Dalyelgaard4114

The formation and decomposition of inclusion compounds with a solid-solid phase transition may be very selective to the guest molecular structure. This selectivity may function in essentially different ways than defined by the classical concept of molecular recognition, which implies the preferential binding of complementary molecules. Solid inclusion compounds may take part as an initial or/and final state in several processes of different types summarized in this review, which selectivity is boosted by cooperativity of participating molecular crystals. Some of these processes resemble switching electronic devices and can be called smart giving practically absolute molecular recognition. Copyright © 2020 Gatiatulin, Ziganshin and Gorbatchuk.The Ubiquitin CODE constitutes a unique post-translational modification language relying on the covalent attachment of Ubiquitin (Ub) to substrates, with Ub serving as the minimum entity to generate a message that is translated into different cellular pathways. The creation of this message is brought about by the dedicated action of writers, erasers, and readers of the Ubiquitin CODE. This CODE is greatly expanded through the generation of polyUb chains of different architectures on substrates thus regulating their fate. Through additional post-translational modification by Ub-like proteins (UbL), hybrid Ub/UbL chains, which either alter the originally encrypted message or encode a completely new one, are formed. Hybrid Ub/UbL chains are generated under both stress or physiological conditions and seem to confer improved specificity and affinity toward their cognate receptors. In such a manner, their formation must play a specific, yet still undefined role in cellular signaling and thus understanding the UbCODE message is crucial. Here, we discuss the evidence for the existence of hybrid Ub/UbL chains in addition to the current understanding of its biology. find more The modification of Ub by another UbL complicates the deciphering of the spatial and temporal order of events warranting the development of a hybrid chain toolbox. We discuss this unmet need and expand upon the creation of tailored tools adapted from our previously established toolkit for the Ubiquitin Proteasome System to specifically target these hybrid Ub/UbL chains. Copyright © 2020 Pérez Berrocal, Witting, Ovaa and Mulder.Ca2+-overload contributes to the oxidation of mitochondrial membrane lipids and associated events such as the permeability transition pore (MPTP) opening. Numerous experimental studies about the Ca2+/cardiolipin (CL) interaction are reported in the literature, but there are few studies in conjunction with theoretical approaches based on ab initio calculations. In the present study, the lipid fraction of the inner mitochondrial membrane was modeled as POPC/CL large unilamellar vesicles (LUVs). POPC/CL and, comparatively, POPC, and CL LUVs were challenged by singlet molecular oxygen using the anionic porphyrin TPPS4 as a photosensitizer and by free radicals produced by Fe2+-citrate. Calcium ion favored both types of lipid oxidation in a lipid composition-dependent manner. In membranes containing predominantly or exclusively POPC, Ca2+ increased the oxidation at later reaction times while the oxidation of CL membranes was exacerbated at the early times of reaction. Considering that Ca2+ interaction affects the lipid structure and packing, density functional theory (DFT) calculations were applied to the Ca2+ association with totally and partially protonated and deprotonated CL, in the presence of water. The interaction of totally and partially protonated CL head groups with Ca2+ decreased the intramolecular P-P distance and increased the hydrophobic volume of the acyl chains. Consistently with the theoretically predicted effect of Ca2+ on CL, in the absence of pro-oxidants, giant unilamellar vesicles (GUVs) challenged by Ca2+ formed buds and many internal vesicles. Therefore, Ca2+ induces changes in CL packing and increases the susceptibility of CL to the oxidation promoted by free radicals and excited species. Copyright © 2020 Miranda, Araujo-Chaves, Kawai, Brito, Dias, Arantes and Nantes-Cardoso.Active agents targeting key bacterial interactions that initiate biofilm formation in the oral cavity, may alter periodontitis progression; however, to date, specifically-targeted prophylactic and treatment strategies have been limited. link2 Previously we developed a peptide, BAR (SspB Adherence Region), that inhibits oral P. gingivalis/S. gordonii biofilm formation in vitro and in vivo, and BAR nanoparticles that increase BAR effectiveness via multivalency and prolonged delivery. However, limited BAR loading and nanoparticle retention in the oral cavity can result in inadequate release and efficaciousness. Given this, an effective delivery platform that can release concentrations of BAR suitable for twice-daily applications, may offer an alternative that enhances loading, ease of administration, and retention in the oral cavity. With this in mind, the study objectives were to develop and characterize a rapid-release platform, composed of polymeric electrospun fibers (EFs) that encapsulate BAR, and to evaluate fiber safety and functionality against P. gingivalis/S. gordonii biofilms in vitro. Poly(lactic-co-glycolic acid) (PLGA), poly(L-lactic acid) (PLLA), and polycaprolactone (PCL) were electrospun alone or blended with polyethylene oxide (PEO), to provide high BAR loading and rapid-release. The most promising formulation, 1090 PLGAPEO EFs, provided 95% BAR release after 4 h, dose-dependent inhibition of biofilm formation (IC50 = 1.3 μM), disruption of established dual-species biofilms (IC50 = 2 μM), and maintained high cell viability. These results suggest that BAR-incorporated EFs may provide a safe and specifically-targeted rapid-release platform to inhibit and disrupt dual-species biofilms, that we envision may be applied twice-daily to exert prophylactic effect in the oral cavity. Copyright © 2020 Mahmoud, Sapare, Curry, Demuth and Steinbach-Rankins.The interferon (IFN)-stimulated gene product 15 (ISG15) represents an ubiquitin-like protein (Ubl), which in a process termed ISGylation can be covalently linked to target substrates via a cascade of E1, E2, and E3 enzymes. Furthermore, ISG15 exerts functions in its free form both, as an intracellular and as a secreted protein. In agreement with its role as a type I IFN effector, most functions of ISG15 and ISGylation are linked to the anti-pathogenic response. However, also key roles in other cellular processes such as protein translation, cytoskeleton dynamics, exosome secretion, autophagy or genome stability and cancer were described. Ubiquitin-specific protease 18 (USP18) constitutes the major ISG15 specific protease which counteracts ISG15 conjugation. Remarkably, USP18 also functions as a critical negative regulator of the IFN response irrespective of its enzymatic activity. Concordantly, lack of USP18 function causes fatal interferonopathies in humans and mice. The negative regulatory function of USP18use models for translational perspectives, cell-based and biochemical assays as well as chemical probes. Copyright © 2020 Jiménez Fernández, Hess and Knobeloch.Ubiquitination is a process in which a protein is modified by the covalent attachment of the C-terminal carboxylic acid of ubiquitin (Ub) to the ε-amine of lysine or N-terminal methionine residue of a substrate protein or another Ub molecule. Each of the seven internal lysine residues and the N-terminal methionine residue of Ub can be linked to the C-terminus of another Ub moiety to form 8 distinct Ub linkages and the resulting differences in linkage types elicit different Ub signaling pathways. Cellular responses are triggered when proteins containing ubiquitin-binding domains (UBDs) recognize and bind to specific polyUb linkage types. To get more insight into the differences between polyUb chains, all of the seven lysine-linked di-ubiquitin molecules (diUbs) were prepared and used as a model to study their structural conformations in solution using NMR spectroscopy. link3 We report the synthesis of diUb molecules, fully 15N-labeled on the distal (N-terminal) Ub moiety and revealed their structural orientation wit Ub signaling. The isotopically labeled diUb compounds described here and the use of NMR to study their interactions with relevant partner molecules will help accelerate our understanding of Ub signaling pathways. Copyright © 2020 Shahul Hameed, van Tilburg, Merkx, Flierman, Wienk, El Oualid, Hofmann, Boelens and Ovaa.EGFR and VEGFR-2 represent promising targets for cancer treatment as they are very important in tumor development as well as in angiogenesis and metastasis. In this work, 6-amino-4-(2-bromophenyl)-3-methyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile 1 and (E)-4-(2-Bromobenzylidene)-5-methyl-2,4-dihydro-3H-pyrazol-3-one 11 were selected as starting materials to synthesize different fused pyrazole derivatives; dihydropyrano[2,3-c]pyrazole 1, 2, 7-9, and 15, pyrazolo[4',3'5,6]pyrano[2,3-d]pyrimidine 3-6, pyrazolo[3,4-d]pyrimidine 12 and 13, and pyrazolo[3,4-c]pyrazole 14 derivatives were synthesized to evaluate their anticancer activity against HEPG2 human cancer cell lines compared to erlotinib and sorafenib as reference drugs. Seven compounds 1, 2, 4, 8, 11, 12, and 15 showed nearly 10 fold higher activity than erlotinib (10.6 μM) with IC50 ranging from 0.31 to 0.71 μM. In vitro EGFR and VEGFR-2 inhibitory activity were performed for the synthesized compounds, and the results identified compound 3 as the most potent EGFR inhibitor (IC50 = 0.06 μM) and compound 9 as the most potent VEGFR-2 inhibitor (IC50 = 0.22 μM). Moreover, compounds 9 and 12 revealed potent dual EGFR and VEGFR-2 inhibition, and these results were supported by docking studies of these two compounds within the active sites of both enzymes. Copyright © 2020 Saleh, El-Gazzar, Aly and Othman.Phytochemical investigation of Aesculus chinensis Bge. var. chekiangensis (Hu et Fang) Fang obtained 33 triterpenoid saponins, including 14 new ones, aesculiside C-P (1-14). The structure elucidations were performed through comprehensive MS, 1D and 2D-NMR analysis, and their absolute configuration was unambiguously determined by X-ray diffraction analysis as well as Mo2(OAc)4-induced ECD method for the first time. All the substances were examined for their cytotoxic activities against three tumor cell lines, Hep G2, HCT-116, and MGC-803. Of these, compounds 8, 9, 14-16, 18, and 22 exhibited potent cytotoxicities against all cell lines with IC50 of 2-21 μM, while compounds 3, 6, 7, 17-19, 20, 24, and 28 depicted moderate activity (IC50 13 to >40 μM). On these bases, the preliminary structure-activity correlations were also discussed. Meanwhile the neuroprotective properties of triterpenoid saponins from Aesculus genus were evaluated for the first time. Among them, compounds 1, 4, 12, 20, 22, 25, 29, and 31 exhibited moderate activities against COCl2-induced PC12 cell injury. Copyright © 2020 Zhang, Wei, Cao, Zhang, Kang, Ding and Qiu.Gas sensors were fabricated from Cr2WO6 nanoparticles for NO2 detection. Low dimensional materials Cr2WO6 were prepared by a wet chemistry method followed by hydrothermal treatment. The morphology of the nanoparticles and their sensing properties to NO2 were investigated in both dry and humid conditions. Additionally, the sensing response was also characterized in a non-oxygen condition. It was concluded that the sensor responses in N2 conditions were higher than that in air conditions at 200°C. Moreover, the sensing characteristics were inhibited by water vapor at 200°C. The oxygen adsorption behavior was also investigated to verify the basic sensing mechanism of Cr2WO6 in the absence and presence of NO2 and water vapor separately. Based on the power law response, it was indicated that both NO2 and water vapor have a strong adsorption ability than oxygen ions of Cr2WO6 sensors. Copyright © 2020 Wu, Yan, Tian, Liu and Hua.