Mucosal delivery of tuberculosis vaccines: a review of current approaches and challenges.

Introduction: Tuberculosis (TB) remains a major health threat and it is now clear that the current vaccine, BCG, is unable to arrest the global TB epidemic. A new vaccine is needed to either replace or boost BCG so that a better level of protection could be achieved. The route of entry of Mycobacterium tuberculosis, the causative organism, is via inhalation making TB primarily a respiratory disease. There is therefore good reason to hypothesize that a mucosally delivered vaccine against TB could be more effective than one delivered via the systemic route.Areas covered: This review summarizes the progress that has been made in the area of TB mucosal vaccines in the last few years. It highlights some of the strengths and shortcomings of the published evidence and aims to discuss immunological and practical considerations in the development of mucosal vaccines.Expert opinion: There is a growing body of evidence that the mucosal approach to vaccination against TB is feasible and should be pursued. However, further key studies are necessary to both improve our understanding of the protective immune mechanisms operating in the mucosa and the technical aspects of aerosolized delivery, before such a vaccine could become a feasible, deployable strategy

G×E interaction effects on yield and yield components of cassava (landraces and improved) genotypes in the savanna regions of Nigeria

Genetic enhancement of cassava aimed at increasing production and productivity through the provision of broad-based improved germplasm is a major goal for cassava breeders. At the International Institute of Tropical Agriculture (IITA), Nigeria, 18 varieties comprising 12 landraces and 6broad-based and improved varieties were evaluated at 4 locations in 3 years in a randomized complete block design in 4 replicates to determine variability among cultivars for yield components and adaptation to different environments. Results showed fresh root yield was significantly correlated (P < 0.001) with number of roots, harvest index, shoot weight and number of stands harvested. AMMI analysis partitioned main effects into genotypes, environments and G × E with all the componentsshowing highly significant effects (P < 0.001). Environment had the greatest effect (70.3%), G × E interaction (19.0%) and genotype (10.7%). AMMI1 and unadjusted means selected the same winner in 9out of 12 environments (75%),but differently in 3 environments. The GGE biplot (E and GxE interaction) delineated environments into  ega-environments. Cultivar 4(2)1425 (moderately yielding) was the moststable and specifically adapted to Zaria. ABBEY-IFE, ATU-IWO and  2ND-AGRIC though moderately yielding were highly tolerant to CMD, suggesting a rich resource within the germplasm that could beenhanced for further genetic improvement of the crop

On "New Massive" 4D Gravity

We construct a four-dimensional (4D) gauge theory that propagates, unitarily, the five polarization modes of a massive spin-2 particle. These modes are described by a "dual" graviton gauge potential and the Lagrangian is 4th-order in derivatives. As the construction mimics that of 3D "new massive gravity", we call this 4D model (linearized) "new massive dual gravity". We analyse its massless limit, and discuss similarities to the Eddington-Schroedinger model.Comment: 17 pages, v2 : version published in JHE

Importing statistical measures into Artemis enhances gene identification in the Leishmania genome project

BACKGROUND: Seattle Biomedical Research Institute (SBRI) as part of the Leishmania Genome Network (LGN) is sequencing chromosomes of the trypanosomatid protozoan species Leishmania major. At SBRI, chromosomal sequence is annotated using a combination of trained and untrained non-consensus gene-prediction algorithms with ARTEMIS, an annotation platform with rich and user-friendly interfaces. RESULTS: Here we describe a methodology used to import results from three different protein-coding gene-prediction algorithms (GLIMMER, TESTCODE and GENESCAN) into the ARTEMIS sequence viewer and annotation tool. Comparison of these methods, along with the CODONUSAGE algorithm built into ARTEMIS, shows the importance of combining methods to more accurately annotate the L. major genomic sequence. CONCLUSION: An improvised and powerful tool for gene prediction has been developed by importing data from widely-used algorithms into an existing annotation platform. This approach is especially fruitful in the Leishmania genome project where there is large proportion of novel genes requiring manual annotation

Library subject guides: A case study of evidence-informed library development

This paper describes the process whereby a university library investigated the value of its subject guides to its users. A literature review and surveys of library staff, library users and other libraries were carried out. Existing library subject guides and those of other higher education libraries were evaluated. The project team reported regularly to the wider library team throughout the year long investigation and made recommendations. The project served to develop the professional skills of the project team, to expand the knowledge of the wider library team and encouraged new ways of thinking about guide provision to users

A random cell motility gradient downstream of FGF controls elongation of amniote embryos

Vertebrate embryos are characterized by an elongated antero-posterior (AP) body axis, which forms by progressive cell deposition from a posterior growth zone in the embryo. Here, we used tissue ablation in the chicken embryo to demonstrate that the caudal presomitic mesoderm (PSM) has a key role in axis elongation. Using time-lapse microscopy, we analysed the movements of fluorescently labelled cells in the PSM during embryo elongation, which revealed a clear posterior-to-anterior gradient of cell motility and directionality in the PSM. We tracked the movement of the PSM extracellular matrix in parallel with the labelled cells and subtracted the extracellular matrix movement from the global motion of cells. After subtraction, cell motility remained graded but lacked directionality, indicating that the posterior cell movements associated with axis elongation in the PSM are not intrinsic but reflect tissue deformation. The gradient of cell motion along the PSM parallels the fibroblast growth factor (FGF)/mitogen-activated protein kinase (MAPK) gradient1, which has been implicated in the control of cell motility in this tissue2. Both FGF signalling gain- and loss-of-function experiments lead to disruption of the motility gradient and a slowing down of axis elongation. Furthermore, embryos treated with cell movement inhibitors (blebbistatin or RhoK inhibitor), but not cell cycle inhibitors, show a slower axis elongation rate. We propose that the gradient of random cell motility downstream of FGF signalling in the PSM controls posterior elongation in the amniote embryo. Our data indicate that tissue elongation is an emergent property that arises from the collective regulation of graded, random cell motion rather than by the regulation of directionality of individual cellular movements

Radial dyssynchrony assessed by cardiovascular magnetic resonance in relation to left ventricular function, myocardial scarring and QRS duration in patients with heart failure

Radial dyssynchrony is almost universal in patients with heart failure. This vies against the notion that a lack of response to CRT is related to a lack of dyssynchrony