection of Human Foreskin

Study of the infectious process of human papillomavirus type 11 (HPV-11) has been facilitated by the discovery that HPV- 11 – infected neonatal human foreskin epithelium can proliferate as xenografts into condyloma-like growths within athymic nude mice. Here we describe detection of HPV-1 1 infection of neonatal human foreskin-derived keratinocytes, infected and cultured entirely in vitro, by use of the polymerase chain reaction and primers straddling the splice donor/ acceptor site of the most prevalent early gene HPV-11 transcript (E1∧E4). Expression of the E1∧E4 HPV-11 mRNA is abrogated by 60°C heat inactivation of the inoculum. HPV- 11 – infected foreskin explants continue to produce the E1∧E4 mRNA for up to 5 weeks in culture, and second-passage keratinocytes derived from infected explant outgrowths continue to produce the E1∧E4 mRNA. The in vitro system described here provides a new way to study HPV-11 infection and may be useful in evaluating early events of infection

Effect of Continuous Infusion of Relaxin on Progesterone, Oxytocin, and Relaxin Blood Concentrations and Time of Parturition in Beef Heifers

These studies were designed to determine whether continuous intravenous infusion of increasing dosages of porcine relaxin during late pregnancy in beef heifers would influence circulating blood concentrations of relaxin, progesterone, and oxytocin, and time of onset of parturition. Beef heifers were bred by artificial insemination and, on Day 277, fitted with indwelling jugular cannulas for hormone infusion and blood sampling from Day 277 to 286. Intravenous infusion of purified porcine relaxin (pRLX, 3000 U mg-1) was started in heifers (n = 8) at increasing dosages (200 U h-1 on Days 277 and 278, 300 U h-1 on Days 279 and 280, 500 U h-1 on Day 281, 600 U h-1 on Day 282, and 700 U h-1 on Days 283 to 286). Phosphate buffer saline (PBS, 10 ml h-1) was infused during these same times to control (n = 6) animals. Relaxin treatment steadily increased the circulating plasma concentration of immunoreactive relaxin to more than 120 ng ml-1 compared with less than 0.5 ng ml-1 in PBStreated controls. Relaxin infusion in increasing dosages over the treatment time was associated with a significant decrease (P \u3c 0.01) in plasma progesterone concentration compared with the PBS controls. Plasma levels of oxytocin at 4- hour intervals remained similar (P \u3e 0.05) during the pretreatment period and throughout continuous infusion of pRLX and PBS. Although continuous intravenous infusion of relaxin resulted in a decrease in circulating blood levels of progesterone, it did not significantly reduce the interval between the beginning of pRLX treatment and parturition compared with the PBS-infused control heifers. These results indicate that continuous intravenous infusion of high levels of porcine relaxin resulted in a decrease in progesterone secretion in late pregnant beef heifers

Breast cancer worry in higher-risk women offered preventive therapy: a UK multicentre prospective study

PURPOSE: Women's worry about developing breast cancer may influence their decision to use preventive therapy. However, the direction of this relationship has been questioned. We prospectively investigated the relationship between breast cancer worry and uptake of preventive therapy. The socio-demographic and clinical factors associated with high breast cancer worry were also investigated. METHODS: Women at increased risk of developing breast cancer were recruited from clinics across England (n = 408). Participants completed a survey on their breast cancer worry, socio-demographic and clinical factors. Uptake of tamoxifen was recorded at 3 months (n = 258 women, 63.2%). Both primary and sensitivity analyses were conducted using different classifications of low, medium and high worry. RESULTS: 39.5% of respondents reported medium breast cancer worry at baseline and 21.2% reported high worry. Ethnic minority women were more likely to report high worry than white women (OR = 3.02, 95%CI 1.02, 8.91, p = 0.046). Women educated below degree level were more likely to report high worry than those with higher education (OR = 2.29, 95%CI 1.28, 4.09, p = 0.005). No statistically significant association was observed between worry and uptake. In the primary analysis, fewer respondents with medium worry at baseline initiated tamoxifen (low worry = 15.5%, medium = 13.5%, high = 15.7%). In the sensitivity analysis, participants with medium worry reported the highest uptake of tamoxifen (19.7%). CONCLUSIONS: No association was observed between worry and uptake, although the relationship was affected by the categorisation of worry. Standardised reporting of the classification of worry is warranted to allow transparent comparisons across cohorts

Cross-species pathogen spillover across ecosystem boundaries: mechanisms and theory

Pathogen spillover between different host species is the trigger for many infectious disease outbreaks and emergence events, and ecosystem boundary areas have been suggested as spatial hotspots of spillover. This hypothesis is largely based on suspected higher rates of zoonotic disease spillover and emergence in fragmented landscapes and other areas where humans live in close vicinity to wildlife. For example, Ebola virus outbreaks have been linked to contacts between humans and infected wildlife at the rural-forest border, and spillover of yellow fever via mosquito vectors happens at the interface between forest and human settlements. Because spillover involves complex interactions between multiple species and is difficult to observe directly, empirical studies are scarce, particularly those that quantify underlying mechanisms. In this review, we identify and explore potential ecological mechanisms affecting spillover of pathogens (and parasites in general) at ecosystem boundaries. We borrow the concept of ‘permeability’ from animal movement ecology as a measure of the likelihood that hosts and parasites are present in an ecosystem boundary region. We then discuss how different mechanisms operating at the levels of organisms and ecosystems might affect permeability and spillover. This review is a step towards developing a general theory of cross-species parasite spillover across ecosystem boundaries with the eventual aim of improving predictions of spillover risk in heterogeneous landscapes

Exploring the behavioural drivers of veterinary surgeon antibiotic prescribing: a qualitative study of companion animal veterinary surgeons in the UK

Background: Multi-drug resistant bacteria are an increasing concern in both human and veterinary medicine. Inappropriate prescribing and use of antibiotics within veterinary medicine may be a contributory factor to antimicrobial resistance (AMR). The ‘One Health’ Initiative aims to work across species and environments to reduce AMR, however; little is currently known about the factors which influence antibiotic prescribing among veterinary surgeons in companion animal practice. This paper reports on qualitative data analysis of interviews with veterinary surgeons whose practice partially or wholly focuses on companion animals (N = 16). The objective of the research was to explore the drivers of companion animal veterinary surgeons’ antibiotic prescribing behaviours. The veterinary surgeons interviewed were all practising within the UK (England (n = 4), Scotland (n = 11), Northern Ireland (n = 1)). A behavioural thematic analysis of the data was undertaken, which identified barriers and facilitators to specific prescribing-related behaviours. Results: Five components of prescribing behaviours were identified: 1) confirming clinical need for antibiotics; 2) responding to clients; 3) confirming diagnosis; 4) determining dose, duration and type of antibiotic; and 5) preventing infection around surgery (with attendant appropriate and inappropriate antibiotic prescribing behaviours). Barriers to appropriate prescribing identified include: business, diagnostic, fear, habitual practice and pharmaceutical factors. Facilitators include: AMR awareness, infection prevention, professional learning and regulation and government factors. Conclusion: This paper uses a behavioural lens to examine drivers which are an influence on veterinary surgeons’ prescribing behaviours. The paper contributes new understandings about factors which influence antibiotic prescribing behaviours among companion animal veterinary surgeons. This analysis provides evidence to inform future interventions, which are focused on changing prescribing behaviours, in order to address the pressing public health concern of AMR

Construction and testing of the optical bench for LISA pathfinder

eLISA is a space mission designed to measure gravitational radiation over a frequency range of 0.1–100 mHz (European Space Agency LISA Assessment Study Report 2011). It uses laser interferometry to measure changes of order $10\,{\rm pm /\sqrt{Hz}}$ in the separation of inertial test masses housed in spacecraft separated by 1 million km. LISA Pathfinder (LPF) is a technology demonstrator mission that will test the key eLISA technologies of inertial test masses monitored by laser interferometry in a drag-free spacecraft. The optical bench that provides the interferometry for LPF must meet a number of stringent requirements: the optical path must be stable at the few ${\rm pm /\sqrt{Hz}}$ level; it must direct the optical beams onto the inertial masses with an accuracy of better than ±25 μm, and it must be robust enough not only to survive launch vibrations but to achieve full performance after launch. In this paper we describe the construction and testing of the flight optical bench for LISA Pathfinder that meets all the design requirements

A biocatalytic approach towards the stereoselective synthesis of protected inositols

The authors thank the EPSRC and the University of St Andrews for PhD studentship funding.A biocatalytic flow system utilising Trypanosoma brucei L-myo-inositol 1-phosphate synthase has been developed to prepare significant quantities of L-myo-inositol 1-phosphate. Using this highly valuable biochemical, we have demonstrated its utility as a viable starting material in a drastically improved and shortened synthesis of a key intermediate in the synthesis of the biologically important myo-inositol derivatives. This biotransformation allows rapid and stereospecific inositol derivatives to be synthesized, on a larger scale than ever before.PostprintPeer reviewe

\u3ci\u3eIn situ\u3c/i\u3e Synthesis of Oligonucleotide Arrays on Surfaces Coated with Crosslinked Polymer Multilayers

We report an approach to the in situ synthesis of oligonucleotide arrays on surfaces coated with crosslinked polymer multilayers. Our approach makes use of methods for the reactive layer-by-layer assembly of thin, amine-reactive multilayers using branched polyethyleneimine (PEI) and the azlactone-functionalized polymer poly(2-vinyl-4,4′-dimethylazlactone) (PVDMA). Postfabrication treatment of film-coated glass substrates with d-glucamine or 4-amino-1-butanol yielded hydroxyl-functionalized films suitable for the Maskless Array Synthesis (MAS) of oligonucleotide arrays. Glucamine-functionalized films yielded arrays of oligonucleotides with fluorescence intensities and signal-to-noise ratios (after hybridization with fluorescently labeled complementary strands) comparable to those of arrays fabricated on conventional silanized glass substrates. These arrays could be exposed to multiple hybridization/dehybridization cycles with only moderate loss of hybridization density. The versatility of the layer-by-layer approach also permitted synthesis directly on thin sheets of film-coated poly(ethylene terephthalate) (PET) to yield flexible oligonucleotide arrays that could be readily manipulated (e.g., bent) and cut into smaller arrays. To our knowledge, this work presents the first use of polymer multilayers as a substrate for the multistep synthesis of complex molecules. Our results demonstrate that these films are robust and able to withstand the ∼450 individual chemical processing steps associated with MAS (as well as manipulations required to hybridize, image, and dehybridize the arrays) without large-scale cracking, peeling, or delamination of the thin films. The combination of layer-by-layer assembly and MAS provides a means of fabricating functional oligonucleotide arrays on a range of different materials and substrates. This approach may also prove useful for the fabrication of supports for the solid-phase synthesis and screening of other macromolecular or small-molecule agents

Astrophysical Fluids of Novae: High Resolution Pre-decay X-ray spectrum of V4743 Sagittarii

Eight X-ray observations of V4743 Sgr (2002), observed with Chandra and XMM-Newton are presented. The nova turned off some time between days 301.9 and 371, and the X-ray flux subsequently decreased from day 301.9 to 526 following an exponential decline time scale of $(96 \pm 3)$ days. We use the absorption lines present in the SSS spectrum for diagnostic purposes, and characterize the physics and the dynamics of the expanding atmosphere during the explosion of the nova. The information extracted from this first stage is then used as input for computing full photoionization models of the ejecta in V4743 Sgr. The SSS spectrum is modeled with a simple black-body and multiplicative Gaussian lines, which provides us of a general kinematical picture of the system, before it decays to its faint phase (Ness et al. 2003). In the grating spectra taken between days 180.4 and 370, we can resolve the line profiles of absorption lines arising from H-like and He-like C, N, and O, including transitions involving higher principal quantum numbers. Except for a few interstellar lines, all lines are significantly blue-shifted, yielding velocities between 1000 and 6000 km/s which implies an ongoing mass loss. It is shown that significant expansion and mass loss occur during this phase of the explosion, at a rate $\dot{M} \approx (3-5) \times 10^{-4} ~ (\frac{L}{L_{38}}) ~ M_{\odot}/yr$. Our measurements show that the efficiency of the amount of energy used for the motion of the ejecta, defined as the ratio between the kinetic luminosity $L_{\rm kin}$ and the radiated luminosity $L_{\rm rad}$, is of the order of one.Comment: 25 pages, 9 figures. Accepted in book: Recent Advances in Fluid Dynamics with Environmental Applications, pp.365-39

Kinematics of the ring-like nebula SuWt 2

We present the first detailed spatio-kinematical analysis and modelling of the Southern planetary nebula SuWt 2. This object presents a problem for current theories of planetary nebula formation and evolution, as it is not known to contain a central post-main sequence star. Deep narrowband [NII]6584 images reveal the presence of faint bipolar lobes emanating fromthe edges of the nebular ring. Longslit observations of the H-alpha and [NII]6584 emission lines were obtained using EMMI on the 3.6-m ESO-NTT. The spectra reveal the nebular morphology as a bright torus encircling the waist of an extended bipolar structure. By deprojection, the inclination of the ring is found to be 68\degr $\pm$ 2\degr (c.f. ~90\degr for the double A-type binary believed to lie at the centre of the nebula), and the ring expansion velocity is found to be 28 km/s. Our findings are discussed with relation to possible formation scenarios for SuWt 2. Through comparison of the nebular heliocentric systemic velocity, found here to be -25 $\pm$ 5 km/s, and the heliocentric systemic velocity of the double A-type binary, we conclude that neither component of the binary could have been the nebular progenitor. However, we are unable to rule out the presence of a third component to the system, which would have been the nebula progenitor.Comment: 7 pages, 4 figures. Accepted for publication in MNRA