Autophagy has been implicated in the ageing process, but whether autophagy activation extends lifespan in mammals is unknown. Here we show that ubiquitous overexpression of Atg5, a protein essential ...for autophagosome formation, extends median lifespan of mice by 17.2%. We demonstrate that moderate overexpression of Atg5 in mice enhances autophagy, and that Atg5 transgenic mice showed anti-ageing phenotypes, including leanness, increased insulin sensitivity and improved motor function. Furthermore, mouse embryonic fibroblasts cultured from Atg5 transgenic mice are more tolerant to oxidative damage and cell death induced by oxidative stress, and this tolerance was reversible by treatment with an autophagy inhibitor. Our observations suggest that the leanness and lifespan extension in Atg5 transgenic mice may be the result of increased autophagic activity.
Abstract
ZNF746 was identified as parkin‐interacting substrate (PARIS). Investigating its pathophysiological properties, we find that PARIS undergoes liquid–liquid phase separation (LLPS) and ...amorphous solid formation. The N‐terminal low complexity domain 1 (LCD1) of PARIS is required for LLPS, whereas the C‐terminal prion‐like domain (PrLD) drives the transition from liquid to solid phase. In addition, we observe that poly(ADP‐ribose) (PAR) strongly binds to the C‐terminus of PARIS near the PrLD, accelerating its LLPS and solidification.
N
‐Methyl‐
N′
‐nitro‐
N
‐nitrosoguanidine (MNNG)‐induced PAR formation leads to PARIS oligomerization in human iPSC‐derived dopaminergic neurons that is prevented by the PARP inhibitor, ABT‐888. Furthermore, SDS‐resistant PARIS species are observed in the substantia nigra (SN) of aged mice overexpressing wild‐type PARIS, but not with a PAR binding‐deficient PARIS mutant. PARIS solidification is also found in the SN of mice injected with preformed fibrils of α‐synuclein (α‐syn PFF) and adult mice with a conditional knockout (KO) of parkin, but not if α‐syn PFF is injected into mice deficient for PARP1. Herein, we demonstrate that PARIS undergoes LLPS and PAR‐mediated solidification in models of Parkinson's disease.
Synopsis
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ZNF746 (PARIS) forms liquid condensates that transition to amorphous aggregates in a PAR‐dependent manner. PARIS accumulation is observed during aging and in animal models of Parkinson's disease.
PARIS undergoes dynamic liquid–liquid phase separation (LLPS) and liquid–solid transition via PARIS self‐assembly.
Low complexity domain 1 (LCD1) and prion‐like domain (PrLD) of PARIS are required for liquid and solid assembly, respectively.
Poly(ADP‐ribose) (PAR) binds to the C‐terminus of PARIS near the PrLD and accelerates amorphous aggregation of PARIS.
PAR‐mediated PARIS solidification is observed in animal models for sporadic PD.
Background:
Lateral epicondylitis is a chronic tendinopathy of humeral origin of the common extensor tendon. Most patients show improvement after nonoperative treatment. However, 4% to 11% of ...patients require surgical treatment. Although corticosteroid injection is one of the most commonly applied nonoperative treatment methods, to the authors’ knowledge, no study has reported the effect of the number of preoperative corticosteroid injections on the final postoperative outcome. Thus, the objective of this study was to determine the effect of the number of preoperative corticosteroid injections on postoperative clinical outcomes.
Hypothesis:
The number of corticosteroid injections before surgical treatment does not affect postoperative clinical outcomes.
Study Design:
Case series; Level of evidence, 4.
Methods:
As a retrospective review, from January 2007 to December 2019, a total of 99 patients who had undergone surgical treatment of lateral epicondylitis with a modified Nirschl technique were enrolled. The number of preoperative corticosteroid injections was investigated by medical record review. Outcome measurements included visual analog pain scale; Disabilities of the Arm, Shoulder and Hand (DASH) score; Mayo Elbow Performance Score; and the Nirschl and Pettrone grade. Grip power and wrist extension power were measured using a digital dynamometer.
Results:
A total of 99 patients were included in this study. The mean total number of injections of patients was 4.37 ± 2.46 times (range, 1-15 times). Total duration of nonoperative treatment before surgery was 25.4 ± 20.5 months (range, 4-124.8 months). The mean postoperative follow-up period was 42.8 ± 28.0 months (range, 12-110 months). For all injection numbers, clinical scores showed significant improvement in visual analog pain scale, DASH score, Mayo elbow score, grip power, and wrist extension power after surgery. Regression analysis showed that the degree of improvement according to the injection number was not statistically significant. The Nirschl and Pettrone grade was excellent in 82 (82.8%) patients, good in 14 (14.1%) patients, fair in 2 (2%) patient, and failure in 1 (1%) patient.
Conclusion:
The number of preoperative corticosteroid injections does not appear to affect postoperative clinical outcomes of patients with lateral epicondylitis who undergo surgery with a modified Nirschl technique.
Root-zone environment is considered difficult to analyze, particularly in interpreting interactions between environment and plant. Closed-loop soilless cultures have been introduced to prevent ...environmental pollution, but difficulties in managing nutrients can cause nutrient imbalances with an adverse effect on crop growth. Recently, deep learning has been used to draw meaningful results from nonlinear data and long short-term memory (LSTM) is showing state-of-the-art results in analyzing time-series data. Therefore the macronutrient ion concentrations affected by accumulated environment conditions can be analyzed using LSTM.
The trained LSTM can estimate macronutrient ion concentrations in closed-loop soilless cultures using environmental and growth data. The average training accuracy of six macronutrients was R
= 0.84 and the test accuracy was R
= 0.67 with RMSE = 1.48 meq L
. The used values of input interval and time step were 1 h and 168 (1 week), respectively. The accuracy was improved when the input interval became shorter, but not improved when the LSTM consisted of a multilayer structure. Regarding training methods, the LSTM improved the accuracy better than the non-LSTM. The trained LSTM showed relatively adequate accuracies and the interpolated ion concentrations showed variations similar to those seen during traditional cultivation.
We could analyze the nutrient balance in the closed-loop soilless culture, the model showed potential in estimating the macronutrient ion concentrations using environmental and growth factors measured in greenhouses. Since the LSTM is a powerful and flexible tool used to interpret accumulative changes, it is easily applicable to various plant and cultivation conditions. In the future, this approach can be used to analyze interactions between plant physiology and root-zone environment.
Crop fresh weight and leaf area are considered non-destructive growth factors due to their direct relation to vegetative growth and carbon assimilation. Several methods to measure these parameters ...have been introduced; however, measuring these parameters using the existing methods can be difficult. Therefore, a non-destructive measurement method with high versatility is essential. The objective of this study was to establish a non-destructive monitoring system for estimating the fresh weight and leaf area of trellised crops. The data were collected from a greenhouse with sweet peppers (Capsicum annuum var. annuum); the target growth factors were the crop fresh weight and leaf area. The crop fresh weight was estimated based on the total system weight and volumetric water content using a simple formula. The leaf area was estimated using top-view images of the crops and a convolutional neural network (ConvNet). The estimated crop fresh weight and leaf area exhibited average R2 values of 0.70 and 0.95, respectively. The simple calculation was able to avoid overfitting with fewer limitations compared with the previous study. ConvNet was able to analyze raw images and evaluate the leaf area without additional sensors and features. As the simple calculation and ConvNet could adequately estimate the target growth factors, the monitoring system can be used for data collection in practice owing to its versatility. Therefore, the proposed monitoring system can be widely applied for diverse data analyses.
In existing closed-loop soilless cultures, nutrient solutions are controlled by the electrical conductivity (EC) of the solution. However, the EC of nutrient solutions is affected by both growth ...environments and crop growth, so it is hard to predict the EC of nutrient solution. The objective of this study was to predict the EC of root-zone nutrient solutions in closed-loop soilless cultures using recurrent neural network (RNN). In a test greenhouse with sweet peppers (
L.), data were measured every 10 s from October 15 to December 31, 2014. Mean values for every hour were analyzed. Validation accuracy (
) of a single-layer long short-term memory (LSTM) was 0.92 and root-mean-square error (RMSE) was 0.07, which were the best results among the different RNNs. The trained LSTM predicted the substrate EC accurately at all ranges. Test accuracy (
) was 0.72 and RMSE was 0.08, which were lower than values for the validation. Deep learning algorithms were more accurate when more data were added for training. The addition of other environmental factors or plant growth data would improve model robustness. A trained LSTM can control the nutrient solutions in closed-loop soilless cultures based on predicted future EC. Therefore, the algorithm can make a planned management of nutrient solutions possible, reducing resource waste.
In this study, a time-dependent corrosion depth estimation method using atmospheric corrosion monitor (ACM) sensor data to evaluate time-dependent corrosion behaviors is proposed. For the ...time-dependent corrosion depth estimation of uncoated carbon steel and weathering steel, acceleration corrosion tests were conducted in salt-spray corrosion environments and evaluated with a corrosion damage estimation method using ACM sensing data and corrosion loss data of the tested steel specimens. To estimate the time-dependent corrosion depth using corrosion current by an ACM sensor, the relationship between the mean corrosion depth calculated from the weight loss method and the corrosion current was evaluated. The mean corrosion depth was estimated by calculating the corrosion current and evaluating the relationship between the mean corrosion depth and corrosion current during the expected period. From the test and estimation results, the corrosion current demonstrated a good linear correlation with the mean corrosion depth of carbon steel and weathering. The calculated mean corrosion depth is nearly the same as that of the tested specimen, which can be well used to estimate corrosion rate for the uncoated carbon steel and weathering steel.
Background/Aim: This study was conducted to comprehensively evaluate programmed cell death ligand 1 (PD-L1) expression, and analyze the clinical and prognostic implications of PD-L1 expression in ...oropharyngeal squamous cell carcinoma (OPSCC). Patients and Methods: We evaluated the expression of PD-L1 using the antibodies SP263 and SP142 in 106 patients with OPSCC, using immunohistochemistry. PD-L1 expression was subdivided into tumor cell score (TC), immune cell score (IC), and combined score (CS). Correlations between each PD-L1 expression and HPV status, clinicopathological features, and survival were analyzed. Results: The expression levels of PD-L1 SP263 and SP142 were significantly correlated. High PD-L1 SP263 TC and CS and SP142 IC and CS were associated with HPV positivity. PD-L1 expression showed no effect on survival in all patients' group. However, in the subgroup analysis, high TC and CS of both PD-L1 SP263 and SP142 were correlated with shorter time to recurrence in the HPV positive group. Conclusion: High expression of PD-L1 was associated with HPV positivity in OPSCC. In addition, high expression of PD-L1 might suggest a poorer outcome, especially in the HPV positive subgroup. PD-L1 could be a useful predictive and prognostic biomarker in OPSCC.
The nutrient replenishment method primarily impacts the nutrient variations in a closed-loop soilless culture system. However, there is still a lack of systematic approaches for the effective way of ...nutrient replenishment. Our previous study theoretically derived and experimentally validated an alternative nutrient replenishment method expecting synchronized total fertilizer supply to total nutrient absorption by crops and lower concentration fluctuations than conventional methods. However, no individual nutrient management has been performed. The objective of this study was to apply individual nutrient management to the alternative nutrient replenishment technique under experimental- and commercial-scale electrical conductivity (EC)-based closed-loop soilless cultures. Automated nutrient solution mixing modules and sweet peppers grown on rockwool slabs were used. Nutrient concentrations and crop productivity were compared between the closed-loop system using the alternative nutrient replenishment and the conventional open-loop systems. During early treatment, rapid decreases in K+ and H2PO4− were observed in the closed-loop system. However, after the stock solution nutrient adjustment, the decreasing trend was stabilized and returned close to initial concentrations. No significant differences in sugar content, incidence of blossom-end rot, and productivity of sweet peppers were observed between the closed- and open-loop soilless cultures. We confirmed that the nutrient variation stabilizing effect of the alternative nutrient replenishment method was valid under nutrient adjustment conditions and had comparable nutrient management performance with the open-loop system.
The fluorine (F) effect originating from the chemical vapor deposited (CVD) tungsten (W) process on charge-trap flash memory devices was systematically investigated, and the CVD-W memory was compared ...with physical vapor deposited (PVD) W memory. The residual F in the CVD-W diffused into Al 2 O 3 and Si 3 N 4 layers, generating shallow charge-trapping sites in each layer. These generated charge-trapping sites were considered to be responsible for the fast-erase and poor-retention characteristics at room temperature in the CVD-W compared to the related characteristics in the PVD-W memory. The generation of charge-trapping sites caused by the residual F in each layer was also supported by the trap density calculation in the Si 3 N 4 and constant current stress test for the Al 2 O 3 layer.
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