Intrinsically disordered region-mediated condensation of IFN-inducible SCOTIN/SHISA-5 inhibits ER-to-Golgi vesicle transport.

Newly synthesized proteins in the endoplasmic reticulum (ER) are sorted by coat protein complex II (COPII) at the ER exit site en route to the Golgi. Under cellular stresses, COPII proteins become targets of regulation to control the transport. Here, we show that the COPII outer coat proteins Sec31 and Sec13 are selectively sequestered into the biomolecular condensate of SCOTIN/SHISA-5, which interferes with COPII vesicle formation and inhibits ER-to-Golgi transport. SCOTIN is an ER transmembrane protein with a cytosolic intrinsically disordered region (IDR), which is required and essential for the formation of condensates. Upon IFN-γ stimulation, which is a cellular condition that induces SCOTIN expression and condensation, ER-to-Golgi transport was inhibited in a SCOTIN-dependent manner. Furthermore, cancer-associated mutations of SCOTIN perturb its ability to form condensates and control transport. Together, we propose that SCOTIN impedes the ER-to-Golgi transport through its ability to form biomolecular condensates at the ER membrane.

Estimating exposures from spray products using robotic simulations.

There is an increasing need for exposure data to enable more precise information for risk estimates and improved public health protection. While personal monitoring data are preferred, it is often difficult to collect due to the resources needed to complete a human research study. In this study, we successfully programmed a robotic arm to mimic human use (spraying) of a fabric crafts protector (FCP) and human cleaning (spraying and wiping) of a glass pane with glass cleaner (GC). The robot was then used in place of human subjects to assess inhalation exposures to volatile organic compounds (VOCs) during the use of the FCP and GC. Air sampling data were collected while the robot used the products to estimate personal exposures to VOCs. Average VOC concentrations were 1.57 ppm for FCP spraying and 0.17 ppm for GC spraying and wiping. During FCP spraying, average acetone concentrations were 0.88 ppm and average isopropyl alcohol concentrations were 0.26 ppm. During GC spraying and wiping, average 2-butoxyethanol concentrations were 0.15 ppm. Air sampling data were found to be within the range of data reported in the literature during human use of similar glass cleaning products. No data was found in the literature during use of fabric protector spray products. This study contributes exposure measurement data with detailed contextual information to help characterize inhalation exposures during the use of 2 spray products. In addition, the study offers a systematic, efficient method for generating exposure data which can be used to improve health and safety risk assessments used for public health protection.

Adaptive robot climbing with magnetic feet in unknown slippery structure.

Firm foot contact is the top priority of climbing robots to avoid catastrophic events, especially when working at height. This study proposes a robust planning and control framework for climbing robots that provides robustness to slippage in unknown environments. The framework includes 1) a center of mass (CoM) trajectory optimization under the estimated contact condition, 2) Kalman filter-like approach for uncertain environment parameter estimation and subsequent CoM trajectory re-planing, and 3) an online weight adaptation approach for whole-body control (WBC) framework that can adjust the ground reaction force (GRF) distribution in real time. Though the friction and adhesion characteristics are often assumed to be known, the presence of several factors that lead to a reduction in adhesion may cause critical problems for climbing robots. To address this issue safely and effectively, this study suggests estimating unknown contact parameters in real time and using the evaluated contact information to optimize climbing motion. Since slippage is a crucial behavior and requires instant recovery, the computation time for motion re-planning is also critical. The proposed CoM trajectory optimization algorithm achieved state-of-art fast computation via trajectory parameterization with several reasonable assumptions and linear algebra tricks. Last, an online weight adaptation approach is presented in the study to stabilize slippery motions within the WBC framework. This can help a robot to manage the slippage at the very last control step by redistributing the desired GRF. In order to verify the effectiveness of our method, we have tested our algorithm and provided benchmarks in simulation using a magnetic-legged climbing robot Manegto.

SHISA5/SCOTIN restrains spontaneous autophagy induction by blocking contact between the ERES and phagophores.

ABBREVIATIONS: ATG2: autophagy related 2; BECN1: beclin 1; COPII: coat protein II; DMSO: dimethyl sulfoxide; EBSS: Earle's balanced salt solution; EGFP: enhanced green fluorescent protein; ER: endoplasmic reticulum; ERES: ER exit site(s); GFP: green fluorescent protein; H89: H-89 dihydrochloride hydrate; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MTORC1: mechanistic target of rapamycin kinase complex 1; NS5A: nonstructural protein 5A; PIK3C3/VPS34: phosphatidylinositol 3-kinase catalytic subunit type 3; PLA: proximity ligation assay; PtdIns3P: phosphatidylionositol-3-phosphate; RB1CC1/FIP200: RB1 inducible coiled-coil 1; RFP: red fluorescent protein; RPS6KB1/S6K: ribosomal protein S6 kinase B1; SBP: streptavidin binding protein; SEC16A: SEC16 homolog A, endoplasmic reticulum export factor; SEC31A: SEC31 homolog A, COPII coat complex component; siRNA: small interfering RNA; Str: streptavidin; ULK1: unc-51-like autophagy activating kinase 1; VSVG: vesicular stomatitis virus glycoprotein; WIPI2: WD repeat domain, phosphoinositide interacting 2; WT: wild type.

Respiration Rate Estimation Based on Independent Component Analysis of Accelerometer Data: Pilot Single-Arm Intervention Study.

BACKGROUND: As the mobile environment has developed recently, there have been studies on continuous respiration monitoring. However, it is not easy for general users to access the sensors typically used to measure respiration. There is also random noise caused by various environmental variables when respiration is measured using noncontact methods in a mobile environment. OBJECTIVE: In this study, we aimed to estimate the respiration rate using an accelerometer sensor in a smartphone. METHODS: First, data were acquired from an accelerometer sensor by a smartphone, which can easily be accessed by the general public. Second, an independent component was extracted to calibrate the three-axis accelerometer. Lastly, the respiration rate was estimated using quefrency selection reflecting the harmonic component because respiration has regular patterns. RESULTS: From April 2018, we enrolled 30 male participants. When the independent component and quefrency selection were used to estimate the respiration rate, the correlation with respiration acquired from a chest belt was 0.7. The statistical results of the Wilcoxon signed-rank test were used to determine whether the differences in the respiration counts acquired from the chest belt and from the accelerometer sensor were significant. The P value of the difference in the respiration counts acquired from the two sensors was .27, which was not significant. This indicates that the number of respiration counts measured using the accelerometer sensor was not different from that measured using the chest belt. The Bland-Altman results indicated that the mean difference was 0.43, with less than one breath per minute, and that the respiration rate was at the 95% limits of agreement. CONCLUSIONS: There was no relevant difference in the respiration rate measured using a chest belt and that measured using an accelerometer sensor. The accelerometer sensor approach could solve the problems related to the inconvenience of chest belt attachment and the settings. It could be used to detect sleep apnea through constant respiration rate estimation in an internet-of-things environment.

Radar-Based Detection of Respiration Rate with Adaptive Harmonic Quefrency Selection.

Continuous respiration monitoring is important for predicting a potential disease. Due to respiration measurements using contact sensors, it is difficult to achieve continuous measurement because the sensors are inconvenient to attach. In this study, a radar sensor was used for non-contact respiration measurements. The radar sensor had a high precision and could even be used in the dark. It could also be used continuously regardless of time and place. The radar sensor relied on the periodicity of respiration to detect the respiration rate. A respiration adaptive interval was set and the respiration rate was detected through harmonic quefrency selection. As a result, it was confirmed that there was no difference between the respiratory rate measured using a respiration belt and the respiratory rate detected using a radar sensor. Furthermore, case studies on changes in the radar position and about measurement for long periods confirmed that the radar sensor could detect respiration rate continuously regardless of the position and measurement duration.

Recognition of Negative Emotion using Long Short-Term Memory with Bio-Signal Feature Compression.

Negative emotion is one reason why stress causes negative feedback. Therefore, many studies are being done to recognize negative emotions. However, emotion is difficult to classify because it is subjective and difficult to quantify. Moreover, emotion changes over time and is affected by mood. Therefore, we measured electrocardiogram (ECG), skin temperature (ST), and galvanic skin response (GSR) to detect objective indicators. We also compressed the features associated with emotion using a stacked auto-encoder (SAE). Finally, the compressed features and time information were used in training through long short-term memory (LSTM). As a result, the proposed LSTM used with the feature compression model showed the highest accuracy (99.4%) for recognizing negative emotions. The results of the suggested model were 11.3% higher than with a neural network (NN) and 5.6% higher than with SAE.

Synthesis of Electrocardiogram V-Lead Signals From Limb-Lead Measurement Using R-Peak Aligned Generative Adversarial Network.

Recently, portable electrocardiogram (ECG) hardware devices have been developed using limb-lead measurements. However, portable ECGs provide insufficient ECG information because of limitations in the number of leads and measurement positions. Therefore, in this study, V-lead ECG signals were synthesized from limb leads using an R-peak aligned generative adversarial network (GAN). The data used the Physikalisch-Technische Bundesanstalt (PTB) dataset provided by PhysioNet. First, R-peak alignment was performed to maintain the physiological information of the ECG. Second, time domain ECG was converted to bi-dimensional space by ordered time-sequence embedding. Finally, the GAN was learned through the pairs between the modified limb II (MLII) lead and each chest (V) lead. The result showed that the mean structural similarity index (SSIM) was 0.92, and the mean error rate of the percent mean square difference (PRD) of the chest leads was 7.21%.

Initial Versus Follow-up Sequential Myocardial 123I-MIBG Scintigraphy to Discriminate Parkinson Disease From Atypical Parkinsonian Syndromes.

PURPOSE: Previous single-center or meta-analysis studies analyzed myocardial I-metaiodobenzylguanidine (I-MIBG) scintigraphy in a single image session and demonstrated low sensitivity and high specificity for discriminating Parkinson disease (PD) from atypical Parkinsonian syndromes (APS). This study aimed to assess diagnostic ability of myocardial I-MIBG scintigraphy at 2 phases to discriminate PD from APS. PATIENTS AND METHODS: This hospital-based prospective study enrolled 162 PD and 26 APS patients who underwent 2 sequential I-MIBG scintigraphy evaluations. Patients were stratified into normal and decreased I-MIBG groups according to early and delayed heart-to-mediastinum (H/M) ratios. Patients with PD and normal I-MIBG uptake (initial delayed H/M ratio, ≥1.78) were considered scans without evidence of cardiac norepinephrine deficit (SWEND). Early and delayed H/M ratios on the initial and 2-year follow-up scintigraphs were studied. The diagnostic sensitivity and specificity were calculated from these confusion matrices and were analyzed according to receiver-operating characteristic curve analysis. A repeated-measures general linear model was used to investigate differences among groups over time in H/M ratio changes and washout rates. RESULTS: Follow-up I-MIBG scintigraphy analysis had a higher diagnostic sensitivity (89.5%) than the initial imaging (72.2%). The improved sensitivity was associated with a steeper decrease in H/M ratio in the SWEND group than in the APS group. CONCLUSIONS: Follow-up I-MIBG scintigraphy can identify cardiac sympathetic denervation and its progression in patients with PD and may be effective in discriminating PD from APS. A later decrease in myocardial I-MIBG uptake in the group with SWEND meets the Braak staging threshold hypothesis for synucleinopathy.

Design of User-Customized Negative Emotion Classifier Based on Feature Selection Using Physiological Signal Sensors.

First, the Likert scale and self-assessment manikin are used to provide emotion analogies, but they have limits for reflecting subjective factors. To solve this problem, we use physiological signals that show objective responses from cognitive status. The physiological signals used are electrocardiogram, skin temperature, and electrodermal activity (EDA). Second, the degree of emotion felt, and the related physiological signals, vary according to the individual. KLD calculates the difference in probability distribution shape patterns between two classes. Therefore, it is possible to analyze the relationship between physiological signals and emotion. As the result, features from EDA are important for distinguishing negative emotion in all subjects. In addition, the proposed feature selection algorithm showed an average accuracy of 92.5% and made it possible to improve the accuracy of negative emotion recognition.

Cardiac Sympathetic Denervation Can Predict the Wearing-off Phenomenon in Patients with Parkinson Disease.

Recent studies have suggested that preserved cardiac sympathetic denervation may be associated with a small motor burden in Parkinson disease (PD) and serve as a good marker, which is not associated with other nonmotor symptoms. We sought to investigate whether cardiac sympathetic denervation increases the risk of the early wearing-off phenomenon in PD. Methods: This hospital-based prospective study enrolled 266 de novo patients with PD who underwent 123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy on initial evaluation. The patients visited the outpatient clinic every 2-6 mo and were followed for a minimum of 18 mo from the time they began taking dopaminergic medication. Each patient was assessed for the wearing-off phenomenon on the basis of the clinical assessments and symptom diaries. Clinical events were analyzed from the date of evaluation by 123I-MIBG scintigraphy until the date of the first occurrence of the wearing-off phenomenon, or until the last follow-up date without wearing-off. Results: During a mean follow-up period of 30.4 ± 14.8 mo, 71 patients developed wearing-off. The wearing-off phenomenon occurred more in patients with decreased 123I-MIBG uptake. A Cox regression analysis revealed that both low 123I-MIBG uptake and early onset age significantly predicted the development of wearing-off. Conclusion: Our study suggests that a reduction in myocardial 123I-MIBG uptake in PD patients may be associated with a subsequent increased risk for the wearing-off phenomenon. Findings strongly support that PD patients with normal cardiac sympathetic innervation might have less involvement of the midbrain dopaminergic circuitry and a concomitant reduced risk for motor complications, such as wearing-off.

Urinary Dysfunctions and Post-Void Residual Urine in Typical and Atypical Parkinson Diseases.

BACKGROUND: Urinary dysfunction is relatively common, however, is often underestimated and diagnosed by subjective questionnaires in patients with Parkinsonism. OBJECTIVE: To determine the correlation between subjective urinary dysfunction and post-void residual urine volume in patients with Parkinson's disease (PD), multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), and to assess the relationship between clinical characteristics and subjective or objective urinary dysfunction. METHODS: A total of 196 patients with de novo Parkinsonism without urological and gynecological disorders were included. For all subjects, data were collected on sonographic post-void residual urine volume and urinary symptoms. All patients were also assessed on motor symptom severity, cognitive and affective measurements, other nonmotor symptoms, 39-item Parkinson's Disease Questionnaire, and renal functions. RESULTS: Seventeen out of 196 parkinsonian patients showed abnormal post-void residual urine volumes, with ≥100 ml. The MSA group showed significantly higher post-void residual urine volume compared to the PD and PSP groups. Symptoms of the sense of incomplete emptying, weak urine stream, and nocturia were strongly correlated with post-void residual urine volume. Post-void residual urine volume was positively related to autonomic symptoms, other non-motor symptoms, patient activities of daily living, and negatively related to renal function. CONCLUSION: Increased post-void residual urine volumes were observed in small portion of early drug-naïve Parkinsonian patients, especially in MSA. Post-void residual urine volume was significantly related to subjective urinary and other autonomic dysfunctions. Voiding dysfunction is associated with not only end organ damage, but also other nonmotor dysfunctions and patient activities of daily living.

Comparison of odor identification among amnestic and non-amnestic mild cognitive impairment, subjective cognitive decline, and early Alzheimer's dementia.

Olfactory impairment might be an important clinical marker and predictor of Alzheimer's disease (AD). In the present study, we aimed to compare the degree of olfactory identification impairment in each mild cognitive impairment (MCI) subtype, subjective memory impairment, and early AD dementia and assessed the relationship between olfactory identification and cognitive performance. We consecutively included 50 patients with amnestic MCI, 28 patients with non-amnestic MCI, 20 patients with mild AD, and 17 patients with subjective memory impairment (SMI). All patients underwent clinical and neuropsychological assessments. A multiple choice olfactory identification cross-cultural smell identification test was also utilized. Controlling for age and gender, olfactory impairment was significantly more severe in patients with AD and amnestic MCI compared with the results from the non-amnestic MCI and SMI groups. Higher scores on MMSE, verbal and non-verbal memory, and frontal executive function tests were significantly related to olfactory identification ability. In conclusion, olfactory identification is impaired in amnestic MCI and AD. These findings are consistent with previous studies. In amnestic MCI patients, this dysfunction is considered to be caused by underlying AD pathology.

Association of arterial stiffness with cognition in patients with Lewy body disorder.

The brachial-ankle pulse wave velocity (baPWV) is a marker for arterial stiffness, which is associated with cardiovascular diseases. Arterial stiffness is associated with cognitive function in the elderly and patients with Alzheimer's disease (AD). We aimed to investigate the association between arterial stiffness and cognitive function in patients with Lewy body disorder (LBD), including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). We consecutively included 123 patients with PD, 10 patients with DLB, and 27 AD controls. Patients with PD were divided into three groups of normal cognition (PD-NC, n = 63), mild cognitive impairment (PD-MCI, n = 43), and dementia (PD-D, n = 17). Arterial stiffness, measured as baPWV, was compared between the PD-NC, PD-MCI, PD-D, DLB, and AD patients. In LBD, we analyzed the association between arterial stiffness and each cognitive domain with adjustment for covariates. Higher baPWV was significantly associated with cognitive decline in patients with LBD (baPWV in PD-D > PD-MCI > PD-NC; DLB > PD-NC). There was no significant difference in baPWV between PD-D, DLB, and AD patients. In LBD patients, higher baPWV was associated with lower mini mental state examination score (ß ± SE = -0.003 ± 0.001, p = 0.007) and more severe dementia. Higher baPWV was also associated with lower performance in attention, language, visuospatial function, memory, and executive function in LBD patients. This suggests that vascular brain injury is associated with cognitive dysfunction in LBD.

Mitochondrial chaperone HSP-60 regulates anti-bacterial immunity via p38 MAP kinase signaling.

Mitochondria play key roles in cellular immunity. How mitochondria contribute to organismal immunity remains poorly understood. Here, we show that HSP-60/HSPD1, a major mitochondrial chaperone, boosts anti-bacterial immunity through the up-regulation of p38 MAP kinase signaling. We first identify 16 evolutionarily conserved mitochondrial components that affect the immunity of Caenorhabditis elegans against pathogenic Pseudomonas aeruginosa (PA14). Among them, the mitochondrial chaperone HSP-60 is necessary and sufficient to increase resistance to PA14. We show that HSP-60 in the intestine and neurons is crucial for the resistance to PA14. We then find that p38 MAP kinase signaling, an evolutionarily conserved anti-bacterial immune pathway, is down-regulated by genetic inhibition of hsp-60, and up-regulated by increased expression of hsp-60 Overexpression of HSPD1, the mammalian ortholog of hsp-60, increases p38 MAP kinase activity in human cells, suggesting an evolutionarily conserved mechanism. Further, cytosol-localized HSP-60 physically binds and stabilizes SEK-1/MAP kinase kinase 3, which in turn up-regulates p38 MAP kinase and increases immunity. Our study suggests that mitochondrial chaperones protect host eukaryotes from pathogenic bacteria by up-regulating cytosolic p38 MAPK signaling.

A minimum attention control law for ball catching.

Digital implementations of control laws typically involve discretization with respect to both time and space, and a control law that can achieve a task at coarser levels of discretization can be said to require less control attention, and also reduced implementation costs. One means of quantitatively capturing the attention of a control law is to measure the rate of change of the control with respect to changes in state and time. In this paper we present an attention-minimizing control law for ball catching and other target tracking tasks based on Brockett's attention criterion. We first highlight the connections between this attention criterion and some well-known principles from human motor control. Under the assumption that the optimal control law is the sum of a linear time-varying feedback term and a time-varying feedforward term, we derive an LQR-based minimum attention tracking control law that is stable, and obtained efficiently via a finite-dimensional optimization over the symmetric positive-definite matrices. Taking ball catching as our primary task, we perform numerical experiments comparing the performance of the various control strategies examined in the paper. Consistent with prevailing theories about human ball catching, our results exhibit several familiar features, e.g., the transition from open-loop to closed-loop control during the catching movement, and improved robustness to spatiotemporal discretization. The presented control laws are applicable to more general tracking problems that are subject to limited communication resources.

A case of central cord syndrome related status epilepticus - a case report -.

Central cord syndrome (CCS) is extremely rare as a direct consequence of generalized epileptic seizure. CCS is associated with hyperextension of the spinal cord and has characteristic radiologic findings including posterior ligamentous injury and prevertebral hyperintensity following magnetic resonance imaging (MRI). We experienced the case of a 25-year-old man who suffered CCS after status epilepticus. Cervical spinal MRI revealed high signal intensity at the C1 level but with no signal or structural changes in other sites. After rehabilitation management, the patient significantly improved on the ASIA (American Spinal Injury Association) motor scale and bladder function. We proposed that epilepsy related CCS may be caused by muscle contractions during generalized seizure, which can induce traction injury of the spinal cord or relative narrowing of spinal canal via transient herniated nucleus pulposus or transient subluxation of vertebra. We also suggest CCS without radiologic findings of trauma has good prognosis compared with other CCS.