Visual cognition during real social interaction

Copyright @ 2012 The Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and 85 reproduction in any medium, provided the original author and source are credited. The article was made available through the Brunel University Open Access Publishing Fund.This article has been made available through the Brunel Open Access Publishing Fund.Laboratory studies of social visual cognition often simulate the critical aspects of joint attention by having participants interact with a computer-generated avatar. Recently, there has been a movement toward examining these processes during authentic social interaction. In this review, we will focus on attention to faces, attentional misdirection, and a phenomenon we have termed social inhibition of return (Social IOR), that have revealed aspects of social cognition that were hitherto unknown. We attribute these discoveries to the use of paradigms that allow for more realistic social interactions to take place. We also point to an area that has begun to attract a considerable amount of interest—that of Theory of Mind (ToM) and automatic perspective taking—and suggest that this too might benefit from adopting a similar approach

Analysis of residues resulting from mafic silicate impacts into aluminium 1100

Accepted versio

Are goal states represented during kinematic imitation?

A number of studies have shown that observation of another person's actions can modulate one's own actions, such as when 2 individuals cooperate in order to complete a joint task. However, little is known about whether or not direct matching of specific movements is modulated by the goals of the actions observed. In a series of 7 experiments, we employed an action observation paradigm in which 2 coactors sat opposite each other and took turns to reach out to targets presented on a shared workspace. Importantly, coactors performed either the same goal at the reached-to location or a different goal. Although results consistently showed that the reaching action of 1 individual slows the observer's reaching action to the same spatial location, the effect was not modulated according to the adopted goals of coactors. These findings challenge the notion that the processes involved in the imitation of specific movements code for the action goals of those movements

A guide to integrating immunohistochemistry and chemical imaging

© 2018 The Royal Society of Chemistry. Chemical imaging provides new insight into the fundamental atomic, molecular, and biochemical composition of tissue and how they are interrelated in normal physiology. Visualising and quantifying products of pathogenic reactions long before structural changes become apparent also adds a new dimension to understanding disease pathogenesis. While chemical imaging in isolation is somewhat limited by the nature of information it can provide (e.g. peptides, metals, lipids, or functional groups), integrating immunohistochemistry allows simultaneous, targeted imaging of biomolecules while also mapping tissue composition. Together, this approach can provide invaluable information on the inner workings of the cell and the molecular basis of diseases

Worse Physical Disability Is Associated With the Expression of PD-1 on Inflammatory T-Cells in Multiple Sclerosis Patients With Older Appearing Brains

Background: Magnetic Resonance Imaging (MRI) analysis method “brain-age” paradigm could offer an intuitive prognostic metric (brain-predicted age difference: brain-PAD) for disability in Multiple Sclerosis (MS), reflecting structural brain health adjusted for aging. Equally, cellular senescence has been reported in MS using T-cell biomarker CD8+CD57+. Objective: Here we explored links between MRI-derived brain-age and blood-derived cellular senescence. We examined the value of combining brain-PAD with CD8+CD57+(ILT2+PD-1+) T-cells when predicting disability score in MS and considered whether age-related biological mechanisms drive disability. Methods: Brain-age analysis was applied to T1-weighted MRI images. Disability was assessed and peripheral blood was examined for CD8+CD57+ T-cell phenotypes. Linear regression models were used, adjusted for sex, age and normalized brain volume. Results: We included 179 mainly relapsing-remitting MS patients. A high brain-PAD was associated with high physical disability (mean brain-PAD = +6.54 [5.12–7.95]). CD8+CD57+(ILT2+PD-1+) T-cell frequency was neither associated with disability nor with brain-PAD. Physical disability was predicted by the interaction between brain-PAD and CD8+CD57+ILT2+PD-1+ T-cell frequency (AR2 = 0.196), yet without improvement compared to brain-PAD alone (AR2 = 0.206; AICc = 1.8). Conclusion: Higher frequency of CD8+CD57+ILT2+PD-1+ T-cells in the peripheral blood in patients with an older appearing brain was associated with worse disability scores, suggesting a role of these cells in the development of disability in MS patients with poorer brain health

Matrix permeability of reservoir rocks, Ngatamariki geothermal field, Taupo Volcanic Zone, New Zealand

The Taupo Volcanic Zone (TVZ) hosts 23 geothermal fields, seven of which are currently utilised for power generation. Ngatamariki geothermal field (NGF) is one of the latest geothermal power generation developments in New Zealand (commissioned in 2013), located approximately 15 km north of Taupo. Samples of reservoir rocks were taken from the Tahorakuri Formation and Ngatamariki Intrusive Complex, from five wells at the NGF at depths ranging from 1354 to 3284 m. The samples were categorised according to whether their microstructure was pore or microfracture dominated. Image analysis of thin sections impregnated with an epoxy fluorescent dye was used to characterise and quantify the porosity structures and their physical properties were measured in the laboratory. Our results show that the physical properties of the samples correspond to the relative dominance of microfractures compared to pores. Microfracture-dominated samples have low connected porosity and permeability, and the permeability decreases sharply in response to increasing confining pressure. The pore-dominated samples have high connected porosity and permeability, and lower permeability decrease in response to increasing confining pressure. Samples with both microfractures and pores have a wide range of porosity and relatively high permeability that is moderately sensitive to confining pressure. A general trend of decreasing connected porosity and permeability associated with increasing dry bulk density and sonic velocity occurs with depth; however, variations in these parameters are more closely related to changes in lithology and processes such as dissolution and secondary veining and re-crystallisation. This study provides the first broad matrix permeability characterisation of rocks from depth at Ngatamariki, providing inputs for modelling of the geothermal system. We conclude that the complex response of permeability to confining pressure is in part due to the intricate dissolution, veining, and recrystallization textures of many of these rocks that lead to a wide variety of pore shapes and sizes. While the laboratory results are relevant only to similar rocks in the Taupo Volcanic Zone, the relationships they highlight are applicable to other geothermal fields, as well as rock mechanic applications to, for example, aspects of volcanology, landslide stabilisation, mining, and tunnelling at depth

Quantitative immuno-mass spectrometry imaging of skeletal muscle dystrophin

Emerging and promising therapeutic interventions for Duchenne muscular dystrophy (DMD) are confounded by the challenges of quantifying dystrophin. Current approaches have poor precision, require large amounts of tissue, and are difficult to standardize. This paper presents an immuno-mass spectrometry imaging method using gadolinium (Gd)-labeled anti-dystrophin antibodies and laser ablation-inductively coupled plasma-mass spectrometry to simultaneously quantify and localize dystrophin in muscle sections. Gd is quantified as a proxy for the relative expression of dystrophin and was validated in murine and human skeletal muscle sections following k-means clustering segmentation, before application to DMD patients with different gene mutations where dystrophin expression was measured up to 100 µg kg−1 Gd. These results demonstrate that immuno-mass spectrometry imaging is a viable approach for pre-clinical to clinical research in DMD. It rapidly quantified relative dystrophin in single tissue sections, efficiently used valuable patient resources, and may provide information on drug efficacy for clinical translation

The epigenetic regulators CBP and p300 facilitate leukemogenesis and represent therapeutic targets in acute myeloid leukemia.

Growing evidence links abnormal epigenetic control to the development of hematological malignancies. Accordingly, inhibition of epigenetic regulators is emerging as a promising therapeutic strategy. The acetylation status of lysine residues in histone tails is one of a number of epigenetic post-translational modifications that alter DNA-templated processes, such as transcription, to facilitate malignant transformation. Although histone deacetylases are already being clinically targeted, the role of histone lysine acetyltransferases (KAT) in malignancy is less well characterized. We chose to study this question in the context of acute myeloid leukemia (AML), where, using in vitro and in vivo genetic ablation and knockdown experiments in murine models, we demonstrate a role for the epigenetic regulators CBP and p300 in the induction and maintenance of AML. Furthermore, using selective small molecule inhibitors of their lysine acetyltransferase activity, we validate CBP/p300 as therapeutic targets in vitro across a wide range of human AML subtypes. We proceed to show that growth retardation occurs through the induction of transcriptional changes that induce apoptosis and cell-cycle arrest in leukemia cells and finally demonstrate the efficacy of the KAT inhibitors in decreasing clonogenic growth of primary AML patient samples. Taken together, these data suggest that CBP/p300 are promising therapeutic targets across multiple subtypes in AML.Funding in the Huntly laboratory comes from Cancer Research UK, Leukemia Lymphoma Research, the Kay Kendal Leukemia Fund, the Leukemia lymphoma Society of America, the Wellcome Trust, The Medical Research Council and an NIHR Cambridge Biomedical Research Centre grant. Patient samples were processed in the Cambridge Blood and Stem Cell Biobank.This is the author accepted manuscript. The final version is available via NPG at http://dx.doi.org/10.1038/onc.2015.9

Visualising mouse neuroanatomy and function by metal distribution using laser ablation-inductively coupled plasma-mass spectrometry imaging

© The Royal Society of Chemistry 2015. Metals have a number of important roles within the brain. We used laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) to map the three-dimensional concentrations and distributions of transition metals, in particular iron (Fe), copper (Cu) and zinc (Zn) within the murine brain. LA-ICP-MS is one of the leading analytical tools for measuring metals in tissue samples. Here, we present a complete data reduction protocol for measuring metals in biological samples, including the application of a pyramidal voxel registration technique to reproducibly align tissue sections. We used gold (Au) nanoparticle and ytterbium (Yb)-tagged tyrosine hydroxylase antibodies to assess the co-localisation of Fe and dopamine throughout the entire mouse brain. We also examined the natural clustering of metal concentrations within the murine brain to elucidate areas of similar composition. This clustering technique uses a mathematical approach to identify multiple 'elemental clusters', avoiding user bias and showing that metal composition follows a hierarchical organisation of neuroanatomical structures. This work provides new insight into the distinct compartmentalisation of metals in the brain, and presents new avenues of exploration with regard to region-specific, metal-associated neurodegeneration observed in several chronic neurodegenerative diseases