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症例は57歳，男性．胸部大動脈瘤フォロー中の前医CTで前縦隔に36 mm大の腫瘤性病変を認め，当院を受診した．浸潤性胸腺腫を疑い，胸骨正中切開により腫瘍を含む拡大胸腺摘出術を施行した．術中所見にて腫瘍の浸潤を疑った局所心膜を合併切除し，心膜欠損部位をGore-Texシートで再建した．術後8日目より38℃台の発熱と心囊水貯留，また心電図で広範な誘導におけるST上昇を認め，心膜切開後症候群を疑いコルヒチンとNSAIDsを投与するも腎障害を来し内服困難となった．その後も著明な隔壁形成を伴う心囊水が増加したため，初回手術後15日目に胸腔鏡下心膜開窓術を施行した．再手術後よりステロイド投与も開始し，心囊水は減少，解熱を得て，白血球数とCRP値は正常化した．心膜切開後症候群は，心臓手術後の合併症として比較的よく知られるが，心膜切開を要する縦隔腫瘍手術後においても認識されるべき病態と考える.

The length of a telomere is regulated via elongation and shortening processes. Telomeric DNA and telomeric repeat-containing RNA (TERRA), which both contain G-rich repeated sequences, form G-quadruplex structures. Previously, translocated in liposarcoma (TLS) protein, also known as fused in sarcoma (FUS) protein, was found to form a ternary complex with the G-quadruplex structures of telomeric DNA and TERRA. We then showed that the third RGG motif of TLS, the RGG3 domain, is responsible for the complex formation. However, the structural basis for their binding remains obscure. Here, NMR-based binding assaying revealed the interactions in the binary and ternary complexes of RGG3 with telomeric DNA or/and TERRA. In the ternary complex, tyrosine bound exclusively to TERRA, while phenylalanine bound exclusively to telomeric DNA. Thus, tyrosine and phenylalanine each play a central role in the recognition of TERRA and telomeric DNA, respectively. Surprisingly in the binary complexes, RGG3 used both tyrosine and phenylalanine residues to bind to either TERRA or telomeric DNA. We propose that the plastic roles of tyrosine and phenylalanine are important for RGG3 to efficiently form the ternary complex, and thereby regulate the telomere shortening.

The spliceosomal protein SF3b49, a component of the splicing factor 3b (SF3b) protein complex in the U2 small nuclear ribonucleoprotein, contains two RNA recognition motif (RRM) domains. In yeast, the first RRM domain (RRM1) of Hsh49 protein (yeast orthologue of human SF3b49) reportedly interacts with another component, Cus1 protein (orthologue of human SF3b145). Here, we solved the solution structure of the RRM1 of human SF3b49 and examined its mode of interaction with a fragment of human SF3b145 using NMR methods. Chemical shift mapping showed that the SF3b145 fragment spanning residues 598–631 interacts with SF3b49 RRM1, which adopts a canonical RRM fold with a topology of β1-α1-β2-β3-α2-β4. Furthermore, a docking model based on NOESY measurements suggests that residues 607–616 of the SF3b145 fragment adopt a helical structure that binds to RRM1 predominantly via α1, consequently exhibiting a helix–helix interaction in almost antiparallel. This mode of interaction was confirmed by a mutational analysis using GST pull-down assays. Comparison with structures of all RRM domains when complexed with a peptide found that this helix–helix interaction is unique to SF3b49 RRM1. Additionally, all amino acid residues involved in the interaction are well conserved among eukaryotes, suggesting evolutionary conservation of this interaction mode between SF3b49 RRM1 and SF3b145., Protein Science, 26 (2), ISSN:1469-896X, ISSN:0961-8368

Further detail of the BMRB/XML, BMRB/RDF and web services including SPARQL endpoint. Complete results of the SPARQL query (Fig. 2a) and many other SPARQL query examples are also available. (PDF 6814 kb)

Xenotropic murine leukemia virus-related virus (XMRV) is a virus created through recombination of two murine leukemia proviruses under artificial conditions during the passage of human prostate cancer cells in athymic nude mice. The homodimeric protease (PR) of XMRV plays a critical role in the production of functional viral proteins and is a prerequisite for viral replication. We synthesized XMRV PR using the wheat germ cell-free expression system and carried out structural analysis of XMRV PR in a complex with an inhibitor, amprenavir (APV), by means of NMR. Five different combinatorially (15)N-labeled samples were prepared and backbone resonance assignments were made by applying Otting's method, with which the amino acid types of the [(1)H, (15)N] HSQC resonances were automatically identified using the five samples (Wu et al., 2006) [14]. A titration experiment involving APV revealed that one APV molecule binds to one XMRV PR dimer. For many residues, two distinct resonances were observed, which is thought to be due to the structural heterogeneity between the two protomers in the APV:XMRV PR=1:2 complex. PR residues at the interface with APV have been identified on the basis of chemical shift perturbation and identification of the intermolecular NOEs by means of filtered NOE experiments. Interestingly, chemical shift heterogeneity between the two protomers of XMRV PR has been observed not only at the interface with APV but also in regions apart from the interface. This indicates that the structural heterogeneity induced by the asymmetry of the binding of APV to the XMRV PR dimer is transmitted to distant regions. This is in contrast to the case of the APV:HIV-1 PR complex, in which the structural heterogeneity is only localized at the interface. Long-range transmission of the structural change identified for the XMRV PR complex might be utilized for the discovery of a new type of drug.

A number of prognostic factors have been reported in non-small cell lung cancer (NSCLC). Although lymph node metastasis is the most poorly predictive value in completely resected NSCLC, a significant number of patients have a fatal recurrence even in node-negative curative NSCLC. Recently inflammatory response has been shown as a predictive value in NSCLC. Neutrophils and lymphocytes play an important role in cancer immune response. In this study, we retrospectively examined the impact of preoperative peripheral neutrophil and lymphocyte counts on survival, and investigated the relationships of these factors to clinicopathological factors in node-negative NSCLC. A total 237 patients were evaluated. When the cut-off value of neutrophil count was 4500 mm−3 with a maximum log-rank statistical value, overall 5-year survival rates were 79.7% for the low-neutrophil-count group and 69.5% for the high-neutrophil-count group (P = 0.04). When the cut-off value of lymphocyte count was 1900 mm−3 with a maximum log-rank statistical value, overall survival rates were 67.9% for the low-lymphocyte group and 87.7% for the high-lymphocyte group (P < 0.001). High-neutrophil-counts were associated with tumor size (P = 0.002) and pleural invasion (P < 0.001). Low-lymphocyte-counts were correlated with vascular invasion (P = 0.018) and recurrence of NSCLC (P = 0.01). Multivariate analysis showed that the lymphocyte count was an independent prognostic factor (hazard ratio: 3.842; 95% confidence interval: 1.827–8.078; P < 0.001), but the neutrophil count was not (P = 0.185). We conclude that a peripheral lymphocyte count, which is associated with vascular invasion, is an independent prognostic factor in node-negative NCSLC.

In the present paper, we study finite-temperature phase structure of two-component hard-core bosons in a cubic optical lattice. The system that we study in the present paper is an effective model for the Bose-Hubbard model with strong on-site repulsions and is called bosonic t-J model. This model is a bosonic counterpart of the t-J model for the strongly-correlated electron systems like the high-temperature superconducting materials. We study the model by means of path-integral methods and Monte-Carlo simulations. We found that this system has a very rich phase structure including checkerboard-type "insulating" state, superfluid, phase-separated state, inhomogeneous cloudlet state, etc. We are also interested in the possible supersolid phase with both the checkerboard order and superfluidity and found that additional nearest-neighbor inter-species attractive force induces the supersolid state. In the supersolid state, paired superfluid appears in addition to the superfluid of single atom. This result gives important insight into mechanism of the high-temperature superconductivity of the cuprate., Comment: 20 pages, 26 figures

Human Transformer2-beta (hTra2-beta) is an important member of the serine/arginine-rich protein family, and contains one RNA recognition motif (RRM). It controls the alternative splicing of several pre-mRNAs, including those of the calcitonin/calcitonin gene-related peptide (CGRP), the survival motor neuron 1 (SMN1) protein and the tau protein. Accordingly, the RRM of hTra2-beta specifically binds to two types of RNA sequences [the CAA and (GAA)2 sequences]. We determined the solution structure of the hTra2-beta RRM (spanning residues Asn110–Thr201), which not only has a canonical RRM fold, but also an unusual alignment of the aromatic amino acids on the beta-sheet surface. We then solved the complex structure of the hTra2-beta RRM with the (GAA)2 sequence, and found that the AGAA tetra-nucleotide was specifically recognized through hydrogen-bond formation with several amino acids on the N- and C-terminal extensions, as well as stacking interactions mediated by the unusually aligned aromatic rings on the beta-sheet surface. Further NMR experiments revealed that the hTra2-beta RRM recognizes the CAA sequence when it is integrated in the stem-loop structure. This study indicates that the hTra2-beta RRM recognizes two types of RNA sequences in different RNA binding modes.

We study the three-dimensional bosonic t-J model, i.e., the t-J model of "bosonic electrons" at finite temperatures. This model describes a system of cold bosonic atoms with two species in an optical lattice. The model is derived from the Hubbard model for very large on-site repulsive interaction between bosons of same species (hard-core nature) and also strong correlations between different species. The operator B_{x\sigma} for an atom at the site x with a two-component (pseudo-) spin \sigma (=1,2) is treated as a hard-core boson operator, and represented by a composite of two slave particles; a spinon described by a CP^1 field (Schwinger boson) z_{x\sigma} and a holon described by a hard-core-boson field \phi_x as B_{x\sigma}=\phi^\dag_x z_{x\sigma}. \phi_x is then expressed by a pseudo-spin, which is, in turn, represented by another CP^1 (pseudo) spinon w_{x\eta} as \phi_x = w_{x2}^\dag w_{x1}. We then have a double-CP^1 representation of the model by z_{x\sigma} and w_{x\eta}. By means of Monte Carlo simulations of this bosonic t-J model, we study its phase structure and the possible phenomena like appearance of antiferromagnetic long-range order, Bose-Einstein condensation, phase separation, etc. They should be compared with the possible experimental results of a recently studied boson-boson mixture like ^87Rb and ^41K in an optical lattice., Comment: 13 pages, 17 figures

1993, 【要旨】