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Background: Although Faecalibacterium prausnitzii is a major bacterium in the intestine of adults, which is known to have anti-inflammatory effects, the development in infants or the response to prebiotics remains unclear. Methods: The counts of F. prausnitzii in the feces were examined by real-time polymerase chain reaction (PCR). Fecal samples were obtained from 65 atopic dermatitis (AD) infants who participated in a randomized controlled clinical trial to investigate the therapeutic effect of kestose, the smallest fructooligosaccharide. Results: Although the F. prausnitzii count was undetectable level in most 0- to 1-y-old infants, the count reached a level comparable to that in adults in 2- to 5-y-old infants. The bacterial number increased about 10-fold by oral administration of kestose every day for 12 wk in the younger infants, but not so much in the older infants. This bacterial increase was significantly correlated with an improvement in the AD symptoms in the older infants. Conclusion: The F. prausnitzii population in the intestine reaches a level comparable to that in adult at approximately 2 y of age. Kestose efficiently stimulates the growth of this bacterium in the intestine, which might lead to an improvement in AD symptoms in infants.

Pancreatic adenocarcinoma (PDAC) with synchronous oligometastases may indicate a surgical benefit after chemotherapy. We investigated whether primary and metastatic resection of PDAC with oligometastases can improve the survival and then explored prognostic factors to identify indications for conversion surgery. We reviewed 425 patients with PDAC who underwent pancreatic resection from 2005 to 2019. Clinical characteristics and outcomes were analyzed. Two-stage resection was defined as preceding metastasectomy and subsequent primary resection after chemotherapy. Fifteen patients (3.5%) had synchronous oligometastases. We evaluated the overall survival of the patients with oligometastases and those without metastases. The survival curves almost completely overlapped (median survival time: 35.9 vs. 32.1 months). The univariate Cox regression analysis revealed a normal level of preoperative CA19-9 (p=0.075), two-stage resection (p=0.072), and R0 resection (p=0.064) were likely promising prognostic factors. The combination of a normal level of preoperative CA19-9 with two-stage resection was a significant prognostic factor (p=0.038). In addition, patients with a normal preoperative CA19-9 level and two-stage resection had better survival (46.1 vs. 28.1 months, p=0.026). The combination of normal preoperative CA19-9 with two-stage resection can be a useful way to identify patients with PDAC and oligometastases for surgical indication.

Rheb is a unique member of the Ras superfamily GTP-binding proteins. We as well as others previously have shown that Rheb is a critical component of the TSC/TOR signaling pathway. In fission yeast, Rheb is encoded by the rhb1 gene. Rhb1p is essential for growth and directly interacts with Tor2p. In this article, we report identification of 22 single amino acid changes in the Tor2 protein that enable growth in the absence of Rhb1p. These mutants also exhibit decreased mating efficiency. Interestingly, the mutations are located in the C-terminal half of the Tor2 protein, clustering mainly within the FAT and kinase domains. We noted some differences in the effect of a mutation in the FAT domain (L1310P) and in the kinase domain (E2221K) on growth and mating. Although the Tor2p mutations bypass Rhb1p's requirement for growth, they are incapable of suppressing Rhb1p's requirement for resistance to stress and toxic amino acids, pointing to multiple functions of Rhb1p. In mammalian systems, we find that mammalian target of rapamycin (mTOR) carrying analogous mutations (L1460P or E2419K), although sensitive to rapamycin, exhibits constitutive activation even when the cells are starved for nutrients. These mutations do not show significant difference in their ability to form complexes with Raptor, Rictor, or mLST8. Furthermore, we present evidence that mutant mTOR can complex with wild-type mTOR and that this heterodimer is active in nutrient-starved cells.

The tunneling nanotube (TNT) is a structure used for intercellular communication, and is a thin membrane protrusion mediating transport of various signaling molecules and cellular components. M-Sec has potent membrane deformation ability and induces TNT formation in cooperation with the Ral/exocyst complex. Here, we show that the N-terminal polybasic region of M-Sec directly binds phosphatidylinositol (4,5)-bisphosphate for its localization to the plasma membrane during the initial stage of TNT formation. We further report a crystal structure of M-Sec, which consists of helix bundles arranged in a straight rod-like shape, similar to the membrane tethering complex subunits. A positively charged surface in the C-terminal domains is required for M-Sec interaction with active RalA to extend the plasma membrane protrusions. Our results suggest that the membrane-associated M-Sec recruits active RalA, which directs the exocyst complex to form TNTs.

Background Pancreatic cancer (PC) has poorer prognosis and higher surgical invasiveness than many other cancers, with associated psychiatric symptoms including depression and anxiety. Perioperative depression has not been investigated in PC patients regarding surgical stress and relevant interventions. Methods We evaluated chronological depressive changes and subjective physical symptoms in surgically treated PC patients preoperatively and at 3 and 6 months postoperatively. Enrolled patients undergoing pancreatic tumor surgery completed questionnaires based on the Self-Rating Depression Scale (SDS) and Functional Assessment of Cancer Therapy for Patients with Hepatobiliary Cancer (FACT-Hep) preoperatively, and at 3 and 6 months postoperatively. Responses were analyzed with JMP® Pro using one-way and two-way ANOVA, Spearman’s rank correlation coefficient, and multiple regression analysis. Results Malignancy was diagnosed in 73 of 101 patients postoperatively; SDS score was significantly higher in these patients than in those with benign tumors at all timepoints: malignant/benign, 41.8/37.9 preoperatively ( p  = 0.004); 43.5/37.8 3 months postoperatively ( p  = 0.006); and 42.9/37.7 6 months postoperatively ( p  = 0.020). SDS scores were significantly higher in patients < 65 years old with malignancy at 3 months than at 6 months postoperatively (44.6/42.5, p  = 0.046) and in patients with malignancy who underwent pancreaticoduodenectomy at 3 months postoperatively than preoperatively (43.4/41.1; p  = 0.028). SDS scores moderately correlated with 8 physical symptom-related FACT-Hep items 3 months postoperatively ( p  < 0.05), showing low-to-moderate correlation with 16 physical symptom-related FACT-Hep items at 6 months postoperatively ( p  < 0.05). Multiple regression analysis of FACT-Hep symptoms significantly correlated with SDS scores revealed the following significant variables: “lack of energy” ( p  < 0.000) and “pain” ( p  = 0.018) preoperatively (R 2  = 0.43); “able to perform usual activities” ( p  = 0.031) and “lack of energy” ( p  < 0.000) at 3 months postoperatively (R 2  = 0.51); and “stomach swelling or cramps” ( p  = 0.034) and “bowel control” ( p  = 0.049) at 6 months postoperatively (R 2  = 0.52). Conclusions PC patients experience persistently high levels of depression preoperatively through 6 months postoperatively, with associated subjective symptoms including pain and gastrointestinal symptoms. Trial registration UMIN Clinical Trials Registry 000009592 , Registered 20 December 2012.

Pancreatic ductal adenocarcinoma (PDAC) is the most lethal cancer, mainly because of its invasive and metastatic characteristics. Pancreatic intraepithelial neoplasia (PanIN) is one of the major precursor lesions of PDAC. Although epithelial‐to‐mesenchymal transition (EMT) is known to play an important role for these malignant behaviors, the association between PanIN and EMT has not been clearly understood. Therefore, we explored possible molecules for regulation of EMT immunohistochemically. Using surgically resected specimens from 71 PDAC patients, expressions of SNAIL, SLUG, TWIST1, and ZEB1 were investigated in high‐grade PanIN (HG‐PanIN) and PDAC. Results demonstrated that PDAC accompanied by SNAIL‐positive HG‐PanIN showed a significantly better relapse‐free survival (RFS) (median survival time (MST) of 11.3 months vs 4.4 months, P < 0.001) and overall survival overall survival (OS) (MST of 25.2 months vs 13.6 months, P < 0.001). In PDAC accompanied by SLUG‐positive HG‐PanIN, RFS and OS (P = 0.09 and P = 0.05) tended to have a better prognosis. In contrast, we could not find any significant prognostic benefits in the expression of TWIST1 or ZEB1 in PDAC accompanied by HG‐PanIN. Our present results suggest that (1) EMT may play an important role in the development of PDAC from HG‐PanIN, and (2) SNAIL may predict a distinct subgroup that shows a better prognosis. Epithelial‐to‐mesenchymal transition may play an important role in the development of pancreatic ductal adenocarcinoma from high‐grade pancreatic intraepithelial neoplasia, and SNAIL may predict a distinct subgroup that shows a better prognosis.

The Japanese lunar explorer SELENE (Kaguya), which was launched on September 14th, 2007, was the target of VLBI observations over the period November 2007 to June 2009. These observations were made in order to improve the lunar gravity field model, in particular the lower degree coefficients and the model near the limb. Differential VLBI Radio sources, called VRAD instruments, were on-board the subsatellites, Rstar (Okina) and Vstar (Ouna), and the radio signals were observed by the Japanese VERA (VLBI Exploration of Radio Astrometry) network, and an international VLBI network. Multi-frequency and same-beam VLBI techniques were utilized and were essential aspects of the successful observing program. Multi-frequency VLBI was employed in order to improve the accuracy of the orbit determination obtained from the phase delay from the narrow-band satellite signals, while the same-beam VLBI method was used to resolve the cycle ambiguity which is inherent in the multi-frequency VLBI method. The observations were made at three S-band frequencies (2212, 2218 and 2287 MHz), and one X-band frequency (8456 MHz). We have succeeded in correlating the recorded signals from Okina/Ouna, and we obtained phase delays with an accuracy of several pico-seconds at S-band.