Histone H3 encoding genes, particularly H3F3A and H3F3B, the genes encoding the variant histone H3.3, are mutated at high frequency in pediatric brain and bone malignancies. Compared to the extensive studies on K27M and K36M mutations, little is known about the mechanism of G34 mutations found in pediatric glioblastoma or giant cell tumors of the bone. Here we report that unlike the K27M or K36M that affect global histone methylation, the giant cell tumors of the bone G34 mutations (G34L/W) only affect histone H3K36 and H3K27 methylation on the same mutated histone tails (in cis), a mechanism distinct from known histone mutations. (C) 2018 Elsevier Ltd. All rights reserved.

Despite years of effort and investment, there are few topical or systemic medications for skin wounds. Identifying natural drivers of wound healing could facilitate the development of new and effective treatments. When skin is injured, there is a massive increase of heat shock protein (Hsp) 90 alpha inside the wound bed. The precise role for these Hsp90 alpha proteins, however, was unclear. The availability of a unique mouse model that lacked the intracellular ATPase-driven chaperoning, but spared the extracellular fragment-5-supported pro-motility function of Hsp90 alpha allowed us to test specifically the role of the non-chaperone function of Hsp90 alpha in normal wound closure. We found that the chaperone-defective Hsp90 alpha-D mutant mice showed similar wound closure rate as the wild-type Hsp90 alpha mice. We generated recombinant proteins from the mouse cDNAs encoding the Hsp90 alpha-D and wild-type Hsp90 alpha. Topical application of Hsp90 alpha-D mutant protein promoted wound closure as effectively as the full-length wild-type Hsp90 alpha protein. More importantly, selective inhibition of the extracellular Hsp90 alpha-D protein function by a monoclonal antibody targeting the fragment-5 region disrupted normal wound closure in both wild-type Hsp90 alpha and Hsp90 alpha-D mice. Thus, this study provides direct support for non-chaperone, extracellular Hsp90 alpha as a potential driver for normal wound closure.

PlxnB2 and its ligand, CD100, were originally identified as axon-guidance molecules that function during neuronal development; however, studies also showed that CD100-plexins participate in various immune responses. In this study, we found that the expression of PlxnB2 on keratinocytes was specifically increased in lesional skin of psoriasis patients but not atopic dermatitis. Levels of soluble CD100 and membrane-bound CD100 were elevated in sera of psoriasis patients and on keratinocytes of psoriatic skin, respectively. By binding to PlxnB2, soluble CD100 promoted the production of CXCL-1, CCL-20, IL-1 beta, and IL-18 by keratinocytes and activated the NLRP3 inflammasome. Moreover, CD100-PlxnB2 stimulated the NF-kappa B signaling pathway in keratinocytes through activation of small GTPase RhoA and Rac1. Our data showed that cooperation of CD100 and PlxnB2 promoted the inflammatory responses in keratinocytes by activating NF-kappa B and the NLRP3 inflammasome and participated in the pathogenesis of psoriasis. CD100/PlxnB2 might be a potential therapeutic target for psoriasis.

The characteristics of micropore (0.32-2 nm), mesopores (2-50 nm) and fractal dimensions of bituminous coal during the process of cyclic gas adsorption/desorption were revealed by combining N-2 (77 K) and CO2 (273 K) adsorption experiments from microscopic aspect. The results indicate that the pore structure characterization in the coal matrix are changed, resulting in decreased mesopore volumes and increased micropore volumes. The mesopore volumes are mainly constituted by the pores of 10-20, and 20-30 nm, and it will increase at first and then decrease with the increasing pressures. The maximum change of micropore volume reaches 65.6%, indicating a great effect on the micropores influenced by pressures. In addition, the main micropore size range, major peak and the model diameter of coals all increase with the increasing pressures, the higher the adsorb pressure is, the higher swelling is. With the help of the conceptual models, we then analyzed the variation reasons, which may be result from transformation of mesopores and the connection of the inaccessible pores. D-1 and D-2 in #1 and D-2 in #2 all increase with the increasing adsorption pressures, enhancing the roughness of surface and complexity of structure, while D-1 in #2 shows an opposite property. The study of variations of microscopic pore structure by cyclic adsorption/desorption was aimed at providing new understanding for the exploration of the changes of diffusion and permeability.

Metal Organic Frameworks or related carbon materials are the ideal materials for supercapacitors due to their high surface area and unique porous structure. Here, we propose a new green and recyclable synthesis method of porous carbon. Aluminum hydroxide (Al(OH)(3)) and trimesic acid (BTC) are employed as raw materials to obtain aluminium trimesic (denoted as Al-BTC) via their covalent reaction. Then, the porous carbon is obtained through carbonization and dissolving process to remove the aluminum oxide (Al2O3). Al(OH)(3) is recovered by the Bayer method for the next batch. The SEM images show that the porous carbon has rugby-like morphology with the same of 400 nm wide and 1000 nm long which indicates the porous carbon with c/a ratio of 2.5 providing the largest specific volume surface area. The sample offers 306.4 F g(-1) at 1 A g(-1), and it can retain 72.2% even at the current density of 50 A g(-1). In addition, the porous carbon provides excellent durability of 50,000 cycles at 50 A g(-1) with only 5.05% decline of capacitance. Moreover, the porous carbon has an ultrafast charge acceptance, and only 4.4 s is required for one single process, which is promising for application in electric vehicles.

Carbon-11-labeled serotonin (5-hydroxytryptamine) 6 receptor (5-HT6R) antagonists, 1-[(2-bromophenyl)sulfonyl]-5-[C-11]methoxy-3-[(4-methyl-1-piperazinyl)methyl]-1H-indole (O-[C-n]2a) and 1-[(2-bromophenyl)sulfonyl]-5-methoxy-3-[(4-[C-11]methyl-1-piperazinyl)methyl]-1H-indole (N-[C-11] 2a), 5-[C-11]methoxy-3-((4-methylpiperazin-1-yl)methyl)-1-(phenylsulfonyl)-1H-indole (O[(n11)]2b) and 5-methoxy-3-((4-[C-11]methylpiperazin-l1yl)methyl)-l1(phenylsulfonyl)-l1-indole (N-[1(1C)]2b), l1((4isopropylphenyl)sulfonyl)-5-[C-11]methoxy-3-((4-methylpiperazin-l1yl)methyl)-l1-indole (0O[C-11]2c) and l1((4-isopropylphenyl)sulfonyl)-5-methoxy-3-((4-[C-11]methylpiperazin-l1yl)methyl)-l1-indole (N-[(n11)]2c), l1((4-fluorophenyl)sulfonyl)-5-[C-11]methoxy-3-((4-methylpiperazin-l1yl)methyl)-lHm-inole (0O[C-11]2d) and l-((4-fluorophenyl)sulfonyl)-5-methoxy-3-((4-[C-11]methylpiperazin-l1yl) methyl)-l1-indole (N-[C-11]2d), were prepared from their 0O or N-desmethylated precursors with [C-11] CH3OTf through 0O or N-f[(11)J]ethylation and isolated by HPLC combined with SPE in 40-50% radiochemical yield, based on [C-11]C0O and decay corrected to end of bombardment (EOB). The radiochemical purity was <99%, and the molar activity (MA) at EOB was 370-740 GBq/p mu ol with a total synthesis time of similar to 40-min from EOB. (C) (C)2018 Elsevier Ltd. All rights reserved.