Naturally-Occurring Zirconolites - Analogues for the Long-Term Encapsulation of Actinides in Synroc

The use of natural zirconolites to assess the effect of α-decay damage and geochemical alteration on the release of actinides from HLW wasteforms is critically examined. There is evidence that the natural zirconolites provide a good chemical and radi-ation damage analogy for the HLW wasteforms, but additional work is required to define the geochemical environments in which zirconolite is stable or unstable (e.g., suffering corrosion or chemical alteration, including loss of actinides)

Retention of Actinides in Natural Pyrochlores and Zirconolites

Natural pyrochlore and zirconolite undergo a crystalline-aperi­odic transformation caused by alpha-decay of 232Th and 2380 at dose levels between 2 X 1014 and 3 X 1017 a/mg. The principal effects of the transformation are volume expansion and micro­fracturing, providing potential pathways for fluids. Geochemical alteration of the minerals may occur under hydrothermal conditions or in low temperature, near surface environments, but Th and U usually remain immobile and can be retained for time scales up to 109 years. However, the Th-U isotope systematics of a zirconolite-bearing vein and dolomite host rock may provide evidence for disequilibrium between 230Th, 234U and 238U

miR-196b target screen reveals mechanisms maintaining leukemia stemness with therapeutic potential.

We have shown that antagomiR inhibition of miRNA miR-21 and miR-196b activity is sufficient to ablate MLL-AF9 leukemia stem cells (LSC) in vivo. Here, we used an shRNA screening approach to mimic miRNA activity on experimentally verified miR-196b targets to identify functionally important and therapeutically relevant pathways downstream of oncogenic miRNA in MLL-r AML. We found Cdkn1b (p27Kip1) is a direct miR-196b target whose repression enhanced an embryonic stem cell–like signature associated with decreased leukemia latency and increased numbers of leukemia stem cells in vivo. Conversely, elevation of p27Kip1 significantly reduced MLL-r leukemia self-renewal, promoted monocytic differentiation of leukemic blasts, and induced cell death. Antagonism of miR-196b activity or pharmacologic inhibition of the Cks1-Skp2–containing SCF E3-ubiquitin ligase complex increased p27Kip1 and inhibited human AML growth. This work illustrates that understanding oncogenic miRNA target pathways can identify actionable targets in leukemia

β-diversity scaling patterns are consistent across metrics and taxa

We thank the University of St Andrews Bioinformatics Unit (Wellcome Trust ISSF grant 105621/Z/14/Z). L.H.A.was supported by Fundação para a Ciência e Tecnologia, Portugal (POPH/FSE SFRH/BD/90469/2012), A.E.M. by the ERC BioTIME (250189) and BioCHANGE (727440), and B.J.M. by USDA Hatch grant to MAFES #1011538 and NSF ABI grant #1660000. The BioTIME database was funded by ERC AdG BioTIME (250189) and ERC PoC BioCHANGE (727440).β‐diversity (variation in community composition) is a fundamental component of biodiversity, with implications for macroecology, community ecology and conservation. However, its scaling properties are poorly understood. Here, we systematically assessed the spatial scaling of β‐diversity using 12 empirical large‐scale datasets including different taxonomic groups, by examining two conceptual types of β‐diversity and explicitly considering the turnover and nestedness components. We found highly consistent patterns across datasets. Multiple‐site β‐diversity (i.e. variation across multiple sites) scaling curves were remarkably consistent, with β‐diversity decreasing with sampled area according to a power law. For pairwise dissimilarities, the rates of increase of dissimilarity with geographic distance remained largely constant across scales, while grain size (or scale level) had a stronger effect on overall dissimilarity. In both analyses, turnover was the main contributor to β‐diversity, following total β‐diversity patterns closely, while the nestedness component was largely insensitive to scale changes. Our results highlight the importance of integrating both inter‐ and intraspecific aggregation patterns across spatial scales, which underpin substantial differences in community structure from local to regional scales.PostprintPeer reviewe

Some anisotropic universes in the presence of imperfect fluid coupling with spatial curvature

We consider Bianchi VI spacetime, which also can be reduced to Bianchi types VI0-V-III-I. We initially consider the most general form of the energy-momentum tensor which yields anisotropic stress and heat flow. We then derive an energy-momentum tensor that couples with the spatial curvature in a way so as to cancel out the terms that arise due to the spatial curvature in the evolution equations of the Einstein field equations. We obtain exact solutions for the universes indefinetly expanding with constant mean deceleration parameter. The solutions are beriefly discussed for each Bianchi type. The dynamics of the models and fluid are examined briefly, and the models that can approach to isotropy are determined. We conclude that even if the observed universe is almost isotropic, this does not necessarily imply the isotropy of the fluid (e.g., dark energy) affecting the evolution of the universe within the context of general relativity.Comment: 17 pages, no figures; to appear in International Journal of Theoretical Physics; in this version (which is more concise) an equation added, some references updated and adde

Multivalent, stabilized mannose-6-phosphates for the targeted delivery of toll-like receptor ligands and peptide antigens

Mannose-6-phosphate (M6P) is recognized by the mannose-6-phosphate receptor and plays an important role in the transport of cargo to the endosomes, making it an attractive tool to improve endosomal trafficking of vaccines. We here describe the assembly of peptide antigen conjugates carrying clusters of mannose-6-C-phosphonates (M6Po). The M6Po's represent stable M6P mimics that are resistant to cleavage of the phosphate group by endogenous phosphatases. Two different strategies for the incorporation of the M6Po clusters in the conjugate have been developed: the first relying on a "post-assembly" click approach employing an M6Po bearing an alkyne functionality; the second hinges on an M6Po C-glycoside amino acid building block that can be used in solid-phase peptide synthesis. The generated conjugates were further equipped with a TLR7-ligand to stimulate dendritic cell (DC) maturation. While antigen presentation is hindered by the presence of the M6Po clusters, the incorporation of the M6Po clusters leads to increased activation of DCs, demonstrating their potential in improving vaccine adjuvanticity by intraendosomally active TLR-ligands.Bio-organic Synthesi

Breaking constraint of mammalian axial formulae

The vertebral column of individual mammalian species often exhibits remarkable robustness in the number and identity of vertebral elements that form (known as axial formulae). The genetic mechanism(s) underlying this constraint however remain ill-defined. Here, we reveal the interplay of three regulatory pathways (Gdf11, miR-196 and Retinoic acid) is essential in constraining total vertebral number and regional axial identity in the mouse, from cervical through to tail vertebrae. All three pathways have differing control over Hox cluster expression, with heterochronic and quantitative changes found to parallel changes in axial identity. However, our work reveals an additional role for Hox genes in supporting axial elongation within the tail region, providing important support for an emerging view that mammalian Hox function is not limited to imparting positional identity as the mammalian body plan is laid down. More broadly, this work provides a molecular framework to interrogate mechanisms of evolutionary change and congenital anomalies of the vertebral column.Gabriel M. Hauswirth, Victoria C. Garside, Lisa S.F. Wong, Heidi Bildsoe, Jan Manent, Yi-Cheng Chang, Christian M. Nefzger, Jaber Firas, Joseph Chen, Fernando J. Rossello, Jose M. Polo, Edwina McGlin

Nr6a1 controls Hox expression dynamics and is a master regulator of vertebrate trunk development

The vertebrate main-body axis is laid down during embryonic stages in an anterior-to-posterior (head-to-tail) direction, driven and supplied by posteriorly located progenitors. Whilst posterior expansion and segmentation appears broadly uniform along the axis, there is developmental and evolutionary support for at least two discrete modules controlling processes within different axial regions: a trunk and a tail module. Here, we identify Nuclear receptor subfamily 6 group A member 1 (Nr6a1) as a master regulator of trunk development in the mouse. Specifically, Nr6a1 was found to control vertebral number and segmentation of the trunk region, autonomously from other axial regions. Moreover, Nr6a1 was essential for the timely progression of Hox signatures, and neural versus mesodermal cell fate choice, within axial progenitors. Collectively, Nr6a1 has an axially-restricted role in all major cellular and tissue-level events required for vertebral column formation, supporting the view that changes in Nr6a1 levels may underlie evolutionary changes in axial formulae.Yi-Cheng Chang, Jan Manent, Jan Schroeder, Siew Fen Lisa Wong, Gabriel M. Hauswirth, Natalia A. Shylo, Emma L. Moore, Annita Achilleos, Victoria Garside, Jose M. Polo, Paul Trainor, Edwina McGlin

Supplementary information files for Regional occupancy increases for widespread species but decreases for narrowly distributed species in metacommunity time series

Supplementary files for article Regional occupancy increases for widespread species but decreases for narrowly distributed species in metacommunity time series   While human activities are known to elicit rapid turnover in species composition through time, the properties of the species that increase or decrease their spatial occupancy underlying this turnover are less clear. Here, we used an extensive dataset of 238 metacommunity time series of multiple taxa spread across the globe to evaluate whether species that are more widespread (large-ranged species) differed in how they changed their site occupancy over the10-90 years the metacommunities were monitored relative to species that are more narrowly distributed (small-ranged species). We found that on average, large-ranged species tended to increase in occupancy through time, whereas small-ranged species tended to decrease. These relationships were stronger in marine than in terrestrial and freshwater realms. However, in terrestrial regions, the directional changes in occupancy were less extreme in protected areas. Our findings provide evidence for systematic decreases in occupancy of small-ranged species, and that habitat protection could mitigate these losses in the face of environmental change.</p