Thermal Destabilization of Azurin by Fatty Acid Ionic Liquids

Azurin is a mixed-structure redox protein involved in bacterial denitrification. Previous studies have shown that azurin is destabilized by imidazolium chloride ionic liquids (ImCl ILs) that can form micelles in aqueous solution, likely by micellar encapsulation. In these ImCl ILs the micelles form from the imidazolium cations. A relatively new class of ionic liquids is fatty acid ionic liquids (FAILs), in which the anion is a fatty acid. In FAILs micelles can form from the fatty acid anions. This presentation presents the results of a thermal unfolding study of azurin in the presence of FAILs in solution. The FAILs tetramethylguanidinium decanoate and choline decanoate both strongly destabilize azurin when present above their critical micelle concentrations, while decanoic acid alone does not affect azurin (at the same concentration). The results point to the special nature of the FAILs and their interactions with the azurin structure and may be related to how the protein is encapsulated by FAIL micelles

Moving beyond the distinction between concrete and abstract concepts

From the perspective of the situated conceptualization framework, the primary purpose of concepts is for categorizing and integrating elements of situations to support goal-directed action (including communication and social interaction). To the extent that important situational elements are categorized and integrated properly, effective goal-directed action follows. Over time, frequent patterns of co-occurring concepts within situations become established in memory as situated conceptualizations, conditioning the conceptual system and producing habitual patterns of conceptual processing. As a consequence, individual concepts are most basically represented within patterns of concepts that become entrained with specific kinds of physical situations. In this framework, the concrete versus abstract distinction between concepts is no longer useful, with two other distinctions becoming important instead: (i) external versus internal situational elements, (ii) situational elements versus situational integrations. Whereas concepts for situational elements originate in distributed neural networks that provide continual feeds about components of situations, concepts for situational integrations originate in association areas that establish temporal co-occurrence relations between situational elements, both external and internal. We propose that studying concepts in the context of situated action is necessary for establishing complete accounts of them, and that continuing to study concepts in isolation is likely to provide relatively incomplete and distorted accounts. This article is part of the theme issue ‘Varieties of abstract concepts: development, use and representation in the brain’

Standard Neutrino Spectrum from B-8 Decay

We present a systematic evaluation of the shape of the neutrino energy spectrum produced by beta-decay of $^8$B. We place special emphasis on determining the range of uncertainties permitted by existing laboratory data and theoretical ingredients (such as forbidden and radiative corrections). We review and compare the available experimental data on the $^8$B$(\beta^+){}^8$Be$(2\alpha)$ decay chain. We analyze the theoretical and experimental uncertainties quantitatively. We give a numerical representation of the best-fit (standard-model) neutrino spectrum, as well as two extreme deviations from the standard spectrum that represent the total (experimental and theoretical) effective $\pm3\sigma$ deviations. Solar neutrino experiments that are currently being developed will be able to measure the shape of the $^8$B neutrino spectrum above about 5 MeV. An observed distortion of the $^8$B solar neutrino spectrum outside the range given in the present work could be considered as evidence, at an effective significance level greater than three standard deviations, for physics beyond the standard electroweak model. We use the most recent available experimental data on the Gamow--Teller strengths in the $A=37$ system to calculate the $^8$B neutrino absorption cross section on chlorine: $\sigma_{\rm Cl}=(1.14\pm0.11)\times10^{-42}$~cm$^2$ ($\pm3\sigma$ errors). The chlorine cross section is also given as a function of the neutrino energy. The $^8$B neutrino absorption cross section in gallium is $\sigma_{\rm Ga}=(2.46^{+2.1}_{-1.1})\times10^{-42}$ cm$^2$ ($\pm3\sigma$ errors).Comment: Revised version, to appear in Phys. Rev.

Natural history of Arabidopsis thaliana and oomycete symbioses

Molecular ecology of plant–microbe interactions has immediate significance for filling a gap in knowledge between the laboratory discipline of molecular biology and the largely theoretical discipline of evolutionary ecology. Somewhere in between lies conservation biology, aimed at protection of habitats and the diversity of species housed within them. A seemingly insignificant wildflower called Arabidopsis thaliana has an important contribution to make in this endeavour. It has already transformed botanical research with deepening understanding of molecular processes within the species and across the Plant Kingdom; and has begun to revolutionize plant breeding by providing an invaluable catalogue of gene sequences that can be used to design the most precise molecular markers attainable for marker-assisted selection of valued traits. This review describes how A. thaliana and two of its natural biotrophic parasites could be seminal as a model for exploring the biogeography and molecular ecology of plant–microbe interactions, and specifically, for testing hypotheses proposed from the geographic mosaic theory of co-evolution

Dietary Supplementation with Soluble Plantain Non-Starch Polysaccharides Inhibits Intestinal Invasion of Salmonella Typhimurium in the Chicken

Soluble fibres (non-starch polysaccharides, NSP) from edible plants but particularly plantain banana (Musa spp.), have been shown in vitro and ex vivo to prevent various enteric pathogens from adhering to, or translocating across, the human intestinal epithelium, a property that we have termed contrabiotic. Here we report that dietary plantain fibre prevents invasion of the chicken intestinal mucosa by Salmonella. In vivo experiments were performed with chicks fed from hatch on a pellet diet containing soluble plantain NSP (0 to 200 mg/d) and orally infected with S.Typhimurium 4/74 at 8 d of age. Birds were sacrificed 3, 6 and 10 d post-infection. Bacteria were enumerated from liver, spleen and caecal contents. In vitro studies were performed using chicken caecal crypts and porcine intestinal epithelial cells infected with Salmonella enterica serovars following pre-treatment separately with soluble plantain NSP and acidic or neutral polysaccharide fractions of plantain NSP, each compared with saline vehicle. Bacterial adherence and invasion were assessed by gentamicin protection assay. In vivo dietary supplementation with plantain NSP 50 mg/d reduced invasion by S.Typhimurium, as reflected by viable bacterial counts from splenic tissue, by 98.9% (95% CI, 98.1–99.7; P<0.0001). In vitro studies confirmed that plantain NSP (5–10 mg/ml) inhibited adhesion of S.Typhimurium 4/74 to a porcine epithelial cell-line (73% mean inhibition (95% CI, 64–81); P<0.001) and to primary chick caecal crypts (82% mean inhibition (95% CI, 75–90); P<0.001). Adherence inhibition was shown to be mediated via an effect on the epithelial cells and Ussing chamber experiments with ex-vivo human ileal mucosa showed that this effect was associated with increased short circuit current but no change in electrical resistance. The inhibitory activity of plantain NSP lay mainly within the acidic/pectic (homogalacturonan-rich) component. Supplementation of chick feed with plantain NSP was well tolerated and shows promise as a simple approach for reducing invasive salmonellosis

Factors Influencing Engagement, Perceived Usefulness and Behavioral Mechanisms Associated with a Text Message Support Program

Introduction Many studies have now demonstrated the efficacy of text messaging in positively changing behaviours. We aimed to identify features and factors that explain the effectiveness of a successful text messaging program in terms of user engagement, perceived usefulness, behavior change and program delivery preferences. Methods Mixed methods qualitative design combining four data sources; (i) analytic data extracted directly from the software system, (ii) participant survey, (iii) focus groups to identify barriers and enablers to implementation and mechanisms of effect and (iv) recruitment screening logs and text message responses to examine engagement. This evaluation was conducted within the TEXT ME trial—a parallel design, single-blind randomized controlled trial (RCT) of 710 patients with coronary heart disease (CHD). Qualitative data were interpreted using inductive thematic analysis. Results 307/352 (87% response rate) of recruited patients with CHD completed the program evaluation survey at six months and 25 participated in a focus group. Factors increasing engagement included (i) ability to save and share messages, (ii) having the support of providers and family, (iii) a feeling of support through participation in the program, (iv) the program being initiated close to the time of a cardiovascular event, (v) personalization of the messages, (vi) opportunity for initial face-to-face contact with a provider and (vii) that program and content was perceived to be from a credible source. Clear themes relating to program delivery were that diet and physical activity messages were most valued, four messages per week was ideal and most participants felt program duration should be provided for at least for six months or longer. Conclusions This study provides context and insight into the factors influencing consumer engagement with a text message program aimed at improving health-related behavior. The study suggests program components that may enhance potential success but will require integration at the development stage to optimize up-scaling

Validation of CIP2A as a Biomarker of Subsequent Disease Progression and Treatment Failure in Chronic Myeloid Leukaemia

From MDPI via Jisc Publications RouterHistory: accepted 2021-04-01, pub-electronic 2021-04-29Publication status: PublishedFunder: Bristol-Myers Squibb; Grant(s): CA180 659Background: It would be clinically useful to prospectively identify the risk of disease progression in chronic myeloid leukaemia (CML). Overexpression of cancerous inhibitor of protein phosphatase 2A (PP2A) (CIP2A) protein is an adverse prognostic indicator in many cancers. Methods: We examined CIP2A protein levels in diagnostic samples from the SPIRIT2 trial in 172 unselected patients, of whom 90 received imatinib and 82 dasatinib as first-line treatment. Results: High CIP2A levels correlated with inferior progression-free survival (p = 0.04) and with worse freedom from progression (p = 0.03), and these effects were confined to dasatinib recipients. High CIP2A levels were associated with a six-fold higher five-year treatment failure rate than low CIP2A levels (41% vs. 7.5%; p = 0.0002), in both imatinib (45% vs. 11%; p = 0.02) and dasatinib recipients (36% vs. 4%; p = 0.007). Imatinib recipients with low CIP2A levels had a greater risk of treatment failure (p = 0.0008). CIP2A levels were independent of Sokal, Hasford, EUTOS (EUropean Treatment and Outcome Study), or EUTOS long-term survival scores (ELTS) or the presence of major route cytogenetic abnormalities. No association was seen between CIP2A levels and time to molecular response or the levels of the CIP2A-related proteins PP2A, SET, SET binding protein 1 (SETBP1), or AKT. Conclusions: These data confirm that high diagnostic CIP2A levels correlate with subsequent disease progression and treatment failure. CIP2A is a simple diagnostic biomarker that may be useful in planning treatment strategies

Gravitational Waves From Known Pulsars: Results From The Initial Detector Era

We present the results of searches for gravitational waves from a large selection of pulsars using data from the most recent science runs (S6, VSR2 and VSR4) of the initial generation of interferometric gravitational wave detectors LIGO (Laser Interferometric Gravitational-wave Observatory) and Virgo. We do not see evidence for gravitational wave emission from any of the targeted sources but produce upper limits on the emission amplitude. We highlight the results from seven young pulsars with large spin-down luminosities. We reach within a factor of five of the canonical spin-down limit for all seven of these, whilst for the Crab and Vela pulsars we further surpass their spin-down limits. We present new or updated limits for 172 other pulsars (including both young and millisecond pulsars). Now that the detectors are undergoing major upgrades, and, for completeness, we bring together all of the most up-to-date results from all pulsars searched for during the operations of the first-generation LIGO, Virgo and GEO600 detectors. This gives a total of 195 pulsars including the most recent results described in this paper.United States National Science FoundationScience and Technology Facilities Council of the United KingdomMax-Planck-SocietyState of Niedersachsen/GermanyAustralian Research CouncilInternational Science Linkages program of the Commonwealth of AustraliaCouncil of Scientific and Industrial Research of IndiaIstituto Nazionale di Fisica Nucleare of ItalySpanish Ministerio de Economia y CompetitividadConselleria d'Economia Hisenda i Innovacio of the Govern de les Illes BalearsNetherlands Organisation for Scientific ResearchPolish Ministry of Science and Higher EducationFOCUS Programme of Foundation for Polish ScienceRoyal SocietyScottish Funding CouncilScottish Universities Physics AllianceNational Aeronautics and Space AdministrationOTKA of HungaryLyon Institute of Origins (LIO)National Research Foundation of KoreaIndustry CanadaProvince of Ontario through the Ministry of Economic Development and InnovationNational Science and Engineering Research Council CanadaCarnegie TrustLeverhulme TrustDavid and Lucile Packard FoundationResearch CorporationAlfred P. Sloan FoundationAstronom

First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data

Spinning neutron stars asymmetric with respect to their rotation axis are potential sources of continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a fully coherent search, based on matched filtering, which uses the position and rotational parameters obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signalto- noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have been developed, allowing a fully coherent search for gravitational waves from known pulsars over a fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of 11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial outliers, further studies show no significant evidence for the presence of a gravitational wave signal. Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for the first time. For an additional 3 targets, the median upper limit across the search bands is below the spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried out so far