The Electronic and Superconducting Properties of Oxygen-Ordered MgB2 compounds of the form Mg2B3Ox

Possible candidates for the Mg2B3Ox nanostructures observed in bulk of polycrystalline MgB2 (Ref.1) have been studied using a combination of Z-contrast imaging, electron energy loss spectroscopy (EELS) and first-principles calculations. The electronic structures, phonon modes, and electron phonon coupling parameters are calculated for two oxygen-ordered MgB2 compounds of composition Mg2B3O and Mg2B3O2, and compared with those of MgB2. We find that the density of states for both Mg2B3Ox structures show very good agreement with EELS, indicating that they are excellent candidates to explain the observed coherent oxygen precipitates. Incorporation of oxygen reduces the transition temperature and gives calculated TC values of 18.3 K and 1.6 K for Mg2B3O and Mg2B3O2, respectively.Comment: Submitted to PR

Dietary treatment of Crohn’s disease: perceptions of families with children treated by exclusive enteral nutrition, a questionnaire survey

Background: Diet is strongly associated with the aetiology of Crohn’s Disease (CD) and exclusive enteral nutrition (EEN) is the primary induction treatment in paediatric CD. This study explored opinions around the use of EEN and alternative novel, solid food-based diets (SFDs) expressed by paediatric patients with CD, previously treated with EEN and their parents. Methods: This anonymous questionnaire surveyed families of CD patients treated with EEN over 1 year. Two questionnaire forms were completed; one asking the patients’ opinions and another referring to their main carer. This questionnaire explored participants’ demographic characteristics; acceptability of a repeat EEN course to treat a future flare (EEN repeat); their opinion on how difficult EEN would be compared to an example SFD; and their intention to participate in a future clinical trial assessing the therapeutic efficacy of an SFD in CD. Results: Forty-one families of CD patients were approached with 29 sending replies (71%). Most of our participants were positive on completing another EEN course, however the majority would choose an SFD alternative (Patients: 66, Parents:72%). Both patients and their parents rated EEN to be more difficult to adhere to compared to an example SFD (p < 0.05), and their ratings were strongly correlated (EEN:r = 0.83, SFD:r = 0.75, p < 0.001). The majority of our respondents would agree to participate in a clinical trial assessing an SFD’s effectiveness (Patients:79, Parents:72%) for the management of active CD. Conclusions: While patients with CD and their families would accept an EEN repeat, the majority would prefer an SFD alternative. CD families surveyed are supportive of the development of solid food-based dietary treatments

A Natural Chimeric Pseudomonas Bacteriocin with Novel Pore-Forming Activity Parasitizes the Ferrichrome Transporter

Modular bacteriocins represent a major group of secreted protein toxins with a narrow spectrum of activity, involved in interference competition between Gram-negative bacteria. These antibacterial proteins include a domain for binding to the target cell and a toxin module at the carboxy terminus. Self-inhibition of producers is provided by coexpression of linked immunity genes that transiently inhibit the toxin''s activity through formation of bacteriocin-immunity complexes or by insertion in the inner membrane, depending on the type of toxin module. We demonstrate strain-specific inhibitory activity for PmnH, a Pseudomonas bacteriocin with an unprecedented dual-toxin architecture, hosting both a colicin M domain, potentially interfering with peptidoglycan synthesis, and a novel colicin N-type domain, a pore-forming module distinct from the colicin Ia-type domain in Pseudomonas aeruginosa pyocin S5. A downstream-linked gene product confers PmnH immunity upon susceptible strains. This protein, ImnH, has a transmembrane topology similar to that of Pseudomonas colicin M-like and pore-forming immunity proteins, although homology with either of these is essentially absent. The enhanced killing activity of PmnH under iron-limited growth conditions reflects parasitism of the ferrichrome-type transporter for entry into target cells, a strategy shown here to be used as well by monodomain colicin M-like bacteriocins from pseudomonads. The integration of a second type of toxin module in a bacteriocin gene could offer a competitive advantage against bacteria displaying immunity against only one of both toxic activities

Structural and Functional Insights Into the Role of BamD and BamE Within the \u3cem\u3eβ\u3c/em\u3e-Barrel Assembly Machinery in \u3cem\u3eNeisseria gonorrhoeae\u3c/em\u3e

The β-barrel assembly machinery (BAM) is a conserved multicomponent protein complex responsible for the biogenesis of β-barrel outer membrane proteins (OMPs) in Gram-negative bacteria. Given its role in the production of OMPs for survival and pathogenesis, BAM represents an attractive target for the development of therapeutic interventions, including drugs and vaccines against multidrug-resistant bacteria such as Neisseria gonorrhoeae. The first structure of BamA, the central component of BAM, was from N. gonorrhoeae, the etiological agent of the sexually transmitted disease gonorrhea. To aid in pharmaceutical targeting of BAM, we expanded our studies to BamD and BamE within BAM of this clinically relevant human pathogen. We found that the presence of BamD, but not BamE, is essential for gonococcal viability. However, BamE, but not BamD, was cell-surface–displayed under native conditions; however, in the absence of BamE, BamD indeed becomes surface-exposed. Loss of BamE altered cell envelope composition, leading to slower growth and an increase in both antibiotic susceptibility and formation of membrane vesicles containing greater amounts of vaccine antigens. Both BamD and BamE are expressed in diverse gonococcal isolates, under host-relevant conditions, and throughout different phases of growth. The solved structures of Neisseria BamD and BamE share overall folds with Escherichia coli proteins but contain differences that may be important for function. Together, these studies highlight that, although BAM is conserved across Gram-negative bacteria, structural and functional differences do exist across species, which may be leveraged in the development of species-specific therapeutics in the effort to combat multidrug resistance

Structural insight into mitochondrial β-barrel outer membrane protein biogenesis.

In mitochondria, -barrel outer membrane proteins mediate protein import, metabolite transport, lipid transport, and biogenesis. The Sorting and Assembly Machinery (SAM) complex consists of three proteins that assemble as a 1:1:1 complex to fold -barrel proteins and insert them into the mitochondrial outer membrane. We report cryoEM structures of the SAM complex from Myceliophthora thermophila, which show that Sam50 forms a 16-stranded transmembrane -barrel with a single polypeptide-transport associated (POTRA) domain extending into the intermembrane space. Sam35 and Sam37 are located on the cytosolic side of the outer membrane, with Sam35 capping Sam50, and Sam37 interacting extensively with Sam35. Sam35 and Sam37 each adopt a GST-like fold, with no functional, structural, or sequence similarity to their bacterial counterparts. Structural analysis shows how the Sam50 barrel opens a lateral gate to accommodate its substrates

Protein secretion and outer membrane assembly in Alphaproteobacteria

The assembly of β-barrel proteins into membranes is a fundamental process that is essential in Gram-negative bacteria, mitochondria and plastids. Our understanding of the mechanism of β-barrel assembly is progressing from studies carried out in Escherichia coli and Neisseria meningitidis. Comparative sequence analysis suggests that while many components mediating β-barrel protein assembly are conserved in all groups of bacteria with outer membranes, some components are notably absent. The Alphaproteobacteria in particular seem prone to gene loss and show the presence or absence of specific components mediating the assembly of β-barrels: some components of the pathway appear to be missing from whole groups of bacteria (e.g. Skp, YfgL and NlpB), other proteins are conserved but are missing characteristic domains (e.g. SurA). This comparative analysis is also revealing important structural signatures that are vague unless multiple members from a protein family are considered as a group (e.g. tetratricopeptide repeat (TPR) motifs in YfiO, β-propeller signatures in YfgL). Given that the process of the β-barrel assembly is conserved, analysis of outer membrane biogenesis in Alphaproteobacteria, the bacterial group that gave rise to mitochondria, also promises insight into the assembly of β-barrel proteins in eukaryotes

Randomized trial of DVD, telephone, and usual care for increasing mammography adherence

The purpose of this study was to test an intervention to increase mammography screening in women 51-75 years of age who had not received a mammogram in the last 15 months. A total of 1681 women were randomized to (1) a mailed tailored interactive DVD, (2) a computer-tailored telephone counseling, or (3) usual care. Women with income below US$75,000 who were in the interactive DVD group had significantly more mammograms than women in usual care. Women with income above US$75,000 had significantly fewer mammograms than women with income less than US$75,000 regardless of group. Further investigation is needed to understand why women with income above US$75,000 did not show the same benefit of the intervention

Structural insight into mitochondrial β-barrel outer membrane protein biogenesis

Abstract: In mitochondria, β-barrel outer membrane proteins mediate protein import, metabolite transport, lipid transport, and biogenesis. The Sorting and Assembly Machinery (SAM) complex consists of three proteins that assemble as a 1:1:1 complex to fold β-barrel proteins and insert them into the mitochondrial outer membrane. We report cryoEM structures of the SAM complex from Myceliophthora thermophila, which show that Sam50 forms a 16-stranded transmembrane β-barrel with a single polypeptide-transport-associated (POTRA) domain extending into the intermembrane space. Sam35 and Sam37 are located on the cytosolic side of the outer membrane, with Sam35 capping Sam50, and Sam37 interacting extensively with Sam35. Sam35 and Sam37 each adopt a GST-like fold, with no functional, structural, or sequence similarity to their bacterial counterparts. Structural analysis shows how the Sam50 β-barrel opens a lateral gate to accommodate its substrates