D3-brane from D-instantons in the hybrid formalism of superstring

A Dp-brane can be regarded as a configuration of infinitely many D(p-2k)-branes in bosonic string. We will show this property of D-branes in the superstring case using the hybrid formalism. It is convenient to study the boundary state for such D-branes to study such property between D-branes. We show that the boundary state for a D3-brane in a constant self-dual gauge field background can be expressed in terms of the boundary state for D-instantons in the hybrid formalism.Comment: 10 pages, minor corrections, reference adde

Examination of prognostic factors in patients undergoing surgery for colorectal perforation: A case controlled study

AbstractObjectiveTo determine if the POSSUM, SOFA, MPI, and SAS scores provide a better measure of severity for patients with prognostic factors undergoing surgery for colorectal perforation.SubjectsFifty-nine patients who underwent surgery between 1996 and 2012.MethodsWe retrospectively reviewed background factors, blood and physiological test results, and intraoperative findings of patients who survived and those who died. We also compared the POSSUM, SOFA, MPI, and SAS scores. Multivariate analysis was performed for factors that were significant by univariate analysis, and selected factors were used to produce a predictive prognostic model.ResultsUnivariate analysis revealed significant differences in age, anticoagulant/steroid administration, serum creatinine level, PF ratio, base excess (BE), chest radiography, pulse rate, and severity of peritoneal soiling. Age, serum creatinine level, pulse rate, and severity of peritoneal soiling were selected for multivariate analysis; only pulse rate was significantly different. There were significant differences between the two groups in POSSUM PS, OSS, SOFA, and MPI scores, and a comparison in terms of the ROC curve showed that our model had the highest peak; the area under the curve was 94.8% compared with 70–80% for the other systems, suggesting that our model is better than those systems.ConclusionsPOSSUM and SOFA are valid methods of evaluating risk from colorectal perforation, but our study revealed addition risk factors: (1) the PF ratio and BE, which are not included in POSSUM; (2) the pulse rate and severity of peritonitis, which are not included in SOFA; and (3) anticoagulant/steroid hormone administration

Cryo-EM structures of human zinc transporter ZnT7 reveal the mechanism of Zn²⁺ uptake into the Golgi apparatus

クライオ電子顕微鏡により、ゴルジ体の亜鉛輸送体による亜鉛輸送機構の全容を解明 細胞の亜鉛恒常性維持機構の理解に大きな進展. 京都大学プレスリリース. 2023-08-29.Zinc ions (Zn²⁺) are vital to most cells, with the intracellular concentrations of Zn²⁺ being tightly regulated by multiple zinc transporters located at the plasma and organelle membranes. We herein present the 2.2-3.1 Å-resolution cryo-EM structures of a Golgi-localized human Zn²⁺/H+ antiporter ZnT7 (hZnT7) in Zn²⁺-bound and unbound forms. Cryo-EM analyses show that hZnT7 exists as a dimer via tight interactions in both the cytosolic and transmembrane (TM) domains of two protomers, each of which contains a single Zn²⁺-binding site in its TM domain. hZnT7 undergoes a TM-helix rearrangement to create a negatively charged cytosolic cavity for Zn²⁺ entry in the inward-facing conformation and widens the luminal cavity for Zn²⁺ release in the outward-facing conformation. An exceptionally long cytosolic histidine-rich loop characteristic of hZnT7 binds two Zn²⁺ ions, seemingly facilitating Zn²⁺ recruitment to the TM metal transport pathway. These structures permit mechanisms of hZnT7-mediated Zn²⁺ uptake into the Golgi to be proposed

Structural insights into the G protein selectivity revealed by the human EP3-Gi signaling complex

熱、炎症などに関与するプロスタグランジン受容体EP3シグナリング複合体の可視化 --緑内障、高眼圧症治療薬の合理的設計に貢献--. 京都大学プレスリリース. 2022-09-15.Prostaglandin receptors have been implicated in a wide range of functions, including inflammation, immune response, reproduction, and cancer. Our group has previously determined the crystal structure of the active-like EP3 bound to its endogenous agonist, prostaglandin E₂. Here, we present the single-particle cryoelectron microscopy (cryo-EM) structure of the human EP3-Gi signaling complex at a resolution of 3.4 Å. The structure reveals the binding mode of Gi to EP3 and the structural changes induced in EP3 by Gi binding. In addition, we compare the structure of the EP3-Gi complex with other subtypes of prostaglandin receptors (EP2 and EP4) bound to Gs that have been previously reported and examine the differences in amino acid composition at the receptor-G protein interface. Mutational analysis reveals that the selectivity of the G protein depends on specific amino acid residues in the second intracellular loop and TM5

Myelodysplastic Syndrome-Associated SRSF2 Mutations Cause Splicing Changes by Altering Binding Motif Sequences

Serine/arginine-rich splicing factor 2 (SRSF2) is a member of the SR protein family that is involved in both constitutive and alternative mRNA splicing. Mutations in SRSF2 gene are frequently reported in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). It is imperative to understand how these mutations affect SRSF2-mediated splicing and cause MDS. In this study, we characterized MDS-associated SRSF2 mutants (P95H, P95L, and P95R). We found that those mutants and wild-type SRSF2 proteins showed nuclear localization in HeLa cells. In vitro splicing reaction also revealed that mutant proteins associated with both precursor and spliced mRNAs, suggesting that the mutants directly participate in splicing. We established the human myeloid leukemia K562 cell lines that stably expressed myc-tagged wild-type or mutant SRSF2 proteins, and then performed RNA-sequence to analyze the splicing pattern of each cell line. The results revealed that both wild-type and mutants affected splicing of approximately 3,000 genes. Although splice site sequences adjacent to the affected exons showed no significant difference compared to the total exons, exonic motif analyses with both inclusion- and exclusion-enhanced exons demonstrated that wild-type and mutants have different binding sequences in exons. These results indicate that mutations of SRSF2 in MDS change binding properties of SRSF2 to exonic motifs and this causes aberrant splicing

Structural insights into the HBV receptor and bile acid transporter NTCP

B型肝炎ウイルスの受容体“胆汁酸輸送体”の立体構造を解明. 京都大学プレスリリース. 2022-05-18.Roughly 250 million people are infected with hepatitis B virus (HBV) worldwide, and perhaps 15 million also carry the satellite virus HDV, which confers even greater risk of severe liver disease. Almost ten years ago the HBV receptor was identified as NTCP (sodium taurocholate co-transporting polypeptide), which interacts directly with the first 48 amino acid residues of the N-myristoylated N-terminal preS1 domain of the viral large (L) protein. Despite the pressing need for therapeutic agents to counter HBV, the structure of NTCP remains unsolved. This 349-residue protein is closely related to human apical sodium-dependent bile acid transporter (ASBT), another member of the solute carrier family SLC10. Crystal structures have been reported of similar bile acid transporters from bacteria, and these models with ten transmembrane helices are believed to resemble strongly both NTCP and ASBT. Using cryo-electron microscopy we have solved the structure of NTCP bound to an antibody, clearly showing the transporter has no equivalent to the first transmembrane helix of other SLC10 models, leaving the N-terminus exposed on the extracellular face. Comparison of the different structures indicates a common mechanism of bile acid transport, but the NTCP structure also displays a pocket formed by residues known to interact with preS1, presenting new and enticing opportunities for structure-based drug design