353 research outputs found

    You turn me cold: evidence for temperature contagion

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    Introduction During social interactions, our own physiological responses influence those of others. Synchronization of physiological (and behavioural) responses can facilitate emotional understanding and group coherence through inter-subjectivity. Here we investigate if observing cues indicating a change in another's body temperature results in a corresponding temperature change in the observer. Methods Thirty-six healthy participants (age; 22.9±3.1 yrs) each observed, then rated, eight purpose-made videos (3 min duration) that depicted actors with either their right or left hand in visibly warm (warm videos) or cold water (cold videos). Four control videos with the actors' hand in front of the water were also shown. Temperature of participant observers' right and left hands was concurrently measured using a thermistor within a Wheatstone bridge with a theoretical temperature sensitivity of <0.0001°C. Temperature data were analysed in a repeated measures ANOVA (temperature × actor's hand × observer's hand). Results Participants rated the videos showing hands immersed in cold water as being significantly cooler than hands immersed in warm water, F(1,34) = 256.67, p0.1). There was however no evidence of left-right mirroring of these temperature effects p>0.1). Sensitivity to temperature contagion was also predicted by inter-individual differences in self-report empathy. Conclusions We illustrate physiological contagion of temperature in healthy individuals, suggesting that empathetic understanding for primary low-level physiological challenges (as well as more complex emotions) are grounded in somatic simulation

    Prebiotic synthesis of phosphoenol pyruvate by α-phosphorylation-controlled triose glycolysis

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    Phosphoenol pyruvate is the highest-energy phosphate found in living organisms and is one of the most versatile molecules in metabolism. Consequently, it is an essential intermediate in a wide variety of biochemical pathways, including carbon fixation, the shikimate pathway, substrate-level phosphorylation, gluconeogenesis and glycolysis. Triose glycolysis (generation of ATP from glyceraldehyde 3-phosphate via phosphoenol pyruvate) is among the most central and highly conserved pathways in metabolism. Here, we demonstrate the efficient and robust synthesis of phosphoenol pyruvate from prebiotic nucleotide precursors, glycolaldehyde and glyceraldehyde. Furthermore, phosphoenol pyruvate is derived within an α-phosphorylation controlled reaction network that gives access to glyceric acid 2-phosphate, glyceric acid 3-phosphate, phosphoserine and pyruvate. Our results demonstrate that the key components of a core metabolic pathway central to energy transduction and amino acid, sugar, nucleotide and lipid biosyntheses can be reconstituted in high yield under mild, prebiotically plausible conditions

    Antibody-free magnetic cell sorting of genetically modified primary human CD4+ T cells by one-step streptavidin affinity purification.

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    Existing methods for phenotypic selection of genetically modified mammalian cells suffer disadvantages of time, cost and scalability and, where antibodies are used to bind exogenous cell surface markers for magnetic selection, typically yield cells coated with antibody-antigen complexes and beads. To overcome these limitations we have developed a method termed Antibody-Free Magnetic Cell Sorting in which the 38 amino acid Streptavidin Binding Peptide (SBP) is displayed at the cell surface by the truncated Low Affinity Nerve Growth Receptor (LNGFRF) and used as an affinity tag for one-step selection with streptavidin-conjugated magnetic beads. Cells are released through competition with the naturally occurring vitamin biotin, free of either beads or antibody-antigen complexes and ready for culture or use in downstream applications. Antibody-Free Magnetic Cell Sorting is a rapid, cost-effective, scalable method of magnetic selection applicable to either viral transduction or transient transfection of cell lines or primary cells. We have optimised the system for enrichment of primary human CD4+ T cells expressing shRNAs and exogenous genes of interest to purities of >99%, and used it to isolate cells following Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 genome editing

    Cell-surface sensors for real-time probing of cellular environments

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    Author Manuscript 2012 August 1.The ability to explore cell signalling and cell-to-cell communication is essential for understanding cell biology and developing effective therapeutics. However, it is not yet possible to monitor the interaction of cells with their environments in real time. Here, we show that a fluorescent sensor attached to a cell membrane can detect signalling molecules in the cellular environment. The sensor is an aptamer (a short length of single-stranded DNA) that binds to platelet-derived growth factor (PDGF) and contains a pair of fluorescent dyes. When bound to PDGF, the aptamer changes conformation and the dyes come closer to each other, producing a signal. The sensor, which is covalently attached to the membranes of mesenchymal stem cells, can quantitatively detect with high spatial and temporal resolution PDGF that is added in cell culture medium or secreted by neighbouring cells. The engineered stem cells retain their ability to find their way to the bone marrow and can be monitored in vivo at the single-cell level using intravital microscopy.National Institutes of Health (U.S.) (Grant HL097172)National Institutes of Health (U.S.) (Grant HL095722)National Institutes of Health (U.S.) (Grant DE019191)National Institutes of Health (U.S.) (Grant NIAID 5RC1AI086152)Charles A. Dana FoundationAmerican Heart Association (Grant 0970178N)National Science Foundation (U.S.) (Graduate Fellowship

    The NEWMEDS rodent touchscreen test battery for cognition relevant to schizophrenia.

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    RATIONALE: The NEWMEDS initiative (Novel Methods leading to New Medications in Depression and Schizophrenia, http://www.newmeds-europe.com ) is a large industrial-academic collaborative project aimed at developing new methods for drug discovery for schizophrenia. As part of this project, Work package 2 (WP02) has developed and validated a comprehensive battery of novel touchscreen tasks for rats and mice for assessing cognitive domains relevant to schizophrenia. OBJECTIVES: This article provides a review of the touchscreen battery of tasks for rats and mice for assessing cognitive domains relevant to schizophrenia and highlights validation data presented in several primary articles in this issue and elsewhere. METHODS: The battery consists of the five-choice serial reaction time task and a novel rodent continuous performance task for measuring attention, a three-stimulus visual reversal and the serial visual reversal task for measuring cognitive flexibility, novel non-matching to sample-based tasks for measuring spatial working memory and paired-associates learning for measuring long-term memory. RESULTS: The rodent (i.e. both rats and mice) touchscreen operant chamber and battery has high translational value across species due to its emphasis on construct as well as face validity. In addition, it offers cognitive profiling of models of diseases with cognitive symptoms (not limited to schizophrenia) through a battery approach, whereby multiple cognitive constructs can be measured using the same apparatus, enabling comparisons of performance across tasks. CONCLUSION: This battery of tests constitutes an extensive tool package for both model characterisation and pre-clinical drug discovery.This work was supported by the Innovative Medicine Initiative Joint Undertaking under grant agreement no. 115008 of which resources are composed of EFPIA in-kind contribution and financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013). The authors thank Charlotte Oomen for valuable comments on the manuscript.This is the author accepted manuscript. The final version is available from Springer via http://dx.doi.org/10.1007/s00213-015-4007-

    Controlled clinical trials in cancer pain. How controlled should they be? A qualitative systematic review

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    This qualitative systematic review of the clinical methodology used in randomised, controlled trials of oral opioids (morphine, hydromorphone, oxycodone) for cancer pain underlines the difficulties of good pain research in palliative care. The current literature lacks placebo-controlled superiority trials. Recommendations for future research are discussed

    DNA Aptamers against the Lup an 1 Food Allergen

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    Using in vitro selection, high affinity DNA aptamers to the food allergen Lup an 1, ß-conglutin, were selected from a pool of DNA, 93 bases in length, containing a randomised sequence of 49 bases. ß-conglutin was purified from lupin flour and chemically crosslinked to carboxylated magnetic beads. Peptide mass fingerprinting was used to confirm the presence of the ß-conglutin. Single stranded DNA was generated from the randomised pool using T7 Gene 6 Exonuclease and was subsequently incubated with the magnetic beads and the captured DNA was released and amplified prior to a further round of Systematic Evolution of Ligands by Exponential Enrichment (SELEX). Evolution was monitored using enzyme linked oligonucleotide assay and surface plasmon resonance. Once a plateau in evolution was reached, the isolated DNA sequences were cloned and sequenced. The consensus motif was identified via alignment of the sequences and the affinities of these sequences for immobilised ß-conglutin were determined using surface plasmon resonance. The selected aptamer was demonstrated to be highly specific, showing no cross-reactivity with other flour ingredients or with other conglutin fractions of lupin. The secondary structures of the selected aptamers were predicted using m-fold. Finally, the functionality of the selected aptamers was demonstrated using a competitive assay for the quantitative detection of ß-conglutin. . Future work will focus on structure elucidation and truncation of the selected sequences to generate a smaller aptamer for application to the analysis of the Lup an 1 allergen in foodstuffs

    Patients with schizophrenia show deficits of working memory maintenance components in circuit-specific tasks

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    Working memory (WM) deficits are a neuropsychological core finding in patients with schizophrenia and also supposed to be a potential endophenotype of schizophrenia. Yet, there is a large heterogeneity between different WM tasks which is partly due to the lack of process specificity of the tasks applied. Therefore, we investigated WM functioning in patients with schizophrenia using process- and circuit-specific tasks. Thirty-one patients with schizophrenia and 47 controls were tested with respect to different aspects of verbal and visuospatial working memory using modified Sternberg paradigms in a computer-based behavioural experiment. Total group analysis revealed significant impairment of patients with schizophrenia in each of the tested WM components. Furthermore, we were able to identify subgroups of patients showing different patterns of selective deficits. Patients with schizophrenia exhibit specific and, in part, selective WM deficits with indirect but conclusive evidence of dysfunctions of the underlying neural networks. These deficits are present in tasks requiring only maintenance of verbal or visuospatial information. In contrast to a seemingly global working memory deficit, individual analysis revealed differential patterns of working memory impairments in patients with schizophrenia
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