Magnetic Quantum Tunneling: Insights from Simple Molecule-Based Magnets

This article takes a broad view of the understanding of magnetic bistability and magnetic quantum tunneling in single-molecule magnets (SMMs), focusing on three families of relatively simple, low-nuclearity transition metal clusters: spin S = 4 Ni4, Mn(III)3 (S = 2 and 6) and Mn(III)6 (S = 4 and 12). The Mn(III) complexes are related by the fact that they contain triangular Mn3 units in which the exchange may be switched from antiferromagnetic to ferromagnetic without significantly altering the coordination around the Mn(III) centers, thereby leaving the single-ion physics more-or-less unaltered. This allows for a detailed and systematic study of the way in which the individual-ion anisotropies project onto the molecular spin ground state in otherwise identical low- and high-spin molecules, thus providing unique insights into the key factors that control the quantum dynamics of SMMs, namely: (i) the height of the kinetic barrier to magnetization relaxation; and (ii) the transverse interactions that cause tunneling through this barrier. Numerical calculations are supported by an unprecedented experimental data set (17 different compounds), including very detailed spectroscopic information obtained from high-frequency electron paramagnetic resonance and low-temperature hysteresis measurements. Diagonalization of the multi-spin Hamiltonian matrix is necessary in order to fully capture the interplay between exchange and local anisotropy, and the resultant spin-state mixing which ultimately gives rise to the tunneling matrix elements in the high symmetry SMMs (ferromagnetic Mn3 and Ni4). The simplicity (low-nuclearity, high-symmetry, weak disorder, etc..) of the molecules highlighted in this study proves to be of crucial importance.Comment: 32 pages, incl. 6 figure

A hexameric [MnIII18Na6] wheel based on [MnIII3O]7+ sub-units

International audienc

A Virus-Encoded Cell–Cell Fusion Machine Dependent on Surrogate Adhesins

The reovirus fusion-associated small transmembrane (FAST) proteins function as virus-encoded cellular fusogens, mediating efficient cell–cell rather than virus–cell membrane fusion. With ectodomains of only ∼20–40 residues, it is unclear how such diminutive viral fusion proteins mediate the initial stages (i.e. membrane contact and close membrane apposition) of the fusion reaction that precede actual membrane merger. We now show that the FAST proteins lack specific receptor-binding activity, and in their natural biological context of promoting cell–cell fusion, rely on cadherins to promote close membrane apposition. The FAST proteins, however, are not specifically reliant on cadherin engagement to mediate membrane apposition as indicated by their ability to efficiently utilize other adhesins in the fusion reaction. Results further indicate that surrogate adhesion proteins that bridge membranes as close as 13 nm apart enhance FAST protein-induced cell–cell fusion, but active actin remodelling is required for maximal fusion activity. The FAST proteins are the first example of membrane fusion proteins that have specifically evolved to function as opportunistic fusogens, designed to exploit and convert naturally occurring adhesion sites into fusion sites. The capacity of surrogate, non-cognate adhesins and active actin remodelling to enhance the cell–cell fusion activity of the FAST proteins are features perfectly suited to the structural and functional evolution of these fusogens as the minimal fusion component of a virus-encoded cellular fusion machine. These results also provide a basis for reconciling the rudimentary structure of the FAST proteins with their capacity to fuse cellular membranes

The copper centers of tyramine β-monooxygenase and its catalytic-site methionine variants: an X-ray absorption study

Tyramine β-monooxygenase (TBM) is a member of a family of copper monooxygenases containing two noncoupled copper centers, and includes peptidylglycine monooxygenase and dopamine β-monooxygenase. In its Cu(II) form, TBM is coordinated by two to three His residues and one to two non-His O/N ligands consistent with a [CuM(His)2(OH2)2–CuH(His)3(OH2)] formulation. Reduction to the Cu(I) state causes a change in the X-ray absorption spectroscopy (XAS) spectrum, consistent with a change to a [CuM(His)2S(Met)–CuH(His)3] environment. Lowering the pH to 4.0 results in a large increase in the intensity of the Cu(I)–S extended X-ray absorption fine structure (EXAFS) component, suggesting a tighter Cu–S bond or the coordination of an additional sulfur donor. The XAS spectra of three variants, where the CuM Met471 residue had been mutated to His, Cys, and Asp, were examined. Significant differences from the wild-type enzyme are evident in the spectra of the reduced mutants. Although the side chains of His, Cys, and Asp are expected to substitute for Met at the CuM site, the data showed identical spectra for all three reduced variants, with no evidence for coordination of residue 471. Rather, the K-edge data suggested a modest decrease in coordination number, whereas the EXAFS indicated an average of two His residues at each Cu(I) center. These data highlight the unique role of the Met residue at the CuM center, and pose interesting questions as to why replacement by the cuprophilic thiolate ligand leads to detectable activity whereas replacement by imidazole generates inactive TBM

Simultaneous detection of lung fusions using a multiplex RT-PCR next generation sequencing-based approach:A multi-institutional research study

Contains fulltext : 195300.pdf (publisher's version ) (Open Access

In search for molecules displaying ferromagnetic exchange: multiple-decker Ni12 and Ni16 complexes from the use of pyridine-2-amidoxime

The use of pyridine-2-amidoxime (pyaoxH2) in Ni chemistry has provided access to a dodecanuclear complex and a hexadecanuclear Ni cluster, namely [Ni12(pyaox)6(pyaoxH)6(MeOH)2Cl2]Cl4·5MeOH (1·5MeOH) and [Ni16(pyaox)8(pyaoxH)8(MeOH)4](SO4)4·10H2O·26MeOH (2·10H2O·26MeOH). Complex 1·5MeOH was isolated by the reaction of NiCl2·6H2O, pyaoxH2 and NaOMe in a 1 : 1 : 2 molar ratio in MeOH in 60% yield. Treatment of NiSO4·6H2O with pyaoxH2 and NEt3 in a 1 : 1 : 2 molar ratio in MeOH afforded 2·10H2O·26MeOH in good yield (65%). The two compounds display a multi-decker configuration based on stacked Ni4 layers, {Ni4(pyaox)2(pyaoxH)2}2+x (x = 3, 1·5MeOH; x = 4, 2·10H2O·26MeOH); each deck consists of two square planar and two octahedral NiII centres. The number of decks observed in 1·5MeOH and 2·10H2O·26MeOH depends on the nature of the inorganic anion that is present in the reaction system, which provides elements of synthetic control towards new high nuclearity NiII species. 2·10H2O·26MeOH is the first structurally characterized complex of any metal displaying a quadruple-decker configuration, being also the highest nuclearity metal cluster bearing pyaoxH2 and the highest nuclearity NiII cluster with any type of 2-pyridyl oxime. Each cluster cation displays ferromagnetic exchange between the octahedral NiII ions resulting in a spin ground state of S = 6 for 1 and S = 8 for 2. Magnetothermal studies have been performed and discussed for both clusters.CP and CE thank the School of Chemistry, NUI Galway, for the financial support. RI thanks the Royal Society of Edinburgh and ME thanks Spanish MINECO (MAT2015-68204-R) for funding. LCS acknowledges the financial support by FEDER (Fundo Europeu de Desenvolvimento Regional) through PT2020, by FCT (Fundação para a Ciência e a Tecnologia) for the research centre REQUIMTE/LAQV (UID/QUI/50006/2013) and for the grant SFRH/BPD/111899/2015.Peer Reviewe

Are mesenchymal stromal cells immune cells?

Mesenchymal stromal cells (MSCs) are considered to be promising agents for the treatment of immunological disease. Although originally identified as precursor cells for mesenchymal lineages, in vitro studies have demonstrated that MSCs possess diverse immune regulatory capacities. Pre-clinical models have shown beneficial effects of MSCs in multiple immunological diseases and a number of phase 1/2 clinical trials carried out so far have reported signs of immune modulation after MSC infusion. These data indicate that MSCs play a central role in the immune response. This raises the academic question whether MSCs are immune cells or whether they are tissue precursor cells with immunoregulatory capacity. Correct understanding of the immunological properties and origin of MSCs will aid in the appropriate and safe use of the cells for clinical therapy. In this review the whole spectrum of immunological properties of MSCs is discussed with the aim of determining the position of MSCs in the immune system