TORC1 regulates autophagy induction in response to proteotoxic stress in yeast and human cells

Misfolded and aggregated proteins are eliminated to maintain protein homeostasis. Autophagy contributes to the removal of protein aggregates. However, if and how proteotoxic stress induces autophagy is poorly understood. Here we show that proteotoxic stress after treatment with azetidine-2-carboxylic acid (AZC), a toxic proline analog, induces autophagy in budding yeast. AZC treatment attenuated target of rapamycin complex 1 (TORC1) activity, resulting in the dephosphorylation of Atg13, a key factor of autophagy. By contrast, AZC treatment did not affect target of rapamycin complex 2 (TORC2). Proteotoxic stress also induced TORC1 inactivation and autophagy in fission yeast and human cells. This study suggested that TORC1 is a conserved key factor to cope with proteotoxic stress in eukaryotic cells

Nursing Activity Sensing Using Mobile Sensors and Proximity Sensors

In recent years, big data are utilized in many industries.In this study, in order to analyze duties of thenurses, we performed experiments to collect the dutiesactivity data of the nurses for a long term. Weset 38 nurses as subjects and asked them to carry outduties while attaching a wearable small sensor device,and collected the acceleration data, meeting informationbetween nurses and the nurse duties information.In addition, we collected the location information of the nurses by using infrared information and communication equipment at the same time. From various data collected, we analyzed intensity and positional information of duties activity of the nurse, meeting information and the duties information between nurses and considered the influence that each factor affected to the nurse. As the result, we found that intensity of the activity increases in such nurses as who has many times of meeting with other nurses, visits the patient room many times, or who works on jobs concerning with the assistance of the patients such as rehabilitation assistance duties or the activity assistance dutiesThe 47th ISCIE International Symposium on Stochastic Systems Theory and Its Applications (SSS\u2715), December 5-8, 2015, Waikiki Beach Marriott Resort & Spa, Hawaii, US

Trace element concentrations in the small Indian mongoose (\u3ci\u3eHerpestes auropunctatus\u3c/i\u3e) from Hawaii, USA

Concentrations of 26 trace elements including essential (Mg, Ca, Cr, V, Mn, Fe, Co, Ni, Cu, Zn, Se, Sr and Mo) and toxic (As, Cd and Pb), were determined in the liver, kidney, brain, hair, muscle, and stomach contents of the small Indian mongooses inhabiting eight areas on three Hawaiian Islands, Oahu, Maui and Hawaii. There were significant differences in concentrations of some metals among the habitats. Cadmium concentrations in mongooses from the macadamia nut orchards on Island of Hawaii were relatively higher than those in populations from other seven areas. Lead concentrations in mongooses from the Ukumehame firing range were significantly higher than those from other areas. Compared to data reported in mongooses from other countries, Pb concentrations in the brain were higher in the animals from Hawaiian islands, but almost similar levels were observed in the liver and kidney. Intriguingly, brain concentrations of Pb in three specimens from the Ukumehame firing range exceeded 3.79 μg g−1 WW, which was the mean cerebral Pb level in rats that caused some toxic symptoms after administration in the previous study. Furthermore, two fetuses exhibited higher brain Pb concentrations than each of their dams. These results prompted us to consider the potential exposure and health effects of Pb derived from firing range operations on the small Indian mongoose and other animal species including human

Trace element concentrations in the small Indian mongoose (\u3ci\u3eHerpestes auropunctatus\u3c/i\u3e) from Hawaii, USA

Concentrations of 26 trace elements including essential (Mg, Ca, Cr, V, Mn, Fe, Co, Ni, Cu, Zn, Se, Sr and Mo) and toxic (As, Cd and Pb), were determined in the liver, kidney, brain, hair, muscle, and stomach contents of the small Indian mongooses inhabiting eight areas on three Hawaiian Islands, Oahu, Maui and Hawaii. There were significant differences in concentrations of some metals among the habitats. Cadmium concentrations in mongooses from the macadamia nut orchards on Island of Hawaii were relatively higher than those in populations from other seven areas. Lead concentrations in mongooses from the Ukumehame firing range were significantly higher than those from other areas. Compared to data reported in mongooses from other countries, Pb concentrations in the brain were higher in the animals from Hawaiian islands, but almost similar levels were observed in the liver and kidney. Intriguingly, brain concentrations of Pb in three specimens from the Ukumehame firing range exceeded 3.79 μg g−1 WW, which was the mean cerebral Pb level in rats that caused some toxic symptoms after administration in the previous study. Furthermore, two fetuses exhibited higher brain Pb concentrations than each of their dams. These results prompted us to consider the potential exposure and health effects of Pb derived from firing range operations on the small Indian mongoose and other animal species including human

Induction of Expandable Tissue-Specific Progenitor Cells from Human Pancreatic Tissue through Transient Expression of Defined Factors

We recently demonstrated the generation of mouse induced tissue-specific stem (iTS) cells through transient overexpression of reprogramming factors combined with tissue-specific selection. Here we induced expandable tissue-specific progenitor (iTP) cells from human pancreatic tissue through transient expression of genes encoding the reprogramming factors OCT4 (octamer-binding transcription factor 4), p53 small hairpin RNA (shRNA), SOX2 (sex-determining region Y-box 2), KLF4 (Kruppel-like factor 4), L-MYC, and LIN28. Transfection of episomal plasmid vectors into human pancreatic tissue efficiently generated iTP cells expressing genetic markers of endoderm and pancreatic progenitors. The iTP cells differentiated into insulin-producing cells more efficiently than human induced pluripotent stem cells (iPSCs). iTP cells continued to proliferate faster than pancreatic tissue cells until days 100–120 (passages 15–20). iTP cells subcutaneously inoculated into immunodeficient mice did not form teratomas. Genomic bisulfite nucleotide sequence analysis demonstrated that the OCT4 and NANOG promoters remained partially methylated in iTP cells. We compared the global gene expression profiles of iPSCs, iTP cells, and pancreatic cells (islets >80%). Microarray analyses revealed that the gene expression profiles of iTP cells were similar, but not identical, to those of iPSCs but different from those of pancreatic cells. The generation of human iTP cells may have important implications for the clinical application of stem/progenitor cells

Development and Performance of Kyoto's X-ray Astronomical SOI pixel (SOIPIX) sensor

We have been developing monolithic active pixel sensors, known as Kyoto's X-ray SOIPIXs, based on the CMOS SOI (silicon-on-insulator) technology for next-generation X-ray astronomy satellites. The event trigger output function implemented in each pixel offers microsecond time resolution and enables reduction of the non-X-ray background that dominates the high X-ray energy band above 5--10 keV. A fully depleted SOI with a thick depletion layer and back illumination offers wide band coverage of 0.3--40 keV. Here, we report recent progress in the X-ray SOIPIX development. In this study, we achieved an energy resolution of 300~eV (FWHM) at 6~keV and a read-out noise of 33~e- (rms) in the frame readout mode, which allows us to clearly resolve Mn-K$\alpha$ and K$\beta$. Moreover, we produced a fully depleted layer with a thickness of $500~{\rm \mu m}$. The event-driven readout mode has already been successfully demonstrated.Comment: 7pages, 12figures, SPIE Astronomical Telescopes and Instrumentation 2014, Montreal, Quebec, Canada. appears as Proc. SPIE 9147, Space Telescopes and Instrumentation 2014: Ultraviolet to Gamma Ra

Two new maltol glycosides and cyanogenic glycosides from Elsholtzia rugulosa Hemsl.

Two new maltol glycosides, maltol 6\u27-O-beta-D-apiofuranosyl-beta-D-glucopyranoside and maltol 6\u27-O-(5-O-p-coumaroyl)-beta-D-apiofuranosyl-beta-D-glucopyranoside, were isolated from Elsholtzia rugulosa Hemsl. along with 11 known compounds including prunasin and amygdalin. The structures were determined on the basis of spectroscopic and chemical evidence. This is the second example of isolation of cyanogenic glycosides from Lamiaceous plants

Impact of a learning health system on acute care and medical complications after intracerebral hemorrhage

Introduction: Patients with stroke often experience pneumonia during the acute stage after stroke onset. Oral care may be effective in reducing the risk of stroke‐associated pneumonia (SAP). We aimed to determine the changes in oral care, as well as the incidence of SAP, in patients with intracerebral hemorrhage, following implementation of a learning health system in our hospital. Methods: We retrospectively analyzed the data of 1716 patients with intracerebral hemorrhage who were hospitalized at a single stroke center in Japan between January 2012 and December 2018. Data were stratified on the basis of three periods of evolving oral care: period A, during which conventional, empirically driven oral care was provided (n = 725); period B, during which standardized oral care was introduced, with SAP prophylaxis based on known risk factors (n = 469); and period C, during which oral care was risk‐appropriate based on learning health system data (n = 522). Logistic regression analysis was performed to evaluate associations between each of the three treatment approaches and the risk of SAP. Results: Among the included patients, the mean age was 71.3 ± 13.6 years; 52.6% of patients were men. During the course of each period, the frequency of oral care within 24 hours of admission increased (P < .001), as did the adherence rate to oral care ≥3 times per day (P < .001). After adjustment for confounding factors, a change in the risk of SAP was not observed in period B; however, the risk significantly decreased in period C (odds ratio 0.61; 95% confidence interval 0.43‐0.87) compared with period A. These associations were maintained for SAP diagnosed using strict clinical criteria or after exclusion of 174 patients who underwent neurosurgical treatment. Conclusions: Risk‐appropriate care informed by the use of learning health system data could improve care and potentially reduce the risk of SAP in patients with intracerebral hemorrhage in the acute stage

Isolation and identification of ubiquitin-related proteins from Arabidopsis seedlings

The majority of proteins in eukaryotic cells are modified according to highly regulated mechanisms to fulfill specific functions and to achieve localization, stability, and transport. Protein ubiquitination is one of the major post-translational modifications occurring in eukaryotic cells. To obtain the proteomic dataset related to the ubiquitin (Ub)-dependent regulatory system in Arabidopsis, affinity purification with an anti-Ub antibody under native condition was performed. Using MS/MS analysis, 196 distinct proteins represented by 251 distinct genes were identified. The identified proteins were involved in metabolism (23.0%), stress response (21.4%), translation (16.8%), transport (6.7%), cell morphology (3.6%), and signal transduction (1.5%), in addition to proteolysis (16.8%) to which proteasome subunits (14.3%) is included. On the basis of potential ubiquitination-targeting signal motifs, in-gel mobilities, and previous reports, 78 of the identified proteins were classified as ubiquitinated proteins and the rest were speculated to be associated proteins of ubiquitinated proteins. The degradation of three proteins predicted to be ubiquitinated proteins was inhibited by a proteasome inhibitor, suggesting that the proteins were regulated by Ub/proteasome-dependent proteolysis

Effect of Saxagliptin on Endothelial Function in Patients with Type 2 Diabetes : A Prospective Multicenter Study

The dipeptidyl peptidase-4 inhibitor saxagliptin is a widely used antihyperglycemic agent in patients with type 2 diabetes. The purpose of this study was to evaluate the effects of saxagliptin on endothelial function in patients with type 2 diabetes. This was a prospective, multicenter, interventional study. A total of 34 patients with type 2 diabetes were enrolled at four university hospitals in Japan. Treatment of patients was initially started with saxagliptin at a dose of 5 mg daily. Assessment of endothelial function assessed by flow-mediated vasodilation (FMD) and measurement of stromal cell-derived factor-1α (SDF-1α) were conducted at baseline and at 3 months after treatment with saxagliptin. A total of 31 patients with type 2 diabetes were included in the analysis. Saxagliptin significantly increased FMD from 3.1 ± 3.1% to 4.2 ± 2.4% (P = 0.032) and significantly decreased total cholesterol from 190 ± 24 mg/dL to 181 ± 25 mg/dL (P = 0.002), glucose from 160 ± 53 mg/dL to 133 ± 25 mg/dL (P < 0.001), HbA1c from 7.5 ± 0.6% to 7.0 ± 0.6% (P < 0.001), urine albumin-to-creatinine ratio from 63.8 ± 134.2 mg/g to 40.9 ± 83.0 mg/g (P = 0.043), and total SDF-1α from 2108 ± 243 pg/mL to 1284 ± 345 pg/mL (P < 0.001). These findings suggest that saxagliptin is effective for improving endothelial function