Blood coagulation factor X exerts differential effects on adenovirus entry into human lymphocytes

It has been proposed that blood coagulation factors, principally factor X (FX), enhance the uptake of human adenovirus type 5 (Ad5) into cultured epithelial cells by bridging the viral hexon capsid protein and cell-surface heparan sulphate proteoglycans (HSPGs). We studied the effects of FX on Ad transduction of lymphoid cell lines (NK92MI, a natural killer cell line; Daudi, a B-cell line and Jurkat, a T-cell line) as well as primary peripheral blood lymphocytes (PBL) and HeLa epithelial cells using either replication-deficient Ad5, or a derivative in which the Ad5 fiber was replaced with that of another Ad type, Ad35, termed Ad5F35. PBL and NK92MI were resistant to Ad5 transduction. Transduction of Jurkat and Daudi cells by Ad5 was reduced by FX but without discernible effects on cell-surface Ad5 binding. FX reduced virus binding and transduction of all lymphoid cell lines by Ad5F35, as well as transduction of the T- and Natural Killer (NK)-cell populations of PBL. Flow cytometry analysis showed that all lymphoid cell lines were negative for HSPG components, in contrast to HeLa cells. FX reduced transduction of an HSPG-negative mutant Chinese hamster ovary cell line (CHOpgsA745) by Ad5 and Ad5F35, with Ad5F35 binding also being reduced by FX. These results point to fiber-dependent differences (Ad5 versus Ad35 fiber) in Ad binding to and transduction of human lymphoid and epithelial cells in the presence of FX

PyPhi: A toolbox for integrated information theory

Integrated information theory provides a mathematical framework to fully characterize the cause-effect structure of a physical system. Here, we introduce PyPhi, a Python software package that implements this framework for causal analysis and unfolds the full cause-effect structure of discrete dynamical systems of binary elements. The software allows users to easily study these structures, serves as an up-to-date reference implementation of the formalisms of integrated information theory, and has been applied in research on complexity, emergence, and certain biological questions. We first provide an overview of the main algorithm and demonstrate PyPhi's functionality in the course of analyzing an example system, and then describe details of the algorithm's design and implementation. PyPhi can be installed with Python's package manager via the command 'pip install pyphi' on Linux and macOS systems equipped with Python 3.4 or higher. PyPhi is open-source and licensed under the GPLv3; the source code is hosted on GitHub at https://github.com/wmayner/pyphi . Comprehensive and continually-updated documentation is available at https://pyphi.readthedocs.io/ . The pyphi-users mailing list can be joined at https://groups.google.com/forum/#!forum/pyphi-users . A web-based graphical interface to the software is available at http://integratedinformationtheory.org/calculate.html .Comment: 22 pages, 4 figures, 6 pages of appendices. Supporting information "S1 Calculating Phi" can be found in the ancillary file

Measurement of vacuum pressure with a magneto-optical trap : a pressure-rise method

This research was supported by UK EPSRC grant GR/T08272/01, IOP Scotland and the Leverhulme Trust Research Project Grant RPG-2013-074.The lifetime of an atom trap is often limited by the presence of residual background gases in the vacuum chamber. This leads to the lifetime being inversely proportional to the pressure. Here we use this dependence to estimate the pressure and to obtain pressure rate-of-rise curves, which are commonly used in vacuum science to evaluate the performance of a system. We observe different rates of pressure increase in response to different levels of outgassing in our system. Therefore we suggest that this is a sensitive method which will find useful applications in cold atom systems, in particular where the inclusion of a standard vacuum gauge is impractical.Peer reviewe

A review of independent living adaptations

This study will explore and test potential changes to the structural and delivery mechanisms for independent living adaptations. This is in order to move towards the Welsh Government goal of ensuring that adaptations can be delivered more speedily to those who need them. In doing so, it will help reduce inherent inequalities in the current system by ensuring joined up solutions, prevention and early intervention activity. This Review was commissioned in the light of some £35 million being spent annually by local authorities in Wales on Disabled Facilities Grants (DFGs) and the Welsh Government’s own spending of approximately £8 million on Physical Adaptations Grants (PAG) for social tenants. The Review was carried out between May and November 2014 and addressed three aims: mapping the current system performance Indicators testing the feasibility of options for change

Synthesis and properties of novel star-shaped oligofluorene conjugated systems with BODIPY cores

Star-shaped conjugated systems with varying oligofluorene arm length and substitution patterns of the central BODIPY core have been synthesised, leading to two families of compounds, T-B1-T-B4 and Y-B1-Y-B4, with T- and Y-shaped motifs, respectively. Thermal stability, cyclic voltammetry, absorption and photoluminescence spectroscopy of each member of these two families were studied in order to determine their suitability as emissive materials in photonic applications

Sperm motility and fertilisation success in an acidified and hypoxic environment

The distribution and function of many marine species is largely determined by the effect of abiotic drivers on their reproduction and early development, including those drivers associated with elevated CO2 and global climate change. A number of studies have therefore investigated the effects of elevated pCO2 on a range of reproductive parameters, including sperm motility and fertilisation success. To date, most of these studies have not examined the possible synergistic effects of other abiotic drivers, such as the increased frequency of hypoxic events that are also associated with climate change. The present study is therefore novel in assessing the impact that a hypoxic event could have on reproduction in a future high CO2 ocean. Specifically, this study assesses sperm motility and fertilisation success in the sea urchin Paracentrotus lividus exposed to elevated pCO2 for 6 months. Gametes extracted from these pre acclimated individuals were subjected to hypoxic conditions simulating an hypoxic event in a future high CO2 ocean. Sperm swimming speed increased under elevated pCO2 and decrease under hypoxic conditions resulting in the elevated pCO2 and hypoxic treatment being approximately equivalent to the control. There was also a combined negative effect of increased pCO2 and hypoxia on the percentage of motile sperm. There was a significant negative effect of elevated pCO2 on fertilisation success, and when combined with a simulated hypoxic event there was an even greater effect. This could potentially affect cohort recruitment and in turn reduce the density of this ecologically and economically important ecosystem engineer therefore potentially effecting biodiversity and ecosystem services

Differential clonal evolution in oesophageal cancers in response to neo-adjuvant chemotherapy

How chemotherapy affects carcinoma genomes is largely unknown. Here we report whole-exome and deep sequencing of 30 paired oesophageal adenocarcinomas sampled before and after neo-adjuvant chemotherapy. Most, but not all, good responders pass through genetic bottlenecks, a feature associated with higher mutation burden pre-treatment. Some poor responders pass through bottlenecks, but re-grow by the time of surgical resection, suggesting a missed therapeutic opportunity. Cancers often show major changes in driver mutation presence or frequency after treatment, owing to outgrowth persistence or loss of sub-clones, copy number changes, polyclonality and/or spatial genetic heterogeneity. Post-therapy mutation spectrum shifts are also common, particularly C>A and TT>CT changes in good responders or bottleneckers. Post-treatment samples may also acquire mutations in known cancer driver genes (for example, SF3B1, TAF1 and CCND2) that are absent from the paired pre-treatment sample. Neo-adjuvant chemotherapy can rapidly and profoundly affect the oesophageal adenocarcinoma genome. Monitoring molecular changes during treatment may be clinically useful

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

A simple method for estimating larval supply in reef fishes and a preliminary test of population limitation by larval delivery in the kelp bass \u3cem\u3eParalabrax clathratus\u3c/em\u3e

This paper describes a method for estimating larval supply of a temperate reef fish, the kelp bass Paralabrax clathratus, that is simple, inexpensive, requires relatively low effort, and integrates larval supply over time. Using this method, we sampled larval supply concurrently at 4 sites spread over about 35 km for nearly an entire settlement season. With these data and visual estimates of recruitment (the density of young-of-the-year after the end of the settlement season), we tested the hypothesis that spatial patterns in recruitment were set by larval supply. This hypothesis was rejected: kelp bass recruitment to the 4 sites was not related to patterns of larval supply. Furthermore, in contrast to the findings of an earlier study, recruitment was not related to the density of the macroalga Macrocystis pyrifera. Recruitment was, however, strongly correlated with the density of 1 yr old kelp bass, suggesting that spatial patterns of recruitment were consistent between the 2 cohorts. Recruitment, however, was not correlated with the density of bass 2+ yr old. We also measured larval supply in a second year and found that spatial patterns of supply were strongly correlated between years at a relatively small scale of 10s to 100s m, but not at a larger scale of several km. This finding suggests that some deterministic process (or set of processes) sets spatial patterns of larval supply at small, but not large scales. At large scales, consistent patterns of recruitment between 2 cohorts in the face of variable larval supply suggest that deterministic, postsettlement processes may generate predictable patterns of recruitment even when the supply of larvae is variable. In addition to demonstrating that spatial patterns in the abundance of demersal fish are not always well predicted by larval supply, this study introduces a technique that may facilitate more thorough exploration of the role of larval supply in determining the dynamics of populations of reef fishes

Detection of Estrogen Receptor Alpha and Assessment of Fulvestrant Activity in MCF-7 Tumor Spheroids Using Microfluidics and SERS

Breast cancer is one of the leading causes of cancer death in women. Novel in vitro tools that integrate three-dimensional (3D) tumor models with highly sensitive chemical reporters can provide useful information to aid biological characterization of cancer phenotype and understanding of drug activity. The combination of surface-enhanced Raman scattering (SERS) techniques with microfluidic technologies offers new opportunities for highly selective, specific, and multiplexed nanoparticle-based assays. Here, we explored the use of functionalized nanoparticles for the detection of estrogen receptor alpha (ERα) expression in a 3D tumor model, using the ERα-positive human breast cancer cell line MCF-7. This approach was used to compare targeted versus nontargeted nanoparticle interactions with the tumor model to better understand whether targeted nanotags are required to efficiently target ERα. Mixtures of targeted anti-ERα antibody-functionalized nanotags (ERα-AuNPs) and nontargeted (against ERα) anti-human epidermal growth factor receptor 2 (HER2) antibody-functionalized nanotags (HER2-AuNPs), with different Raman reporters with a similar SERS signal intensity, were incubated with MCF-7 spheroids in microfluidic devices and spectroscopically analyzed using SERS. MCF-7 cells express high levels of ERα and no detectable levels of HER2. 2D and 3D SERS measurements confirmed the strong targeting effect of ERα-AuNP nanotags to the MCF-7 spheroids in contrast to HER2-AuNPs (63% signal reduction). Moreover, 3D SERS measurements confirmed the differentiation between the targeted and the nontargeted nanotags. Finally, we demonstrated how nanotag uptake by MCF-7 spheroids was affected by the drug fulvestrant, the first-in-class approved selective estrogen receptor degrader (SERD). These results illustrate the potential of using SERS and microfluidics as a powerful in vitro platform for the characterization of 3D tumor models and the investigation of SERD activity