Molecular basis for resistance of acanthamoeba tubulins to all major classes of antitubulin compounds

Tubulin is essential to eukaryotic cells and is targeted by several antineoplastics, herbicides, and antimicrobials. We demonstrate that Acanthamoeba spp. are resistant to five antimicrotubule compounds, unlike any other eukaryote studied so far. Resistance correlates with critical amino acid differences within the inhibitor binding sites of the tubulin heterodimers

Development status of AEOLDOS - a deorbit module for small satellites

A prototype CubeSat module to deploy a gossamer aerobrake, using strain stored in tape-springs, at end-of-life is described. A novel hub geometry to reduce bending shock at end-of-deployment while simultaneously permitting radial, as opposed to tangential, deployment is proposed. The rpm of the hub is measured under various deployment conditions to verify that the system offers highly-repeatable performance, while high-speed photography is used to characterise the behaviour of the tape-spring during unspooling and contrast it to the behaviour of a traditional tangential-deployment system. Secondly the folding pattern of the membrane, which takes advantage of the symmetrical deployment offered by the petal hub, is developed and the unfolding mechanism is verified by numerical and experimental analysis. Finally, the release of the stored strain is considered and a novel burn-though device is designed and prototyped to meet this requirement

A mathematical investigation into the uptake kinetics of nanoparticles in vitro.

Nanoparticles have the potential to increase the efficacy of anticancer drugs whilst reducing off-target side effects. However, there remain uncertainties regarding the cellular uptake kinetics of nanoparticles which could have implications for nanoparticle design and delivery. Polymersomes are nanoparticle candidates for cancer therapy which encapsulate chemotherapy drugs. Here we develop a mathematical model to simulate the uptake of polymersomes via endocytosis, a process by which polymersomes bind to the cell surface before becoming internalised by the cell where they then break down, releasing their contents which could include chemotherapy drugs. We focus on two in vitro configurations relevant to the testing and development of cancer therapies: a well-mixed culture model and a tumour spheroid setup. Our mathematical model of the well-mixed culture model comprises a set of coupled ordinary differential equations for the unbound and bound polymersomes and associated binding dynamics. Using a singular perturbation analysis we identify an optimal number of ligands on the polymersome surface which maximises internalised polymersomes and thus intracellular chemotherapy drug concentration. In our mathematical model of the spheroid, a multiphase system of partial differential equations is developed to describe the spatial and temporal distribution of bound and unbound polymersomes via advection and diffusion, alongside oxygen, tumour growth, cell proliferation and viability. Consistent with experimental observations, the model predicts the evolution of oxygen gradients leading to a necrotic core. We investigate the impact of two different internalisation functions on spheroid growth, a constant and a bond dependent function. It was found that the constant function yields faster uptake and therefore chemotherapy delivery. We also show how various parameters, such as spheroid permeability, lead to travelling wave or steady-state solutions

Body odor quality predicts behavioral attractiveness in humans

Growing effort is being made to understand how different attractive physical traits co-vary within individuals, partly because this might indicate an underlying index of genetic quality. In humans, attention has focused on potential markers of quality such as facial attractiveness, axillary odor quality, the second-to-fourth digit (2D:4D) ratio and body mass index (BMI). Here we extend this approach to include visually-assessed kinesic cues (nonverbal behavior linked to movement) which are statistically independent of structural physical traits. The utility of such kinesic cues in mate assessment is controversial, particularly during everyday conversational contexts, as they could be unreliable and susceptible to deception. However, we show here that the attractiveness of nonverbal behavior, in 20 male participants, is predicted by perceived quality of their axillary body odor. This finding indicates covariation between two desirable traits in different sensory modalities. Depending on two different rating contexts (either a simple attractiveness rating or a rating for long-term partners by 10 female raters not using hormonal contraception), we also found significant relationships between perceived attractiveness of nonverbal behavior and BMI, and between axillary odor ratings and 2D:4D ratio. Axillary odor pleasantness was the single attribute that consistently predicted attractiveness of nonverbal behavior. Our results demonstrate that nonverbal kinesic cues could reliably reveal mate quality, at least in males, and could corroborate and contribute to mate assessment based on other physical traits

A comparison of substrate oxidation during prolonged exercise in men at terrestrial altitude and normobaric normoxia following the coingestion of 13C glucose and 13C fructose

This study compared the effects of co-ingesting glucose and fructose on exogenous and endogenous substrate oxidation during prolonged exercise at altitude and sea level, in men. Seven male British military personnel completed two bouts of cycling at the same relative workload (55% Wmax) for 120 minutes on acute exposure to altitude (3375m) and at sea level (~113m). In each trial, participants ingested 1.2 g.min-1 of glucose (enriched with 13C glucose) and 0.6 g.min-1 of fructose (enriched with 13C fructose) directly before and every 15 minutes during exercise. Indirect calorimetry and isotope ratio mass spectrometry were used to calculate fat oxidation, total and exogenous carbohydrate oxidation, plasma glucose oxidation and endogenous glucose oxidation derived from liver and muscle glycogen. Total carbohydrate oxidation during the exercise period was lower at altitude (157.7±56.3 grams) than sea level (286.5±56.2 grams, P=0.006, ES=2.28), whereas fat oxidation was higher at altitude (75.5±26.8 grams) than sea level (42.5±21.3 grams, P=0.024, ES=1.23). Peak exogenous carbohydrate oxidation was lower at altitude (1.13±0.2 g.min-1) than sea level (1.42±0.16 g.min-1, P=0.034, ES=1.33). There were no differences in rates, or absolute and relative contributions of plasma or liver glucose oxidation between conditions during the second hour of exercise. However, absolute and relative contributions of muscle glycogen during the second hour were lower at altitude (29.3±28.9 grams, 16.6±15.2%) than sea level (78.7±5.2 grams (P=0.008, ES=1.71), 37.7±13.0% (P=0.016, ES=1.45). Acute exposure to altitude reduces the reliance on muscle glycogen and increases fat oxidation during prolonged cycling in men, compared with sea level

Human Parahippocampal Cortex Supports Spatial Binding in Visual Working Memory

Studies investigating the functional organization of the medial temporal lobe (MTL) suggest that parahippocampal cortex (PHC) generates representations of spatial and contextual information used by the hippocampus in the formation of episodic memories. However, evidence from animal studies also implicates PHC in spatial binding of visual information held in short term, working memory. Here we examined a 46-year-old man (P.J.), after he had recovered from bilateral medial occipitotemporal cortex strokes resulting in ischemic lesions of PHC and hippocampal atrophy, and a group of age-matched healthy controls. When recalling the color of 1 of 2 objects, P.J. misidentified the target when cued by its location, but not shape. When recalling the position of 1 of 3 objects, he frequently misidentified the target, which was cued by its color. Increasing the duration of the memory delay had no impact on the proportion of binding errors, but did significantly worsen recall precision in both P.J. and controls. We conclude that PHC may play a crucial role in spatial binding during encoding of visual information in working memory.Biotechnology and Biological Sciences Research Counci

Stories of people who have attended a lesbian, gay, bisexual and trans support group in a secure intellectual disability service

Background This research is about people who have intellectual disabilities and live in a secure hospital. It is about a group of people who meet at a support group. The support group is for people who are lesbian, gay, bisexual or transgender. Methods These people with intellectual disabilities helped with planning, doing, and telling other people about the research. They told their stories about going to the support group. Results Their stories were joined together into a group story. The story said that the group helped people in lots of different ways. For some people going to the group was difficult at first because it was 'coming out'. This means telling other people you are lesbian, gay, bisexual, or transgender. Then it got easier and people started to feel better about themselves. Then they wanted to help others and this was important in their lives. Conclusions This group seemed to help people get better. We have given some ideas for setting up other groups and doing more research

Comparison of Methods for Modeling Fractional Cover Using Simulated Satellite Hyperspectral Imager Spectra

Remotely sensed data can be used to model the fractional cover of green vegetation (GV), non-photosynthetic vegetation (NPV), and soil in natural and agricultural ecosystems. NPV and soil cover are difficult to estimate accurately since absorption by lignin, cellulose, and other organic molecules cannot be resolved by broadband multispectral data. A new generation of satellite hyperspectral imagers will provide contiguous narrowband coverage, enabling new, more accurate, and potentially global fractional cover products. We used six field spectroscopy datasets collected in prior experiments from sites with partial crop, grass, shrub, and low-stature resprouting tree cover to simulate satellite hyperspectral data, including sensor noise and atmospheric correction artifacts. The combined dataset was used to compare hyperspectral index-based and spectroscopic methods for estimating GV, NPV, and soil fractional cover. GV fractional cover was estimated most accurately. NPV and soil fractions were more difficult to estimate, with spectroscopic methods like partial least squares (PLS) regression, spectral feature analysis (SFA), and multiple endmember spectral mixture analysis (MESMA) typically outperforming hyperspectral indices. Using an independent validation dataset, the lowest root mean squared error (RMSE) values were 0.115 for GV using either normalized difference vegetation index (NDVI) or SFA, 0.164 for NPV using PLS, and 0.126 for soil using PLS. PLS also had the lowest RMSE averaged across all three cover types. This work highlights the need for more extensive and diverse fine spatial scale measurements of fractional cover, to improve methodologies for estimating cover in preparation for future hyperspectral global monitoring missions