Coherence of Nitrogen-Vacancy Electronic Spin Ensembles in Diamond

We present an experimental and theoretical study of electronic spin decoherence in ensembles of nitrogen-vacancy (NV) color centers in bulk high-purity diamond at room temperature. Under appropriate conditions, we find ensemble NV spin coherence times (T_2) comparable to that of single NVs, with T_2 > 600 microseconds for a sample with natural abundance of 13C and paramagnetic impurity density ~10^15 cm^(-3). We also observe a sharp decrease of the coherence time with misalignment of the static magnetic field relative to the NV electronic spin axis, consistent with theoretical modeling of NV coupling to a 13C nuclear spin bath. The long coherence times and increased signal-to-noise provided by room-temperature NV ensembles will aid many applications of NV centers in precision magnetometry and quantum information.Comment: 5 pages, 3 figures; v2 minor correction

Fourier Magnetic Imaging with Nanoscale Resolution and Compressed Sensing Speed-up using Electronic Spins in Diamond

Optically-detected magnetic resonance using Nitrogen Vacancy (NV) color centres in diamond is a leading modality for nanoscale magnetic field imaging, as it provides single electron spin sensitivity, three-dimensional resolution better than 1 nm, and applicability to a wide range of physical and biological samples under ambient conditions. To date, however, NV-diamond magnetic imaging has been performed using real space techniques, which are either limited by optical diffraction to 250 nm resolution or require slow, point-by-point scanning for nanoscale resolution, e.g., using an atomic force microscope, magnetic tip, or super-resolution optical imaging. Here we introduce an alternative technique of Fourier magnetic imaging using NV-diamond. In analogy with conventional magnetic resonance imaging (MRI), we employ pulsed magnetic field gradients to phase-encode spatial information on NV electronic spins in wavenumber or k-space followed by a fast Fourier transform to yield real-space images with nanoscale resolution, wide field-of-view (FOV), and compressed sensing speed-up.Comment: 31 pages, 10 figure

Enhanced solid-state multi-spin metrology using dynamical decoupling

We use multi-pulse dynamical decoupling to increase the coherence lifetime (T2) of large numbers of nitrogen-vacancy (NV) electronic spins in room temperature diamond, thus enabling scalable applications of multi-spin quantum information processing and metrology. We realize an order-of-magnitude extension of the NV multi-spin T2 for diamond samples with widely differing spin environments. For samples with nitrogen impurity concentration <~1 ppm, we find T2 > 2 ms, comparable to the longest coherence time reported for single NV centers, and demonstrate a ten-fold enhancement in NV multi-spin sensing of AC magnetic fields

Magnetic field imaging with nitrogen-vacancy ensembles

Part of Focus on Diamond-Based Photonics and Spintronics We demonstrate a method of imaging spatially varying magnetic fields using a thin layer of nitrogen-vacancy (NV) centers at the surface of a diamond chip. Fluorescence emitted by the two-dimensional NV ensemble is detected by a CCD array, from which a vector magnetic field pattern is reconstructed. As a demonstration, ac current is passed through wires placed on the diamond chip surface, and the resulting ac magnetic field patterns are imaged using an echo-based technique with sub-micron resolution over a 140 μm×140 μm field of view, giving single-pixel sensitivity \sim100\,{\rm nT}/\sqrt{{\rm Hz}} . We discuss ongoing efforts to further improve the sensitivity, as well as potential bioimaging applications such as real-time imaging of activity in functional, cultured networks of neurons. PACS 61.72.J- Point defects and defect clusters 78.55.Hx Other solid inorganic materials 87.50.C- Static and low-frequency electric and magnetic fields effects 85.30.Tv Field effect devices Subjects Electronics and devices Condensed matter: electrical, magnetic and optical Semiconductors Medical physics Biological physics Condensed matter: structural, mechanical & thermalUnited States. Defense Advanced Research Projects AgencyNational Institute of Standards and Technology (U.S.)National Science Foundation (U.S.

Paleomagnetism. Solar nebula magnetic fields recorded in the Semarkona meteorite.

Magnetic fields are proposed to have played a critical role in some of the most enigmatic processes of planetary formation by mediating the rapid accretion of disk material onto the central star and the formation of the first solids. However, there have been no experimental constraints on the intensity of these fields. Here we show that dusty olivine-bearing chondrules from the Semarkona meteorite were magnetized in a nebular field of 54 ± 21 microteslas. This intensity supports chondrule formation by nebular shocks or planetesimal collisions rather than by electric currents, the x-wind, or other mechanisms near the Sun. This implies that background magnetic fields in the terrestrial planet-forming region were likely 5 to 54 microteslas, which is sufficient to account for measured rates of mass and angular momentum transport in protoplanetary disks.This is the accepted manuscript. The final version is available from Science at http://www.sciencemag.org/content/346/6213/1089.abstract

Ucma/GRP inhibits phosphate-induced vascular smooth muscle cell calcification via SMAD-dependent BMP signalling

Vascular calcification (VC) is the process of deposition of calcium phosphate crystals in the blood vessel wall, with a central role for vascular smooth muscle cells (VSMCs). VC is highly prevalent in chronic kidney disease (CKD) patients and thought, in part, to be induced by phosphate imbalance. The molecular mechanisms that regulate VC are not fully known. Here we propose a novel role for the mineralisation regulator Ucma/GRP (Upper zone of growth plate and Cartilage Matrix Associated protein/Gla Rich Protein) in phosphate-induced VSMC calcification. We show that Ucma/GRP is present in calcified atherosclerotic plaques and highly expressed in calcifying VSMCs in vitro. VSMCs from Ucma/GRP(-/-) mice showed increased mineralisation and expression of osteo/chondrogenic markers (BMP-2, Runx2, beta-catenin, p-SMAD1/5/8, ALP, OCN), and decreased expression of mineralisation inhibitor MGP, suggesting that Ucma/GRP is an inhibitor of mineralisation. Using BMP signalling inhibitor noggin and SMAD1/5/8 signalling inhibitor dorsomorphin we showed that Ucma/GRP is involved in inhibiting the BMP-2-SMAD1/5/8 osteo/chondrogenic signalling pathway in VSMCs treated with elevated phosphate concentrations. Additionally, we showed for the first time evidence of a direct interaction between Ucma/GRP and BMP-2. These results demonstrate an important role of Ucma/GRP in regulating osteo/chondrogenic differentiation and phosphate-induced mineralisation of VSMCs.NWO ZonMw [MKMD 40-42600-98-13007]; FCT [SFRH/BPD/70277/2010]info:eu-repo/semantics/publishedVersio

Induction of microRNAs, mir-155, mir-222, mir-424 and mir-503, promotes monocytic differentiation through combinatorial regulation

Acute myeloid leukemia (AML) involves a block in terminal differentiation of the myeloid lineage and uncontrolled proliferation of a progenitor state. Using phorbol myristate acetate (PMA), it is possible to overcome this block in THP-1 cells (an M5-AML containing the MLL-MLLT3 fusion), resulting in differentiation to an adherent monocytic phenotype. As part of FANTOM4, we used microarrays to identify 23 microRNAs that are regulated by PMA. We identify four PMA-induced micro- RNAs (mir-155, mir-222, mir-424 and mir-503) that when overexpressed cause cell-cycle arrest and partial differentiation and when used in combination induce additional changes not seen by any individual microRNA. We further characterize these prodifferentiative microRNAs and show that mir-155 and mir-222 induce G2 arrest and apoptosis, respectively. We find mir-424 and mir-503 are derived from a polycistronic precursor mir-424-503 that is under repression by the MLL-MLLT3 leukemogenic fusion. Both of these microRNAs directly target cell-cycle regulators and induce G1 cell-cycle arrest when overexpressed in THP-1. We also find that the pro-differentiative mir-424 and mir-503 downregulate the anti-differentiative mir-9 by targeting a site in its primary transcript. Our study highlights the combinatorial effects of multiple microRNAs within cellular systems.Comment: 45 pages 5 figure

MIR376A is a regulator of starvation-induced autophagy

Background: Autophagy is a vesicular trafficking process responsible for the degradation of long-lived, misfolded or abnormal proteins, as well as damaged or surplus organelles. Abnormalities of the autophagic activity may result in the accumulation of protein aggregates, organelle dysfunction, and autophagy disorders were associated with various diseases. Hence, mechanisms of autophagy regulation are under exploration. Methods: Over-expression of hsa-miR-376a1 (shortly MIR376A) was performed to evaluate its effects on autophagy. Autophagy-related targets of the miRNA were predicted using Microcosm Targets and MIRanda bioinformatics tools and experimentally validated. Endogenous miRNA was blocked using antagomirs and the effects on target expression and autophagy were analyzed. Luciferase tests were performed to confirm that 3’ UTR sequences in target genes were functional. Differential expression of MIR376A and the related MIR376B was compared using TaqMan quantitative PCR. Results: Here, we demonstrated that, a microRNA (miRNA) from the DlkI/Gtl2 gene cluster, MIR376A, played an important role in autophagy regulation. We showed that, amino acid and serum starvation-induced autophagy was blocked by MIR376A overexpression in MCF-7 and Huh-7 cells. MIR376A shared the same seed sequence and had overlapping targets with MIR376B, and similarly blocked the expression of key autophagy proteins ATG4C and BECN1 (Beclin 1). Indeed, 3’ UTR sequences in the mRNA of these autophagy proteins were responsive to MIR376A in luciferase assays. Antagomir tests showed that, endogenous MIR376A was participating to the control of ATG4C and BECN1 transcript and protein levels. Moreover, blockage of endogenous MIR376A accelerated starvation-induced autophagic activity. Interestingly, MIR376A and MIR376B levels were increased with different kinetics in response to starvation stress and tissue-specific level differences were also observed, pointing out to an overlapping but miRNA-specific biological role. Conclusions: Our findings underline the importance of miRNAs encoded by the DlkI/Gtl2 gene cluster in stress-response control mechanisms, and introduce MIR376A as a new regulator of autophagy

3′UTR-Mediated Gene Silencing of the Mixed Lineage Leukemia (MLL) Gene

Translocations involving the Mixed Lineage Leukemia (MLL) gene generate in-frame fusions of MLL with more than 50 different partner genes (PGs). Common to all MLL translocations is the exchange not only of coding regions, but also of MLL and PG 3′-untranslated regions (3′UTRs). As a result, the MLL-PG fusion is normally highly expressed and considered the main driver of leukemia development, whereas the function of the PG-MLL fusions in leukemic disease is unclear. As 3′UTRs have been recognized as determinant regions for regulation of gene expression, we hypothesized that loss of the MLL 3′UTR could have a role in generating high MLL-PG levels and leukemia development. Here, we first tested the MLL-PG and PG-MLL mRNA levels in different leukemic cells and tumours and uncovered differential expression that indicates strong repression by the MLL-3′UTR. Reporter assays confirmed that the 3′UTR of MLL, but not of its main PGs, harbours a region that imposes a strong gene silencing effect. Gene suppression by the MLL 3′UTR was largely microRNA independent and did not affect mRNA stability, but inhibited transcription. This effect can at least partially be attributed to a tighter interaction of the MLL 3′UTR with RNA polymerase II than PG 3′UTRs, affecting its phosphorylation state. Altogether, our findings indicate that MLL translocations relieve oncogenic MLL-PG fusions from the repressive MLL 3′UTR, contributing to higher activity of these genes and leukaemia development

Fuzzy Tandem Repeats Containing p53 Response Elements May Define Species-Specific p53 Target Genes

Evolutionary forces that shape regulatory networks remain poorly understood. In mammals, the Rb pathway is a classic example of species-specific gene regulation, as a germline mutation in one Rb allele promotes retinoblastoma in humans, but not in mice. Here we show that p53 transactivates the Retinoblastoma-like 2 (Rbl2) gene to produce p130 in murine, but not human, cells. We found intronic fuzzy tandem repeats containing perfect p53 response elements to be important for this regulation. We next identified two other murine genes regulated by p53 via fuzzy tandem repeats: Ncoa1 and Klhl26. The repeats are poorly conserved in evolution, and the p53-dependent regulation of the murine genes is lost in humans. Our results indicate a role for the rapid evolution of tandem repeats in shaping differences in p53 regulatory networks between mammalian species