Vacuolating cytotoxin (vacA) alleles of Helicobacter pylori comprise two geographically widespread types, m1 and m2, and have evolved through limited recombination

Vacuolating cytotoxin (vacA) alleles of Helicobacter pylori vary, particularly in their mid region (which may be type m1 or m2) and their signal peptide coding region (type s1 or s2). We investigated nucleotide diversity among vacA alleles in strains from several locales in Asia, South America, and the USA. Phylogenetic analysis of vacA mid region sequences from 18 strains validated the division into two main groups (m1 and m2) and showed further significant divisions within these groups. Informative site analysis demonstrated one example of recombination between m1 and m2 alleles, and several examples of recombination among alleles within these groups. Recombination was not sufficiently extensive to destroy phylogenetic structure entirely. Synonymous nucleotide substitution rates were markedly different between regions of vacA, suggesting different evolutionary divergence times and implying horizontal transfer of genetic elements within vacA. Non-synonymous/synonymous rate ratios were greater between m1 and m2 sequences than among m1 sequences, consistent with m1 and m2 alleles encoding functions fitting strains for slightly different ecological niches

Emergence of structure in mouse embryos: Structural Entropy morphometry applied to digital models of embryonic anatomy

We apply an information-theoretic measure to anatomical models of the Edinburgh Mouse Atlas Project. Our goal is to quantify the anatomical complexity of the embryo and to understand how this quantity changes as the organism develops through time. Our measure, Structural Entropy, takes into account the geometrical character of the intermingling of tissue types in the embryo. It does this by a mathematical process that effectively imagines a point-like explorer that starts at an arbitrary place in the 3D structure of the embryo and takes a random path through the embryo, recording the sequence of tissues through which it passes. Consideration of a large number of such paths yields a probability distribution of paths making connections between specific tissue types, and Structural Entropy is calculated from this (mathematical details are given in the main text). We find that Structural Entropy generally decreases (order increases) almost linearly throughout developmental time (4–18 days). There is one `blip’ of increased Structural Entropy across days 7–8: this corresponds to gastrulation. Our results highlight the potential for mathematical techniques to provide insight into the development of anatomical structure, and also the need for further sources of accurate 3D anatomical data to support analyses of this kind

Seasonal cycle of precipitation variability in South America on intraseasonal timescales

The seasonal cycle of the intraseasonal (IS) variability of precipitation in South America is described through the analysis of bandpass filtered outgoing longwave radiation (OLR) anomalies. The analysis is discriminated between short (10--30 days) and long (30--90 days) intraseasonal timescales. The seasonal cycle of the 30--90-day IS variability can be well described by the activity of first leading pattern (EOF1) computed separately for the wet season (October--April) and the dry season (May--September). In agreement with previous works, the EOF1 spatial distribution during the wet season is that of a dipole with centers of actions in the South Atlantic Convergence Zone (SACZ) and southeastern South America (SESA), while during the dry season, only the last center is discernible. In both seasons, the pattern is highly influenced by the activity of the Madden--Julian Oscillation (MJO). Moreover, EOF1 is related with a tropical zonal-wavenumber-1 structure superposed with coherent wave trains extended along the South Pacific during the wet season, while during the dry season the wavenumber-1 structure is not observed. The 10--30-day IS variability of OLR in South America can be well represented by the activity of the EOF1 computed through considering all seasons together, a dipole but with the stronger center located over SESA. While the convection activity at the tropical band does not seem to influence its activity, there are evidences that the atmospheric variability at subtropical-extratropical regions might have a role. Subpolar wavetrains are observed in the Pacific throughout the year and less intense during DJF, while a path of wave energy dispersion along a subtropical wavetrain also characterizes the other seasons. Further work is needed to identify the sources of the 10--30-day-IS variability in South America

Cytochrome P450 from Plants: Platforms for Valuable Phytopharmaceuticals

Cytochrome P450 enzymes are important for biotechnology due to their capacity to modify diverse secondary metabolites that may produce chemicals with pharmacological properties. Most terpenes, flavonoids and alkaloids require P450 catalytic functions to reach their biological activity. In the last ten years, several efforts have focused on the expression and production of these three main types of secondary metabolites in engineered microorganisms and plants using P450 of ethnobotanical origin. Despite this, several P450 coding sequences from plant sources are discovered yearly but only a few have been screened by functional genomics. Amongst them, only a few have shown potentials for use in sustainable production of novel drugs and highly valuable products. Cytochrome P450 involvement in the biosynthesis of these products is discussed in this work.Keywords: Biotechnological platforms, Cytochrome P450, Phytopharmaceuticals, Yield improvement, Terpenes, Flavonoids, Alkaloids, Microbial expressio

Cellular strategies for retinal repair by photoreceptor replacement

Loss of photoreceptors due to retinal degeneration is a major cause of blindness in the developed world. While no effective treatment is currently available, cell replacement therapy, using pluripotent stem cell-derived photoreceptor precursor cells, may be a feasible future treatment. Recent reports have demonstrated rescue of visual function following the transplantation of immature photoreceptors and we have seen major advances in our ability to generate transplantation-competent donor cells from stem cell sources. Moreover, we are beginning to realise the possibilities of using endogenous populations of cells from within the retina itself to mediate retinal repair. Here, we present a review of our current understanding of endogenous repair mechanisms together with recent progress in the use of both ocular and pluripotent stem cells for the treatment of photoreceptor loss. We consider how our understanding of retinal development has underpinned many of the recent major advances in translation and moved us closer to the goal of restoring vision by cellular means

Preserving the impossible: conservation of soft-sediment hominin footprint sites and strategies for three-dimensional digital data capture.

Human footprints provide some of the most publically emotive and tangible evidence of our ancestors. To the scientific community they provide evidence of stature, presence, behaviour and in the case of early hominins potential evidence with respect to the evolution of gait. While rare in the geological record the number of footprint sites has increased in recent years along with the analytical tools available for their study. Many of these sites are at risk from rapid erosion, including the Ileret footprints in northern Kenya which are second only in age to those at Laetoli (Tanzania). Unlithified, soft-sediment footprint sites such these pose a significant geoconservation challenge. In the first part of this paper conservation and preservation options are explored leading to the conclusion that to 'record and digitally rescue' provides the only viable approach. Key to such strategies is the increasing availability of three-dimensional data capture either via optical laser scanning and/or digital photogrammetry. Within the discipline there is a developing schism between those that favour one approach over the other and a requirement from geoconservationists and the scientific community for some form of objective appraisal of these alternatives is necessary. Consequently in the second part of this paper we evaluate these alternative approaches and the role they can play in a 'record and digitally rescue' conservation strategy. Using modern footprint data, digital models created via optical laser scanning are compared to those generated by state-of-the-art photogrammetry. Both methods give comparable although subtly different results. This data is evaluated alongside a review of field deployment issues to provide guidance to the community with respect to the factors which need to be considered in digital conservation of human/hominin footprints

Comparison of DC Bead-irinotecan and DC Bead-topotecan drug eluting beads for use in locoregional drug delivery to treat pancreatic cancer

DC Bead is a drug delivery embolisation system that can be loaded with doxorubicin or irinotecan for the treatment of a variety of liver cancers. In this study we demonstrate that the topoisomerase I inhibitor topotecan hydrochloride can be successfully loaded into the DC Bead sulfonate-modified polyvinyl alcohol hydrogel matrix, resulting in a sustained-release drug eluting bead (DEBTOP) useful for therapeutic purposes. The in vitro drug loading capacity, elution characteristics and the effects on mechanical properties of the beads are described with reference to our previous work with irinotecan hydrochloride (DEBIRI). Results showed that drug loading was faster when the solution was agitated compared to static loading and a maximum loading of ca. 40–45 mg topotecan in 1 ml hydrated beads was achievable. Loading the drug into the beads altered the size, compressibility moduli and colour of the bead. Elution was shown to be reliant on the presence of ions to perform the necessary exchange with the electrostatically bound topotecan molecules. Topotecan was shown by MTS assay to have an IC50 for human pancreatic adenocarcinoma cells (PSN-1) of 0.22 and 0.27 lM compared to 28.1 and 19.2 lM for irinotecan at 48 and 72 h, respectively. The cytotoxic efficacy of DEBTOP on PSN-1 was compared to DEBIRI. DEPTOP loaded at 6 & 30 mg ml-1, like its free drug form, was shown to be more potent than DEBIRI of comparable doses at 24, 48 & 72 h using a slightly modified MTS assay. Using a PSN-1 mouse xenograft model, DEBIRI doses of 3.3–6.6 mg were shown to be well tolerated (even with repeat administration) and effective in reducing the tumour size. DEBTOP however, was lethal after 6 days at doses of 0.83–1.2 mg but demonstrated reasonable efficacy and tolerability (again with repeat injection possible) at 0.2–0.4 mg doses. Care must therefore be taken when selecting the dose of topotecan to be loaded into DC Bead given its greater potency and potential toxicity