Search

A multi-omic analysis of 11 Mycobacterium tuberculosis (Mtb) isolates with different drug resistance profiles leads to the discovery of Rv3094c, an enzyme capable of activating the clinically relevant Mtb drug, ethionamide.

Abstract The Legionella pneumophila effector MavC is a transglutaminase that carries out atypical ubiquitination of the host ubiquitin (Ub)‐conjugation enzyme UBE2N by catalyzing the formation of an isopeptide bond between Gln40Ub and Lys92UBE2N, which leads to inhibition of signaling in the NF‐κB pathway. In the absence of UBE2N, MavC deamidates Ub at Gln40 or catalyzes self‐ubiquitination. However, the mechanisms underlying these enzymatic activities of MavC are poorly understood at the molecular level. This study reports the structure of the MavC–UBE2N–Ub ternary complex representing a snapshot of MavC‐catalyzed crosslinking of UBE2N and Ub, which reveals the way by which UBE2N–Ub binds to the Insertion and Tail domains of MavC. Based on the structural and experimental data, the catalytic mechanism for the deamidase and transglutaminase activities of MavC is proposed. Finally, by comparing the structures of MavC and MvcA, the homologous protein that reverses MavC‐induced UBE2N ubiquitination, several essential regions and two key residues (Trp255MavC and Phe268MvcA) responsible for their respective enzymatic activities are identified. The results provide insights into the mechanisms for substrate recognition and ubiquitination mediated by MavC as well as explanations for the opposite activity of MavC and MvcA in terms of regulation of UBE2N ubiquitination.

Expression of major histocompatibility complex class II (MHC II) molecules, which determines both the immune repertoire during development and subsequent triggering of immune responses, is always under the control of a unique (MHC class II) transactivator, CIITA. The IFN-γ-inducible MHC II expression has been extensively and thoroughly studied in humans, but not in bony fish. In this study, the characterization of CIITA was identified and its functional domains were analyzed in grass carp. The absence of GAS and E-box in the promoter region of grass carp CIITA, might imply that the cooperative interaction between STAT1 and USF1 to active the CIITA expression, found in mammals, is not present in bony fish. After the transfection of IFN-γ or IFN-γ rel, only IFN-γ could induce MHC II expression mediated by CIITA. Moreover, interferon regulatory factor (IRF) 2, which cooperates with IRF1 to active the CIITA promoter IV expression in mammals, played an antagonistic role to IRF1 in the activation of grass carp CIITA. These data suggested that grass carp, compared with mammals, has both conservative and unique mechanisms in the regulation of MHC II expression.

Experimental determination of the fatigue limit is expensive considering the time and effort involved. To overcome this drawback, several empirical relations based on monotonic tensile properties and/or hardness have been developed for estimating the fatigue limit. In this study, ten estimation methods are evaluated and compared using the experimental data of 171 steels from literature. The scatter band criterion, standard deviation criterion, and statistical analysis are all used to evaluate and compare the predictability of the considered empirical relations. It is found that the fatigue limit can be well correlated with the Brinell hardness. In the absence of Brinell hardness, the ultimate tensile strength-based direct estimation method may be an alternative to estimate the fatigue limit of steels. It is not recommended to estimate the fatigue limit by using the indirect method on the basis of Basquin’s fatigue properties estimated by the monotonic tensile properties even though the fatigue limit of steel is often determined by the experimental Basquin’s curve at 106 cycles.

In aquafeeds, fish-meal has been commonly replaced with plant protein, which often causes enteritis. Currently, foodborne enteritis has few solutions in regards to prevention or cures. The recovery mechanism from enteritis in herbivorous fish may further help understand prevention or therapy. However, few reports could be found regarding the recovery or resilience to fish foodborne enteritis. In this study, grass carp was used as an animal model for soybean meal induced enteritis and it was found that the fish could adapt to the soybean meal at a moderate level of substitution. Resilience to soybean meal stress was found in the 40% soybean meal group for juvenile fish at growth performance, morphological and gene expression levels, after a 7-week feeding trial. Furthermore, the intestinal transcriptomic data, including transcriptome and miRNAome, was applied to demonstrate resilience mechanisms. The result of this study revealed that in juvenile grass carp after a 7-week feeding cycle with 40% soybean meal, the intestine recovered via enhancing both an immune tolerance and wound healing, the liver gradually adapted via re-balancing immune responses, such as phagosome and complement cascades. Also, many immune factors in the gut and liver were systemically revealed among stages of on-setting, remising, and recovering (or relief). In addition, miRNA regulation played a key role in switching immune states. Thus, the present data systemically demonstrated that the molecular adaptation mechanism of fish gut-liver immunity is involved in the resilience to soybean meal stress.

Two new mixed-ligand complexes of formula [Cu(mal)(abpt)(H2O)].3/2H2O (1) and [Cu2(sq)(abpt)2].2H2O (2) [mal = malonate, abpt = 4-amino-3,5-di-2-pyridyl-4H-1,2,4 triazole and sq = squarate], have been prepared and characterized by X-ray crystal structure determination and magnetic studies. Complex 1 crystallizes in the monoclinic system, space group C2/c, with a = 14.0086(2) Å, b = 10.0980(2) Å, c = 25.630(4) Å; β = 97.5900(10) o, and Z = 8. Complex 2 crystallizes in the triclinic system, space group P-1 with a = 7.5696(15) Å, b = 8.4697(17) Å, c = 11.049(2) Å; β = 93.00(3)o, α = 96.98(3), γ = 90.111(3) and Z = 1. Complex 1 consist of a neutral mononuclear [Cu(mal)(abpt)(H2O)] unit and water molecule of crystallization in a distorted square pyramidal coordination sphere, while complex 2 is viewed as being made up of [Cu(sq)(abpt)2] units with the squarato ligand bridging the two copper(II) cations. Variable temperature magnetic behaviour of the complexes reveals the existence of weak antiferromagnetic interaction for complex 1 and weak ferromagnetic intrachain interaction for complex 2.

Two new cadmium(II) coordination polymers [Cd(HL)(H2O)]·1.5H2O (1) and [Cd(HL)(4-bpmp)0.5]·2H2O (2) (H3L = 4,4'-phosphinicobis-dibenzoic acid, and 4-bpmp = N,N'-bis(4-pyridylmethyl)piperazine) have been synthesized by self-assembly of CdCl2 with 4,4'-phosphinicobis-dibenzoate, and N,N'-bis(4-pyridylmethyl)piperazine through solvothermal/hydrothermal method. Their structures were confirmed by X-ray single crystal diffraction, infrared spectrometer (IR), and powder X-ray diffraction (PXRD) and TGA techniques. Both compounds are in Pī space group and exhibited a 2D networks constructed from dinuclear [Cd2(POO)2] or paddle-wheel [Cd2(COO)2(POO)2] units, respectively. In 2, the Cd2+ is five-coordinated and shows a rare tetragonal pyramidal geometry. At room temperature, the compounds exhibit moderately intense blue and green fluorescence emission with peaks at 381 nm and 509 nm, respectively. [ABSTRACT FROM AUTHOR]

Spring viremia of carp virus (SVCV) is a highly pathogenic Vesiculovirus infecting the common carp, yet neither a vaccine nor effective therapies are available to treat spring viremia of carp (SVC). Like all negative-sense viruses, SVCV contains an RNA genome that is encapsidated by the nucleoprotein (N) in the form of a ribonucleoprotein (RNP) complex, which serves as the template for viral replication and transcription. Here, the three-dimensional (3D) structure of SVCV RNP was resolved through cryo-electron microscopy (cryo-EM) at a resolution of 3.7 Å. RNP assembly was stabilized by N and C loops; RNA was wrapped in the groove between the N and C lobes with 9 nt nucleotide per protomer. Combined with mutational analysis, our results elucidated the mechanism of RNP formation. The RNA binding groove of SVCV N was used as a target for drug virtual screening, and it was found suramin had a good antiviral effect. This study provided insights into RNP assembly, and anti-SVCV drug screening was performed on the basis of this structure, providing a theoretical basis and efficient drug screening method for the prevention and treatment of SVC. IMPORTANCE Aquaculture accounts for about 70% of global aquatic products, and viral diseases severely harm the development of aquaculture industry. Spring viremia of carp virus (SVCV) is the pathogen causing highly contagious spring viremia of carp (SVC) disease in cyprinids, especially common carp (Cyprinus carpio), yet neither a vaccine nor effective therapies are available to treat this disease. In this study, we have elucidated the mechanism of SVCV ribonucleoprotein complex (RNP) formation by resolving the 3D structure of SVCV RNP and screened antiviral drugs based on the structure. It is found that suramin could competitively bind to the RNA binding groove and has good antiviral effects both in vivo and in vitro. Our study provides a template for rational drug discovery efforts to treat and prevent SVCV infections. [ABSTRACT FROM AUTHOR]

A novel zero-dimensional (0D) octacyanotungstate(V)-manganese(II) bimetallic assembly is prepared in methanol solution containing oxalic acid. The magnetostructural correlation has disclosed that cyanide and oxalate bridges have mediated weak intracluster antiferromagnetic coupling between Mn and W ions and between Mn ions, respectively.

Spring viremia of carp virus (SVCV) is a highly pathogenic Vesiculovirus in the common carp. The phosphoprotein (P protein) of SVCV is a multifunctional protein that acts as a polymerase cofactor and an antagonist of cellular interferon (IFN) response. Here, we report the 1.5 Å-resolution crystal structure of the P protein central domain (PCD) of SVCV (SVCVPCD). The PCD monomer consists of two β sheets, an α helix, and another two β sheets. Two PCD monomers pack together through their hydrophobic surfaces to form a dimer. The mutations of residues on the hydrophobic surfaces of PCD disrupt the dimer formation to different degrees and affect the expression of host IFN consistently. Therefore, the oligomeric state formation of the P protein of SVCV is an important mechanism to negatively regulate host IFN response. [ABSTRACT FROM AUTHOR]

Seven novel coordination polymers based on 2,2′-phosphinico-dibenzoic acid (H3L), namely, {[Zn3L2(H2O)4]·2H2O}n (1), [Zn3L2(4,4′-bipy)2]n (2), [Zn(HL)(2,2′-bipy)(H2O)]n (3), {[Cd9L6(H2O)8]·4H2O}n (4), [Cd8L4(OH)2(OAc)2(4,4′-bipy)]n (5), [Mn3L2(4,4′-bipy)(EtOH)(H2O)2]n (6), and [Mn(HL)(2,2′-bipy)(H2O)]n (7), were synthesized under hydro(solvo)thermal conditions. These compounds crystallize in the triclinic P1̅ space group for 1, 4, 5, and 6, the monoclinic space group C2/c for 2, and the monoclinic P21/c space group for 3 and 7. The L3- ligand displays versatile binding modes in 1-7. Compound 1 is a one-dimensional (1-D) chain coordination polymer with a three-dimensional (3-D) supramolecular framework. Compound 2 is a 3-D porous metal-organic framework (MOF) with two different 4,4′-bipyridine linkers. Compounds 3 and 7 show 1-D zigzag chain structures. Compound 4 exhibits a sophisticated 3-D MOF constructed from two types of Cd8 clusters and one Cd2 dimer, which is the first example exhibiting the coexistence of four coordination modes of L3- ligands and four geometries of Cd(II) ions in one network. Compound 5 displays a two-dimensional (2-D) network containing a ring-like Cd8 cluster. Compound 6 shows a 2-D layered network with 4,4′-bipyridine linker. Their luminescence and variable-temperature magnetic property were investigated, which indicated ligand-centered emission in 1-5 and weak antiferromagnetic coupling between Mn(II) ions in 6 and 7. [ABSTRACT FROM AUTHOR]

The hydrothermal reaction of silver nitrate and 2,2'-phosphinico-dibenzoic acid (H3L) with different metal to ligand ratios under hydrothermal conditions yielded two unusual complexes with the formulae of [Ag(H2L)]n (1) and [Ag3(L)]n (2). Both complexes were well characterized by single-crystal X-ray diffraction, elemental analysis, IR spectroscopic and fluorescence studies. Complex 1 crystallizes in a centrosymmetric Pbcn space group and presents a two-dimensional (2D) layer structure through silver(I)-aromatic interaction, whereas complex 2 adopts a noncentrosymmetric Iba2 space group, in which the different coordination modes of the four groups around the phosphorus atom in the L3-ligand occurs. Both complexes display green emissions, assigned as the ligand-to-metal charge-transfer character. [ABSTRACT FROM AUTHOR]

Seven coordination polymers, namely [Mn(4-cptpy)2]n (1), [Co(4-cptpy)2]n (2), [Mn3(4-cptpy)6(H2O)]n. 2nH2O (3), [Co(4-cptpy)(HCOO)(H2O)]n'nDMF (4), [Zn2(4-Hcptpy)2Cl4]n.2nC2H5OH.nH2O (5), [Co4- (3-cptpy)4(HCOO)4(H2O)2]n (6), and [Mn(3-cptpy)2]n (7) (4-Hcptpy = 4-(4-carboxyphenyl)-4,2':6',4"-terpyridine; 3-Hcptpy = 4-(4-carboxyphenyl)-3,2':6',3"-terpyridine), have been synthesized under hydro- (solvo)thermal conditions and structurally characterized. A general solvothermal method is proposed for preparing carboxylate complexes in DMF solution without any basic additive. 1 and 2 possess isostructural 3D metal-organic frameworks containing nanosized cavities. 3 is a beautiful 2D coordination polymer assembled by flower-like Mn3(4-cptpy)6(H2O) subunits. 4 and 6 both display 2D polymeric networks constructed from 4/3-cptpy- ligands, in which the formate ligands originate from the hydrolysis of DMF. 5 is a 1D 21 helical chain polymer. 7 shows a 2D network with a (3.6) two-nodal kgd topology. 4/3-Hcptpy ligands display seven types of coordination modes. The zinc complex 5 emits strong violet luminescence. 1 and 2 are both thermally stable below 440 °C and exhibit antiferromagnetic interactions. [ABSTRACT FROM AUTHOR]

Five novel hybrid compounds, [Mo8O26Cu2(4-abpt)2]n·4nH2O (1), (4-H2abpt)2[Mo8O26] (2), [Mo8O26Cu2(3-abpt)2(H2O)2]n(3), [MoO4Cu(3-abpt)(H2O)]n(4), and [Mo6O19Co(3-abpt)2]n·4nH2O (5) were prepared by reacting MoO3/(NH4)6Mo7O24with 4-amino-3,5-bis(3/4-pyridyl)-1,2,4-triazole (3/4-abpt) and corresponding metal salts. Compound 1is a 2D coordination polymer containing extended γ-[Mo8O26]4−and [Cu2(4-abpt)2]4+ribbons. Compound 2is a supramolecular hybrid aggregate composed of H-bond linking β-[Mo8O26]4−and 4-H2abpt2+. Compound 3exhibits a 2D rectangular network constructed by isolated β-[Mo8O26]4−clusters and [Cu2(3-abpt)2]4+. In compound 4, each MoO42−anion links two Cu(ii) ions to form a S-type [CuMoO4]nchain, which is further linked by bidentate 3-abpt to form a 2D wave-like network. In complex 5, unprecedented cyclic [Mo6O19]2−cluster links two neighbouring hexamolybdates and two Co(ii) ions to form a 2D [CoMo6O19]nnetwork, which is further pillared by tetradentate 3-abpt to generate a 3D metal–organic framework. These compounds are thermally stable under 250 °C. The composites of the final residues were analyzed by PXRD. [ABSTRACT FROM AUTHOR]

The fracture behavior of pipes with penetrating cracks was experimentally investigated with the results of the load-deflection curves and crack length. J-R curves were obtained from the testing results for different temperatures. With the decrement in temperature, the critical J integral decreases and the tearing modulus increases. An updated continuum damage model was proposed, in which the fracture energy density as a function of the stress triaxiality, temperature and strain rate in the transition region was taken as the critical damage factor. The uni-axial tension experiments at different temperatures were carried out to obtain the basic material properties and the critical fracture energy density, to verify the validity of the damage model. Based on detailed finite element analyses with the proposed updated continuum damage model, the loading level of pipes with penetrating cracks was estimated and compared with the experimental results, meanwhile the fracture processes of the pipeline structure in the ductile-brittle-transition-temperature region were reproduced. It has been shown that the fracture process in the transition region strongly depends on both the stress and strain state, and can be effectively predicted using the continuum damage models incorporating with the stress state effect. [ABSTRACT FROM AUTHOR]

In the Ductile–Brittle Transition Temperature (DBTT) region, it is not realistic to take unique fracture stress or fracture strain as the fracture criterion to investigate the fracture properties. In this paper, an updated continuum damage model was proposed, in which the fracture energy density, a function of the stress triaxiality, temperature and strain rate in the transition region was taken as the critical damage factor. Uniaxial tension tests were carried out to get the basic material properties at different temperatures, to calibrate the fracture model constants and verify the validity of the damage model. The fracture behaviour of pipes with penetrating cracks under the internal pressure was experimentally investigated with the load–deflection curves and the crack propagation length captured from tests. The J– R curves were obtained from the testing results for different temperatures. Based on the Finite Element Analyses (FEA) with the proposed fracture criterion of the updated continuum damage model, the loading level of pipes with penetrating cracks were estimated and compared with the experimental results. Meanwhile the fracture processes of the pipeline structures in the transition region were reproduced. The experimental and numerical results agreed very well in present calculations. It has been shown that the fracture process in the transition region strongly depends on both the stress and strain states, and could be effectively predicted using the continuum damage model. [ABSTRACT FROM AUTHOR]

This paper presents a fast and accurate solution for crack interaction problems in infinite- and half- plane solids. The new solution is based on the method of complex potentials developed by Muskhelishvili for the analysis of plane linear elasticity, and it is formulated through three steps. First, the problem is decomposed into a set of basic problems, and for each sub-problem, there is only one crack in the solid. Next, after a crack-dependent conformal mapping, the modified complex potentials associated with the sub-problems are expanded into Laurent’s series with unknown coefficients, which in turn provides a mechanism to exactly implement in the form of Fourier series the boundary condition in each sub-problem. Finally, taking into account the crack interaction via a perturbation approach, an iterative algorithm based on fast Fourier transforms (FFT) is developed to solve the unknown Fourier coefficients, and the solution of the whole problem is readily obtained with the superposition of the complex potentials in each sub-problem. The performance of the proposed method is fully investigated by comparing with benchmark results in the literatures, and superb accuracy and efficiency is observed in all situations including patterns where cracks are closely spaced. Also, the new method is able to cope with interactions among a large number of cracks, and this capability is demonstrated by a calculation of effective moduli of an elastic solid with thousands of randomly-spaced cracks. [ABSTRACT FROM AUTHOR]

Magnetic Cu4 clusters with S = 2 are bridged by octacyanometaltate(iv) to form two 3D cluster arrays of metal–organic frameworks. Magnetic investigation shows the ferromagnetic coupling between Cu(ii) ions and very weak antiferromagnetic interaction between clusters. [ABSTRACT FROM AUTHOR]

A novel zero-dimensional (0D) octacyanotungstate(V)-manganese(II) bimetallic assembly, {[MnII(bipy)2]2(ox)}·{[MnII(bipy)2W(CN)8]2}·4H2O (1) (bipy = 2,2′-bipyridine, ox = C2O42-), was synthesized in methanol solution containing oxalic acid. X-ray analysis shows 1 is crystallized in monoclinic crystal system with C2/c space group and composed of two components of a dimeric Mn2 cation and a quadrate tetrameric Mn2W2 anion. The Mn2 and Mn2W2 moieties are connected by their respective π-π stacking to yield the alternative 2D layers, and the 2D layers are linked by hydrogen bonding to form a 3D network. The investigation of the magnetostructural correlation reveals that cyanide and oxalate bridges mediate weak intracluster antiferromagnetic coupling between Mn and W ions and between Mn ions, respectively. Further magnetic measurements and analysis show the spin glasses and intercluster ferromagnetic interaction exist in complex 1. [ABSTRACT FROM AUTHOR]

Although fish possess an efficient interferon (IFN) system to defend against aquatic virus infection, grass carp reovirus (GCRV) still causes hemorrhagic disease in grass carp. To date, GCRV's strategy for evading the fish IFN response is still unknown. Here, we report that GCRV VP41 inhibits fish IFN production by suppressing the phosphorylation of mediator of IFN regulatory factor 3 (IRF3) activation (MITA). First, the activation of the IFN promoter (IFNpro) stimulated by mitochondrial antiviral signaling protein (MAVS) and MITA was decreased by the overexpression of VP41, whereas such activation induced by TANK-binding kinase 1 (TBK1) was not affected. Second, VP41 was colocalized in the cellular endoplasmic reticulum (ER) and associated with MITA. Furthermore, as a phosphorylation substrate of TBK1, VP41 significantly decreased the phosphorylation of MITA. Truncation assays indicated that the transmembrane (TM) region of VP41 was indispensable for the suppression of IFNpro activity. Finally, after infection with GCRV, VP41 blunted the transcription of host IFN and facilitated viral RNA synthesis. Taken together, our findings suggest that GCRV VP41 prevents the fish IFN response by attenuating the phosphorylation of MITA for viral evasion. [ABSTRACT FROM AUTHOR]

Spring viremia of carp virus (SVCV) is an efficient pathogen causing high mortality in the common carp. Fish interferon (IFN) is a powerful cytokine enabling host cells to establish an antiviral response; therefore, the strategies that SVCV uses to avoid the cellular IFN response were investigated. Here, we report that the SVCV P protein is phosphorylated by cellular TANK-binding kinase 1 (TBK1), which decreases IFN regulatory factor 3 (IRF3) phosphorylation and suppresses IFN production. First, overexpression of P protein inhibited the IFN promoter activation induced by SVCV and the IFN activity activated by the mitochondrial antiviral signaling protein (MAVS) although TBK1 activity was not blocked by P protein. Second, P protein colocalized and interacted with TBK1. Dominant negative experiments suggested that the TBK1 N-terminal kinase domain interacted with P protein and was essential for P protein and IRF3 phosphorylation. Finally, P protein overexpression reduced the IRF3 phosphorylation activated by TBK1 and reduced host cellular ifn transcription. Collectively, our data demonstrated that the SVCV P protein is a decoy substrate for the host phosphokinase TBK1, preventing IFN production and facilitating SVCV replication. [ABSTRACT FROM AUTHOR]

Two new compounds, {[Cu 2 (tza) 3 (4,4'-bipy) 2 (H 2 O)](ClO 4 )(H 2 O)} n ( 1 ) and {[Cu 2 (4,4'-bipy) 2 (C 2 O 4 )(H 2 O) 2 ](ClO 4 ) 2 } n ( 2 ) were synthesized and structurally characterized. Compound 1 shows a 2D layered structure, which ultimately stacked by ABAB repeat pattern. Compound 2 features a three-fold interpenetrating 3D structure with 3-connected ths network. An interesting phenomenon has been found that tetrazole-1-acetic acid in situ generated oxalate ligand during the syntheses of compound 2. [ABSTRACT FROM AUTHOR]

Viral infection activates the transcription factor IFN regulatory factor 7 (IRF7), which plays a critical role in the induction of IFNs and innate antiviral immune response. How virus-induced IFN signaling is controlled in fish is not fully understood. In this study, we demonstrate that N-myc downstream-regulated gene 1a (NDRG1a) in zebrafish plays a role as a negative regulator for virus-triggered IFN induction. First, the activation of the IFN promoter stimulated by the polyinosinic-polycytidylic acid or spring viremia of carp virus was decreased by the overexpression of NDRG1a. Second, NDRG1a interacted with IRF7 and blocked the IFN transcription activated by IRF7. Furthermore, NDRG1a was phosphorylated by TANK-binding kinase 1 (TBK1) and promoted the K48-linked ubiquitination and degradation of IRF7. Finally, the overexpression of NDRG1a blunted the transcription of several IFN-stimulated genes, resulting in the host cells becoming susceptible to spring viremia of carp virus infection. Our findings suggest that fish NDRG1a negatively regulates the cellular antiviral response by targeting IRF7 for ubiquitination and degradation, providing insights into the novel role of NDRG1a on the innate antiviral immune response in fish. [ABSTRACT FROM AUTHOR]