Imaging the Single Cell Dynamics of CD4+ T Cell Activation by Dendritic Cells in Lymph Nodes

The adaptive immune response is initiated in secondary lymphoid organs by contact between antigen-bearing dendritic cells (DCs) and antigen-specific CD4+ T cells. However, there is scant information regarding the single cell dynamics of this process in vivo. Using two-photon microscopy, we imaged the real-time behavior of naive CD4+ T cells and in vivo–labeled DCs in lymph nodes during a robust T cell response. In the first 2 h after entry into lymph nodes, T cells made short-lived contacts with antigen-bearing DCs, each contact lasting an average of 11–12 min and occurring mainly on dendrites. Altered patterns of T cell motility during this early stage of antigen recognition promoted serial engagement with several adjacent DCs. Subsequently, T cell behavior progressed through additional distinct stages, including long-lived clusters, dynamic swarms, and finally autonomous migration punctuated by cell division. These observations suggest that the immunological synapse in native tissues is remarkably fluid, and that stable synapses form only at specific stages of antigen presentation to T cells. Furthermore, the serial nature of these interactions implies that T cells activate by way of multiple antigen recognition events

Message on a bottle: are alcohol warning labels about cancer appropriate?

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background Although most Australians are unaware of the risk, there is strong evidence for a direct link between alcohol consumption and many types of cancer. Warning labels on alcohol products have been proposed as a cost-effective strategy to inform the community of this health risk. We aimed to identify how Australians might respond to such an approach. Methods We conducted a national online survey canvassing responses to four separate cancer warning messages on labels. The graphically presented messages were informed by qualitative data from a series of focus groups among self-identified ‘light-to-moderate’ drinkers. For each label, participants were asked their level of agreement with impact statements about raising awareness, prompting conversation, influencing drinking behaviour and educating others about cancer risk. We analysed responses according to demographic and other factors, including self-reported drinking behaviour (using the 3-item Alcohol Use Disorder Test – AUDIT-C – scores). Results Approximately 1600 participants completed the survey, which was open to all Australian adults over a period of 1 month in 2014. Overall, the labels were well received, with the majority (>70 %) agreeing all labels could raise awareness and prompt conversations about the cancer risk associated with alcohol. Around 50 % or less agreed that the labels could influence drinking behaviour, but larger proportions agreed that the labels would prompt them to discuss the issue with family and friends. Although sex, AUDIT-C score and age were significantly associated with agreement on bivariate analysis, multivariate analyses demonstrated that being inclined to act upon warning label recommendations in general was the most important predictor of agreement with all of the impact statements. Having a low AUDIT-C score also predicted agreement that the labels might prompt behaviour change in friends. Conclusions The findings suggest that providing detailed warnings about cancer risk on alcohol products is a viable means of increasing public awareness of the health risks associated with alcohol consumption. Further research is needed to explore the ability of such warnings to influence behavioural intentions and actual drinking behaviour

Efficiency of TTAC's ORTEC IDM

ORNL's Technical Testing and Analysis Center (TTAC) acquired a High Purity Germanium Detector (HPGe) from ORTEC - a variant called an Interchangeable Detection Module (IDM). This detector has excellent energy resolution as well as high intrinsic efficiency. The purpose of this report is to detail the determination of the efficiency curve of the IDM, so future measurements can quantify the (otherwise unknown) activity of sources. Without such a curve, the activity cannot be directly reported by use of the IDM alone - a separate device such as an ion chamber would be required. This builds upon the capability of TTAC. The method for determining the energy-dependent intrinsic efficiency is laid-out in this report. It's noteworthy that this basic technique can be applied to any spectroscopic radiation detector, independent of the specific type (e.g. NaI, CzT, ClYC)

The photochemical thiol-ene reaction as a versatile method for the synthesis of glutathione S-conjugates targeting the bacterial potassium efflux system Kef

Acknowledgements This work was funded by The Wellcome Trust (WT092552MA) and the Oxford University Press John Fell fund (093/380). SJC thanks St Hugh’s College, Oxford, for research support.Peer reviewedPublisher PD

Message on a bottle: are alcohol warning labels about cancer appropriate?

Background Although most Australians are unaware of the risk, there is strong evidence for a direct link between alcohol consumption and many types of cancer. Warning labels on alcohol products have been proposed as a cost-effective strategy to inform the community of this health risk. We aimed to identify how Australians might respond to such an approach. Methods We conducted a national online survey canvassing responses to four separate cancer warning messages on labels. The graphically presented messages were informed by qualitative data from a series of focus groups among self-identified ‘light-to-moderate’ drinkers. For each label, participants were asked their level of agreement with impact statements about raising awareness, prompting conversation, influencing drinking behaviour and educating others about cancer risk. We analysed responses according to demographic and other factors, including self-reported drinking behaviour (using the 3-item Alcohol Use Disorder Test – AUDIT-C – scores). Results Approximately 1600 participants completed the survey, which was open to all Australian adults over a period of 1 month in 2014. Overall, the labels were well received, with the majority (>70 %) agreeing all labels could raise awareness and prompt conversations about the cancer risk associated with alcohol. Around 50 % or less agreed that the labels could influence drinking behaviour, but larger proportions agreed that the labels would prompt them to discuss the issue with family and friends. Although sex, AUDIT-C score and age were significantly associated with agreement on bivariate analysis, multivariate analyses demonstrated that being inclined to act upon warning label recommendations in general was the most important predictor of agreement with all of the impact statements. Having a low AUDIT-C score also predicted agreement that the labels might prompt behaviour change in friends. Conclusions The findings suggest that providing detailed warnings about cancer risk on alcohol products is a viable means of increasing public awareness of the health risks associated with alcohol consumption. Further research is needed to explore the ability of such warnings to influence behavioural intentions and actual drinking behaviour

Opposite variations in fumarate and malate dominate metabolic phenotypes of Arabidopsis salicylate mutants with abnormal biomass under chilling

In chilling conditions (5 degrees C), salicylic acid (SA)-deficient mutants (sid2, eds5 and NahG) of Arabidopsis thaliana produced more biomass than wild type (Col-0), whereas the SA overproducer cpr1 was extremely stunted. The hypothesis that these phenotypes were reflected in metabolism was explored using 600MHz H-1 nuclear magnetic resonance (NMR) analysis of unfractionated polar shoot extracts. Biomass-related metabolic phenotypes were identified as multivariate data models of these NMR fingerprints'. These included principal components that correlated with biomass. Also, partial least squares-regression models were found to predict the relative size of plants in previously unseen experiments in different light intensities, or relative size of one genotype from the others. The dominant signal in these models was fumarate, which was high in SA-deficient mutants, intermediate in Col-0 and low in cpr1 at 5 degrees C. Among signals negatively correlated with biomass, malate was prominent. Abundance of transcripts of the FUM2 cytosolic fumarase (At5g50950) showed strong positive correlation with fumarate levels and with biomass, whereas no significant differences were found for the FUM1 mitochondrial fumarase (At2g47510). It was confirmed that the morphological effects of SA under chilling find expression in the metabolome, with a role of fumarate highlighted

Dynamic Evolution of Permeability in Response to Chemo‐Mechanical Compaction

Pressure‐solution creep is an important fluid‐mediated deformation mechanism, causing chemo‐mechanical transformations and porosity and permeability changes in rocks. The presence of phyllosilicates, in particular, has previously been hypothesized to further reduce porosity and pore connectivity. Nevertheless, a full characterization of the spatio‐temporal evolution of permeability during this process has yet to be reported. A pure NaCl aggregate and a mixture of NaCl and biotite were deformed through pressure‐solution creep while monitoring their microstructural evolution through computed X‐ray micro‐tomography. The evolution of permeability and fluid velocity of the samples were computed by using the pore geometries from the X‐ray micro‐tomography as input for the Lattice‐Boltzmann modeling. The results indicate that, as deformation proceeds, porosity and permeability decrease in both samples. In the salt ‐biotite sample pressure solution creep causes the formation of a compaction band perpendicular to the direction of loading, forming a barrier for permeability. Along the other two directions, pore connectivity and permeability are retained in the marginal salt layers, making the sample strongly anisotropic. The presence of biotite controls the way pore coordination number evolves and hence, the connectivity of the pathways. Biotite flakes create an enhanced porosity decrease leading to compaction and reduction of pore connectivity. This reduction in porosity affects local stresses and local contact areas, reducing over time the driving force. According to a texture‐porosity process, the reduction in porosity causes salt ions to dissolve in the marginal salt and precipitate within the biotite‐bearing layer, where the bulk volume of salt grains increases over time