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Background: The nucleolar MSP58 protein is a candidate oncogene implicated in cellular transformation.Results: MSP58 is associated with BRG1 and induces cellular senescence through the p53/p21 pathway.Conclusion: MSP58 has both tumor-suppressing and -promoting functions.Significance: This work reveals a novel role for MSP58 in cellular senescence and suggests that MSP58 may have further prognostic and therapeutic implications.

SummaryHelicobacter pylori inhabits the gastric mucosa where it senses and responds to various stresses via a twocomponent systems (TCSs) that enable its persistent colonization. The aim of this study was to investigate whether any of the three paired TCSs (ArsRS, FleRS and CrdRS) in H. pylori respond to nitrosative stress. The results showed that the expression of crdS was significantly increased upon exposure to nitric oxide (NO). crdS-knockout (ΔcrdS) and crdR/crdS-knockout (ΔcrdRS) H. pylori, but not arsS-knockout (ΔarsS) or fleS-knockout (ΔfleS) H. pylori, showed a significant loss of viability upon exposure to NO compared with wild-type strain. Knockin crdS (ΔcrdS-in) significantly restored viability in the presence of NO. Global transcriptional profiling analysis of wild-type and ΔcrdS H. pylori in the presence or absence of NO showed that 101 genes were differentially expressed, including copper resistance determinant A (crdA), transport, binding and envelope proteins. The CrdR binding motifs were investigated by competitive electrophoretic mobility shift assay, which revealed that the two AC-rich regions in the crdA promoter region are required for binding. These results demonstrate that CrdR-crdA interaction enables H. pylori to survive under nitrosative stress.

DBE-ERC was effective for both populations with biliary disorders. Reaching the blind end was more difficult but ERC was easier for patients with BEA in terms of procedure time rather than success rates.

There is a significant learning curve for endoscopic submucosal dissection of esophageal neoplasms that has not been fully characterized. This retrospective study included 33 consecutive superficial esophageal neoplasms for analysis of the learning curve for esophageal endoscopic submucosal dissection based on a single, novice endoscopist's experience. The study was divided into three periods (T1, T2, and T3) of 10 endoscopic submucosal dissection procedures in chronological order, with 13 procedures in the last period. Patient factors (age, sex, coexistent esophageal varices, or submucosal fibrosis) and tumor factors (location at upper esophagus, involving >3/4 esophageal circumference) for endoscopic submucosal dissection were not statistically different between the periods. The mean procedure time was 74.6 min/cm(2) , 23.4 min/cm(2) , and 10.5 min/cm(2) for T1, T2, and T3, respectively. The procedure time decreased over time (P = 0.02) and post hoc test revealed significant difference was only between T3 and T1 (P = 0.019). The en bloc resection rate was 50%, 100%, and 92.3% for T1, T2, and T3, respectively (P for trend = 0.015). R0 resection rate was 40%, 100%, and 84.6% for T1, T2, and T3, respectively (P for trend = 0.023). Two patients had complications: each one patient in T1 and T3 period experienced major bleeding during the procedure (P for trend = 0.875). None of the patients had esophageal perforation. The results of the study concluded that at least 30 cases of endoscopic submucosal dissection of esophageal neoplasms are needed for a novice endoscopist to gain early proficiency in this technique.

Bioconversion is useful to produce optically pure enantiomers in the pharmaceutical industry, thereby avoiding problems with side reactions during organic synthesis processes. A short-chain dehydrogenase/reductase from Serratia marcescens BCRC 10948 (SmSDR) can stereoselectively convert 1-(3-hydroxyphenyl)-2-(methylamino) ethanone (HPMAE) into (R)-phenylephrine [(R)-PE], which is marketed medically as a nasal decongestant agent. The whole-cell conversion process for the synthesis of (R)-PE using SmSDR was reported to have an unexpectedly low conversion rate. We reported the crystal structure of the SmSDR and designed profitable variants to improve the enzymatic activity by structure-guided approach. Several important residues in the structure were observed to form hydrophobic clusters that stabilize the mobile loops surrounding the pocket. Of these, Phe98 and Phe202 face toward each other and connect the upper curvature from the two arms (i.e., the α7 helix and loopβ4–α4). The mutant structure of the double substitutions (F98YF202Y) exhibited a hydrogen bond between the curvatures that stabilizes the flexible arms. Site-directed mutagenesis characterization revealed that the mutations (F98Y, F98YF202Y, and F98YF202L) of the flexible loops that stabilize the region exhibited a higher transformation activity toward HPMAE. Together, our results suggest a robust structure-guided approach that can be used to generate a valuable engineered variant for pharmaceutical applications.

BackgroundMSP58 is a nucleolar protein associated with rRNA transcription and cell proliferation. Its mechanism of translocation into the nucleus or the nucleolus, however, is not entirely known. In order to address this lack, the present study aims to determine a crucial part of this mechanism: the nuclear localization signal (NLS) and the nucleolar localization signal (NoLS) associated with the MSP58 protein.ResultsWe have identified and characterized two NLSs in MSP58. The first is located between residues 32 and 56 (NLS1) and constitutes three clusters of basic amino acids (KRASSQALGTIPKRRSSSRFIKRKK); the second is situated between residues 113 and 123 (NLS2) and harbors a monopartite signal (PGLTKRVKKSK). Both NLS1 and NLS2 are highly conserved among different vertebrate species. Notably, one bipartite motif within the NLS1 (residues 44–56) appears to be absolutely necessary for MSP58 nucleolar localization. By yeast two-hybrid, pull-down, and coimmunoprecipitation analysis, we show that MSP58 binds to importin α1 and α6, suggesting that nuclear targeting of MSP58 utilizes a receptor-mediated and energy-dependent import mechanism. Functionally, our data show that both nuclear and nucleolar localization of MSP58 are crucial for transcriptional regulation on p21 and ribosomal RNA genes, and context-dependent effects on cell proliferation.ConclusionsResults suggest that MSP58 subnuclear localization is regulated by two nuclear import signals, and that proper subcellular localization of MSP58 is critical for its role in transcriptional regulation. Our study reveals a molecular mechanism that controls nuclear and nucleolar localization of MSP58, a finding that might help future researchers understand the MSP58 biological signaling pathway.Electronic supplementary materialThe online version of this article (doi:10.1186/s12929-015-0136-0) contains supplementary material, which is available to authorized users.

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