• Object size determines the spatial spread of visual time

      Fulcher, Corinne; McGraw, Paul V.; Roach, N.W.; Whitaker, David J.; Heron, James (2016-07-27)
      A key question for temporal processing research is how the nervous system extracts event duration, despite a notable lack of neural structures dedicated to duration encoding. This is in stark contrast with the orderly arrangement of neurons tasked with spatial processing. In this study, we examine the linkage between the spatial and temporal domains. We use sensory adaptation techniques to generate after-effects where perceived duration is either compressed or expanded in the opposite direction to the adapting stimulus’ duration. Our results indicate that these after-effects are broadly tuned, extending over an area approximately five times the size of the stimulus. This region is directly related to the size of the adapting stimulus—the larger the adapting stimulus the greater the spatial spread of the aftereffect. We construct a simple model to test predictions based on overlapping adapted versus non-adapted neuronal populations and show that our effects cannot be explained by any single, fixed-scale neural filtering. Rather, our effects are best explained by a self-scaled mechanism underpinned by duration selective neurons that also pool spatial information across earlier stages of visual processing.
    • Observation of highly decoupled conductivity in protic ionic conductors

      Wojnarowska, Z.; Wang, Y.; Paluch, Krzysztof J.; Sokolov, A.P.; Paluch, M. (2014-03)
      Ionic liquids (ILs) are key materials for the development of a wide range of emerging technologies. Protic ionic liquids, an important class of ILs, have long been envisioned as promising anhydrous electrolytes for fuel cells. It is well known that in comparison to all other cations, protons exhibit abnormally high conductivity in water. Such superprotonic dynamics was expected in protic ionic conductors as well. However, many years of extensive studies led to the disappointing conclusion that this is not the case and most protic ionic liquids display subionic behavior. Therefore, the relatively low conductivity seems to be the main obstacle for the application of protic ionic liquids in fuel cells. Using dielectric spectroscopy, herein we report the observation of highly decoupled conductivity in a newly synthesized protic ionic conductor. We show that its proton transport is strongly decoupled from the structural relaxation, in terms of both temperature dependence and characteristic rates. This finding offers a fresh look on the charge transport mechanism in PILs and also provides new ideas for design of anhydrous materials with exceptionally high proton conductivity.
    • Oestrogen promotes healing in a bacterial LPS model of delayed cutaneous wound repair

      Crompton, R.; Williams, H.; Ansell, David M.; Campbell, Laura; Holden, K.; Cruickshank, S.; Hardman, M.J. (2016-04)
      Wound infection is a major clinical problem, yet understanding of bacterial host interactions in the skin remains limited. Microbe-derived molecules, known as pathogen-associated molecular patterns, are recognised in barrier tissues by pattern-recognition receptors. In particular, the pathogen-associated molecular pattern, lipopolysaccharide (LPS), a component of microbial cell walls and a specific ligand for Toll-like receptor 4, has been widely used to mimic systemic and local infection across a range of tissues. Here we administered LPS derived from Klebsiella pneumoniae, a species of bacteria that is emerging as a wound-associated pathogen, to full-thickness cutaneous wounds in C57/BL6 mice. Early in healing, LPS-treated wounds displayed increased local apoptosis and reduced proliferation. Subsequent healing progression was delayed with reduced re-epithelialisation, increased proliferation, a heightened inflammatory response and perturbed wound matrix deposition. Our group and others have previously demonstrated the beneficial effects of 17β-estradiol treatment across a range of preclinical wound models. Here we asked whether oestrogen would effectively promote healing in our LPS bacterial infection model. Intriguingly, co-treatment with 17β-estradiol was able to promote re-epithelialisation, dampen inflammation and induce collagen deposition in our LPS-delayed healing model. Collectively, these studies validate K. pneumoniae-derived LPS treatment as a simple yet effective model of bacterial wound infection, while providing the first indication that oestrogen could promote cutaneous healing in the presence of infection, further strengthening the case for its therapeutic use.
    • Oestrogenic compounds and oxidative stress (in human sperm and lymphocytes in the Comet assay)

      Anderson, Diana; Baumgartner, Adolf; Brinkworth, Martin H.; Schmid, Thomas E.; Cemeli, Eduardo; Wood, John M. (2003)
      Reactive oxygen species (ROS) are produced by a wide variety of chemicals and physiological processes in which enzymes catalyse the transfer of electrons from a substrate to molecular oxygen. The immediate products of such reactions, superoxide anion radicals and hydrogen peroxide can be metabolised by enzymes such as superoxide dismutase (SOD) and catalase (CAT), respectively, and depending on its concentration by Vitamin C (Vit C). Under certain circumstances the ROS form highly reactive hydroxyl radicals. We examined human sperm and lymphocytes after treatment with six oestrogenic compounds in the Comet assay, which measures DNA damage, and observed that all caused damage in both cell types. The damage was diminished in nearly all cases by catalase, and in some instances by SOD and Vit C. This response pattern was also seen with hydrogen peroxide. This similarity suggests that the oestrogen-mediated effects could be acting via the production of hydrogen peroxide since catalase always markedly reduced the response. The variable responses with SOD indicate a lesser involvement of superoxide anion radicals due to SOD-mediated conversion of superoxide to hydrogen peroxide generally causing a lower level of DNA damage than other ROS. The variable Vit C responses are explained by a reduction of hydrogen peroxide at low Vit C concentrations and a pro-oxidant activity at higher concentrations. Together these data provide evidence that inappropriate exposure to oestrogenic compounds could lead to free-radical mediated damage. It is believed that the observed activities were not generated by cell free cell culture conditions because increased responses were observed over and above control values when the compounds were added, and also increasing dose¿response relationships have been found after treatment with such oestrogenic compounds in previously reported studies.
    • Off with their heads: The Anglo-Saxon execution cemetery at Walkington Wold, East Yorkshire.

      Buckberry, Jo (http://www.oxbowbooks.com/bookinfo.cfm/ID/84691//Location/Oxbow, 2008)
    • Old Scatness excavation manual: A case study in archaeological recording.

      Dockrill, Stephen J.; Bond, Julie M.; Turner, V.E.; Brown, L.D. (Shetland Heritage Publications, 2008)
    • Olive oil or lard? Distinguishing plant oils from animal fats in the archaeological record of the eastern Mediterranean using gas chromatography/combustion/isotope ratio mass spectrometry

      Steele, Valerie J.; Stern, Ben; Stott, A.W. (2010-12-15)
      Distinguishing animal fats from plant oils in archaeological residues is not straightforward. Characteristic plant sterols, such as ¿-sitosterol, are often missing in archaeological samples and specific biomarkers do not exist for most plant fats. Identification is usually based on a range of characteristics such as fatty acid ratios, all of which indicate that a plant oil may be present, none of which uniquely distinguish plant oils from other fats. Degradation and dissolution during burial alter fatty acid ratios and remove short chain fatty acids, resulting in degraded plant oils with similar fatty acid profiles to other degraded fats. Compound specific stable isotope analysis of ¿13C18:0 and ¿13C16:0, carried out by gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS), has provided a means of distinguishing fish oils, dairy fats, ruminant and non-ruminant adipose fats but plant oils are rarely included in these analyses. For modern plant oils where C18:1 is abundant, ¿13C18:1 and ¿13C16:0 are usually measured. These results cannot be compared with archaeological data or other modern reference fats where ¿13C18:0 and ¿13C16:0 are measured, as C18:0 and C18:1 are formed by different processes resulting in different isotopic values. Eight samples of six modern plant oils were saponified releasing sufficient C18:0 to measure the isotopic values, which were plotted against ¿13C16:0. The isotopic values for these oils, with one exception, formed a tight cluster between ruminant and non-ruminant animal fats. This result complicates the interpretation of mixed fatty residues in geographical areas where both animal fats and plant oils were in use.
    • Omega-3 Polyunsaturated Fatty Acids: Photoprotective Macronutrients

      Nicolaou, Anna; Pilkington, S.M.; Rhodes, L.E.; Watson, R.B. (2011)
      Ultraviolet radiation (UVR) in sunlight has deleterious effects on skin, while behavioural changes have resulted in people gaining more sun exposure. The clinical impact includes a year-on-year increase in skin cancer incidence, and topical sunscreens alone provide an inadequate measure to combat overexposure to UVR. Novel methods of photoprotection are being targeted as additional measures, with growing interest in the potential for systemic photoprotection through naturally sourced nutrients. Omega-3 polyunsaturated fatty acids (n-3 PUFA) are promising candidates, showing potential to protect the skin from UVR injury through a range of mechanisms. In this review, we discuss the biological actions of n-3 PUFA in the context of skin protection from acute and chronic UVR overexposure and describe how emerging new technologies such as nutrigenomics and lipidomics assist our understanding of the contribution of such nutrients to skin health.
    • On lipidomic methodologies [Editorial]

      Nicolaou, Anna (Wiley, 2009)
    • On the effective number of tracked trajectories in normal human vision.

      Tripathy, Srimant P.; Narasimhan, Sathyasri; Barrett, Brendan T. (2007)
      Z. W. Pylyshyn and R. W. Storm (1988) have shown that human observers can accurately track four to five items at a time. However, when a threshold paradigm is used, observers are unable to track more than a single trajectory accurately (S. P. Tripathy & B. T. Barrett, 2004). This difference between the two studies is examined systematically using substantially suprathreshold stimuli. The stimuli consisted of one (Experiment 1) or more (Experiments 2 and 3) bilinear target trajectories embedded among several linear distractor trajectories. The target trajectories deviated clockwise (CW) or counterclockwise (CCW) (by 19°, 38°, or 76° in Experiments 1 and 2 and by 19°, 38°, or 57° in Experiment 3), and observers reported the direction of deviation. From the percentage of correct responses, the ¿effective¿ number of tracked trajectories was estimated for each experimental condition. The total number of trajectories in the stimulus and the number of deviating trajectories had only a small effect on the effective number of tracked trajectories; the effective number tracked was primarily influenced by the angle of deviation of the targets and ranged from four to five trajectories for a ±76° deviation to only one to two trajectories for a ±19° deviation, regardless of whether the different magnitudes of deviation were blocked (Experiment 2) or interleaved (Experiment 3). Simple hypotheses based on ¿averaging of orientations,¿ ¿preallocation of resources,¿ or pop-out, crowding, or masking of the target trajectories are unlikely to explain the relationship between the effective number tracked and the angle of deviation of the target trajectories. This study reconciles the difference between the studies cited above in terms of the number of trajectories that can be tracked at a time.
    • On the importance of blind testing in archaeological science: the example from lithic functional studies

      Evans, Adrian A. (2014)
      Blind-testing is an important tool that should be used by all analytical fields as an approach for validating method. Several fields do this well outside of archaeological science. It is unfortunate that many applied methods do not have a strong underpinning built on, what should be considered necessary, blind-testing. Historically lithic microwear analysis has been subjected to such testing, the results of which stirred considerable debate. However, putting this aside, it is argued here that the tests have not been adequately exploited. Too much attention has been focused on basic results and the implications of those rather than using the tests as a powerful tool to improve the method. Here the tests are revisited and reviewed in a new light. This approach is used to highlight specific areas of methodological weakness that can be targeted by developmental research. It illustrates the value in having a large dataset of consistently designed blind-tests in method evaluation and suggests that fields such as lithic microwear analysis would greatly benefit from such testing. Opportunity is also taken to discuss recent developments in quantitative methods within lithic functional studies and how such techniques might integrate with current practices.
    • On the origin of the Murchison meteorite phosphonates. Implications for pre-biotic chemistry.

      Gorrell, I.B.; Wang, Liming; Marks, Alison J.; Bryant, D.E.; Bouillot, F; Goddard, A; Heard, D.E.; Kee, T.P. (2006)
      Ab initio calculations, combined with experimental studies on the anaerobic hydrolysis of phosphaalkynes under thermal and photochemical conditions suggest a potential, exogenous source of reduced oxidation state phosphorus for the early Earth.
    • One-Pot Stepwise Approach to β-Enaminoketoesters through “Masked” 1,3-Aza-Dipoles

      Yan, Z.; Wu, Na (Anna); Liang, D.; Wang, H.; Pan, Y. (2014-08-01)
      t-BuOK-mediated rearrangement of 1,3-ketoesters with 2-(azidomethyl) aromatics in a two-step, one-pot telescoped sequence affords β-enaminoketoesters in moderate to good yields. A novel pathway is proposed in which the umpolung of the azide is achieved from electrophilicity to nucleophilicity via deprotonation and undergoes nucleophilic attack onto the 1,3-ketoester.
    • One-Pot Synthesis of Highly Emissive Dipyridinium Dihydrohelicenes

      Santoro, A.; Lord, Rianne M.; Loughrey, J.J.; McGowan, P.C.; Halcrow, M.A.; Henwood, A.F.; Thomson, C.; Zysman-Colman, E. (2015-05)
      Condensation of a pyridyl-2-carbaldehyde derivative with 2-(bromoethyl)amine hydrobromide gave tetracyclic pyrido[1,2-a]pyrido[1’,2’:3,4]imidazo-[2,1-c]-6,7-dihydropyrazinium dications in excellent yields. Crystal structures and NOE data demonstrated the helical character of the dications, the dihedral angles between the two pyrido groups ranging from 28–458. An intermediate in the synthesis was also characterized. A much brighter emission compared to literature helicenes has been found, with quantum yields as high as 60% in the range of l=460– 600 nm. Preliminary cytotoxicity studies against HT-29 cancer cells demonstrated moderate-to-good activity, with IC50 values 12–30x that of cisplatin.
    • Opioid prescribing for cancer patients in the last year of life: a longitudinal population cohort study

      Ziegler, Lucy; Mulvey, M.; Blenkinsopp, Alison; Petty, Duncan R.; Bennett, M.I. (2015-11)
      We linked UK cancer registry data with the corresponding electronic primary care medical records of 6080 patients who died of cancer over a 7-year period in a large United Kingdom city. We extracted all prescriptions for analgesics issued to each patient in the linked cohort during the 12 months before death and analysed the extent and duration of strong opioid treatment with clinical and patient characteristics. Strong opioids were prescribed for 48% of patients in the last year of life. Median interval between first prescription of a strong opioid and death was 9 weeks (interquartile range 3-23). Strong opioid prescribing was not influenced by cancer type, duration of illness, or gender but was adversely influenced by older age. Compared with patients who died in a hospice, those who died in a hospital were 60% less likely to receive a strong opioid in primary care before admission (relative risk ratio 0.4, CI 0.3-0.5, P < 0.01). The study provides the first detailed analysis of the relatively late onset and short duration of strong opioid treatment in patients with cancer before death in a representative UK cohort. This pattern of prescribing does not match epidemiological data which point to earlier onset of pain. Although persistent undertreatment of cancer pain is well documented, this study suggests that strategies for earlier pain assessment and initiation of strong opioid treatment in community-based patients with cancer could help to improve pain outcomes.
    • Opioid receptor involvement in the adaptation to motion sickness in Suncus murinus.

      Javid, Farideh A.; Naylor, Robert J. (2001)
      The aim of the present study was to investigate an opioid receptor involvement in the adaptation response to motion sickness in Suncus murinus. Different groups of animals were treated intraperitoneally with either saline, morphine (0.1 and 1.0 mg/kg), naloxone (1.0, 10.0 and 5.0 mg/kg) or a combination of naloxone plus morphine in the absence or 30 min prior to a horizontal motion stimulus of I Hz and 40 mm amplitude. For the study of adaptation, different groups received saline on the first trial, and in subsequent trials (every 2 days) they received either saline, naloxone (1.0 and 10.0 mg/kg, ip) or morphine (0.1 mg/kg, ip) 30 min prior to the motion stimulus. Pretreatment with morphine caused a dose-related reduction in emesis induced by a single challenge to a motion stimulus. Pretreatment with naloxone alone did not induce emesis in its own right nor did it modify emesis induced by a single challenge to a motion stimulus. However, pretreatment with naloxone (5.0 mg/kg, ip) revealed an emetic response to morphine (P<.001) (1.0 mg/kg, ip) and antagonised the reduction of motion sickness induced by morphine. In animals that received saline or naloxone (1.0 mg/kg), a motion stimulus inducing emesis decreased the responsiveness of animals to a second and subsequent motion stimulus challenge when applied every 2 days for 11 trials. However, the animals receiving naloxone 10.0 mg/kg prior to the second and subsequent challenges showed no significant reduction in the intensity of emesis compared to the first trial. The data are revealing of an emetic potential of morphine when administered in the presence of a naloxone pretreatment. The administration of naloxone is also revealing of an additional inhibitory opioid system whose activation by endogenous opioid(s) may play a role in the adaptation to motion sickness on repeated challenge in S. murinus.
    • Optical actuation of inorganic/organic interfaces: comparing peptide-azobenzene ligand reconfiguration on gold and silver nanoparticles

      Palafox-Hernandez, J.P.; Lim, C-K.; Tang, Z.; Drew, K.L.M.; Hughes, Zak E.; Li, Y.; Swihart, M.T.; Prasad, P.N.; Knecht, M.R.; Walsh, T.R. (2016-01-13)
      Photoresponsive molecules that incorporate peptides capable of material-specific recognition provide a basis for biomolecule-mediated control of the nucleation, growth, organization, and activation of hybrid inorganic/organic nanostructures. These hybrid molecules interact with the inorganic surface through multiple noncovalent interactions which allow reconfiguration in response to optical stimuli. Here, we quantify the binding of azobenzene-peptide conjugates that exhibit optically triggered cis-trans isomerization on Ag surfaces and compare to their behavior on Au. These results demonstrate differences in binding and switching behavior between the Au and Ag surfaces. These molecules can also produce and stabilize Au and Ag nanoparticles in aqueous media where the biointerface can be reproducibly and reversibly switched by optically triggered azobenzene isomerization. Comparisons of switching rates and reversibility on the nanoparticles reveal differences that depend upon whether the azobenzene is attached at the peptide N- or C-terminus, its isomerization state, and the nanoparticle composition. Our integrated experimental and computational investigation shows that the number of ligand anchor sites strongly influences the nanoparticle size. As predicted by our molecular simulations, weaker contact between the hybrid biomolecules and the Ag surface, with fewer anchor residues compared with Au, gives rise to differences in switching kinetics on Ag versus Au. Our findings provide a pathway toward achieving new remotely actuatable nanomaterials for multiple applications from a single system, which remains difficult to achieve using conventional approaches.
    • Optical control of nanoparticle catalysis influenced by photoswitch positioning in hybrid peptide capping ligands

      Lawrence, R.L.; Hughes, Zak E.; Cendan, V.J.; Liu, Y.; Lim, C.K.; Prasad, P.N.; Swihart, M.T.; Walsh, T.R.; Knecht, M.R. (2018-10)
      Here we present an in-depth analysis of structural factors that modulate peptide-capped nanoparticle catalytic activity via optically driven structural reconfiguration of the biointerface present at the particle surface. Six different sets of peptide-capped Au nanoparticles were prepared, in which an azobenzene photoswitch was incorporated into one of two well-studied peptide sequences with known affinity for Au, each at one of three different positions: The N- or C-terminus, or mid-sequence. Changes in the photoswitch isomerization state induce a reversible structural change in the surface-bound peptide, which modulates the catalytic activity of the material. This control of reactivity is attributed to changes in the amount of accessible metallic surface area available to drive the reaction. This research specifically focuses on the effect of the peptide sequence and photoswitch position in the biomolecule, from which potential target systems for on/off reactivity have been identified. Additionally, trends associated with photoswitch position for a peptide sequence (Pd4) have been identified. Integrating the azobenzene at the N-terminus or central region results in nanocatalysts with greater reactivity in the trans and cis conformations, respectively; however, positioning the photoswitch at the C-terminus gives rise to a unique system that is reactive in the trans conformation and partially deactivated in the cis conformation. These results provide a fundamental basis for new directions in nanoparticle catalyst development to control activity in real time, which could have significant implications in the design of catalysts for multistep reactions using a single catalyst. Additionally, such a fine level of interfacial structural control could prove to be important for applications beyond catalysis, including biosensing, photonics, and energy technologies that are highly dependent on particle surface structures.