Vacuum Stability of the wrong sign (−ϕ6)(-\phi^{6}) Scalar Field Theory

We apply the effective potential method to study the vacuum stability of the bounded from above $(-\phi^{6})$ (unstable) quantum field potential. The stability ($\partial E/\partial b=0)$ and the mass renormalization ($\partial^{2} E/\partial b^{2}=M^{2})$ conditions force the effective potential of this theory to be bounded from below (stable). Since bounded from below potentials are always associated with localized wave functions, the algorithm we use replaces the boundary condition applied to the wave functions in the complex contour method by two stability conditions on the effective potential obtained. To test the validity of our calculations, we show that our variational predictions can reproduce exactly the results in the literature for the $\mathcal{PT}$-symmetric $\phi^{4}$ theory. We then extend the applications of the algorithm to the unstudied stability problem of the bounded from above $(-\phi^{6})$ scalar field theory where classical analysis prohibits the existence of a stable spectrum. Concerning this, we calculated the effective potential up to first order in the couplings in $d$ space-time dimensions. We find that a Hermitian effective theory is instable while a non-Hermitian but $\mathcal{PT}$-symmetric effective theory characterized by a pure imaginary vacuum condensate is stable (bounded from below) which is against the classical predictions of the instability of the theory. We assert that the work presented here represents the first calculations that advocates the stability of the $(-\phi^{6})$ scalar potential.Comment: 21pages, 12 figures. In this version, we updated the text and added some figure

Systems impact of zinc chelation by the epipolythiodioxopiperazine dithiol gliotoxin in Aspergillus fumigatus: a new direction in natural product functionality.

The non-ribosomal peptide gliotoxin, which autoinduces its own biosynthesis, has potent anti-fungal activity, especially in the combined absence of the gliotoxin oxidoreductase GliT and bis-thiomethyltransferase GtmA. Dithiol gliotoxin (DTG) is a substrate for both of these enzymes. Herein we demonstrate that DTG chelates Zn2+ (m/z 424.94), rapidly chelates Zn2+ from Zn(4-(2-pyridylazo)-resorcinol) (Zn(PAR)2) and also inhibits a Zn2+-dependent alkaline phosphatase (AP). Zn2+ addition rescues AP function following DTG-associated inhibition, and pre-incubation of DTG with Zn2+ completely protects AP activity. Zn2+ (1-50 μM) also significantly relieves the potent gliotoxin-mediated inhibition of Aspergillus fumigatus ΔgliT::ΔgtmA (p < 0.05), which infers in vivo dithiol gliotoxin-mediated sequestration of free Zn2+ or chelation from intracellular metalloenzymes as inhibitory mechanisms. Quantitative proteomic analysis revealed that excess Zn2+ alters the effect of gliotoxin on A. fumigatus ΔgliT, with differential abundance of secondary metabolism-associated proteins in the combinatorial condition. GtmA abundance increased 18.8 fold upon co-addition of gliotoxin and Zn2+ compared to gliotoxin alone, possibly to compensate for disruption to GtmA activity, as seen in in vitro assays. Furthermore, DTG effected significant in vitro aggregation of a number of protein classes, including Zn2+-dependent enzymes, while proteins were protected from aggregation by pre-incubating DTG with Zn2+. We conclude that DTG can act in vivo as a Zn2+ chelator, which can significantly impede A. fumigatus growth in the absence of GliT and GtmA

Isolation and characterization of the full-length cDNA encoding a member of a novel cytochrome p450 family (CYP320A1) from the tropical freshwater snail, Biomphalaria glabrata, intermediate host for Schistosoma mansoni

Cytochrome p450s (cyp450s) are a family of structurally related proteins, with diverse functions, including steroid synthesis and breakdown of toxins. This paper reports the full-length sequence of a novel cyp450 gene, the first to be isolated from the tropical freshwater snail Biomphalaria glabrata, an important intermediate host of Schistosoma mansoni. The nucleotide sequence is 2291 bp with a predicted amino acid sequence of 584aa. The sequence demonstrates conserved cyp450 structural motifs, but is sufficiently different from previously reported cyp450 sequences to be given a new classification, CYP320A1. Initially identified as down-regulated in partially resistant snails in response to S. mansoni infection, amplification of this gene using RT-PCR in both totally resistant or susceptible snail lines when exposed to infection, and all tissues examined, suggests ubiquitous expression. Characterization of the first cyp450 from B. glabrata is significant in understanding the evolution of these metabolically important proteins

TaxMan: a taxonomic database manager

BACKGROUND: Phylogenetic analysis of large, multiple-gene datasets, assembled from public sequence databases, is rapidly becoming a popular way to approach difficult phylogenetic problems. Supermatrices (concatenated multiple sequence alignments of multiple genes) can yield more phylogenetic signal than individual genes. However, manually assembling such datasets for a large taxonomic group is time-consuming and error-prone. Additionally, sequence curation, alignment and assessment of the results of phylogenetic analysis are made particularly difficult by the potential for a given gene in a given species to be unrepresented, or to be represented by multiple or partial sequences. We have developed a software package, TaxMan, that largely automates the processes of sequence acquisition, consensus building, alignment and taxon selection to facilitate this type of phylogenetic study. RESULTS: TaxMan uses freely available tools to allow rapid assembly, storage and analysis of large, aligned DNA and protein sequence datasets for user-defined sets of species and genes. The user provides GenBank format files and a list of gene names and synonyms for the loci to analyse. Sequences are extracted from the GenBank files on the basis of annotation and sequence similarity. Consensus sequences are built automatically. Alignment is carried out (where possible, at the protein level) and aligned sequences are stored in a database. TaxMan can automatically determine the best subset of taxa to examine phylogeny at a given taxonomic level. By using the stored aligned sequences, large concatenated multiple sequence alignments can be generated rapidly for a subset and output in analysis-ready file formats. Trees resulting from phylogenetic analysis can be stored and compared with a reference taxonomy. CONCLUSION: TaxMan allows rapid automated assembly of a multigene datasets of aligned sequences for large taxonomic groups. By extracting sequences on the basis of both annotation and BLAST similarity, it ensures that all available sequence data can be brought to bear on a phylogenetic problem, but remains fast enough to cope with many thousands of records. By automatically assisting in the selection of the best subset of taxa to address a particular phylogenetic problem, TaxMan greatly speeds up the process of generating multiple sequence alignments for phylogenetic analysis. Our results indicate that an automated phylogenetic workbench can be a useful tool when correctly guided by user knowledge

Platelet responses to agonists in a cohort of highly characterised platelet donors are consistent over time.

BACKGROUND AND OBJECTIVES: Platelet function shows significant inheritance that is at least partially genetically controlled. There is also evidence that the platelet response is stable over time, but there are few studies that have assessed consistency of platelet function over months and years. We aimed to measure platelet function in platelet donors over time in individuals selected from a cohort of 956 donors whose platelet function had been previously characterised. MATERIALS AND METHODS: Platelet function was assessed by flow cytometry, measuring fibrinogen binding and P-selectin expression after stimulation with either cross-linked collagen-related peptide or adenosine 5'-diphosphate. Eighty-nine donors from the Cambridge Platelet Function Cohort whose platelet responses were initially within the lower or upper decile of reactivity were retested between 4 months and five and a half years later. RESULTS: There was moderate-to-high correlation between the initial and repeat platelet function results for all assays (P ≤ 0·007, r2 0·2961-0·7625); furthermore, the range of results observed in the initial low and high responder groups remained significantly different at the time of the second test (P ≤ 0·0005). CONCLUSION: Platelet function remains consistent over time. This implies that this potential influence on quality of donated platelet concentrates will remain essentially constant for a given donor

An Evaluation of Phase One of the Youth Mental Health First Aid (MHFA) in Schools programme: “The training has given us a vocabulary to use”

Researchers from University College London evaluated the first year of the Youth MHFA in Schools programme. During the first year of the programme over 1,200 school staff attended a Youth MHFA One Day course, qualifying them as Youth MHFA Champions – someone who is skilled in understanding how to spot the signs and symptoms of mental health issues in young people and who has the confidence to guide a young person to a place of support. The study involved over 1,000 school staff and found that following the training, staff reported around a three-fold (190%) increase in confidence in knowledge, skills and awareness to support a young person struggling with their mental health. 1) Before taking Youth MHFA training, only 30% of staff reported feeling knowledgeable, skilled and aware to support a young person experiencing mental ill health. 2) After acquiring Youth MHFA skills, 59% of staff said they felt highly knowledgeable, aware and confident to support a young person. 3) This increased to 87% up to three terms later, highlighting a sustained improvement as staff put their skills into practice and had time to reflect on their training

Cytomegalovirus replication kinetics in solid organ transplant recipients managed by preemptive therapy.

After allotransplantation, cytomegalovirus (CMV) may be transmitted from the donor organ, giving rise to primary infection in a CMV negative recipient or reinfection in one who is CMV positive. In addition, latent CMV may reactivate in a CMV positive recipient. In this study, serial blood samples from 689 kidney or liver transplant recipients were tested for CMV DNA by quantitative PCR. CMV was managed using preemptive antiviral therapy and no patient received antiviral prophylaxis. Dynamic and quantitative measures of viremia and treatment were assessed. Median peak viral load, duration of viremia and duration of treatment were highest during primary infection, followed by reinfection then reactivation. In patients who experienced a second episode of viremia, the viral replication rate was significantly slower than in the first episode. Our data provide a clear demonstration of the immune control of CMV in immunosuppressed patients and emphasize the effectiveness of the preemptive approach for prevention of CMV syndrome and end organ disease. Overall, our findings provide quantitative biomarkers which can be used in pharmacodynamic assessments of the ability of novel CMV vaccines or antiviral drugs to reduce or even interrupt such transmission

The Phyre2 web portal for protein modeling, prediction and analysis

Phyre2 is a suite of tools available on the web to predict and analyze protein structure, function and mutations. The focus of Phyre2 is to provide biologists with a simple and intuitive interface to state-of-the-art protein bioinformatics tools. Phyre2 replaces Phyre, the original version of the server for which we previously published a paper in Nature Protocols. In this updated protocol, we describe Phyre2, which uses advanced remote homology detection methods to build 3D models, predict ligand binding sites and analyze the effect of amino acid variants (e.g., nonsynonymous SNPs (nsSNPs)) for a user's protein sequence. Users are guided through results by a simple interface at a level of detail they determine. This protocol will guide users from submitting a protein sequence to interpreting the secondary and tertiary structure of their models, their domain composition and model quality. A range of additional available tools is described to find a protein structure in a genome, to submit large number of sequences at once and to automatically run weekly searches for proteins that are difficult to model. The server is available at http://www.sbg.bio.ic.ac.uk/phyre2. A typical structure prediction will be returned between 30 min and 2 h after submission