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

Role of MHC-linked genes in autoantigen selection and renal disease in a murine model of systemic lupus erythematosus

We previously described a renal protective effect of factor B deficiency in MRL/lpr mice. Factor B is in the MHC cluster; thus, the deficient mice were H2b, the haplotype on which the knockout was derived, whereas the wild-type littermates were H2k, the H2 of MRL/lpr mice. To determine which protective effects were due to H2 vs factor B deficiency, we derived H2b congenic MRL/lpr mice from the 129/Sv (H2b) strain. Autoantibody profiling using autoantigen microarrays revealed that serum anti-Smith and anti-small nuclear ribonucleoprotein complex autoantibodies, while present in the majority of H2k/k MRL/lpr mice, were absent in the H2b/b MRL/lpr mice. Surprisingly, 70% of MRL/lpr H2b/b mice were found to be serum IgG3 deficient (with few to no IgG3-producing B cells). In addition, H2b/b IgG3-deficient MRL/lpr mice had significantly less proteinuria, decreased glomerular immune complex deposition, and absence of glomerular subepithelial deposits compared with MRL/lpr mice of any H2 type with detectable serum IgG3. Despite these differences, total histopathologic renal scores and survival were similar among the groups. These results indicate that genes encoded within or closely linked to the MHC region regulate autoantigen selection and isotype switching to IgG3 but have minimal effect on end-organ damage or survival in MRL/lpr mice

Coligand modifications fine-tuned the structure and magnetic properties of two triple-bridged azido-Cu(II) chain compounds exhibiting ferromagnetic ordering and slow relaxation

Employing two benzoate derivatives with different numbers of non-coordinated fluoro-substituents, 2-fluorobenzoic acid (2-Hfba) and 2,6-difluorobenzoic acid (2,6-Hdfba), two new azido-copper coordination polymers, [Cu(2-fba)(N-3)(CH3OH)](n) (1) and [Cu(2,6-dfba)(N-3)(CH3OH)](n) (2), have been successfully isolated, and then structurally and magnetically investigated. Single crystal structure analysis demonstrates that the metal cations in the two resulting compounds are connected by the alternating triple-bridge of mu-1,1-azido, syn, syn-carboxylate and eta 2-methanol, contributing to analogously linear 1D Cu(II) chain-like motifs with slightly different intrachain and interchain geometric parameters. The fine-tuned structures lead to variant magnetic properties in the two title compounds. Although a dominant ferromagnetic coupling between adjacent Cu(II) ions within each chain due to the counter-complementarity of the multiple superexchange pathways is observed in both compounds, the interesting plots of magnetic ordering and slow magnetic relaxation, which are rare in most of the reported azido-Cu(II) architectures, only occur in compound 1, while 2 behaves as an antiferromagnet consisting of ferromagnetic Cu(II) chains. The heat-capacity experiments further emphasize the characteristic long-range ferromagnetic ordering in 1 and the typical behavior of antiferromagnets in 2. Moreover, density functional theory (DFT) calculations (using different methods and basis sets) have been performed on both compounds to obtain the qualitatively theoretical interpretation of the magnetic behaviors

Coligand modifications fine-tuned the structure and magnetic properties of two triple-bridged azido-Cu(II) chain compounds exhibiting ferromagnetic ordering and slow relaxation

Employing two benzoate derivatives with different numbers of non-coordinated fluoro-substituents, 2-fluorobenzoic acid (2-Hfba) and 2,6-difluorobenzoic acid (2,6-Hdfba), two new azido-copper coordination polymers, [Cu(2-fba)(N-3)(CH3OH)](n) (1) and [Cu(2,6-dfba)(N-3)(CH3OH)](n) (2), have been successfully isolated, and then structurally and magnetically investigated. Single crystal structure analysis demonstrates that the metal cations in the two resulting compounds are connected by the alternating triple-bridge of mu-1,1-azido, syn, syn-carboxylate and eta 2-methanol, contributing to analogously linear 1D Cu(II) chain-like motifs with slightly different intrachain and interchain geometric parameters. The fine-tuned structures lead to variant magnetic properties in the two title compounds. Although a dominant ferromagnetic coupling between adjacent Cu(II) ions within each chain due to the counter-complementarity of the multiple superexchange pathways is observed in both compounds, the interesting plots of magnetic ordering and slow magnetic relaxation, which are rare in most of the reported azido-Cu(II) architectures, only occur in compound 1, while 2 behaves as an antiferromagnet consisting of ferromagnetic Cu(II) chains. The heat-capacity experiments further emphasize the characteristic long-range ferromagnetic ordering in 1 and the typical behavior of antiferromagnets in 2. Moreover, density functional theory (DFT) calculations (using different methods and basis sets) have been performed on both compounds to obtain the qualitatively theoretical interpretation of the magnetic behaviors