Crystal structure and magnetic properties of spin-1/21/2 frustrated two-leg ladder compounds (C4_4H14_{14}N2_2)Cu2X6_2X_6 (XX= Cl and Br)

We have successfully synthesized single crystals, solved the crystal structure, and studied the magnetic properties of a new family of copper halides (C$_4$H$_{14}$N$_2$)Cu$_2X_6$ ($X$= Cl, Br). These compounds crystallize in an orthorhombic crystal structure with space group $Pnma$. The crystal structure features Cu$^{2+}$ dimers arranged parallel to each other that makes a zig-zag two-leg ladder-like structure. Further, there exists a diagonal interaction between two adjacent dimers which generates inter-dimer frustration. Both the compounds manifest a singlet ground state with a large gap in the excitation spectrum. Magnetic susceptibility is analyzed in terms of both interacting spin-$1/2$ dimer and two-leg ladder models followed by exact diagonalization calculations. Our theoretical calculations in conjunction with the experimental magnetic susceptibility establish that the spin-lattice can be described well by a frustrated two-leg ladder model with strong rung coupling ($J_0/k_{\rm B} \simeq 116$ K and 300 K), weak leg coupling ($J^{\prime\prime}/k_{\rm B} \simeq 18.6$ K and 105 K), and equally weak diagonal coupling ($J^{\prime }/k_{\rm B} \simeq 23.2$ K and 90 K) for Cl and Br compounds, respectively. These exchange couplings set the critical fields very high, making them experimentally inaccessible. The correlation function decays exponentially as expected for a gapped spin system. The structural aspects of both the compounds are correlated with their magnetic properties. The calculation of entanglement witness divulges strong entanglement in both the compounds which persists upto high temperatures, even beyond 370~K for the Br compound.Comment: 13 pages, 9 figures, 2 table

A case study of bilayered spin-1/21/2 square lattice compound [VO(HCOO)2⋅_2\cdot(H2_2O)]

We present the synthesis and a detail investigation of structural and magnetic properties of polycrystalline [VO(HCOO)$_2\cdot$(H$_2$O)] by means of x-ray diffraction, magnetic susceptibility, high-field magnetization, heat capacity, and electron spin resonance measurements. It crystallizes in a orthorhombic structure with space group $Pcca$. It features distorted VO$_6$ octahedra connected via HCOO linker (formate anions) forming a two-dimensional square lattice network with a bilayered structure. Analysis of magnetic susceptibility, high field magnetization, and heat capacity data in terms of the frustrated square lattice model unambiguously establish quasi-two-dimensional nature of the compound with nearest neighbour interaction $J_1/k_{\rm B} \simeq 11.7$~K and next-nearest-neighbour interaction $J_2/k_{\rm B} \simeq 0.02$~K. It undergoes a N\'eel antiferromagnetic ordering at $T_{\rm N} \simeq 1.1$~K. The ratio $\theta_{\rm CW}/T_{\rm N} \simeq 10.9$ reflects excellent two-dimensionality of the spin-lattice in the compound. A strong in-plane anisotropy is inferred from the linear increase of $T_{\rm N}$ with magnetic field, consistent with the structural data.Comment: 9 pages, 7 figures, 1 tabl

Biocatalytic Transfer of Pseudaminic Acid (Pse5Ac7Ac) Using Promiscuous Sialyltransferases in a Chemoenzymatic Approach to Pse5Ac7Ac-Containing Glycosides

Pseudaminic acid (Pse5Ac7Ac) is a nonmammalian sugar present on the cell surface of a number of bacteria including Pseudomonas aeruginosa, Campylobacter jejuni, and Acinetobacter baumannii. However, the role Pse5Ac7Ac plays in host–pathogen interactions remains underexplored, particularly compared to its ubiquitous sialic acid analogue Neu5Ac. This is primarily due to a lack of access to difficult to prepare Pse5Ac7Ac glycosides. Herein, we describe the in vitro biocatalytic transfer of an activated Pse5Ac7Ac donor onto glycosyl acceptors, enabling the enzymatic synthesis of Pse5Ac7Ac-containing glycosides. In a chemoenzymatic approach, chemical synthesis initially afforded access to a late-stage Pse5Ac7Ac biosynthetic intermediate, which was subsequently converted to the desired CMP-glycosyl donor in a one-pot two-enzyme process using biosynthetic enzymes. Finally, screening a library of 13 sialyltransferases (SiaT) with the unnatural substrate enabled the identification of a promiscuous inverting SiaT capable of turnover to afford β-Pse5Ac7Ac-terminated glycosides.</p

Phosphorylation of Serine 248 of C/EBPα Is Dispensable for Myelopoiesis but Its Disruption Leads to a Low Penetrant Myeloid Disorder with Long Latency

BACKGROUND: Transcription factors play a key role in lineage commitment and differentiation of stem cells into distinct mature cells. In hematopoiesis, they regulate lineage-specific gene expression in a stage-specific manner through various physical and functional interactions with regulatory proteins that are simultanously recruited and activated to ensure timely gene expression. The transcription factor CCAAT/enhancer binding protein α (C/EBPα) is such a factor and is essential for the development of granulocytic/monocytic cells. The activity of C/EBPα is regulated on several levels including gene expression, alternative translation, protein interactions and posttranslational modifications, such as phosphorylation. In particular, the phosphorylation of serine 248 of the transactivation domain has been shown to be of crucial importance for granulocytic differentiation of 32Dcl3 cells in vitro. METHODOLOGY/PRINCIPAL FINDINGS: Here, we use mouse genetics to investigate the significance of C/EBPα serine 248 in vivo through the construction and analysis of Cebpa(S248A/S248A) knock-in mice. Surprisingly, 8-week old Cebpa(S248A/S248A) mice display normal steady-state hematopoiesis including unaltered development of mature myeloid cells. However, over time some of the animals develop a hematopoietic disorder with accumulation of multipotent, megakaryocytic and erythroid progenitor cells and a mild impairment of differentiation along the granulocytic-monocytic lineage. Furthermore, BM cells from Cebpa(S248A/S248A) animals display a competitive advantage compared to wild type cells in a transplantation assay. CONCLUSIONS/SIGNIFICANCE: Taken together, our data shows that the substitution of C/EBPα serine 248 to alanine favors the selection of the megakaryocytic/erythroid lineage over the monocytic/granulocytic compartment in old mice and suggests that S248 phosphorylation may be required to maintain proper hematopoietic homeostasis in response to changes in the wiring of cellular signalling networks. More broadly, the marked differences between the phenotype of the S248A variant in vivo and in vitro highlight the need to exert caution when extending in vitro phenotypes to the more appropriate in vivo context

Bilateral inhibition of HAUSP deubiquitinase by a viral interferon regulatory factor protein

Herpesvirus-associated ubiquitin specific protease (HAUSP) regulates the stability of p53 and MDM2, implicating HAUSP as a therapeutic target for tuning p53-mediated anti-tumor activity. Here, we report the structural analysis of HAUSP with Kaposi’s sarcoma-associated herpesvirus vIRF4 and the discovery of two vIRF4-derived peptides, vif1 and vif2, as potent and selective HAUSP antagonists. This analysis reveals a bilateral belt-type interaction resulting in inhibition of HAUSP. The vif1 peptide binds the HAUSP TRAF domain, competitively blocking substrate binding, while the vif2 peptide binds both the HAUSP TRAF and catalytic domains, robustly suppressing its deubiquitination activity. Consequently, peptide treatments comprehensively blocked HAUSP, leading to p53-dependent cell cycle arrest and apoptosis in culture and tumor regression in xenograft mouse model. Thus, the virus has developed a unique molecular strategy to target the HAUSP-MDM2-p53 pathway, and these virus-derived short peptides represent biologically active HAUSP antagonists

Noncovalent Interactions of Hydrated DNA and RNA Mapped by 2D-IR Spectroscopy

Biomolecules couple to their aqueous environment through a variety of noncovalent interactions. Local structures at the surface of DNA and RNA are frequently determined by hydrogen bonds with water molecules, complemented by non-specific electrostatic and many-body interactions. Structural fluctuations of the water shell result in fluctuating Coulomb forces on polar and/or ionic groups of the biomolecular structure and in a breaking and reformation of hydrogen bonds. Two-dimensional infrared (2D-IR) spectroscopy of vibrational modes of DNA and RNA gives insight into local hydration geometries, elementary molecular dynamics, and the mechanisms behind them. In this chapter, recent results from 2D-IR spectroscopy of native and artificial DNA and RNA are presented, together with theoretical calculations of molecular couplings and molecular dynamics simulations. Backbone vibrations of DNA and RNA are established as sensitive noninvasive probes of the complex behavior of hydrated helices. The results reveal the femtosecond fluctuation dynamics of the water shell, the short-range character of Coulomb interactions, and the strength and fluctuation amplitudes of interfacial electric fields.Comment: To appear as Chapter 8 of Springer Series in Optical Sciences: Coherent Multidimensional Spectroscopy -- Editors: Cho, Minhaeng (Ed.), 201

IL-3 and oncogenic Abl regulate the myeloblast transcriptome by altering mRNA stability

The growth factor interleukin-3 (IL-3) promotes the survival and growth of multipotent hematopoietic progenitors and stimulates myelopoiesis. It has also been reported to oppose terminal granulopoiesis and to support leukemic cell growth through autocrine or paracrine mechanisms. The degree to which IL-3 acts at the posttranscriptional level is largely unknown. We have conducted global mRNA decay profiling and bioinformatic analyses in 32Dcl3 myeloblasts indicating that IL-3 caused immediate early stabilization of hundreds of transcripts in pathways relevant to myeloblast function. Stabilized transcripts were enriched for AU-Response elements (AREs), and an ARE-containing domain from the interleukin-6 (IL-6) 3′-UTR rendered a heterologous gene responsive to IL-3-mediated transcript stabilization. Many IL-3-stabilized transcripts had been associated with leukemic transformation. Deregulated Abl kinase shared with IL-3 the ability to delay turnover of transcripts involved in proliferation or differentiation blockade, relying, in part, on signaling through the Mek/ Erk pathway. These findings support a model of IL-3 action through mRNA stability control and suggest that aberrant stabilization of an mRNA network linked to IL-3 contributes to leukemic cell growth. © 2009 Ernst et al