Control of bipedal locomotion with a neural oscillator-based brain-computer interface

This study proposes a neural oscillator-based brain–computer interface (BCI) that controls a bipedal neuromusculoskeletal (NMS) model by inputting electroencephalogram (EEG) signals.In this BCI system, while the bipedal NMS system realizes bipedal locomotion through internal entrainment among neural oscillators and a musculoskeletal system, the locomotion of the system is controlled via external entrainment of the neural oscillators to the external input of EEG signals.As the first step in developing the neural oscillator-based BCI controlling a bipedal NMS model, exploratory numerical simulations were conducted to investigate the behavior of the proposed BCI when sinusoidal waves and alpha waves were inputted.The following tendencies were observed: (a) inputting sinusoidal waves with small amplitudes and high frequencies did not affect the natural walking behavior of the bipedal NMS model that was generated by including only offset values in the external input, (b) inputting sinusoidal waves with small amplitudes and low frequencies disturbed and decelerated the walking behavior, (c) inputting sinusoidal waves with large amplitudes accelerated the walking behavior, (d) inputting sinusoidal waves with large amplitudes and a particular frequency changed walking behavior to running behavior, (e) changing the external input of alpha waves between an eyes-open condition and an eyes-closed condition successfully changed the walking behavior.The eyes-open condition led to faster walking compared with the eyes-closed condition

Evolutionary Selection of the Nuclear Localization Signal in the Viral Nucleoprotein Leads to Host Adaptation of the Genus Orthobornavirus.

Adaptation of the viral life cycle to host cells is necessary for efficient viral infection and replication. This evolutionary process has contributed to the mechanism for determining the host range of viruses. Orthobornaviruses, members of the family Bornaviridae, are non-segmented, negative-strand RNA viruses, and several genotypes have been isolated from different vertebrate species. Previous studies revealed that some genotypes isolated from avian species can replicate in mammalian cell lines, suggesting the zoonotic potential of avian orthobornaviruses. However, the mechanism by which the host specificity of orthobornaviruses is determined has not yet been identified. In this study, we found that the infectivity of orthobornaviruses is not determined at the viral entry step, mediated by the viral glycoprotein and matrix protein. Furthermore, we demonstrated that the nuclear localization signal (NLS) sequence in the viral nucleoprotein (N) has evolved under natural selection and determines the host-specific viral polymerase activity. A chimeric mammalian orthobornavirus, which has the NLS sequence of avian orthobornavirus N, exhibited a reduced propagation efficiency in mammalian cells. Our findings indicated that nuclear transport of the viral N is a determinant of the host range of orthobornaviruses, providing insights into the evolution and host adaptation of orthobornaviruses

Inhibition of microRNA-33b in humanized mice ameliorates nonalcoholic steatohepatitis

マイクロRNA-33bの阻害は非アルコール性脂肪肝炎を改善する --核酸医薬による治療応用へ--. 京都大学プレスリリース. 2023-06-13.Nonalcoholic steatohepatitis (NASH) can lead to cirrhosis and hepatocellular carcinoma in their advanced stages; however, there are currently no approved therapies. Here, we show that microRNA (miR)-33b in hepatocytes is critical for the development of NASH. miR-33b is located in the intron of sterol regulatory element–binding transcription factor 1 and is abundantly expressed in humans, but absent in rodents. miR-33b knock-in (KI) mice, which have a miR-33b sequence in the same intron of sterol regulatory element–binding transcription factor 1 as humans and express miR-33b similar to humans, exhibit NASH under high-fat diet feeding. This condition is ameliorated by hepatocyte-specific miR-33b deficiency but unaffected by macrophage-specific miR-33b deficiency. Anti-miR-33b oligonucleotide improves the phenotype of NASH in miR-33b KI mice fed a Gubra Amylin NASH diet, which induces miR-33b and worsens NASH more than a high-fat diet. Anti-miR-33b treatment reduces hepatic free cholesterol and triglyceride accumulation through up-regulation of the lipid metabolism–related target genes. Furthermore, it decreases the expression of fibrosis marker genes in cultured hepatic stellate cells. Thus, inhibition of miR-33b using nucleic acid medicine is a promising treatment for NASH

Adoptive transfer of antithyrotropin receptor (TSHR) autoimmunity from TSHR knockout mice to athymic nude mice

We have recently shown that wild type mice are highly tolerant, whereas thyrotropin receptor (TSHR) knockout (KO) mice are susceptible to immunization with the mouse TSHR, the autoantigen in Graves\u27 disease. However, because TSHR KO mice lack the endogenous TSHR, Graves-like hyperthyroidism cannot be expected to occur in these mice. We therefore performed adoptive transfer of splenocytes from TSHR KO mice into nude mice expressing the endogenous TSHR. Anti-TSHR autoantibodies were detected in approximately 50% recipient mice 4 wk after adoptive transfer of splenocytes (5 × 10 7/mouse) from TSHR KO mice immunized with adenovirus expressing mTSHR A subunit and persisted for 24 wk. Depletion of regulatory T cells by anti-CD25 antibody in the donor mice increased successful transfer rates without increasing antibody levels. Some recipient mice showed transient increases in thyroid-stimulating antibodies and T4 levels 4-8 wk after transfer, but many became thyroid-blocking antibody positive and hypothyroid 24 wk later. Adoptive transfer of splenocytes from naïve TSHR KO mice transiently induced very low antibody titers when the recipient mice were treated with anticytotoxic lymphocyte antigen 4 and antiprogrammed cell death 1 ligand 1 antibodies for 8 wk after transfer. Histologically, macrophages infiltrated the retrobulbar adipose tissues and extraocular muscles in a small fraction of the recipients. Our findings demonstrate successful adoptive transfer of anti-TSHR immune response from TSHR KO mice to nude mice. Although the recipient mice developed only transient and infrequent hyperthyroidism, followed by eventual hypothyroidism, induction of orbital inflammation suggests the possible role of anti-TSHR immune response for Graves\u27 orbitopathy

The relationship between skeletal muscle and ventilatory response to exercise in myocardial infarction

Background: Skeletal muscle is important to determine physical activity and exercise capacity in cardiovascular disease. This study aims to investigate the relationship between skeletal muscle volume measured by bioelectrical impedance analysis and ventilation indices assessed by cardiopulmonary exercise test in patients with myocardial infarction. Methods: A total of 60 patients (57 men; 59 ± 9 years) who underwent percutaneous coronary intervention for ST-elevation myocardial infarction were enrolled into this study. All patients performed cardiac rehabilitation and then achieved physical activity of daily life. No patient was complicated by diabetes mellitus. In symptom-limited cardiopulmonary exercise test, minute ventilation (V̇E), oxygen consumption (V̇O2), and carbon dioxide production (V̇CO2) were continuously obtained. A volume of skeletal muscle measured by bioelectrical impedance analysis was normalized for height (skeletal muscle index). Results: The skeletal muscle index showed a significant inverse correlation with peak V̇E/V̇O2 (p = 0.02, r = −0.39) and peak V̇E/V̇CO2 (p = 0.02, r = −0.30). In addition, the skeletal muscle index inversely correlated with V̇E/V̇CO2 slope (p = 0.02, r = −0.30). On the other hand, the skeletal muscle index did not significantly correlate with peak V̇O2 (p = 0.56, r = 0.08) and peak V̇CO2 (p = 0.99, r = 0.001). Besides, the skeletal muscle index did not significantly correlate with ΔV̇O2/Δwork rate slope (p = 0.60, r = 0.07). Conclusions: The increase in skeletal muscle index was associated with the amelioration of ventilatory efficacy to exercise at the peak level. Furthermore, the increase in skeletal muscle index may account for favorable prognosis. These findings could strengthen the role of skeletal muscle in exercise capacity of patients with myocardial infarction