339 research outputs found

    Magnetic resonance imaging (MRI) scanning for research: the experiences of healthy volunteers and patients with remitted depressive illness

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    We report the findings from a study exploring the experiences of individuals undergoing MRI scanning for research. Semi structured interviews took place before and after scanning with 17 participants; 12 were healthy volunteers and 5 were patients with a diagnosis of remitted depression. Themes of apprehension and curiosity prior to scanning were common in both groups. Patients were often confused about the procedure. Negative feelings were an issue at the outset, characterised by shock related to the physical surroundings, after which positive feelings, for example relaxation, were often experienced, and in the case of patients, learning more about their brain. Written information about imaging was deemed satisfactory; however the ability to ‘experience’ aspects of scanning beforehand was suggested. Scanning may be viewed as a process beginning prior to the procedure itself and involving positive and negative emotions. Increased information, reassurance and a more interactive intervention to reduce anxiety may be beneficial and may improve individuals’ experience of this widely used procedure

    Predicting human interruptibility with sensors, in

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    A person seeking someone else’s attention is normally able to quickly assess how interruptible they are. This assessment allows for behavior we perceive as natural, socially appropriate, or simply polite. On the other hand, today’s computer systems are almost entirely oblivious to the human world they operate in, and typically have no way to take into account the interruptibility of the user. This paper presents a Wizard of Oz study exploring whether, and how, robust sensor-based predictions of interruptibility might be constructed, which sensors might be most useful to such predictions, and how simple such sensors might be. The study simulates a range of possible sensors through human coding of audio and video recordings. Experience sampling is used to simultaneously collect randomly distributed self-reports of interruptibility. Based on these simulated sensors, we construct statistical models predicting human interruptibility and compare their predictions with the collected self-report data. The results of these models, although covering a demographically limited sample, are very promising, with the overall accuracy of several models reaching about 78%. Additionally, a model tuned to avoiding unwanted interruptions does so for 90 % of its predictions, while retaining 75 % overall accuracy

    A new microvertebrate assemblage from the Mussentuchit Member, Cedar Mountain Formation: insights into the paleobiodiversity and paleobiogeography of early Late Cretaceous ecosystems in western North America

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    The vertebrate fauna of the Late Cretaceous Mussentuchit Member of the Cedar Mountain Formation has been studied for nearly three decades, yet the fossil-rich unit continues to produce new information about life in western North America approximately 97 million years ago. Here we report on the composition of the Cliffs of Insanity (COI) microvertebrate locality, a newly sampled site containing perhaps one of the densest concentrations of microvertebrate fossils yet discovered in the Mussentuchit Member. The COI locality preserves osteichthyan, lissamphibian, testudinatan, mesoeucrocodylian, dinosaurian, metatherian, and trace fossil remains and is among the most taxonomically rich microvertebrate localities in the Mussentuchit Member. To better refine taxonomic identifications of isolated theropod dinosaur teeth, we used quantitative analyses of taxonomically comprehensive databases of theropod tooth measurements, adding new data on theropod tooth morphodiversity in this poorly understood interval. We further provide the first descriptions of tyrannosauroid premaxillary teeth and document the earliest North American record of adocid remains, extending the appearance of this ancestrally Asian clade by 5 million years in western North America and supporting studies of pre-Cenomaninan Laurasian faunal exchange across Beringia. The overabundance of mesoeucrocodylian remains at the COI locality produces a comparatively low measure of relative biodiversity when compared to other microvertebrate sites in the Mussentuchit Member using both raw and subsampling methods. Much more microvertebrate research is necessary to understand the roles of changing ecology and taphonomy that may be linked to transgression of the Western Interior Seaway or microhabitat variation

    End-Tagging of Ultra-Short Antimicrobial Peptides by W/F Stretches to Facilitate Bacterial Killing

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    BACKGROUND: Due to increasing resistance development among bacteria, antimicrobial peptides (AMPs), are receiving increased attention. Ideally, AMP should display high bactericidal potency, but low toxicity against (human) eukaryotic cells. Additionally, short and proteolytically stable AMPs are desired to maximize bioavailability and therapeutic versatility. METHODOLOGY AND PRINCIPAL FINDINGS: A facile approach is demonstrated for reaching high potency of ultra-short antimicrobal peptides through end-tagging with W and F stretches. Focusing on a peptide derived from kininogen, KNKGKKNGKH (KNK10) and truncations thereof, end-tagging resulted in enhanced bactericidal effect against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. Through end-tagging, potency and salt resistance could be maintained down to 4-7 amino acids in the hydrophilic template peptide. Although tagging resulted in increased eukaryotic cell permeabilization at low ionic strength, the latter was insignificant at physiological ionic strength and in the presence of serum. Quantitatively, the most potent peptides investigated displayed bactericidal effects comparable to, or in excess of, that of the benchmark antimicrobial peptide LL-37. The higher bactericidal potency of the tagged peptides correlated to a higher degree of binding to bacteria, and resulting bacterial wall rupture. Analogously, tagging enhanced peptide-induced rupture of liposomes, particularly anionic ones. Additionally, end-tagging facilitated binding to bacterial lipopolysaccharide, both effects probably contributing to the selectivity displayed by these peptides between bacteria and eukaryotic cells. Importantly, W-tagging resulted in peptides with maintained stability against proteolytic degradation by human leukocyte elastase, as well as staphylococcal aureolysin and V8 proteinase. The biological relevance of these findings was demonstrated ex vivo for pig skin infected by S. aureus and E. coli. CONCLUSIONS/SIGNIFICANCE: End-tagging by hydrophobic amino acid stretches may be employed to enhance bactericidal potency also of ultra-short AMPs at maintained limited toxicity. The approach is of general applicability, and facilitates straightforward synthesis of hydrophobically modified AMPs without the need for post-peptide synthesis modifications

    Rab-GTPase binding effector protein 2 (RABEP2) is a primed substrate for Glycogen Synthase kinase-3 (GSK3)

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    Glycogen synthase kinase-3 (GSK3) regulates many physiological processes through phosphorylation of a diverse array of substrates. Inhibitors of GSK3 have been generated as potential therapies in several diseases, however the vital role GSK3 plays in cell biology makes the clinical use of GSK3 inhibitors potentially problematic. A clearer understanding of true physiological and pathophysiological substrates of GSK3 should provide opportunities for more selective, disease specific, manipulation of GSK3. To identify kinetically favourable substrates we performed a GSK3 substrate screen in heart tissue. Rab-GTPase binding effector protein 2 (RABEP2) was identified as a novel GSK3 substrate and GSK3 phosphorylation of RABEP2 at Ser200 was enhanced by prior phosphorylation at Ser204, fitting the known consensus sequence for GSK3 substrates. Both residues are phosphorylated in cells while only Ser200 phosphorylation is reduced following inhibition of GSK3. RABEP2 function was originally identified as a Rab5 binding protein. We did not observe co-localisation of RABEP2 and Rab5 in cells, while ectopic expression of RABEP2 had no effect on endosomal recycling. The work presented identifies RABEP2 as a novel primed substrate of GSK3, and thus a potential biomarker for GSK3 activity, but understanding how phosphorylation regulates RABEP2 function requires more information on physiological roles of RABEP2

    Complete motor recovery after acute paraparesis caused by spontaneous spinal epidural hematoma: case report

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    <p>Abstract</p> <p>Background</p> <p>Spontaneous spinal epidural hematoma is a relatively rare but potentially disabling disease. Prompt timely surgical management may promote recovery even in severe cases.</p> <p>Case presentation</p> <p>We report a 34-year-old man with a 2-hour history of sudden severe back pain, followed by weakness and numbness over the bilateral lower limbs, progressing to intense paraparesis and anesthesia. A spinal magnetic resonance imaging scan was performed and revealed an anterior epidural hematoma of the thoracic spine. He underwent an emergency decompression laminectomy of the thoracic spine and hematoma evacuation. Just after surgery, his lower extremity movements improved. After 1 week, there was no residual weakness and ambulation without assistance was resumed, with residual paresthesia on the plantar face of both feet. After 5 months, no residual symptoms persisted.</p> <p>Conclusions</p> <p>The diagnosis of spontaneous spinal epidural hematoma must be kept in mind in cases of sudden back pain with symptoms of spinal cord compression. Early recognition, accurate diagnosis and prompt surgical treatment may result in significant improvement even in severe cases.</p

    Cultivation of a novel cold-adapted nitrite oxidizing betaproteobacterium from the Siberian Arctic

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    Permafrost-affected soils of the Siberian Arctic were investigated with regard to identification of nitrite oxidizing bacteria active at low temperature. Analysis of the fatty acid profiles of enrichment cultures grown at 4°C, 10°C and 17°C revealed a pattern that was different from that of known nitrite oxidizers but was similar to fatty acid profiles of Betaproteobacteria. Electron microscopy of two enrichment cultures grown at 10°C showed prevalent cells with a conspicuous ultrastructure. Sequence analysis of the 16S rRNA genes allocated the organisms to a so far uncultivated cluster of the Betaproteobacteria, with Gallionella ferruginea as next related taxonomically described organism. The results demonstrate that a novel genus of chemolithoautotrophic nitrite oxidizing bacteria is present in polygonal tundra soils and can be enriched at low temperatures up to 17°C. Cloned sequences with high sequence similarities were previously reported from mesophilic habitats like activated sludge and therefore an involvement of this taxon in nitrite oxidation in nonarctic habitats is suggested. The presented culture will provide an opportunity to correlate nitrification with nonidentified environmental clones in moderate habitats and give insights into mechanisms of cold adaptation. We propose provisional classification of the novel nitrite oxidizing bacterium as 'Candidatus Nitrotoga arctica'

    A dual-fMRI investigation of the iterated Ultimatum Game reveals that reciprocal behaviour is associated with neural alignment

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    Dyadic interactions often involve a dynamic process of mutual reciprocity; to steer a series of exchanges towards a desired outcome, both interactants must adapt their own behaviour according to that of their interaction partner. Understanding the brain processes behind such bidirectional reciprocity is therefore central to social neuroscience, but this requires measurement of both individuals’ brains during realworld exchanges. We achieved this by performing functional magnetic resonance imaging (fMRI) on pairs of male individuals simultaneously while they interacted in a modifed iterated Ultimatum Game (iUG). In this modifcation, both players could express their intent and maximise their own monetary gain by reciprocating their partner’s behaviour – they could promote generosity through cooperation and/or discourage unfair play with retaliation. By developing a novel model of reciprocity adapted from behavioural economics, we then show that each player’s choices can be predicted accurately by estimating expected utility (EU) not only in terms of immediate payof, but also as a reaction to their opponent’s prior behaviour. Finally, for the frst time we reveal that brain signals implicated in social decision making are modulated by these estimates of EU, and become correlated more strongly between interacting players who reciprocate one another

    Effect of temperature on rates of ammonium uptake and nitrification in the western coastal Arctic during winter, spring, and summer

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    Biogeochemical rate processes in the Arctic are not currently well constrained, and there is very limited information on how rates may change as the region warms. Here we present data on the sensitivity of ammonium (NH4+) uptake and nitrification rates to short-term warming. Samples were collected from the Chukchi Sea off the coast of Barrow, Alaska, during winter, spring, and summer and incubated for 24h in the dark with additions of (NH4+)-N-15 at -1.5, 6, 13, and 20 degrees C. Rates of NH4+ uptake and nitrification were measured in conjunction with bacterial production. In all seasons, NH4+ uptake rates were highest at temperatures similar to current summertime conditions but dropped off with increased warming, indicative of psychrophilic (i.e., cold-loving) microbial communities. In contrast, nitrification rates were less sensitive to temperature and were higher in winter and spring compared to summer. These findings suggest that as the Arctic coastal ecosystem continues to warm, NH4+ assimilation may become increasingly important, relative to nitrification, although the magnitude of NH4+ assimilation would be still be lower than nitrification
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