Membrane-less organelles resulting from liquid-liquid phase separation of biopolymers into intracellular condensates control essential biological functions, including messenger RNA processing, cell ...signalling and embryogenesis
. It has recently been discovered that several such protein condensates can undergo a further irreversible phase transition, forming solid nanoscale aggregates associated with neurodegenerative disease
. While the irreversible gelation of protein condensates is generally related to malfunction and disease, one case where the liquid-to-solid transition of protein condensates is functional, however, is that of silk spinning
. The formation of silk fibrils is largely driven by shear, yet it is not known what factors control the pathological gelation of functional condensates. Here we demonstrate that four proteins and one peptide system, with no function associated with fibre formation, have a strong propensity to undergo a liquid-to-solid transition when exposed to even low levels of mechanical shear once present in their liquid-liquid phase separated form. Using microfluidics to control the application of shear, we generated fibres from single-protein condensates and characterized their structural and material properties as a function of shear stress. Our results reveal generic backbone-backbone hydrogen bonding constraints as a determining factor in governing this transition. These observations suggest that shear can play an important role in the irreversible liquid-to-solid transition of protein condensates, shed light on the role of physical factors in driving this transition in protein aggregation-related diseases and open a new route towards artificial shear responsive biomaterials.
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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
Functional dyspepsia (FD) is a disorder that presents with chronic dyspepsia, which is not only very common but also highly affects quality of life of the patients. In Japan, FD became a ...disease name for national insurance in 2013, and has been gradually recognized, though still not satisfactory. Following the revision policy of Japanese Society of Gastroenterology (JSGE), the first version of FD guideline was revised this time.
Method
Like previously, the guideline was created by the GRADE (grading of recommendations assessment, development and evaluation) system, but this time, the questions were classified to background questions (BQs, 24 already clarified issues), future research questions (FRQs, 9 issues cannot be addressed with insufficient evidence), and 7 clinical questions that are mainly associated with treatment.
Results and Conclusion
These revised guidelines have two major features. The first is the new position of endoscopy in the flow of FD diagnosis. While endoscopy was required to all cases for diagnosis of FD, the revised guidelines specify the necessity of endoscopy only in cases where organic disease is suspected. The second feature is that the drug treatment options have been changed to reflect the latest evidence. The first-line treatment includes gastric acid-secretion inhibitors, acetylcholinesterase (AChE) inhibitors (acotiamide, a prokinetic agent), and Japanese herbal medicine (rikkunshito). The second-line treatment includes anxiolytics /antidepressant, prokinetics other than acotiamide (dopamine receptor antagonists, 5-HT4 receptor agonists), and Japanese herbal medicines other than rikkunshito. The patients not responding to these treatment regimens are regarded as refractory FD.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Recently it has been claimed that the warm dark matter (WDM) model cannot at the same time reproduce the observed Lyman- alpha forests in distant quasar spectra and solve the small-scale issues in ...the cold dark matter (CDM) model. As an alternative candidate, it was shown that the mixed dark matter (MDM) model that consists of WDM and CDM can satisfy the constraint from Lyman- alpha forests and account for the "missing satellite problem" as well as the reported 3.5 keV anomalous x-ray line. We investigate observational constraints on the MDM model using strong gravitational lenses. We first develop a fitting formula for the nonlinear power spectra in the MDM model by performing N-body simulations and estimate the expected perturbations caused by line-of-sight structures in four quadruply lensed quasars that show anomaly in the flux ratios. Our analysis indicates that the MDM model is compatible with the observed anomaly if the mass fraction of the warm component is smaller than 0.47 at the 95% confidence level. The MDM explanation to the anomalous x-ray line and the small-scale issues is still viable even after this constraint is taken into account.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
Nonalcoholic fatty liver disease (NAFLD) has become a serious public health issue not only in Western countries but also in Japan. Within the wide spectrum of NAFLD, nonalcoholic steatohepatitis ...(NASH) is a progressive form of disease that often develops into liver cirrhosis and increases the risk of hepatocellular carcinoma (HCC). While a definite diagnosis of NASH requires liver biopsy to confirm the presence of hepatocyte ballooning, hepatic fibrosis is the most important prognostic factor in NAFLD. With so many NAFLD patients, it is essential to have an effective screening method for NAFLD with hepatic fibrosis. As HCC with non‐viral liver disease has increased markedly in Japan, effective screening and surveillance of HCC are also urgently needed. The most common death etiology in NAFLD patients is cardiovascular disease event. Gastroenterologists must, therefore, pay close attention to CVD when examining NAFLD patients. In the updated guidelines, we propose screening and follow‐up methods for hepatic fibrosis, HCC, and CVD in NAFLD patients. Several drug trials are ongoing for NAFLD/NASH therapy, however, there is currently no specific drug therapy for NAFLD/NASH. In addition to vitamin E and thiazolidinedione derivatives, recent trials have focused on sodium glucose co‐transporter 2 (SGLT2) inhibitors and glucagon‐like peptide‐1 (GLP‐1) analogues, and effective therapies are expected to be developed. These practical guidelines for NAFLD/NASH were established by the Japanese Society of Gastroenterology in conjunction with the Japan Society of Hepatology. Clinical evidence reported internationally between 1983 and October 2018 was collected, and each clinical and background question was evaluated using the Grades of Recommendation Assessment, Development and Evaluation (GRADE) system. This English summary pro‐ vides the core essentials of these clinical practice guidelines, which include the definition and concept, screening systems for hepatic fibrosis, HCC and CVD, and current therapies for NAFLD/NASH in Japan.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
An adaptive structural learning method of restricted Boltzmann machine (RBM) and deep belief network (DBN) has been developed as one of prominent deep learning models. The neuron ...generation-annihilation algorithm in RBM and layer generation algorithm in DBN make an optimal network structure for given input during the learning. In this article, our model is applied to an automatic recognition method of road network system, called RoadTracer. RoadTracer can generate a road map on the ground surface from aerial photograph data. A novel method of RoadTracer using the teacher-student-based ensemble learning model of adaptive DBN is proposed, since the road maps contain many complicated features so that a model with high representation power to detect should be required. The experimental results showed the detection accuracy of the proposed model was improved from 40.0% to 89.0% on average in the seven major cities among the test dataset. In addition, we challenged to apply our method to the detection of available roads when landslide by natural disaster is occurred, in order to rapidly obtain a way of transportation. For fast inference, a small size of the trained model was implemented on a small embedded edge device as lightweight deep learning. We reported the detection results for the satellite image before and after the rainfall disaster in Japan.
Cytokinin activity in plants is closely related to nitrogen availability, and an Arabidopsis gene for adenosine phosphate-isopentenyltransferase (IPT), IPT3, is regulated by inorganic nitrogen ...sources in a nitrate-specific manner. In this study, we have identified another regulatory system of cytokinin de novo biosynthesis in response to nitrogen status. In rice, OsIPT4, OsIPT5, OsIPT7 and OsIPT8 were up-regulated in response to exogenously applied nitrate and ammonium, with accompanying accumulation of cytokinins. Pre-treatment of roots with l-methionine sulfoximine, a potent inhibitor of glutamine synthetase, abolished the nitrate- and ammonium-dependent induction of OsIPT4 and OsIPT5, while glutamine application induced their expression. Thus, neither nitrate nor ammonium, but glutamine or a related metabolite, is essential for the induction of these IPT genes in rice. On the other hand, glutamine-dependent induction of IPT3 occurs in Arabidopsis, at least to some extent. In transgenic lines repressing the expression of OsIPT4, which is the dominant IPT in rice roots, the nitrogen-dependent increase of cytokinin in the xylem sap was significantly reduced, and seedling shoot growth was retarded despite sufficient nitrogen. We conclude that plants possess multiple regulation systems for nitrogen-dependent cytokinin biosynthesis to modulate growth in response to nitrogen availability.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The intracellular sensor Nod2 is activated in response to bacteria, and the impairment of this response is linked to Crohn's disease. However, the function of Nod2 in host defense remains poorly ...understood. We found that
Nod2
−/− mice exhibited impaired intestinal clearance of
Citrobacter rodentium, an enteric bacterium that models human infection by pathogenic
Escherichia coli. The increased bacterial burden was preceded by reduced CCL2 chemokine production, inflammatory monocyte recruitment, and Th1 cell responses in the intestine. Colonic stromal cells, but not epithelial cells or resident CD11b
+ phagocytic cells, produced CCL2 in response to
C. rodentium in a Nod2-dependent manner. Unlike resident phagocytic cells, inflammatory monocytes produced IL-12, a cytokine that induces adaptive immunity required for pathogen clearance. Adoptive transfer of Ly6C
hi monocytes restored the clearance of the pathogen in infected
Ccr2
−/− mice. Thus, Nod2 mediates CCL2-CCR2-dependent recruitment of inflammatory monocytes, which is important in promoting bacterial eradication in the intestine.
► Nod2
−/− mice exhibit impaired
C. rodentium clearance and CCL2 production ► Reduced CCL2 was associated with impaired Gr1
+ monocyte influx to the colon ► Intestinal stromal cells were the main producers of CCL2 ► Adoptive transfer of monocytes restored the clearance of
C. rodentium in Ccr2
−/− mice
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The aim of this study was to determine whether an improved biologically transparent illumination system results in more reliable detection of the correct position of the nasogastric tube in surgical ...patients. In total, 102 patients undergoing general surgery were included in this prospective observational study. After general anesthesia, all patients were inserted a nasogastric tube equipped with an improved biologically transparent illumination catheter. Identification of biologically transparent light in the epigastric area indicated successful insertion of the nasogastric tube into the stomach. The position of the tube was confirmed by X-ray examination, and its findings were compared with those of the biologically transparent illumination system. We observed biologically transparent light in epigastric area in 87 of the 102 patients. X-ray examination revealed that the nasogastric tube was placed in the stomach in all of these 87 patients. Light was not observed in the remaining 15 patients; the tube position was confirmed in the stomach in 11 of these patients but not in the other 4 by X-ray examination. Illumination had a sensitivity of 88.8% and a specificity of 100%. Our results suggest that this improved biologically transparent illumination system increased the accuracy of detecting the correct position of a nasogastric tube in the stomach. X-ray examination is required to check the position of the nasogastric tube in patients when biologically transparent illumination light is negative.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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