Here, we report the first synthesis of oxyphyllin A/belchinoid A, a 7,9-seco-8,12-dinor-guaiane sesquiterpene whose isolation was reported independently by two groups in 2023. This synthesis utilizes ...a key sequential sulfone-mediated intermolecular alkylation/5-endo-tet cyclization reaction to establish the C1, C4, C5 stereocenters. Subsequent transformations, including regio- and stereoselective hydride addition-based desulfonylation via a π–allyl palladium complex and the Wittig reaction with a stable phosphonium ylide, facilitated the synthesis of oxyphyllin A/belchinoid A.
Differentiation of pluripotent stem cells (PSCs) requires transposon silencing throughout the process. PIWIs, best known as key factors in germline transposon silencing, are also known to act in ...somatic differentiation of planarian PSCs (neoblasts). However, how PIWIs control the latter process remains elusive. Here, using Dugesia japonica, we show that a nuclear PIWI, DjPiwiB, was bound to PIWI-interacting RNAs (generally key mediators of PIWI-dependent transposon silencing), and was detected in not only neoblasts but also their descendant somatic cells, which do not express piwi. In contrast, cytoplasmic DjPiwiA and DjPiwiC were detected only in neoblasts, in accord with their transcription there. DjPiwiB was indispensable for regeneration, but dispensable for transposon silencing in neoblasts. However, transposons were derepressed at the onset of differentiation in DjPiwiB-knockdown planarians. Thus, DjPiwiB appears to be inherited by descendant somatic cells of neoblasts to ensure transposon silencing in those cells, which are unable to produce PIWI proteins.
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•Three PIWI proteins temporally switch to repress TE during PSC differentiation•Nuclear DjPiwiB is required for differentiation of neoblasts (PSCs) in planarian•Depletion of DjPiwiB causes activation of TEs in somatic descendants of neoblasts•DjPiwiB produced in neoblasts is inherited and acts in their somatic descendants
PIWI proteins are known to mediate transposon silencing in the germline. Shibata, Kashima et al. show that, in the planarian Dugesia japonica, differentiated somatic cells, which themselves do not express PIWI proteins, inherit a nuclear PIWI from their pluripotent predecessors. The PIWI protein is required for transposon silencing during differentiation and regeneration.
The aims of this study were to analyze the outcomes of fetuses with congenital diaphragmatic hernia (CDH) treated by a lung-protective strategy using high-frequency oscillatory ventilation (HFOV) in ...a single center with a perinatology service and extracorporeal membrane oxygenation (ECMO) capability and to define the natural history of CDH in the era of lung-protective ventilation.
A retrospective chart review of 30 neonates with CDH seen between April 2002 and October 2004 was conducted. All fetuses with a prenatal diagnosis were evaluated by fetal magnetic resonance imaging to define the liver position, and those with a significant volume of the liver in the chest were regarded as liver-up. Patients were managed by a lung-protective strategy using pressure-limited (maximum mean airway pressure MAP, 18 cm H
2O) HFOV. The patients were initially placed on HFOV with a fraction of inspired oxygen (F
io
2) of 1.0 and a MAP of 12 cm H
2O. Hypercapnea and preductal saturation as low as 85% were accepted. Inhaled nitric oxide and ECMO were introduced when the baby could not be oxygenated with a MAP of 18 cm H
2O.
Twenty-six neonates (22 inborns with prenatal diagnosis and 4 outborns) were treated with this protocol. Four cases were not treated or died in utero because of severe associated anomalies. Thirteen of the 14 liver-down cases survived without ECMO and were discharged home (93% survival). On the contrary, 4 of 12 liver-up cases survived (33% survival). ECMO was required for initial stabilization in 5 cases with 1 survivor.
Liver-down CDH babies have a good chance for survival without ECMO by a planned delivery and the lung-protective strategy using HFOV. Liver herniation demonstrated by prenatal magnetic resonance imaging retains a poor prognostic value even with this approach.
Women who receive negative results from non-invasive prenatal genetic testing (NIPT) may find that they later have mixed or ambivalent feelings, for example, feelings of accepting NIPT and regretting ...undergoing the test. This study aimed to investigate the factors generating ambivalent feelings among women who gave birth after having received negative results from NIPT.
A questionnaire was sent to women who received a negative NIPT result, and a contents analysis was conducted focusing on ambivalent expressions for those 1562 women who responded the questionnaire. The qualitative data gathered from the questionnaire were analyzed using the N-Vivo software package.
Environmental factors, genetic counseling-related factors, and increased anticipatory anxiety, affected the feeling of ambivalence among pregnant women. Furthermore, pregnant women desired more information regarding the detailed prognosis for individuals with Down syndrome and living with them and/or termination, assuming the possibility that they were positive.
Three major interrelated factors affected the feeling of ambivalence in women. Highlighting and discussing such factors during genetic counseling may resolve some of these ambivalences, thereby enhancing the quality of decisions made by pregnant women.
Mucins are secreted or transmembrane glycoproteins that are expressed mainly in the digestive tract. This family of proteins has been the focus of much gastric cancer research as some transmembrane ...mucins are implicated in tumorigenesis and make attractive targets for cancer diagnosis and therapeutics. Mucins have also been utilized to classify gastric cancer by differentiating between gastric and intestinal phenotypes. Here we show that transmembrane mucin MUC13 is upregulated in gastric cancer. By quantitative real‐time reverse transcription‐polymerase chain reaction and immunoblot analysis, overexpression of MUC13 was verified in more than half of the samples examined. In immunohistochemical analysis, MUC13 staining was observed in 74 of 114 cases of gastric cancer (64.9%), predominantly in intestinal type (P < 0.001), and in 9 of 10 cases of intestinal metaplasia, precancerous lesions of intestinal‐type gastric cancer, but not observed in normal gastric mucosa. Moreover, MUC13 staining patterns characteristic of histological type were identified: staining was on the apical side of tubular glands in intestinal type and on the cytoplasm in diffuse type. These results suggest that MUC13 is a good differentiation marker for gastrointestinal mucosa and that it may have a causal role that correlates with two distinct gastric tumorigenesis pathways. (Cancer Sci 2005; 96: 265 –274)
The crystal structure of an extremely thermostable multicopper oxidase (McoP) from the hyperthermophilic archaeon Pyrobaculum aerophilum was determined at a resolution of 2.0 Å. The overall fold was ...comprised of three cupredoxin‐like domains and the main‐chain coordinates of the enzyme were similar to those of multicopper oxidases from Escherichia coli (CueO) and Bacillus subtilis (CotA). However, there were clear topological differences around domain 3 between McoP and the other two enzymes: a methionine‐rich helix in CueO and a protruding helix in CotA were not present in McoP. Instead, a large loop (PL‐1) covered the T1 copper centre of McoP and a short α‐helix in domain 3 extended near the N‐terminal end of PL‐1. In addition, the sizes of several surface loops in McoP were markedly smaller than the corresponding loops in CueO and CotA. Structural comparison revealed that the presence of extensive hydrophobic interactions and a smaller cavity volume are likely to be the main factors contributing to the hyperthermostability of McoP.
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