Search

Dysfunctional sociability is a core symptom in autism spectrum disorder (ASD) that may arise from neural-network dysconnectivity between multiple brain regions. However, pathogenic neural-network mechanisms underlying social dysfunction are largely unknown. Here, we demonstrate that circuit-selective mutation (ctMUT) of ASD-risk Shank3 gene within a unidirectional projection from the prefrontal cortex to the basolateral amygdala alters spine morphology and excitatory-inhibitory balance of the circuit. Shank3 ctMUT mice show reduced sociability as well as elevated neural activity and its amplitude variability, which is consistent with the neuroimaging results from human ASD patients. Moreover, the circuit hyper-activity disrupts the temporal correlation of socially tuned neurons to the events of social interactions. Finally, optogenetic circuit activation in wild-type mice partially recapitulates the reduced sociability of Shank3 ctMUT mice, while circuit inhibition in Shank3 ctMUT mice partially rescues social behavior. Collectively, these results highlight a circuit-level pathogenic mechanism of Shank3 mutation that drives social dysfunction. Accepted version Source info: CP-COMMUNITY-D-21-00183

Electric vehicles(EVs) are widely used to address the problem of air pollution and to save energy. The EV charger has been widely used due to its low price and simplified installation. The slow charger transmits power information that can be supplied to the vehicle and EV’s and to its OBC control charging power within the maximum power information transmitted from the charger. To limit the peak power, an even distribution and schedule charging method was studied, but the usage rate of the charger was not considered. In this paper, an algorithm that can efficiently manage the charging usage by checking the vehicle status in real time is proposed. The proposed algorithm was implemented in Python, and the vehicle+charger model was simulated using LabVIEW to perform functional verification.

Although the incidence of severe fever with thrombocytopenia syndrome virus (SFTSV) infection has increased from its discovery with a mortality rate of 10–20%, no effective vaccines are currently available. Here we describe the development of a SFTSV DNA vaccine, its immunogenicity, and its protective efficacy. Vaccine candidates induce both a neutralizing antibody response and multifunctional SFTSV-specific T cell response in mice and ferrets. When the vaccine efficacy is investigated in aged-ferrets that recapitulate fatal clinical symptoms, vaccinated ferrets are completely protected from lethal SFTSV challenge without developing any clinical signs. A serum transfer study reveals that anti-envelope antibodies play an important role in protective immunity. Our results suggest that Gn/Gc may be the most effective antigens for inducing protective immunity and non-envelope-specific T cell responses also can contribute to protection against SFTSV infection. This study provides important insights into the development of an effective vaccine, as well as corresponding immune parameters, to control SFTSV infection., Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne virus with no specific treatment or vaccine available. Here, the authors develop a DNA vaccine for SFTSV that is protective against lethal challenge in ferrets and show that anti-envelope antibodies are important for protection.

Morphological and functional changes in cells during the epithelial-mesenchymal transition (EMT) process are known to be regulated by alternative splicing. However, only a few splicing factors involved in EMT have been reported and their underlying mechanisms remain largely unknown. Here, we showed that an isoform of tight junction protein 1 (TJP1) lacking exon 20 (TJP1-α-) is predominantly expressed in tumor tissues and in A549 cells during transforming growth factor-β (TGF-β)-induced EMT. RBM47 promoted the inclusion of exon 20 of TJP1, the alternative exon encoding the α-domain, by which RBM47 recognizes to (U)GCAUG in the downstream intronic region of exon 20. We also found that the first RNA recognition motif (RRM) domain of RBM47 is critical in the regulation of alternative splicing and its recognition to pre-mRNA of TJP1. Furthermore, we demonstrated that the TJP1-α- isoform enhances the assembly of actin stress fibers, thereby promoting cellular migration in a wound healing assay. Our results suggest the regulatory mechanism for the alternative splicing of TJP1 pre-mRNA by RBM47 during EMT, providing a basis for studies related to the modulation of EMT via alternative splicing.

The RNA-binding protein Rbfox3 is a well-known splicing regulator that is used as a marker for post-mitotic neurons in various vertebrate species. Although recent studies indicate a variable expression of Rbfox3 in non-neuronal tissues, including lung tissue, its cellular function in lung cancer remains largely unknown. Here, we report that the number of RBFOX3-positive cells in tumorous lung tissue is lower than that in normal lung tissue. As the transforming growth factor-β (TGF-β) signaling pathway is important in cancer progression, we investigated its role in RBFOX3 expression in A549 lung adenocarcinoma cells. TGF-β1 treatment inhibited RBFOX3 expression at the transcriptional level. Further, RBFOX3 depletion led to a change in the expression levels of a subset of proteins related to epithelial-mesenchymal transition (EMT), such as E-cadherin and Claudin-1, during TGF-β1-induced EMT. In immunofluorescence microscopic analysis, mesenchymal morphology was more prominent in RBFOX3-depleted cells than in control cells. These findings show that TGF-β-induced RBFOX3 inhibition plays an important role in EMT and propose a novel role for RBFOX3 in cancer progression.

In this paper, a self-excited induction generator that can act as an electric retarder is presented, and an effective control method and circuit for enacting it are proposed. To control braking torque, the equivalent circuit parameters of the retarder are changed by switching the proposed circuit. Even though the retarder is a high-voltage high-current ac machine, it uses readily available and inexpensive components including a low-voltage high current-rating MOSFET, diodes, and a polarity capacitor. Dynamo test results show that the proposed circuit and method is effective.

A self-excited induction generator (SEIG) can be a candidate for isolated applications because it does not require any external exciting power but can independently generate electricity. It is also a good candidate for auxiliary brakes in heavy vehicles for several reasons. First, the power efficiency in a brake system is not important as compared with motors or generators. Second, an SEIG can be controlled by a simple electrical circuit. Third, it can be used for regenerative braking. Finally, it is very robust. In this paper, an auxiliary brake for heavy vehicles is proposed by adapting an SEIG and its analog control circuit. The brake structure is the same as that in conventional eddy current brakes but operates as an SEIG. The suggested control circuit does not adopt an electric controller unit but only consists of simple electric devices. A miniature model was designed and manufactured, and the experimental results using the prototype verify that the proposed brake system, including the controller, is very useful.

Rbfox RNA-binding proteins play important roles in the regulation of alternative pre-mRNA splicing, but their role in other gene regulatory mechanisms is not well understood. Here, we show that Rbfox2 is a novel constituent of cytoplasmic stress granules, the translational silencing machinery assembled in response to cellular stress. We also show that the RNA binding activity of the Rbfox family protein is crucial for its localization into stress granules. To investigate the role of Rbfox2 in stress granules we used RNA-immunoprecipitation sequencing to identify cytoplasmic transcriptome-wide targets of Rbfox2. We report that a subset of cell cycle-related genes including retinoblastoma 1 is the target of Rbfox2 in cytoplasmic stress granules, and Rbfox2 regulates the retinoblastoma 1 mRNA and protein expression levels during and following stress exposure. Our study proposes a novel function for Rbfox2 in cytoplasmic stress granules.

Phosphodiesterase 3A (PDE3A), a member of the cGMP-inhibited cyclic nucleotide phosphodiesterase (PDE) family, plays important roles in oocyte maturation and vascular smooth muscle cell proliferation. However, the molecular mechanisms that regulate PDE3A gene expression remain largely unknown. In this study, we investigated the transcriptional regulation of PDE3A , and found that the splicing factor proline and glutamine rich (SFPQ) protein modulated PDE3A mRNA levels. Multiple transcription start sites (TSS1, 2, and 3) were identified within the first exon of PDE3A using 5'-rapid amplification of cDNA ends (RACE). Variable expression levels of three PDE3A variants were also observed in human tissues and HeLa cells. Several putative SFPQ-binding sites were identified upstream of the regulatory region of PDE3A -TSSs using chromatin immunoprecipitation sequencing (ChIP-seq). Serum-induced PDE3A expression was affected by increasing the amount of SFPQ binding to the upstream regulatory region of PDE3A In addition, transcription of PDE3A was lower in human cervical adenocarcinoma cells compared to normal cervical tissue. Furthermore, over-expression of PDE3A induced sensitivity to anti-cancer therapeutic agent, 6-(4-(diethylamino)-3-nitrophenyl)-5-methyl-4,5-dihydropyridazin-3(2H)-one (DNMDP), in HeLa cells. Taken together, these results suggest that SFPQ functions as a transcriptional activator of PDE3A, which is involved in the regulation of DNMDP sensitivity , offering a novel molecular target for the development of anticancer therapies.

Phosphodiesterase 3A (PDE3A), a member of the cGMP-inhibited cyclic nucleotide phosphodiesterase (PDE) family, plays important roles in oocyte maturation and vascular smooth muscle cell proliferation. However, the molecular mechanisms that regulate PDE3A gene expression remain largely unknown. In the present study, we investigated the transcriptional regulation of PDE3A, and found that the splicing factor proline- and glutamine-rich (SFPQ) protein modulated PDE3A mRNA levels. Multiple transcription start sites (TSS1, 2, and 3) were identified within the first exon of PDE3A using 5′-rapid amplification of cDNA ends (RACE). Variable expression levels of three PDE3A variants were also observed in human tissues and HeLa cells. Several putative SFPQ-binding sites were identified upstream of the regulatory region of PDE3A-TSSs using ChIP sequencing (ChIP-seq). Serum-induced PDE3A expression was affected by increasing the amount of SFPQ binding to the upstream regulatory region of PDE3A. In addition, transcription of PDE3A was lower in human cervical adenocarcinoma cells compared with normal cervical tissue. Furthermore, overexpression of PDE3A induced sensitivity to anticancer therapeutic agent, 6-(4-(diethylamino)-3-nitrophenyl)-5-methyl-4,5-dihydropyridazin-3(2H)-one (DNMDP), in HeLa cells. Taken together, these results suggest that SFPQ functions as a transcriptional activator of PDE3A, which is involved in the regulation of DNMDP sensitivity, offering a novel molecular target for the development of anticancer therapies.

RBFOX3, a nuclear RNA-binding protein, is well known as a regulator of alternative pre-mRNA splicing during neuronal development. However, other functions of RBFOX3 are poorly understood. Here, we investigated the function of RBFOX3 in the cytoplasm with respect to regulation of Claudin-1 expression. In human lung tissue, Claudin-1 is higher in RBFOX3-positive cells than in RBFOX3-negative cells. Immunostaining and mRNA quantification revealed that protein levels, but not mRNA levels, of Claudin-1 are increased by RBFOX3. In addition, cycloheximide treatment of human lung cancer cells revealed that RBFOX3 increases the stability of Claudin-1 through attenuation of its ubiquitination. Our study provides insights into the molecular mechanisms by which RBFOX3 regulates Claudin-1 expression in human lung tissue.

In this paper, a regenerative electromagnetic brake, which has the same structure as conventional electromagnetic brakes and the same principle as self-excited induction generators, is introduced, and a miniature model is designed. The most important part of the design stage is to choose proper equivalent circuit parameters for self-excitation within a given operating speed range. This paper describes a 3-D map, called a CN-map, that consists of the rotating speed, capacitance, and stator resistance to verify the possibility of self-excitation during the design stage. A miniature model is designed using the map, and the experimental results obtained with the miniature model confirm the feasibility of the design process.

This paper presents an error compensation method for fixed-width group canonic signed digit (GCSD) multipliers that receive a W-bit input and generate a W-bit product. To efficiently compensate for the truncation error, the encoded signals from the GCSD multiplier are used for the generation of the error compensation bias. By Synopsys simulations, it is shown that the proposed method leads to up to 84% reduction in power consumption and up to 78% reduction in area compared with the fixed-width modified Booth multipliers.

Introduction: We herein present 2 cases involving the combination of rocuronium and sugammadex in patients with motor neuron disease. The patients were a 54-year-old man with progressive muscular atrophy who underwent removal of internal fixators in the arm and leg, and a 66-year-old woman with amyotrophic lateral sclerosis who underwent skin grafting in the left lower leg. General anesthesia was induced with propofol, rocuronium, and remifentanil and maintained with desflurane and remifentanil. At the end of the surgical procedure, we administered sugammadex. Three or 4 minutes after administration of sugammadex, the patients began to breathe spontaneously and were extubated without complications. Conclusion: Sugammadex can be used successfully to reverse neuromuscular blockade in patients with motor neuron disease.

There are many applications that would be aided by the determination of the physical position and orientation of users. Some of the applications include service robots, video conference, intelligent living environments, security systems and speech separation for hands-free communication devices (Coen, 1998; Wax & Kailath, 1983; Mungamuru & Aarabi, 2004; Sasaki et al., 2006; Lv & Zhang 2008). As an example, without the information on the spatial location of users in a given environment, it would not be possible for a service robot to react naturally to the needs of the user. To localize a user, sound source localization techniques are widely used (Nakadai et al., 2000; Brandstein & Ward, 2001; Cheng & Wakefield, 2001; Sasaki et al., 2006). Sound localization is the process of determining the spatial location of a sound source based on multiple observations of the received sound signals. Current sound localization techniques are generally based upon the idea of computing the time difference of arrival (TDOA) information with microphone arrays (Knnapp & Cater, 1976; Brandstein & Silverman, 1997). An efficient method to obtain TDOA information between two signals is to compute the cross-correlation of the two signals. The computed correlation values give the point at which the two signals from separate microphones are at their maximum correlation. When only two isotropic (i.e., not directional as in the mammalian ear) microphones are used, the system experiences front-back confusion effect: the system has difficulty in determining whether the sound is originating from in front of or behind the system. A simple and efficient method to overcome this problem is to incorporate more microphones (Huang et al., 1999). Various weighting functions or pre-filters such as Roth, SCOT, PHAT, Eckart filter and HT can be used to increase the performance of time difference estimation (Knnapp & Cater, 1976). However, the performance improvement is achieved with the penalty of large power consumption and hardware overhead, which may not be suitable for the implementation of portable systems such as service robots. In this chapter, we propose an efficient sound source localization method under the assumption that three isotropic microphones are used to avoid the front-back confusion

We report a case of lipoid pneumonia in a 57-year-old man who had a history of ingestion of green perilla oil and residual neurologic deficit of cerebral infarction with right hemiparesis. Lipoid pneumonia was diagnosed by bronchoalveolar lavage.