Genetic Basis of Virulence Attenuation Revealed by Comparative Genomic Analysis of Mycobacterium tuberculosis Strain H37Ra versus H37Rv

Tuberculosis, caused by Mycobacterium tuberculosis, remains a leading infectious disease despite the availability of chemotherapy and BCG vaccine. The commonly used avirulent M. tuberculosis strain H37Ra was derived from virulent strain H37 in 1935 but the basis of virulence attenuation has remained obscure despite numerous studies. We determined the complete genomic sequence of H37Ra ATCC25177 and compared that with its virulent counterpart H37Rv and a clinical isolate CDC1551. The H37Ra genome is highly similar to that of H37Rv with respect to gene content and order but is 8,445 bp larger as a result of 53 insertions and 21 deletions in H37Ra relative to H37Rv. Variations in repetitive sequences such as IS6110 and PE/PPE/PE-PGRS family genes are responsible for most of the gross genetic changes. A total of 198 single nucleotide variations (SNVs) that are different between H37Ra and H37Rv were identified, yet 119 of them are identical between H37Ra and CDC1551 and 3 are due to H37Rv strain variation, leaving only 76 H37Ra-specific SNVs that affect only 32 genes. The biological impact of missense mutations in protein coding sequences was analyzed in silico while nucleotide variations in potential promoter regions of several important genes were verified by quantitative RT-PCR. Mutations affecting transcription factors and/or global metabolic regulations related to in vitro survival under aging stress, and mutations affecting cell envelope, primary metabolism, in vivo growth as well as variations in the PE/PPE/PE-PGRS family genes, may underlie the basis of virulence attenuation. These findings have implications not only for improved understanding of pathogenesis of M. tuberculosis but also for development of new vaccines and new therapeutic agents

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Constitutive Model and Fracture Criterion of Q345 Steel Welded Joints

Welding joint is a key component in steel structure engineering, which is often subjected to complex stress and becomes the weak link of building structure, and different fracture modes may appear under different stress. In this study, the ductile fracture of Q345 steel welded joint was investigated by selecting the base material and heat-affected zone (HAZ) material. Based on the J–C (Johnson–Cook) fracture model of stress triaxiality factor, a series of round bar specimens were designed for the tensile test, and the variation of minimum diameter and gauge distance was tracked in real time by digital image correlation (DIC) technology, and the cloud map of strain distribution in the whole loading process was obtained. The constitutive model and fracture criterion model of Q345 steel welded joint base material and HAZ material are established through experimental measurement. The results show that the maximum triaxial stress is at the center root of the minimum diameter of the notched round bar tensile specimen, the sudden change of the notched edge will lead to stress concentration, the stress change of the notch section is the most significant, extending from near the notch, the maximum strain is at the root of the notch, and the fracture position appears at the minimum section of the notch. According to the true stress-strain curve of a standard tensile specimen and the least square method, the values of parameters A, B, and N of the J–C (Johnson–Cook) constitutive model of base material and HAZ material are 379.80, 452.89, and 0.37 and 392.90, 540.61, and 0.49, respectively. The fracture strains of the base metal and HAZ material under different triaxial stresses were measured experimentally, and the J–C fracture model was fitted. The values of failure criterion parameters D1, D2, and D 3 were 1.025, −0.008, and 3.617 and 0.678, −2.689E-5, and 7.683, respectively. This provides experimental parameters for mechanical properties and fracture models of welded joints in structural engineering, refined finite element models considering material failure for structural numerical analysis, and basic data for evaluation and design of building structures, which have good social and economic benefits

Study on the deterioration characteristics of aeolian sand concrete under the coupling effect of multiple factors in harsh environments.

This study takes the aeolian sand concrete as a research object, uses the relative dynamic elastic modulus to study its macro characteristics, and combines nuclear magnetic resonance、scanning electron microscope to study its pore characteristics and micro morphology under the action of prestress, freeze-thaw and salt intrusion. The results show that with the increase of the amount of aeolian sand, the dynamic elastic modulus of aeolian sand concrete shows a pattern of first decreasing, then increasing, and then decreasing; when no prestress is applied, the porosity of aeolian sand concrete first increases, then decreases, and then continues to increase. Among them, the porosity of aeolian sand concrete with a 40% content of aeolian sand decreases by 0.06% compared to that with a 0% content of aeolian sand, and decreases by 0.003% compared to that with a 60% content of aeolian sand; with the increase of prestress, the porosity of aeolian sand concrete with the same amount of aeolian sand increases gradually with the increase of damage degree. The porosity of concrete with 40% aeolian sand content increases by 0.33% when the damage degree is 0.0 compared to 0.3, with a 6.31% increase in the number of multi damage pores; under the coupling effect of multiple factors, when the amount of aeolian sand is 40%, the damage degree of the four groups of aeolian sand concrete before and after the coupling effect is 0.0, 0.1, 0.2, and 0.3, respectively, increases by 25.8%, 32.2%, 73.8%, and 85.8%, respectively; under the coupling effect of multiple factors, the content of aeolian sand is 60%, the damage degree is 0.2 and 0.3 groups, and the content of aeolian sand is 20%, the damage degree is 0.3 groups, which does not meet the standard requirements; under the coupling action of stress, freeze-thaw, salt intrusion and the amount of aeolian sand, the filling effect of aeolian sand on the internal pores of aeolian sand concrete decreases first, then increases, and then decreases with the increase of the amount of aeolian sand. The filling effect is further weakened after the action of stress. After the superposition of freeze-thaw and salt intrusion, the coupling effect of water and salt solution in frost heaving medium makes the variation law and range of physical and chemical characteristics of aeolian sand concrete show a great difference

Identification of a uranium-rhodium triple bond in a heterometallic cluster

International audienceThe chemistry of d-block metal-metal multiple bonds has been extensively investigated in the past 5 decades. However, the synthesis and characterization of species with f-block metal-metal multiple bonds are significantly more challenging and such species remain extremely rare. Here, we report the identification of a uranium-rhodium triple bond in a heterometallic cluster, which was synthesized under routine conditions. The uranium-rhodium triple-bond length of 2.31 angstrom in this cluster is only 3% longer than the sum of the covalent triple-bond radii of uranium and rhodium (2.24 angstrom). Computational studies reveal that the nature of this uranium-rhodium triple bond is 1 covalent bond with 2 rhodium-to-uranium dative bonds. This heterometallic cluster represents a species with f-block metal-metal triple bond structurally authenticated by X-ray diffraction. These studies not only demonstrate the authenticity of the uranium-metal triple bond, but also provide a possibility for the synthesis of other f-block metal-metal multiple bonds. We expect that this work may further our understanding of the bonding between uranium and transition metals, which may help to design new d-f heterometallic catalysts with uranium-metal bonds for small-molecule activation and to promote the utilization of abundant depleted uranium resources

Complexes Featuring a cis ‐[MUM] Core (M=Rh, Ir): A New Route to Uranium‐Metal Multiple Bonds

Although examples of multiple bonds between actinide elements and main‐group elements are quite common, studies of the multiple bonds between actinide elements and transition metals are extremely rare owing to difficulties associated with their synthesis. Here we report the first example of molecular uranium complexes featuring a cis ‐[M U M] core (M=Rh, Ir), which exhibits an unprecedented arrangement of two M U double dative bond linkages to a single U center. These complexes were prepared by the reactions of chlorine‐bridged heterometallic complexes [{U{N(CH 3 )(CH 2 CH 2 NP i Pr 2 ) 2 }(Cl) 2 [( μ ‐Cl)M(COD)] 2 }] (M=Rh, Ir) with MeMgBr or MeLi, a new method for the construction of species with U−M multiple bonds. Theoretical calculations including dispersion confirmed the presence of two U M double dative bonds in these complexes. This study not only enriches the U M multiple bond chemistry, but also provides a new opportunity to explore the bonding of actinide elements

Transition-metal-bridged bimetallic clusters with multiple uranium-metal bonds

International audienceHeterometallic clusters are important in catalysis and small-molecule activation because of the multimetallic synergistic effects from different metals. However, multimetallic species that contain uranium-metal bonds remain very scarce due to the difficulties in their synthesis. Here we present a straightforward strategy to construct a series of heterometallic clusters with multiple uranium-metal bonds. These complexes were created by facile reactions of a uranium precursor with Ni(COD)(2) (COD, cyclooctadiene). The multimetallic clusters' cores are supported by a heptadentate N4P3 scaffold. Theoretical investigations indicate the formation of uranium-nickel bonds in a U2Ni2 and a U2Ni3 species, but also show that they exhibit a uranium-uranium interaction; thus, the electronic configuration of uranium in these species is U(iii)-5f(2)6d(1). This study provides further understanding of the bonding between f-block elements and transition metals, which may allow the construction of d-f heterometallic clusters and the investigation of their potential applications

Heterometallic Clusters with Multiple Rare Earth Metal-Transition Metal Bonding

International audienceAlthough a series of complexes with rare earth (RE) metal-metal bonds have been reported, complexes which have multiple RE-Rh bonds are unknown. Here we present the identification of the first example of a molecule containing multiple RE-Rh bonds. The complex with multiple Ce-Rh bonds was synthesized by the reduction of a d-f heterometallic molecular cluster Ce{N[((CH2CH2NPPr2)-Pr-i)RhCl(COD)](3)} with excess potassium-graphite. The oxidation state of Ce in 3a appears to be a mixture of Ce(III) and Ce(IV), which was confirmed by X-ray photoelectron spectroscopy, magnetism, and theoretical investigations (DFT and CASSCF). For comparison, the analogous species with multiple La(III)-Rh and Nd(III)-Rh bonds were also constructed. This study provides a possible route for the construction of complexes with multiple RE metal-metal bonds and an investigation of their potential properties and applications