Triaxiality near the 110Ru ground state from Coulomb excitation

A multi-step Coulomb excitation measurement with the GRETINA and CHICO2 detector arrays was carried out with a 430-MeV beam of the neutron-rich 110Ru (t1/2=12 s) isotope produced at the CARIBU facility. This represents the first successful measurement following the post-acceleration of an unstable isotope of a refractory element. The reduced transition probabilities obtained for levels near the ground state provide strong evidence for a triaxial shape; a conclusion confirmed by comparisons with the results of beyond-mean-field and triaxial rotor model calculations

Triaxiality near the 110Ru ground state from Coulomb excitation

A multi-step Coulomb excitation measurement with the GRETINA and CHICO2 detector arrays was carried out with a 430-MeV beam of the neutron-rich 110Ru (t1/2=12 s) isotope produced at the CARIBU facility. This represents the first successful measurement following the post-acceleration of an unstable isotope of a refractory element. The reduced transition probabilities obtained for levels near the ground state provide strong evidence for a triaxial shape; a conclusion confirmed by comparisons with the results of beyond-mean-field and triaxial rotor model calculations

Triaxiality near the 110Ru ground state from Coulomb excitation

A multi-step Coulomb excitation measurement with the GRETINA and CHICO2 detector arrays was carried out with a 430-MeV beam of the neutron-rich 110Ru (t1/2=12s) isotope produced at the CARIBU facility. This represents the first successful measurement following the post-acceleration of an unstable isotope of a refractory element. The reduced transition probabilities obtained for levels near the ground state provide strong evidence for a triaxial shape; a conclusion confirmed by comparisons with the results of beyond-mean-field and triaxial rotor model calculations

Evolution and development of the synarcual in early vertebrates

The synarcual is a structure incorporating the anterior vertebrae of the axial skeleton and occurs in vertebrate taxa such as the fossil group Placodermi and the Chondrichthyes (Holocephali, Batoidea). Although the synarcual varies morphologically in these groups, it represents the first indication, phylogenetically, of a differentiation of the vertebral column into separate regions. Among the placoderms, the synarcual of Cowralepis mclachlani Ritchie, 2005 (Arthrodira) shows substantial changes during ontogeny to produce an elongate, spool-shaped structure with a well-developed dorsal keel. Because the placoderm synarcual is covered in perichondral bone, the ontogenetic history of this Cowralepis specimen is preserved as it developed anteroposteriorly, dorsally and ventrally. As well, in the placoderm Materpiscis attenboroughi Long et al., 2008 (Ptyctodontida), incomplete fusion at the posterior synarcual margin indicates that both neural and haemal arch vertebral elements are added to the synarcual. A survey of placoderm synarcuals shows that taxa such as Materpiscis and Cowralepis are particularly informative because perichondral ossification occurs prior to synarcual fusion such that individual vertebral elements can be identified. In other placoderm synarcuals (e.g. Nefudina qalibahensis Lelièvre et al., 1995; Rhenanida), cartilaginous vertebral elements fuse prior to perichondral ossification so that individual elements are more difficult to recognize. This ontogenetic development in placoderms can be compared to synarcual development in Recent chondrichthyans; the incorporation of neural and haemal elements is more similar to the holocephalans, but differs from the batoid chondrichthyans

Contrasting roles for actin in the cellular uptake of cell penetrating peptide conjugates

The increased need for macromolecular therapeutics, such as peptides, proteins and nucleotides, to reach intracellular targets necessitates more effective delivery vectors and a higher level of understanding of their mechanism of action. Cell penetrating peptides (CPPs) can transport a range of macromolecules into cells, either through direct plasma membrane translocation or endocytosis. All known endocytic pathways involve cell-cortex remodelling, a process shown to be regulated by reorganisation of the actin cytoskeleton. Here using flow cytometry, confocal microscopy and a variety of actin inhibitors we identify how actin disorganisation in different cell types differentially influences the cellular entry of three probes: the CPP octaarginine – Alexa488 conjugate (R8-Alexa488), octaarginine conjugated Enhanced Green Fluorescent Protein (EGFP-R8), and the fluid phase probe dextran. Disrupting actin organisation in A431 skin epithelial cells dramatically increases the uptake of EGFP-R8 and dextran, and contrasts strongly to inhibitory effects observed with transferrin and R8 attached to the fluorophore Alexa488. This demonstrates that uptake of the same CPP can occur via different endocytic processes depending on the conjugated fluorescent entity. Overall this study highlights how cargo influences cell uptake of this peptide and that the actin cytoskeleton may act as a gateway or barrier to endocytosis of drug delivery vectors

Glycosylated cell-penetrating peptides and their conjugates to a proapoptotic peptide: preparation by click chemistry and cell viability studies

Cell-penetrating peptides (CPPs), which are usually short basic peptides, are able to cross cell membranes and convey bioactive cargoes inside cells. CPPs have been widely used to deliver inside cells peptides, proteins, and oligonucleotides; however, their entry mechanisms still remain controversial. A major problem concerning CPPs remains their lack of selectivity to target a specific type of cell and/or an intracellular component. We have previously shown that myristoylation of one of these CPPs affected the intracellular distribution of the cargo. We report here on the synthesis of glycosylated analogs of the cell-penetrating peptide (R6/W3): Ac-RRWWRRWRR-NH2. One, two, or three galactose(s), with or without a spacer, were introduced into the sequence of this nonapeptide via a triazole link, the Huisgen reaction being achieved on a solid support. Four of these glycosylated CPPs were coupled via a disulfide bridge to the proapoptotic KLAK peptide, (KLAKLAKKLAKLAK), which alone does not enter into cells. The effect on cell viability and the uptake efficiency of different glycosylated conjugates were studied on CHO cells and were compared to those of the nonglycosylated conjugates: (R6/W3)S-S-KLAK and penetratinS-S-KLAK. We show that glycosylation significantly increases the cell viability of CHO cells compared to the nonglycosylated conjugates and concomitantly decreases the internalization of the KLAK cargo. These results suggest that glycosylation of CPP may be a key point in targeting specific cells