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Sato, J.

Publications and source records attributed to Sato, J..

6 recordsLinked to original sources

Evaluation of Locomotor Activity in Group-Housed Hamsters: Effects of Cage Size and Running Wheel Availability

While hamsters are commonly housed in groups within pet shops in Japan, small cages are often thought to restrict their physical activity, leading to arguments that larger cages should be provided. Although previous research has investigated how cage size and running wheel availability influence activity levels in individually housed hamsters, no studies to date have examined these specific effects in a social housing context. Therefore, this study investigated how cage size and the presence of a running wheel affect the activity levels of individual hamsters using the group-housing conditions with five hamsters. Video recordings were captured for 24 hours across four distinct cage environments using a camera installed directly above each cage. From these recordings, the distances traveled on both the cage floor and the running wheel were calculated for each hamster and statistically analyzed. The results revealed that overall activity levels were significantly higher in cages equipped with a running wheel than in those without. Although cage size did not yield a statistically significant difference, a marginal trend toward higher activity in larger cages was observed.

animal behavior and cognition↗

Revisiting the in vivo Functions of Coilin in Mice

Cajal bodies (CBs), first identified in the early 20th century, are classic nuclear structures organized primarily by the protein coilin. Although CBs have long been implicated in snRNA modification and maturation, their precise roles in mice remain unclear. Here, we revisit the functions of CBs by using genome editing to generate mice that lack nearly the entire coilin protein, retaining only the first seven amino acids. Mass-spectrometry analyses showed reduced 2'-O-methylation of U2 snRNA in coilin mutant liver; however, these reductions had minimal impact on overall gene expression and pre-mRNA splicing patterns. Additionally, detailed analysis recapitulated previously reported testicular size reductions and newly revealed decreased proportions of high-quality sperm. We also identified novel coilin-containing condensates distinct from genuine CBs in the nuclear pocket of elongating spermatids. Our findings implicate that coilin orchestrates membraneless organelles in various compartments, playing multifunctional roles beyond classical CB formation.

molecular biology↗

Discovery of The Clinical Candidate S-892216: A Second-Generation of SARS-CoV-2 3CL Protease Inhibitor for Treating COVID-19

The coronavirus disease 2019 (COVID-19) pandemic crisis has been mitigated by worldwide efforts to develop vaccines and therapeutic drugs. However, there remains concern regarding public health and an unmet need for therapeutic options. Herein, we report the discovery of S-892216, a second-generation SARS-CoV-2 3C-like protease (3CLpro) inhibitor, to treat COVID-19. S-892216 is a reversible covalent 3CLpro inhibitor with highly potent antiviral activity and an EC50 value of 2.48 nM against SARS-CoV-2 infected cells. Structure-based design of a covalent modifier for compound 1 revealed that introducing a nitrile warhead increased 3CLpro inhibition activity by 180-fold. Subsequent optimization efforts yielded S-892216, which combined a favorable pharmacokinetic profile and high off-target selectivity. S-892216 exhibited antiviral activity against diverse SARS-CoV-2 variants, with no cross-resistance to major mutations reducing antiviral activities of nirmatrelvir and ensitrelvir. In SARS-CoV-2-infected mice, S-892216 inhibited viral replication in the lungs similar to ensitrelvir, although at a 30-fold lower dose.

biochemistry↗

Measuring the neurodevelopmental trajectory of excitatory-inhibitory balance via visual gamma oscillations

Disruption of the balance between excitatory and inhibitory neurotransmission (E-I balance) underlies theories of many neurodevelopmental disorders, however, its study is typically restricted to adults, animal models and the lab-bench. Neurophysiological oscillations in the gamma frequency band relate closely to E-I balance, and a new technology - OPM-MEG - offers the possibility to measure such signals across the lifespan. We used OPM-MEG to measure gamma oscillations induced by visual stimulation in >100 participants, aged 2-34 years. We demonstrate a significantly changing spectrum with age, with low amplitude broadband gamma oscillations in children and high amplitude band limited oscillations dominating in adults. We used a canonical cortical microcircuit to model these gamma signals, revealing significant age-related shifts in E-I balance in superficial pyramidal neurons in visual cortex. Our findings detail the first MEG metrics of gamma oscillations and their underlying generators from toddlerhood, providing a benchmark against which future studies can contextualise.

neuroscience↗

The development of aperiodic and periodic resting-state power between early childhood and adulthood: new insights from optically pumped magnetometers

Neurophysiological signals, comprised of both periodic (e.g., oscillatory) and aperiodic (e.g., non-oscillatory) activity, undergo complex developmental changes between childhood and adulthood. With much of the existing literature primarily focused on the periodic features of brain function, our understanding of aperiodic signals is still in its infancy. Here, we are the first to examine age-related changes in periodic (peak frequency and power) and aperiodic (slope and offset) activity using optically pumped magnetometers (OPMs), a new, wearable magnetoencephalography (MEG) technology that is particularly well-suited for studying development. We examined age-related changes in these spectral features in a sample (N=65) of toddlers (1-3 years), children (4-5 years), young adults (20-26 years), and adults (27-38 years). Consistent with the extant literature, we found significant age-related decreases in the aperiodic slope and offset, and changes in peak frequency and power that were frequency-specific; we are the first to show that the effect sizes of these changes also varied across brain regions. This work not only adds to the growing body of work highlighting the advantages of using OPMs, especially for studying development, but also contributes novel information regarding the variation of neurophysiological changes with age across the brain.

neuroscience↗

Decoding affective states across databases using functional near-infrared spectroscopy

Affective decoding is the inference of human emotional states using brain signal measurements. This approach is crucial to develop new therapeutic approaches for psychiatric rehabilitation, such as affective neurofeedback protocols. To reduce the training duration and optimize the clinical outputs, an ideal clinical neurofeedback could be trained using data from an independent group of volunteers before being used by new patients. Here, we investigated if this subject-independent design of affective decoding can be achieved using functional near-infrared spectroscopy (fNIRS) signals from frontal and occipital areas. For this purpose, a linear discriminant analysis classifier was first trained in a dataset (49 participants, 24.65{+/-}3.23 years) and then tested in a completely independent one (20 participants, 24.00{+/-}3.92 years). Significant balanced accuracies between classes were found for positive vs. negative (64.50 {+/-} 12.03%, p<0.01) and negative vs. neutral (68.25 {+/-} 12.97%, p<0.01) affective states discrimination during a reactive block consisting in viewing affective-loaded images. For an active block, in which volunteers were instructed to recollect personal affective experiences, significant accuracy was found for positive vs. neutral affect classification (71.25 {+/-} 18.02%, p<0.01). In this last case, only three fNIRS channels were enough to discriminate between neutral and positive affective states. Although more research is needed, for example focusing on better combinations of features and classifiers, our results highlight fNIRS as a possible technique for subject-independent affective decoding, reaching significant classification accuracies of emotional states using only a few but biologically relevant features.

neuroscience↗