258 research outputs found

    Membrane-protein crystallization in cubo: Temperature-dependent phase behaviour of monoolein-detergent mixtures

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    The lipidic cubic phase of monoolein has proved to be a matrix well suited to the production of three-dimensional crystals of membrane proteins. It consists of a single continuous bilayer, which is contorted in three-dimensional space and separates two distinct water channels. It has previously been proposed that on the addition of precipitants, membrane proteins embedded in the cubic phase migrate through the matrix to nucleation sites and that this process is dependent upon the stability of the lipidic cubic phase. Here, the effect of detergent type (C-8-C-12 glucosides, C-8-C-12 maltosides and C-7 thioglucoside) and concentration (1-3 x the critical micelle concentration; CMC) on cubic phase stability are reported in the form of the temperature-dependent phase behaviour (268-313 K) in 40% aqueous solution. The results are tabulated to show the best monoolein (MO)-detergent mixtures, mixing temperatures and crystallization temperatures identified. Monoolein-detergent mixtures suited for low-temperature in cubo crystallization of temperature-sensitive proteins are also reported for the first time. These mixtures can be prepared at low temperatures (mixed at less than or equal to 288 K) and remain stable at 277 K for a period of at least one month. They include MO- heptyl thioglucoside (1x and 3x CMC), MO-nonyl glucoside (3 x CMC), MO-octyl maltoside (3 x CMC), MO-nonyl maltoside (1 x CMC) and MO-decyl maltoside (1 x CMC)

    Effect of initiating drug treatment on the risk of drug-related poisoning death and acquisitive crime among offending heroin users.

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    BACKGROUND: A recent Cochrane review of randomised trials identified a lack of evidence for interventions provided to drug-using offenders. We use routine data to address whether contact with treatment services reduces heroin users' likelihood of a future acquisitive offence or drug-related poisoning (DRP) death. METHODS: Heroin-users were identified from probation assessments and linked to drug-treatment, mortality and offending records. The study cohort was selected to ensure that the subject was not: in prison, in treatment or had recently left treatment. Subjects were classed as initiators if they attended a triage appointment within two weeks of their assessment; non-initiators otherwise. Initiator and non-initiators were compared over a maximum of one year, with respect to their risk of recorded acquisitive offence or DRP-death. Balance was sought using propensity score matching and missing data were accounted for using multiple imputation. RESULTS: Nine percent of assessments identified for analysis were classed as initiators. Accounting for observed confounding and missing data, there was a reduction in DRPs associated with initiator assessments, however there was uncertainty around this estimate such that a null-effect could not be ruled out (HR: 0.42, 95% CI 0.17-1.04). There was no evidence of a decrease in the recidivism risk, in fact the analysis showed a small increase (HR: 1.10, 95% CI 1.02-1.18). CONCLUSION: For heroin-using offenders, initial contact with treatment services does not appear to reduce the likelihood of a future acquisitive offence

    Chemical variations in Quercus pollen as a tool for taxonomic identification: Implications for long-term ecological and biogeographical research

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    Aim Fossil pollen is an important tool for understanding biogeographical patterns in the past, but the taxonomic resolution of the fossil‐pollen record may be limited to genus or even family level. Chemical analysis of pollen grains has the potential to increase the taxonomic resolution of pollen analysis, but present‐day chemical variability is poorly understood. This study aims to investigate whether a phylogenetic signal is present in the chemical variations of Quercus L. pollen and to assess the prospects of chemical techniques for identification in biogeographical research. Location Portugal. Taxon Six taxa (five species, one subspecies) of Quercus L., Q. faginea, Q. robur, Q. robur ssp. estremadurensis, Q. coccifera, Q. rotundifolia and Q. suber belonging to three sections: Cerris, Ilex and Quercus (Denk, Grimm, Manos, Deng, & Hipp, 2017). Methods We collected pollen samples from 297 individual Quercus trees across a 4° (~450 km) latitudinal gradient and determined chemical differences using Fourier‐transform infrared spectroscopy (FTIR). We used canonical powered partial least squares regression (CPPLS) and discriminant analysis to describe within‐ and between‐species chemical variability. Results We find clear differences in the FTIR spectra from Quercus pollen at the section level (Cerris: ~98%; Ilex: ~100%; Quercus: ~97%). Successful discrimination is based on spectral signals related to lipids and sporopollenins. However, discrimination of species within individual Quercus sections is more challenging: overall, species recall is ~76% and species misidentifications within sections lie between 18% and 31% of the test set. Main Conclusions Our results demonstrate that subgenus level differentiation of Quercus pollen is possible using FTIR methods, with successful classification at the section level. This indicates that operator‐independent FTIR approaches can surpass traditional morphological techniques using light microscopy. Our results have implications both for providing new insights into past colonization pathways of Quercus, and likewise for forecasting future responses to climate change. However, before FTIR techniques can be applied more broadly across palaeoecology and biogeography, our results also highlight a number of research challenges that still need to be addressed, including developing sporopollenin‐specific taxonomic discriminators and determining a more complete understanding of the effects of environmental variation on pollen‐chemical signatures in Quercus.publishedVersio

    CCR5 Is Essential for NK Cell Trafficking and Host Survival following Toxoplasma gondii Infection

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    The host response to intracellular pathogens requires the coordinated action of both the innate and acquired immune systems. Chemokines play a critical role in the trafficking of immune cells and transitioning an innate immune response into an acquired response. We analyzed the host response of mice deficient in the chemokine receptor CCR5 following infection with the intracellular protozoan parasite Toxoplasma gondii. We found that CCR5 controls recruitment of natural killer (NK) cells into infected tissues. Without this influx of NK cells, tissues from CCR5-deficient (CCR5(−/−)) mice were less able to generate an inflammatory response, had decreased chemokine and interferon γ production, and had higher parasite burden. As a result, CCR5(−/−) mice were more susceptible to infection with T. gondii but were less susceptible to the immune-mediated tissue injury seen in certain inbred strains. Adoptive transfer of CCR5(+/+) NK cells into CCR5(−/−) mice restored their ability to survive lethal T. gondii infection and demonstrated that CCR5 is required for NK cell homing into infected liver and spleen. This study establishes CCR5 as a critical receptor guiding NK cell trafficking in host defense

    Plasma Complement Components and Activation Fragments: Associations with Age-Related Macular Degeneration Genotypes and Phenotypes

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    Several genes encoding complement system components and fragments are associated with age-related macular degeneration (AMD). This study was conducted to determine whether alterations in circulating levels of these markers of complement activation and regulation are also independently associated with advanced AMD and whether they are related to AMD genotypes

    Effect of vessel wettability on the foamability of "ideal" surfactants and "real-world" beer heads

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    The ability to tailor the foaming properties of a solution by controlling its chemical composition is highly desirable and has been the subject of extensive research driven by a range of applications. However, the control of foams by varying the wettability of the foaming vessel has been less widely reported. This work investigates the effect of the wettability of the side walls of vessels used for the in situ generation of foam by shaking aqueous solutions of three different types of model surfactant systems (non-ionic, anionic and cationic surfactants) along with four different beers (Guinness Original, Banks’s Bitter, Bass No 1 and Harvest Pale). We found that hydrophilic vials increased the foamability only for the three model systems but increased foam stability for all foams except the model cationic system. We then compared stability of beer foams produced by shaking and pouring and demonstrated weak qualitative agreement between both foam methods. We also showed how wettability of the glass controls bubble nucleation for beers and champagne and used this effect to control exactly where bubbles form using simple wettability patterns
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