Avian G18P17 rotaviruses with similar complete genome constellation, including strains that showed pathogenicity in mammals, have been detected worldwide. However, it remains unclear how these ...strains spread geographically. In this study, to investigate the role of migratory birds in the dispersion of avian rotaviruses, we analysed whole genetic characters of the rotavirus strain RK1 that was isolated from a migratory species of birds velvet scoter (
) in Japan in 1989. Genetic analyses revealed that the genotype constellation of the RK1 strain, G18-P17-I4-R4-C4-M4-A21-N4-T4-E4-H4, was highly consistent with those of other G18P17 strains detected in various parts of the world, supporting the possibility that the G18P17 strains spread via migratory birds that move over a wide area. Furthermore, the RK1 strain induced diarrhoea in suckling mice after oral gastric inoculation, indicating that at least some of the rotaviruses that originated from migratory birds are infectious to and pathogenic in mammals. In conclusion, it was demonstrated that migratory birds may contribute to the global spread of avian rotaviruses that are pathogenic in mammalian species.
Summary
KCNT1 mutations have been found in epilepsy of infancy with migrating focal seizures (EIMFS; also known as migrating partial seizures in infancy), autosomal dominant nocturnal frontal lobe ...epilepsy, and other types of early onset epileptic encephalopathies (EOEEs). We performed KCNT1‐targeted next‐generation sequencing (207 samples) and/or whole‐exome sequencing (229 samples) in a total of 362 patients with Ohtahara syndrome, West syndrome, EIMFS, or unclassified EOEEs. We identified nine heterozygous KCNT1 mutations in 11 patients: nine of 18 EIMFS cases (50%) in whom migrating foci were observed, one of 180 West syndrome cases (0.56%), and one of 66 unclassified EOEE cases (1.52%). KCNT1 mutations occurred de novo in 10 patients, and one was transmitted from the patient's mother who carried a somatic mosaic mutation. The mutations accumulated in transmembrane segment 5 (2/9, 22.2%) and regulators of K+ conductance domains (7/9, 77.8%). Five of nine mutations were recurrent. Onset ages ranged from the neonatal period (<1 month) in five patients (5/11, 45.5%) to 1–4 months in six patients (6/11, 54.5%). A generalized attenuation of background activity on electroencephalography was seen in six patients (6/11, 54.5%). Our study demonstrates that the phenotypic spectrum of de novo KCNT1 mutations is largely restricted to EIMFS.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Avian rotavirus A (RVA) is one of major enteric pathogens that cause diarrhoea in young avian individuals. Importantly, some of the avian RVA strains of G18P17 genotype are naturally transmitted to ...and cause clinical diseases in mammalian species, indicating their potential risks to animal health. Although molecular information on the pathogenesis by avian RVA strains will be useful for estimating their risks, the absence of a reverse genetics (RG) system for these strains has hindered the elucidation of their pathogenic mechanisms. In this study, we aimed to establish an RG system for the avian G18P17 prototype strain PO-13, which was isolated from a pigeon in Japan in 1983 and was experimentally shown to be pathogenic in suckling mice. Transfection with plasmids expressing 11 genomic RNA segments of the strain resulted in rescue of the infectious virus with an artificially introduced genetic marker on its genome, indicating that an RG system for the PO-13 strain was successfully established. The rescued recombinant strain rPO-13 had biological properties almost identical to those of its wild-type strain (wtPO-13). Notably, both rPO-13 and wtPO-13 induced diarrhoea in suckling mice with similar efficiencies. It was thus demonstrated that the RG system will be useful for elucidating the pathogenic mechanisms of the PO-13 strain at the molecular level. This is the first report of the establishment of an RG system for an avian RVA strain.
The rabies virus strain Komatsugawa isolated from a dog in Tokyo in the 1940s retains biological properties as a field strain, providing an effective model for studying rabies pathogenesis. To ...facilitate molecular studies on the pathogenesis, this study aimed to establish a reverse genetics system for the Komatsugawa strain. By transfecting the full-length genome plasmid of this strain, infectious virus with artificially introduced genetic markers in its genome was rescued. The recombinant strain had biological properties similar to those of the original strain. These findings indicate that a reverse genetics system for the Komatsugawa strain has successfully been established.
Canine hemangiosarcoma (HSA), which originates from endothelial cells, is one of the most common malignant neoplasms that frequently develop metastatic lesions. Although anthracycline-based HSA ...treatment strategies have been widely investigated, reliable therapy for dogs with clinically advanced-stage HSA (stage 3 HSA) has not been established yet. Recently, several studies have demonstrated that propranolol, a beta-adrenergic receptor antagonist, exhibits anti-tumor effects against tumors originating from vascular endothelial cells, indicating the possibility that propranolol is a candidate adjunctive agent for anthracycline-based therapy in dogs with stage 3 HSA. This study aimed to evaluate the clinical efficacy and adverse events (AEs) of anthracycline and propranolol combination in stage 3 HSA-affected dogs.
We retrospectively investigated five dogs diagnosed with stage 3 HSA which were administered with both anthracycline and propranolol during the same period between January 2020 and August 2021. Clinical benefit was observed in four of five HSA dogs (one of complete response, one of partial response, and two of stable disease) with gross metastatic lesions by anthracycline and propranolol combination. Notably, some or all of the metastatic lesions were reduced in two cases. In all five dogs administered with anthracycline and propranolol combination, no serious and irreversible AEs were observed.
Our findings demonstrate the efficacy and safety of anthracycline and propranolol combination in stage 3 HSA-affected dogs. Further studies are needed to establish treatment protocols based on anthracycline and propranolol combination for dogs with advanced HSA.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Step-ratio automatic transmission upshift performance can be improved by modulating the off-going (OFG) clutch during the inertia phase. In this paper, a static powertrain performance model is ...derived and applied for the purpose of numerically efficient, multi-objective shift control parameter optimization for the inertia phase. The optimization is aimed at finding the optimal node parameters for simplified, piecewise linear, open-loop profiles of oncoming (ONC) clutch, OFG clutch, and engine torque reduction control variables. The performance indices, i.e., the optimization objectives, include shift comfort, clutch thermal loss, and shift time. The optimization results in 3D Pareto optimal frontiers, which are then analyzed and compared with those obtained by using the previously developed, nonlinear model-based, genetic algorithm optimization tool. The derived method is employed in order to develop a static model-based predictive control (S-MPC) strategy, which commands ONC clutch torque control input while retaining open-loop controls for engine and OFG clutch control inputs. The S-MPC strategy aims at providing the prespecified shift time, while the shift time accuracy is relaxed to some extent by using a control input dead zone element to avoid chattering effect. The S-MPC system performance is verified through simulation and compared with the genetic algorithm benchmark. The simulation results demonstrate that the S-MPC strategy approaches the benchmark performance.
Abstract Patients with 22q13.3 deletion syndrome present with diverse neurological problems such as global developmental delays, hypotonia, delayed or absent speech, autistic behavior, and epilepsy. ...Seizures occur in up to one-third of patients with 22q13.3 deletion syndrome; however, only a few reports have provided details regarding the seizure manifestations. The present report describes a patient with 22q13.3 deletion syndrome who presented with late-onset epileptic spasms (ES) and electroencephalography features like Lennox–Gastaut syndrome. An array comparative genomic hybridization analysis revealed that a chromosomal deletion of this patient included SHANK3 . To the best of our knowledge, this is the first confirmed case of late-onset ES occur in patients with 22q13.3 deletion syndrome with a SHANK3 deletion.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK
Abstract Polymicrogyria is caused by a diverse etiology, one of which is gene mutation. At present, only one gene ( GPR56 ) is known to cause polymicrogyria, which leads to a distinctive phenotype ...termed bilateral frontoparietal polymicrogyria (BFPP). BFPP is an autosomal recessive inherited human brain malformation with abnormal cortical lamination. Here, we identified compound heterozygous GPR56 mutations in a patient with BFPP. The proband was a Japanese female born from non-consanguineous parents. She presented with mental retardation, developmental motor delay, epilepsy exhibiting the feature of Lennox–Gastaut syndrome, exotropia, bilateral polymicrogyria with a relatively spared perisylvian region, bilateral patchy-white-matter MRI signal changes, and hypoplastic pontine basis. GPR56 sequence analysis revealed a c.107G>A substitution leading to a p.S36N, and a c.113G>A leading to a p.R38Q. Although affected individuals with compound heterozygosity in GPR56 have not been previously described, we presume that compound heterozygosity of these two mutations in a ligand binding domain within the extracellular N-terminus of protein could result in BFPP. In addition, we observed unusually less involvement of perisylvian cortex for polymicrogyria, and Lennox–Gastaut syndrome for epilepsy, which are likely common features in patients with BFPP caused by GPR56 mutations.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK
Rett syndrome (RTT) is a neurodevelopmental disorder primarily caused by mutations in the methyl-CpG-binding protein 2 (MECP2) gene, resulting in developmental regression after normal development ...during infancy. Transient presentation of many autistic features is also commonly seen in RTT. Anti-myelin oligodendrocyte glycoprotein (MOG)-antibody encephalitis is an acquired relapsing demyelinating syndrome characterized by a variety of neuroinflammatory symptoms. Here, we report a case of anti-MOG antibody encephalitis in a patient with genetically confirmed RTT, which mimicked many of the features of RTT.
A three-year-old girl presented with subacute verbal and motor dysfunction, along with involuntary movements and marked irritability. Magnetic resonance imaging (MRI) revealed extensive white matter lesions, with anti-MOG antibodies detected in the serum and cerebrospinal fluid, resulting in an initial diagnosis of anti-MOG antibody encephalitis. However, additional testing of the MECP2 gene was performed in response to persistent involuntary hand movements in combination with progressive verbal and motor deterioration. Sequencing analysis revealed a known pathogenic mutation in MEPC2, indicating a concurrent diagnosis of RTT.
Both RTT and anti-MOG antibody encephalitis are rare conditions. Similarities in disease presentation suggest that anti-MOG antibody encephalitis may mimic many of the symptoms of RTT.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK
•Oxidation kinetics of W-Re alloys with Re contents of 5 at% and 15 at% obeyed parabolic rate laws.•The Re oxide sublimated and deposited at the cooler remote area on materials surface.•The deposits ...of the Re oxide can be moved and transported by dissolving in the water contents or moisture in the air.
Oxidation kinetics of pure tungsten (W) and tungsten-rhenium (W-Re) alloys with Re contents of 1%, 5% and 15% has been examined in the oxygen gas atmosphere at 873 K. The oxidation kinetics of the W-Re alloys were well characterized by a parabolic rate law.
During oxidation of the W-Re alloys, the Re oxide sublimated near the top surface of the oxide layer. The sublimation of the Re oxide may play roles as a sintering agent and/or a stress relief agent in the W oxide layer to be more resistant to oxidation than pure W. There will be an effective value of Re content in W oxide layers for suppression of oxidation depending on oxidation temperatures or atmospheres.
The Re oxide in the gas phase could deposit at cooler remote area on materials surface. Furthermore, the Re oxide deposits can be easily moved or transported to different area by dissolving in a water content or a moisture of flowing gas atmosphere.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
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