Multilayered lipid membrane stacks for biocatalysis using membrane enzymes

Multilayered or stacked lipid membranes are a common principle in biology and have various functional advantages compared to single lipid membranes, such as their ability to spatially organize processes, compartmentalize molecules and greatly increase surface area and hence membrane protein concentration. Here we report on a supramolecular assembly of a multilayered lipid membrane system in which poly-L-lysine electrostatically links negatively charged lipid membranes. When suitable membrane enzymes are incorporated, either an ubiquinol oxidase (cytochrome bo3 from Escherichia coli) or an oxygen tolerant hydrogenase (the membrane-bound hydrogenase from Ralstonia eutropha), cyclic voltammetry (CV) reveals a linear increase in biocatalytic activity with each additional membrane layer. Electron transfer between the enzymes and the electrode is mediated by the quinone pool that is present in the lipid phase. We deduce by atomic force microscopy, CV and fluorescence microscopy that quinones are able to diffuse between the stacked lipid membrane layers via defect sites where the lipid membranes are interconnected. This assembly is akin to that of interconnected thylakoid membranes or the folded lamella of mitochondria and have significant potential for mimicry in biotechnology applications such as energy production or biosensing

End-to-End Joint Antenna Selection Strategy and Distributed Compress and Forward Strategy for Relay Channels

Multi-hop relay channels use multiple relay stages, each with multiple relay nodes, to facilitate communication between a source and destination. Previously, distributed space-time codes were proposed to maximize the achievable diversity-multiplexing tradeoff, however, they fail to achieve all the points of the optimal diversity-multiplexing tradeoff. In the presence of a low-rate feedback link from the destination to each relay stage and the source, this paper proposes an end-to-end antenna selection (EEAS) strategy as an alternative to distributed space-time codes. The EEAS strategy uses a subset of antennas of each relay stage for transmission of the source signal to the destination with amplify and forwarding at each relay stage. The subsets are chosen such that they maximize the end-to-end mutual information at the destination. The EEAS strategy achieves the corner points of the optimal diversity-multiplexing tradeoff (corresponding to maximum diversity gain and maximum multiplexing gain) and achieves better diversity gain at intermediate values of multiplexing gain, versus the best known distributed space-time coding strategies. A distributed compress and forward (CF) strategy is also proposed to achieve all points of the optimal diversity-multiplexing tradeoff for a two-hop relay channel with multiple relay nodes.Comment: Accepted for publication in the special issue on cooperative communication in the Eurasip Journal on Wireless Communication and Networkin

New directions in cellular therapy of cancer: a summary of the summit on cellular therapy for cancer

A summit on cellular therapy for cancer discussed and presented advances related to the use of adoptive cellular therapy for melanoma and other cancers. The summit revealed that this field is advancing rapidly. Conventional cellular therapies, such as tumor infiltrating lymphocytes (TIL), are becoming more effective and more available. Gene therapy is becoming an important tool in adoptive cell therapy. Lymphocytes are being engineered to express high affinity T cell receptors (TCRs), chimeric antibody-T cell receptors (CARs) and cytokines. T cell subsets with more naïve and stem cell-like characteristics have been shown in pre-clinical models to be more effective than unselected populations and it is now possible to reprogram T cells and to produce T cells with stem cell characteristics. In the future, combinations of adoptive transfer of T cells and specific vaccination against the cognate antigen can be envisaged to further enhance the effectiveness of these therapies

Evidence of Differential Allelic Effects between Adolescents and Adults for Plasma High-Density Lipoprotein

A recent meta-analysis of genome-wide association (GWA) studies identified 95 loci that influence lipid traits in the adult population and found that collectively these explained about 25–30% of heritability for each trait. Little is known about how these loci affect lipid levels in early life, but there is evidence that genetic effects on HDL- and LDL-cholesterol (HDL-C, LDL-C) and triglycerides vary with age. We studied Australian adults (N = 10,151) and adolescents (N = 2,363) who participated in twin and family studies and for whom we have lipid phenotypes and genotype information for 91 of the 95 genetic variants. Heterogeneity tests between effect sizes in adult and adolescent cohorts showed an excess of heterogeneity for HDL-C (pHet<0.05 at 5 out of 37 loci), but no more than expected by chance for LDL-C (1 out of 14 loci), or trigycerides (0 out 24). There were 2 (out of 5) with opposite direction of effect in adolescents compared to adults for HDL-C, but none for LDL-C. The biggest difference in effect size was for LDL-C at rs6511720 near LDLR, adolescents (0.021±0.033 mmol/L) and adults (0.157±0.023 mmol/L), pHet = 0.013; followed by ZNF664 (pHet = 0.018) and PABPC4 (pHet = 0.034) for HDL-C. Our findings suggest that some of the previously identified variants associate differently with lipid traits in adolescents compared to adults, either because of developmental changes or because of greater interactions with environmental differences in adults

Genetics of Resistance to the Rust Fungus Coleosporium ipomoeae in Three Species of Morning Glory (Ipomoea)

We examined the genetic basis of resistance to the rust pathogen Coleosporium ipomoea in three host species: Ipomoea purpurea, I. hederacea, and I. coccinea (Convolvulaceae). In crosses between resistant and susceptible individuals, second-generation selfed offspring segregated in ratios that did not differ statistically from the 3∶1 ratio indicative of single-gene resistance with the resistant allele dominant. One out of three crosses between resistant individuals from two different populations revealed that resistance loci differed in the two populations, as evidenced by the production of susceptible individuals among the S2 generation. These results suggest that gene-for-gene interactions contribute substantially to the dynamics of coevolution in this natural pathosystem. They also suggest that evolution of resistance to the same pathogen strain may involve different loci in different Ipomoea populations

Effects of C282Y, H63D, and S65C HFE gene mutations, diet, and life-style factors on iron status in a general Mediterranean population from Tarragona, Spain

Mutations in the HFE gene result in iron overload and can produce hereditary hemochromatosis (HH), a disorder of iron metabolism characterized by increased intestinal iron absorption. Dietary quality, alcoholism and other life-style factors can increase the risk of iron overload, especially among genetically at risk populations. Polymorphisms of the HFE gene (C282Y, H63D and S65C) were measured together with serum ferritin (SF), transferrin saturation (TS) and hemoglobin, to measure iron status, in randomly-selected healthy subjects living in the Spanish Mediterranean coast (n = 815; 425 females, 390 males), 18 to 75 years of age. The intake of dietary components that affect iron absorption was calculated from 3-day dietary records. The presence of C282Y/H63D compound heterozygote that had a prevalence of 2.8% in males and 1.2% in females was associated with an elevated TS and SF. No subject was homozygous for C282Y or S65C. The C282Y heterozygote, H63D heterozygote and homozygote and H63D/S65C compound heterozygote genotypes were associated with increased TS relative to the wild type in the general population. These genotypes together with the alcohol and iron intake increase the indicators of iron status, while calcium intake decreases them. We did not observe any affect of the S65C heterozygote genotype on these levels. All the HFE genotypes except for the S65C heterozygote together with the alcohol, iron and calcium intake affect the indicators of iron status. The C282Y/H63D compound heterozygote genotype has the higher phenotypic expression in our Spanish Mediterranean population

Residual susceptibility to measles among young adults in Victoria, Australia following a national targeted measles-mumps-rubella vaccination campaign

<p>Abstract</p> <p>Background</p> <p>Past measles immunisation policies in Australia have resulted in a cohort of young adults who have been inadequately vaccinated, but who also have low levels of naturally acquired immunity because immunisation programs have decreased the circulation of wild virus. A measles-mumps-rubella (MMR) immunisation campaign aimed at addressing this susceptibility to measles among young adults was conducted in Australia in 2001–2. By estimating age-specific immunity, we aimed to evaluate the success of this campaign in the state of Victoria.</p> <p>Methods</p> <p>We conducted serosurveys after the young adult MMR program at state and national levels to estimate immunity among young adults born between 1968–82. We compared results of the Victorian (state) surveys with the Victorian component of the national surveys and compared both surveys with surveys conducted before the campaign. We also reviewed all laboratory confirmed measles cases in Victoria between 2000–4.</p> <p>Results</p> <p>The Victorian state serosurveys indicated no significant change in immunity of the cohort following the young adult MMR campaign (83.9% immune pre and 85.5% immune post campaign) while the Victorian component of the national serosurvey indicated a significant decline in immunity (91.0% to 84.2%; p = 0.006). Both surveys indicated about 15% susceptibility to measles among young Victorian adults after the campaign. Measles outbreaks in Victoria between 2000–4 confirmed the susceptibility of young adults. Outbreaks involved a median of 2.5 cases with a median age of 24.5 years.</p> <p>Conclusion</p> <p>In Victoria, the young adult MMR program appears to have had no effect on residual susceptibility to measles among the 1968–82 birth cohort. Young adults in Victoria, as in other countries where past immunisation policies have left a residual susceptible cohort, represent a potential problem for the maintenance of measles elimination.</p

Judgment of Learning Accuracy in High-functioning Adolescents and Adults with Autism Spectrum Disorder

This study explored whether adults and adolescents with autism spectrum disorder (ASD) demonstrate difficulties making metacognitive judgments, specifically judgments of learning. Across two experiments, the study examined whether individuals with ASD could accurately judge whether they had learnt a piece of information (in this case word pairs). In Experiment 1, adults with ASD demonstrated typical accuracy on a standard ‘cue-alone’ judgment of learning (JOL) task, compared to age- and IQmatched neurotypical adults. Additionally, in Experiment 2, adolescents with ASD demonstrated typical accuracy on both a standard ‘cue-alone’ JOL task, and a ‘cue-target’ JOL task. These results suggest that JOL accuracy is unimpaired in ASD. These results have important implications for both theories of metacognition in ASD and educational practise

Shape-Based Tracking Allows Functional Discrimination of Two Immune Cell Subsets Expressing the Same Fluorescent Tag in Mouse Lung Explant

Dendritic Cells (DC) represent a key lung immune cell population, which play a critical role in the antigen presenting process and initiation of the adaptive immune response. The study of DCs has largely benefited from the joint development of fluorescence microscopy and knock-in technology, leading to several mouse strains with constitutively labeled DC subsets. However, in the lung most transgenic mice do express fluorescent protein not only in DCs, but also in closely related cell lineages such as monocytes and macrophages. As an example, in the lungs of CX3CR1+/gfp mice the green fluorescent protein is expressed mostly by both CD11b conventional DCs and resident monocytes. Despite this non-specific staining, we show that a shape criterion can discriminate these two particular subsets. Implemented in a cell tracking code, this quantified criterion allows us to analyze the specific behavior of DCs under inflammatory conditions mediated by lipopolysaccharide on lung explants. Compared to monocytes, we show that DCs move slower and are more confined, while both populations do not have any chemotactism-associated movement. We could generalize from these results that DCs can be automatically discriminated from other round-shaped cells expressing the same fluorescent protein in various lung inflammation models