Key Points IRF8 induces the Klf4 gene in myeloid progenitors; this transcription factor cascade is essential for Ly6C+ monocyte development. IRF8 binding to genomic targets promotes H3K4me1, a chromatin signature for promoter-distal enhancers, thereby inducing gene expression.
Recombinant glycerol dehydratase of Klebsiella pneumoniae was purified to homogeneity. The subunit composition of the enzyme was most probably a 2 b 2 c 2 . When (R)-and (S)-propane-1,2-diols were used independently as substrates, the rate with the (R)-enantiomer was 2.5 times faster than that with the (S)-isomer. In contrast to diol dehydratase, an isofunctional enzyme, the affinity of the enzyme for the (S)-isomer was essentially the same or only slightly higher than that for the (R)-isomer (K m(R) /K m(S) ¼ 1.5). The crystal structure of glycerol dehydratase in complex with cyanocobalamin and propane-1,2-diol was determined at 2.1 Å resolution. The enzyme exists as a dimer of the abc heterotrimer. Cobalamin is bound at the interface between the a and b subunits in the so-called Ôbase-onÕ mode with 5,6-dimethylbenzimidazole of the nucleotide moiety coordinating to the cobalt atom. The electron density of the cyano group was almost unobservable, suggesting that the cyanocobalamin was reduced to cob(II)alamin by X-ray irradiation. The active site is in a (b/a) 8 barrel that was formed by a central region of the a subunit. The substrate propane-1,2-diol and essential cofactor K + are bound inside the (b/a) 8 barrel above the corrin ring of cobalamin. K + is heptacoordinated by the two hydroxyls of the substrate and five oxygen atoms from the active-site residues. These structural features are quite similar to those of diol dehydratase. A closer contact between the a and b subunits in glycerol dehydratase may be reminiscent of the higher affinity of the enzyme for adenosylcobalamin than that of diol dehydratase. Although racemic propane-1,2-diol was used for crystallization, the substrate bound to glycerol dehydratase was assigned to the (R)-isomer. This is in clear contrast to diol dehydratase and accounts for the difference between the two enzymes in the susceptibility of suicide inactivation by glycerol.Keywords: coenzyme B 12 ; adenosylcobalamin; glycerol dehydratase; crystal structure; radical enzyme catalysis.Adenosylcobalamin is one of the most unique compounds in nature. It is a water-soluble organometallic compound possessing a Co-C r bond and serves as a cofactor for enzymatic radical reactions including carbon skeleton rearrangements, heteroatom eliminations and intramolecular amino group migrations [1]. Diol dehydratase (EC 4.2.1.28) of Klebsiella oxytoca is an adenosylcobalamin (AdoCbl 1 ) dependent enzyme that catalyzes the conversions of 1,2-diols, such as propane-1,2-diol, glycerol, and 1,2-ethanediol, to the corresponding aldehydes [2,3] (Fig. 1). This enzyme has been studied intensively to establish the mechanism of action of AdoCbl [4][5][6][7]. The structurefunction relationship of the coenzyme has also been investigated extensively with this enzyme [5][6][7][8]. Recently, we have reported the three-dimensional structures of its complexes with cyanocobalamin [9] and adeninylpentylcobalamin [10] and theoretical calculations of the entire energy profile along the reaction pathway with a simplifie...
We report the first quantum key distribution (QKD) systems capable of delivering sustainable, real-time secure keys continuously at rates exceeding 10 Mb/s. To achieve such rates, we developed high speed post-processing modules, achieving maximum data throughputs of 60 MC/s, 55 Mb/s, and 108 Mb/s for standalone operation of sifting, error correction and privacy amplification modules, respectively. The photonic layer of the QKD systems features high-speed single photon detectors based on self-differencing InGaAs avalanche photodiodes, phase encoding using asymmetric Mach-Zehnder interferometer, and active stabilization of the interferometer phase and photon polarisation. An efficient variant of the decoy-state BB84 protocol is implemented for security analysis, with a large dataset size of 10 8 bits selected to mitigate finite-size effects. Over a 2 dB channel, a record secure key rate of 13.72 Mb/s has been achieved averaged over 4.4 days of operation. We confirm the robustness and long-term stability on a second QKD system continuously running for 1 month without any user intervention.
Securing information in communication networks is an important challenge in today's world. Quantum Key Distribution (QKD) can provide unique capabilities towards achieving this security, allowing intrusions to be detected and information leakage avoided. We report here a record high bit rate prototype QKD system providing a total of 878 Gbit of secure key data over a 34 day period corresponding to a sustained key rate of around 300 kbit/s. The system was deployed over a standard 45 km link of an installed metropolitan telecommunication fibre network in central Tokyo. The prototype QKD system is compact, robust and automatically stabilised, enabling key distribution during diverse weather conditions. The security analysis includes an efficient protocol, finite key size effects and decoy states, with a quantified key failure probability of ε = 10⁻¹⁰.
Key Points IRF8 promotes Gata2 expression in GPs, thereby playing a key role in the development of basophils and mast cells.
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