Activity-dependent cleavage of dyskinesia-related proline-rich transmembrane protein 2 (PRRT2) by calpain in mouse primary cortical neurons

Mutations of PRRT2 (proline-rich transmembrane protein 2) cause several neurological disorders, represented by paroxysmal kinesigenic dyskinesia (PKD), which is characterized by attacks of involuntary movements triggered by sudden voluntary movements. PRRT2 is reported to suppress neuronal excitation, but it is unclear how the function of PRRT2 is modulated during neuronal excitation. We found that PRRT2 is processed to a 12 kDa carboxy-terminal fragment (12K-CTF) by calpain, a calcium-activated cysteine protease, in a neuronal activity-dependent manner, predominantly via NMDA receptors or voltage-gated calcium channels. Furthermore, we clarified that 12K-CTF is generated by sequential cleavages at Q220 and S244. The amino-terminal fragment (NTF) of PRRT2, which corresponds to PKD-related truncated mutants, is not detected, probably due to rapid cleavage at multiple positions. Given that 12K-CTF lacks most of the proline-rich domain, this cleavage might be involved in the activity-dependent enhancement of neuronal excitation perhaps through transient retraction of PRRT2\u27s function. Therefore, PRRT2 might serve as a buffer for neuronal excitation, and lack of this function in PKD patients might cause neuronal hyperexcitability in their motor circuits

Performance Evaluation of IMU and DVL Integration in Marine Navigation

Global navigation satellite system (GNSS) spoofing poses a significant threat to maritime logistics. Many maritime electronic devices rely on GNSS time, positioning, and speed for safe vessel operation. In this study, inertial measurement unit (IMU) and Doppler velocity log (DVL) devices, which are important in the event of GNSS spoofing or outage, are considered in conventional navigation. A velocity integration method using IMU and DVL in terms of dead-reckoning is investigated in this study. GNSS has been widely used for ship navigation, but IMU, DVL, or combined IMU and DVL navigation have received little attention. Military-grade sensors are very expensive and generally cannot be utilized in smaller vessels. Therefore, this study focuses on the use of consumer-grade sensors. First, the performance of a micro electromechanical system (MEMS)-based yaw rate angle with DVL was evaluated using 60 min of raw data for a 50 m-long ship located in Tokyo Bay. Second, the performance of an IMU-MEMS using three gyroscopes and three accelerometers with DVL was evaluated using the same dataset. A gyrocompass, which is equipped on the ship, is used as a heading reference. The results proved that both methods could achieve less than 1 km horizontal error in 60 min

Performance Evaluation of IMU and DVL Integration in Marine Navigation

Global navigation satellite system (GNSS) spoofing poses a significant threat to maritime logistics. Many maritime electronic devices rely on GNSS time, positioning, and speed for safe vessel operation. In this study, inertial measurement unit (IMU) and Doppler velocity log (DVL) devices, which are important in the event of GNSS spoofing or outage, are considered in conventional navigation. A velocity integration method using IMU and DVL in terms of dead-reckoning is investigated in this study. GNSS has been widely used for ship navigation, but IMU, DVL, or combined IMU and DVL navigation have received little attention. Military-grade sensors are very expensive and generally cannot be utilized in smaller vessels. Therefore, this study focuses on the use of consumer-grade sensors. First, the performance of a micro electromechanical system (MEMS)-based yaw rate angle with DVL was evaluated using 60 min of raw data for a 50 m-long ship located in Tokyo Bay. Second, the performance of an IMU-MEMS using three gyroscopes and three accelerometers with DVL was evaluated using the same dataset. A gyrocompass, which is equipped on the ship, is used as a heading reference. The results proved that both methods could achieve less than 1 km horizontal error in 60 min

Higher incidence of pegfilgrastim-induced bone pain in younger patients receiving myelosuppressive chemotherapy: a real-world experience

Abstract Background Pegfilgrastim is widely used for the prevention of febrile neutropenia (FN) in patients receiving myelosuppressive chemotherapy for various types of cancer. However, pegfilgrastim-induced bone pain (PIBP) is a relevant adverse event occurring during cancer treatment. Thus, we aimed to determine the risk factors for PIBP in real-world clinical practice. Main body We retrospectively collected the clinical records of patients who received pegfilgrastim to support myelosuppressive chemotherapy with at least a 10% risk of FN between 2015 and 2018 at our center. Patients received pegfilgrastim 3.6 mg between days 2 and 7 after chemotherapy administration (day 1) for primary or secondary prophylaxis against FN. All adverse events were recorded according to the Common Terminology Criteria for Adverse Events. Patients who experienced intermittent bone pain in the back, femur, or other anatomic sites after the pegfilgrastim administration were considered to have PIBP. To evaluate the relationship between PIBP incidence and patient characteristics, we performed univariate and multivariate logistic regression analyses to calculate the odds ratios (ORs) of possible risk factors for PIBP. We analyzed the data of 305 patients (median age: 63 years), who underwent 1220 chemotherapy cycles with pegfilgrastim per cycle. Univariate analysis revealed that female sex (vs. male sex), younger age (< 55 years vs. ≥ 55 years), and solid cancers (vs. hematologic cancers) had significantly higher ORs (p < 0.05). However, only younger age (< 55 years) was an independent risk factor for PIBP on multivariate analysis (OR 3.62, 95% confidence interval 1.51–8.69, p = 0.004). Conclusions Younger age (< 55 years) was significantly associated with a higher risk of PIBP among patients receiving chemotherapy with a ≥ 10% risk of FN. Therefore, oncologists should meticulously formulate management plan for PIBP in younger patients after administering pegfilgrastim

Isolation and Characterization of Genes Responsible for Naphthalene Degradation from Thermophilic Naphthalene Degrader, Geobacillus sp. JF8

Geobacillus sp. JF8 is a thermophilic biphenyl and naphthalene degrader. To identify the naphthalene degradation genes, cis-naphthalene dihydrodiol dehydrogenase was purified from naphthalene-grown cells, and its N-terminal amino acid sequence was determined. Using a DNA probe encoding the N-terminal region of the dehydrogenase, a 10-kb DNA fragment was isolated. Upstream of nahB, a gene for dehydrogenase, there were two open reading frames which were designated as nahAc and nahAd, respectively. The products of nahAc and nahAd were predicted to be alpha and beta subunit of ring-hydroxylating dioxygenases, respectively. Phylogenetic analysis of amino acid sequences of NahB indicated that it did not belong to the cis-dihydrodiol dehydrogenase group that includes those of classical naphthalene degradation pathways. Downstream of nahB, four open reading frames were found, and their products were predicted as meta-cleavage product hydrolase, monooxygenase, dehydrogenase, and gentisate 1,2-dioxygenase, respectively. A reverse transcriptase-PCR analysis showed that transcription of nahAcAd was induced by naphthalene. These findings indicate that we successfully identified genes involved in the upper pathway of naphthalene degradation from a thermophilic bacterium